Carbamazepine is an oral antiepileptic, specific analgesic, and mood stabilizer that is structurally similar to tricyclic antidepressants. Carbamazepine is used for the treatment of partial seizures, both simple and complex, and for generalized tonic-clonic seizures. It does not appear to control absence (petit mal) seizures. Carbamazepine is preferred over phenobarbital for children because it has fewer adverse effects on behavior and alertness. Carbamazepine is also used for the treatment of trigeminal neuralgia and acute manic or mixed episodes associated with bipolar I disorder. Antiepileptic drugs, including carbamazepine, are associated with an increased risk of suicidal thoughts and behaviors; patients should be monitored for new or worsening depression, suicidal thoughts and/or behaviors, and changes in mood or behavior. Carbamazepine was FDA-approved in 1968.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 2
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-INJECTABLE Drugs: Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
-ORAL TABLETS/CAPSULES/ORAL LIQUID: Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown; may require eye/face protection.
Route-Specific Administration
Oral Administration
-Administer with meals to minimize GI side effects.
Oral Solid Formulations
-Chewable tablets: Chew well before swallowing.
-Extended-release tablets: Swallow whole. Do not crush, cut, or chew. Do not administer damaged tablets or tablets without a release portal. The tablet coating is not absorbed and is excreted in the feces; the coating may be noticeable in the stool.
-Extended-release capsules: The capsule may be opened and the beads sprinkled over food, such as a teaspoon of applesauce or other similar food product, if desired. Do not crush or chew capsules or the capsule beads.
Oral Liquid Formulations
-Suspension: Shake suspension well prior to use. Measure dose with calibrated oral syringe, spoon, or cup.
-For administration of suspension via nasogastric or enteral feeding tubes: Before drug administration, flush the tube with 15 to 30 mL of water. Dilute carbamazepine suspension with an equal volume of diluent (Sterile Water for Injection, 5% Dextrose Injection, or 0.9% Sodium Chloride Injection) to prevent significant loss of drug due to adherence of the drug to the polyvinyl chloride walls of feeding tubes or diminished absorption during enteral or nasogastric tube feeding. After administration, flush the tube with an additional 15 to 30 mL of water. Do not administer carbamazepine suspension with any other liquid medications or diluents.
-For conversion from oral tablets/capsules to oral suspension: Since a given dose of carbamazepine suspension will produce higher peak concentrations than the same dose given as tablets or capsules, convert to the suspension from the oral tablets or capsules by administering the same mg/day in smaller, more frequent doses (e.g., changing from twice daily for tablets to 4 times daily for the suspension).
Anticonvulsants, including carbamazepine, are thought to carry an increased risk of suicidal ideation and behavior. An analysis by the FDA of previously gathered drug data showed that persons receiving anticonvulsants had approximately twice the risk of suicidal behavior or ideation (0.43%) as persons receiving placebo (0.24%). The relative risk for suicidality was higher in persons with epilepsy compared to those with other conditions. Age was not a determining factor. The increased risk of suicidal ideation and behavior occurred between 1 and 24 weeks after therapy initiation. However, a longer duration of therapy does not preclude the possibility of an association to the drug since most studies included in the analysis did not continue beyond 24 weeks. Closely monitor all persons beginning treatment with anticonvulsants or currently receiving such treatment for emerging or worsening suicidal thoughts/behavior or depression. Advise those receiving anticonvulsants and caregivers of the increased risk of suicidal thoughts and behaviors and to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior.
Dizziness, drowsiness, and unsteadiness were among the most commonly reported adverse reactions with carbamazepine, particularly during the initial phases of therapy. In clinical trials in persons with bipolar I disorder, dizziness, drowsiness, and ataxia were reported in 44%, 32%, and 15% of carbamazepine-treated subjects, respectively, compared to 12%, 13%, and 0.4%, respectively. To minimize the possibility of such reactions, initiate carbamazepine therapy at a low dosage and titrate as recommended. Sedation may be seen for the first few days of therapy or after a dosage increase. Additionally, abnormal thinking (2% vs. 0.4%), blurred vision (6% vs. 2%), paresthesias (2% vs. 1%), speech disorder (6% vs. 0.4%), tremor (3% vs. 1%), and vertigo (2% vs. 1%) were reported in clinical trials in persons with bipolar I disorder. Similar adverse reactions have been reported with carbamazepine use for other indications. Other CNS adverse reactions reported with carbamazepine include confusion, diplopia, headache, fatigue, visual hallucinations, oculomotor disturbances, nystagmus, abnormal involuntary movements, coordination disturbances, peripheral neuritis, depression with agitation, talkativeness, tinnitus, and hyperacusis. Tolerance usually develops, but such side effects may appear if carbamazepine dosage is supratherapeutic for the individual. Dose adjustments may be necessary. There have been reports of associated paralysis and other symptoms of cerebral arterial insufficiency, but the exact relationship of these reactions to the drug has not been established. Isolated cases of neuroleptic malignant syndrome have been reported with and without concomitant use of psychotropic drugs with carbamazepine.
Hepatic effects, ranging from slightly elevated hepatic enzymes to rare cases of hepatic failure, have been reported. In some cases, hepatic effects may progress despite discontinuation of the drug. Cholestasis, hepatitis, and jaundice have also been reported with carbamazepine. Perform baseline and periodic evaluations of liver function during treatment with carbamazepine since liver damage may occur. Discontinue carbamazepine based on clinical judgement, if indicated by newly occurring or worsening clinical or laboratory evidence of liver dysfunction or hepatic damage, or in the case of active liver disease. In addition, rare instances of vanishing bile duct syndrome have been reported. This syndrome consists of a cholestatic process with a variable clinical course ranging from fulminant to indolent, involving the destruction and disappearance of the intrahepatic bile ducts. Some, but not all, cases are associated with features that overlap with other immunoallergenic syndromes. Acute attacks of hepatic porphyria have been reported during carbamazepine therapy. Carbamazepine administration has also been demonstrated to increase porphyrin precursors in rodents, a presumed mechanism for the induction of acute attacks of porphyria.
Hyponatremia can occur as a result of treatment with carbamazepine. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The risk of developing SIADH with carbamazepine treatment may be dose-related. Signs and symptoms of hyponatremia include headache, new or increased seizure frequency, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to falls. Consider discontinuing carbamazepine in persons with symptomatic hyponatremia. Hyperammonemia, decreased concentrations of plasma calcium leading to osteoporosis, and decreases in thyroid function test values (T3, T4) have been reported during postmarketing experience with carbamazepine.
Hypertension was reported in 3% of carbamazepine-treated subjects vs. 0.4% of subjects given placebo in bipolar I disorder clinical trials; hypertension has also been reported with use for other indications. Other cardiovascular adverse effects reported with carbamazepine include second and third degree AV block, cardiac arrhythmias or arrhythmia exacerbation, congestive heart failure, edema, aggravation of coronary artery disease, hypotension, syncope, thrombophlebitis, thromboembolism, and adenopathy or lymphadenopathy. Some cardiovascular complications have resulted in fatalities.
Aplastic anemia, bone marrow suppression, agranulocytosis, pancytopenia, thrombocytopenia, leukopenia, leukocytosis, and eosinophilia have been reported with carbamazepine. If low or decreased white blood cell or platelet counts occur in the course of carbamazepine therapy, monitor closely. Discontinue carbamazepine if any evidence of significant bone marrow suppression develops. Clinical features can include fever, difficulty breathing on exertion, fatigue, easy bruising, petechiae, epistaxis, gingival bleeding, and heavy menses. Case-control population data have demonstrated that the risk of developing aplastic anemia or agranulocytosis is 5 to 8 times greater in persons treated with carbamazepine than in the general population. However, the overall risk of these reactions in the untreated general population is low (i.e., approximately 2 to 6 persons per 1 million population per year). Although reports of transient or persistent decreased white blood cell counts are not uncommon in association with carbamazepine, the majority of cases of leukopenia have not progressed to aplastic anemia or agranulocytosis. Hypogammaglobulinemia has also been reported during carbamazepine treatment.
Serious adverse reactions such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) may occur and require immediate drug discontinuation and appropriate medical attention; in rare cases, fatalities have occurred. Rarely, vanishing bile duct syndrome (VBDS) has been reported in association with carbamazepine. One case of VBDS was associated with SJS. The risk of SJS/TEN is about 1 to 6 per 10,000 new users in countries with mainly Caucasian populations. The risk of these reactions in countries with primarily Asian patients may be 10 times higher because of variants found in the immune system gene HLA-B 1502, which occur at a higher rate in Asian patients. In addition, a moderate association between the risk of developing hypersensitivity reactions, including SJS/TEN and maculopapular eruptions, and the presence of HLA-A 3101 was detected in retrospective case-control studies. In patients known to be positive for HLA-A 3101, the risks and benefits of carbamazepine should be weighed before considering carbamazepine therapy. Because many patients who are HLA-B 1502 or HLA-A 3101 positive will not develop SJS/TEN or other hypersensitivity reactions and these reactions can still occur infrequently in HLA-B 1502 or HLA-A 3101 negative patients of any ethnicity, HLA genotyping as a screening tool must never substitute for appropriate clinical vigilance and patient management. Carbamazepine has been associated with acute generalized exanthematous pustulosis (AGEP). The nonfollicular, pustular, erythematous rash starts suddenly, is associated with fever above 38 degrees C, and is distinct from pustular psoriasis, although biopsy results in each reveal spongiform subcorneal pustules. Drugs are the main cause of AGEP. A period of 2 to 3 weeks after an inciting drug exposure appears necessary for a first episode of AGEP. Unintentional reexposure may cause a second episode within 2 days. Clinical presentation is diverse with cutaneous lesions beyond erythema and pustules present in half of the cases. For example, bullous lesions, edema, purpura, pruritus, and mucosal erosions are possible. The mean duration of the pustules is 9.7 days followed by an annular desquamation, as long as the causative drug or factor is discontinued. The physiopathological mechanisms of AGEP have not been determined but the pathological criteria of edema, leukocytoclastic vasculitis, eosinophil exocytosis, and keratinocyte focal necrosis are distinctive. Pustule confluence or very small pustules may lead a clinician to make an incorrect diagnosis of TEN, of drug-induced erythroderma, or of staphylococcal scalded skin syndrome. There have been rare cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) in patients treated with carbamazepine. Some of these events have been fatal or life-threatening. Rarely, vanishing bile duct syndrome has been reported in association with carbamazepine and in some cases is associated with features overlapping with DRESS (e.g., fever, eosinophilia). Retrospective case-control studies have found a moderate association between the risk of developing hypersensitivity reactions (including DRESS) and the presence of HLA-A 3101, an inherited allelic variant of the HLA-A gene, in patients using carbamazepine. HLA-A 3101 is expected to be carried by more than 15% of patients of Japanese, Native American, Southern Indian, and some Arabic ancestry, up to about 10% in patients of Han Chinese, Korean, European, Latin American, and other Indian ancestry, and up to about 5% in African-Americans and patients of Thai, Taiwanese, and Chinese ancestry. In patients known to be positive for HLA-A 3101, the risks and benefits of carbamazepine should be weighed before considering carbamazepine therapy. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. The disorder is variable in its expression, and other organ systems may also be involved. Of note, early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Discontinue carbamazepine if an alternative etiology for the signs or symptoms cannot be established. Because many patients who are HLA-A 3101 positive will not develop hypersensitivity reactions and these reactions can still occur infrequently in HLA-A 3101 negative patients of any ethnicity, HLA genotyping as a screening tool must never substitute for appropriate clinical vigilance and patient management. Pruritus (8% vs. 2%) and rash (unspecified) (7% vs. 4%) have been reported in placebo-controlled trials of carbamazepine in patients with bipolar I disorder; these adverse effects have also been reported in other patient populations using carbamazepine, although the incidence is not specified. Other dermatological effects of carbamazepine where an incidence is not provided by the manufacturer include photosensitivity, alopecia, urticaria, and alterations in skin pigmentation, exfoliative dermatitis, erythema multiforme and erythema nodosum, purpura, aggravation of disseminated lupus erythematosus, onychomadesis, hirsutism, and diaphoresis. In certain cases, discontinuation of therapy may be necessary.
Pulmonary hypersensitivity characterized by fever, dyspnea, pneumonitis, or pneumonia has been reported with carbamazepine. Additionally, chills, fever, and pancreatitis have been reported with carbamazepine.
Isolated cases of a lupus-like symptoms have been reported with carbamazepine. A case of aseptic meningitis, accompanied by myoclonus and peripheral eosinophilia, has been reported in a person taking carbamazepine in combination with other medications. Dechallenge was successful, and the aseptic meningitis reappeared upon rechallenge with carbamazepine.
Genitourinary adverse reactions reported with carbamazepine include increased urinary frequency, acute urinary retention, oliguria with elevated blood pressure, azotemia, and renal failure (unspecified). Albuminuria, glycosuria, elevated BUN, proteinuria, and microscopic deposits in the urine have also occurred.
Due to the potential for teratogenesis, the risks and benefits of carbamazepine therapy should be weighed carefully in pregnant women or in women of childbearing potential. Epidemiologic data suggest an association between carbamazepine use during pregnancy and congenital malformation, including spina bifida, craniofacial defects, and developmental delay. In reproduction studies in rats, carbamazepine has been associated with fetal anomalies, including malformed ribs, cleft palate, talipes, and anophthalmia. The effects on fetal development appear to be independent of the presence of the seizure disorder itself and the risk for embryopathy is 2- to 3-fold higher for the use of monotherapy (compared to no drug). Risks further increase if more than 1 anticonvulsant drug is ingested, so monotherapy is preferred when possible. Seizures themselves can be detrimental to the viability of a pregnancy, so anticonvulsant therapy is often continued despite potential fetal risks. An estimated > 90% of women will deliver infants without major malformations if monotherapy is used.
Constipation (10% carbamazepine vs. 5% placebo), nausea (29% vs. 10%), vomiting (18% vs. 3%), and xerostomia (8% vs. 3%) were among the most commonly reported adverse reactions with carbamazepine in clinical trials in persons with bipolar I disorder; these adverse effects have also been reported in persons taking carbamazepine for other indications. To minimize nausea and vomiting during the initial phases of therapy, initiate carbamazepine at the lowest dosage recommended. Other gastrointestinal adverse effects associated with carbamazepine include abdominal pain, anorexia, diarrhea, gastric distress, glossitis, and stomatitis.
Ocular adverse effects reported with carbamazepine include scattered punctate cortical lens opacities, increased intraocular pressure (ocular hypertension), as well as conjunctivitis. Although a direct causal relationship has not been established, baseline and periodic eye examinations, including slit-lamp, funduscopy, and tonometry, are recommended since many phenothiazines and related drugs have been shown to cause eye changes.
Asthenia was reported in 8% of carbamazepine-treated subjects compared with 4% of subjects given placebo in clinical trials in persons with bipolar I disorder and has also been reported in persons taking carbamazepine for other indications. Twitching was reported in 2% of carbamazepine-treated subjects compared to 1% of subjects given placebo in clinical trials in persons with bipolar I disorder. Other musculoskeletal adverse events associated with carbamazepine include arthralgia, myalgia, muscle cramps (i.e., leg cramps), and bone loss.
Rare cases of anaphylactoid reactions, including anaphylaxis, and angioedema involving the larynx, glottis, lips, and eyelids have been reported after the first or subsequent doses of carbamazepine. If any of these reactions develop after treatment with carbamazepine, discontinue the drug, and start an alternative therapy. Do not rechallenge with carbamazepine.
Anticonvulsants may enhance the hepatic breakdown of vitamin D into inactive polar metabolites. Monitor persons receiving carbamazepine for more than 6 months for vitamin D deficiency and supplement vitamin D when indicated by low serum concentrations. Anticonvulsants may also impair folate metabolism; monitor for folate deficiency and supplement folate when necessary.
Impotence (erectile dysfunction), abnormal spermatogenesis, and male infertility been reported with carbamazepine. Clinical studies have reported a reduction in semen quality in males of reproductive potential who were given carbamazepine to treat epilepsy. In a study of 101 males (60 with epilepsy and 41 without), males with epilepsy who were taking carbamazepine were noted to have abnormalities in sperm quality, including low sperm concentration (oligospermia, 38% vs. 0% of controls), poor motility (69% vs. 35%), and abnormal morphology (38% vs. 3%). No correlations were found between duration of epilepsy or treatment, drug dose or serum concentration, or serum hormone concentrations. Those with epilepsy demonstrated lower frequency of normal sperm morphology and motility than control (non-epileptic) subjects. Animal studies have demonstrated testicular atrophy and aspermatogenesis in rats after repeated oral administration of carbamazepine at clinically relevant doses. While underlying epileptic disorders may independently play a role in such reproductive changes, consider the effects of carbamazepine on male fertility for anyone requiring treatment.
Increases in total cholesterol (e.g., hypercholesterolemia), HDL, LDL, and triglycerides (e.g., hypertriglyceridemia) have been observed in some persons taking anticonvulsants. Periodic evaluation of these parameters is recommended during carbamazepine therapy.
Carbamazepine may cause life-threatening serious rash, including Stevens-Johnson syndrome and toxic epidermal necrolysis. The estimated risk of developing these serious adverse effects is about 1 to 6 per 10,000 new users of carbamazepine in countries of mainly White populations, and an estimated risk which is 10 times higher in some Asian countries. The inherited variant of an immune system gene (HLA-B 1502), which is associated with the development of some serious skin reactions, is most prevalent in Asian patients. Therefore, it is recommended that Asian patients undergo a genetic blood test prior to initiation of carbamazepine treatment. The benefits of treatment with carbamazepine should be weighed against the risks in patients who test positive for HLA-B 1502. The test does not appear to be beneficial in those who have been taking carbamazepine for more than a few months, since it is unlikely that the skin reactions will develop after that time regardless of the presence or absence of the variant gene.
In January 2008, the FDA alerted healthcare professionals of an increased risk of suicidal ideation and behavior in patients receiving anticonvulsants to treat epilepsy, psychiatric disorders, or other conditions (e.g., migraine, neuropathic pain). This alert followed an initial request by the FDA in March 2005 for manufacturers of marketed anticonvulsants to provide data from existing controlled clinical trials for analysis. Prior to this request, preliminary evidence had suggested a possible link between anticonvulsant use and suicidality. The primary analysis consisted of 199 placebo-controlled clinical studies with a total of 27,863 patients in drug treatment groups and 16,029 patients in placebo groups (>= 5 years of age). There were 4 completed suicides among patients in drug treatment groups versus none in the placebo groups. Patients receiving anticonvulsants had approximately twice the risk of suicidal behavior or ideation as patients receiving placebo (0.43% vs. 0.24%, respectively; RR 1.8, 95% CI: 1.2-2.7). The relative risk for suicidality was higher in patients with epilepsy compared to those with other conditions; however, the absolute risk differences were similar in trials for epilepsy and psychiatric indications. Age was not a determining factor. The increased risk of suicidal ideation and behavior was observed between 1 and 24 weeks after therapy initiation. However, a longer duration of therapy should not preclude the possibility of an association to the drug since most studies included in the analysis did not continue beyond 24 weeks. Data were analyzed from drugs with adequately designed clinical trials including carbamazepine, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, valproate, and zonisamide. However, this is considered to be a class effect. All patients beginning treatment with anticonvulsants or currently receiving such treatment should be closely monitored for emerging or worsening depression or suicidal thoughts/behavior. Patients and caregivers should be informed of the increased risk of suicidal thoughts and behaviors and should be advised to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. Anticonvulsants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. Because of the relationship of carbamazepine to other tricyclic compounds, the possibility of activation of behavioral disorders, such as a latent psychosis should be borne in mind.
Carbamazepine is not recommended for use in petit mal (absence) seizures, atonic seizures, or myoclonic seizures because it can exacerbate these conditions. If a worsening of seizures occurs when therapy is initiated, this possibility should be considered.
Unless severe adverse reactions warrant, abrupt discontinuation of carbamazepine therapy should not be undertaken in patients with seizure disorders. Anticonvulsant drugs should be withdrawn gradually to minimize the potential of increased seizure frequency. If adverse reactions are of such severity that carbamazepine must be discontinued, the practitioner must be aware that abrupt discontinuation of any anticonvulsant drug in a responsive epileptic patient may lead to drug withdrawal seizures or even status epilepticus with its life-threatening hazards.
Carbamazepine is contraindicated in patients with a carbamazepine hypersensitivity. Carbamazepine is structurally related to tricyclic antidepressants and is contraindicated in patients with a tricyclic antidepressant hypersensitivity. Carbamazepine therapy should be prescribed only after critical benefit-to-risk assessment in patients with a history of adverse hematologic, hypersensitivity, adverse reactions to carbamazepine, or other anticonvulsants, and in patients known to be positive for HLA-A 3101. There is a moderate association between the risk of developing hypersensitivity reactions and the presence of HLA-A 3101, an inherited allelic variant of the HLA-A gene. HLA-A 3101 is expected to be carried by greater than 15% of patients of Japanese, Native American, Southern Indian, and some Arabic ancestry; up to about 10% in patients of Han Chinese, Korean, European, Latin American, and other Indian ancestry; and up to about 5% in Black patients and patients of Thai, Taiwanese, and Chinese ancestry. Hypersensitivity reactions to anticonvulsants may present as various organ system problems, including cardiac, liver, renal, and skin disorders. A history of hypersensitivity reactions should be obtained for a patient and the immediate family members. If hypersensitivity histories are positive to other classes of anticonvulsants, caution should be used in prescribing carbamazepine. Hypersensitivity reactions to carbamazepine have been reported in patients who previously experienced hydantoin hypersensitivity (i.e., fosphenytoin, phenytoin) or barbiturate hypersensitivity (i.e., hypersensitivity to phenobarbital or primidone). Estimates of cross-sensitivity vary, but may range from 30 to 80%. Carbamazepine, hydantoins, and phenobarbital are all metabolized to hydroxylated aromatic compounds via the cytochrome P450 hepatic oxidative enzymes; arene oxide intermediates are formed during metabolism and are thought to be responsible for cross-sensitivity among these anticonvulsants in susceptible individuals. Cross sensitivity has also been noted between oxcarbazepine and carbamazepine. Some individuals may have a reduced ability to detoxify the intermediate toxic metabolites (e.g., arene oxides) of these anticonvulsants, which may be genetically mediated. However, studies of familial reactions have also shown that allergies to one anticonvulsant may not translate to allergies to others. There is no way to predict with certainty which patients will exhibit cross-sensitivity. Therefore, patients should be made aware of the early signs and symptoms of a potential hematological problem, as well as dermatological, hypersensitivity, or hepatic reactions. These symptoms may include, but are not limited to, fever, sore throat, rash, ulcers in the mouth, easy bruising, lymphadenopathy, and petechial or purpuric hemorrhage, and in the case of liver reactions, anorexia, nausea/vomiting, or jaundice. The patient should be advised that, because these signs and symptoms may signal a serious reaction, that they must report any occurrence immediately to a physician. In addition, the patient should be advised that these signs and symptoms should be reported even if mild or occurring after extended use.
Carbamazepine is contraindicated in patients with a history of bone marrow suppression. Carbamazepine should be used with caution in patients with blood dyscrasias caused by drug therapies or hematological disease because of the potential increased risk of hematologic toxicity. Although uncommon, carbamazepine can cause hematological toxicity consisting of transient leukopenia, neutropenia, thrombocytopenia, or more severe reactions like agranulocytosis or aplastic anemia. Case-control population data have demonstrated that the risk of developing these reactions is 5-8 times greater in patients treated with carbamazepine than in the general population. However aplastic anemia and agranulocytosis are rare in the untreated general population (i.e., 1-2 persons per one million population per year). It would be uncommon for a patient who is taking carbamazepine to develop a severe blood dyscrasia, even if hematologic changes occur during treatment. Pretreatment baseline hematologic counts should be obtained. Periodic hematologic testing during treatment is recommended; if a patient develops neutropenia or thrombocytopenia the patient should be closely monitored. Discontinuation of carbamazepine should be considered if significant bone marrow suppression develops.
Avoid use of carbamazepine in patients with a history of hepatic porphyria (e.g., acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda). Exacerbation of the condition (i.e., acute attacks) has been reported in such patients receiving carbamazepine therapy. In addition, increased porphyrin precursors in rodents, a presumed mechanism for the induction of acute attacks of porphyria, have been demonstrated following carbamazepine administration.
Carbamazepine should be used with caution in patients with hepatic disease because the drug is metabolized in the liver. Carbamazepine hepatotoxicity also has been reported. Hepatotoxicity may be associated with jaundice, rash and eosinophilia. Liver toxicity may be the result of hypersensitivity to the drug. Baseline and periodic evaluations of liver function, particularly in patients with a history of liver disease, must be performed during treatment with this drug since liver damage may occur. Carbamazepine should be discontinued, based on clinical judgment, if indicated by newly occurring or worsening clinical or laboratory evidence of liver dysfunction or hepatic damage, or in the case of active hepatic disease.
Carbamazepine should be used with caution in any patient with cardiac disease, such as cardiac arrhythmias, congestive heart failure or coronary artery disease, because symptoms may be potentiated or exacerbated. Second and third degree heart block have been reported during use of the drug, primarily in patients with pre-existing EKG abnormalities or risk factors for conduction disturbances. Carbamazepine should be avoided if possible in patients with AV block or other conduction abnormalities (bundle-branch block). Myocardial infarction has been associated with other tricyclic compounds (e.g., amitriptyline).
Hyponatremia may develop during treatment with carbamazepine. Hyponatremia may be caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). SIADH risk with carbamazepine treatment appears to be dose-related. Elderly patients and patients receiving diuretic therapy are at greater risk for developing hyponatremia. Consider discontinuation of carbamazepine in patients who develop signs or symptoms of symptomatic hyponatremia (e.g., headache, new or increased seizure frequency, concentration difficulty, memory impairment, confusion, weakness, or unsteadiness). Consider monitoring sodium concentrations if clinically appropriate.
Carbamazepine should be used with caution in patients with alcoholism because they can experience increased CNS depression and have an increased risk for hepatotoxicity. In addition, concomitant use of carbamazepine and ethanol can decrease the ability to perform tasks requiring mental alertness.
Carbamazepine commonly causes blurred vision, dizziness, drowsiness, and fatigue. Patients should be advised to use caution when driving or operating machinery, or performing other tasks that require mental alertness until they are aware of whether carbamazepine adversely affects their mental and/or motor performance.
In persons with a history of increased intraocular pressure, such as glaucoma, consider assessing intraocular pressure before initiating carbamazepine treatment and periodically during therapy. Baseline and periodic eye examinations, including slit-lamp, funduscopy, and tonometry, are recommended since many phenothiazines and related drugs have been shown to cause eye changes. Carbamazepine has mild anticholinergic activity.
Concomitant use of MAOI therapy with carbamazepine is contraindicated due to the risk for serotonin syndrome. Before beginning treatment with carbamazepine, MAOI therapy should be discontinued for a minimum of 14 days.
Carbamazepine can cause fetal harm when administered during pregnancy. Pregnancy registry and epidemiological data demonstrate an association between carbamazepine use during pregnancy and major congenital malformations, including neural tube defects, craniofacial defects, and cardiovascular malformations. Advise persons of child-bearing potential of the potential risk to the fetus and to contact their health care provider immediately if they become pregnant or intend to become pregnant. If discontinuation of carbamazepine is necessary, reduce the dose gradually. Avoid abrupt discontinuation to reduce the risk of status epilepticus or life-threatening seizures. However, maintenance of anticonvulsant or mood stabilization therapy may be essential for the mother. The risk of maternal or fetal injury may be greatest for persons with untreated or poorly controlled convulsive seizures. Likewise, there are risks to the mother from untreated bipolar disorder, including an increased risk of relapse, hospitalization, and suicide. Conduct tests using currently accepted procedures to detect defects during pregnancy. Folic acid supplementation is recommended both prior to and during pregnancy for persons using carbamazepine, as evidence suggests that supplementation with folic acid prior to conception and during the first trimester of pregnancy may decrease the risk of neural tube defects in the general population. However, it is not known whether the risk of neural tube defects in the offspring of women taking carbamazepine is reduced by folic acid supplementation. In humans, transplacental passage of carbamazepine is rapid (30 to 60 minutes), and the drug is accumulated in the fetal tissues, with higher concentrations found in liver and kidney than in brain and lung. The NAAED Pregnancy Registry has reported a rate of major congential malformations of 3% (95% CI: 2.1, 4.2) among approximately 1,000 women exposed to carbamazepine monotherapy during the first trimester with a relative risk of 2.7 (95% CI: 1, 7) compared to pregnant woman not taking an antiepileptic drug. Cases of developmental delays based on neurobehavioral assessments have been reported during postmarketing experience. Compared with monotherapy, there may be a higher prevalence of teratogenic effects associated with the use of anticonvulsants in combination therapy. In a prospective, multi-center, long-term, observational study (n = 333) of fetal death and malformations during in utero exposure to monotherapy with phenytoin, carbamazepine, lamotrigine, or valproate, 8.2% of subjects who received carbamazepine experienced serious adverse outcomes (fetal death or major congential abnormalities). Serious adverse outcomes occurred in 1% of lamotrigine-treated subjects, 10.7% of phenytoin-treated subjects, and 20.3% of valproate-treated subjects. Fetal deaths occurred for 3.6% and congenital malformations for 4.5% of carbamazepine-treated subjects. Congenital malformations in the carbamazepine group included absent kidney, duplicate renal pelvis, hypospadias, and inguinal hernia. There have been a few cases of neonatal seizures and/or respiratory depression reported in association with maternal carbamazepine and other concomitant anticonvulsant drug use. A few cases of neonatal vomiting, diarrhea, and/or decreased feeding have also been reported in association with maternal carbamazepine use. These symptoms may represent a neonatal withdrawal syndrome. The effects of carbamazepine during labor and delivery are unknown. There is a pregnancy exposure registry that monitors outcomes in pregnant persons exposed to carbamazepine; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.
Because of the potential for serious adverse events in a breast-fed infant exposed to carbamazepine, discontinue breast-feeding or discontinue carbamazepine. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for carbamazepine and any potential adverse effects on the breast-fed child from carbamazepine or the underlying maternal condition. Carbamazepine and its epoxide metabolite are transferred to breast milk. The ratio of the concentration in breast milk to that in maternal plasma is about 0.4 for carbamazepine and about 0.5 for the epoxide. The estimated doses ingested by the newborn during breast-feeding are in the ranges of 2 to 5 mg/day for carbamazepine and 1 to 2 mg/day for the epoxide. Although most infants exposed to carbamazepine via breast milk have not suffered adverse events, there have been cases of poor weight gain, vomiting, regurgitations, and a few reported cases of transient cholestatic hepatitis in infants exposed to maternal carbamazepine monotherapy at doses of 400 to 600 mg/day throughout pregnancy and breast-feeding. Other causes of hepatitis were ruled out; resolution of symptoms occurred upon discontinuation of breast-feeding in 1 infant and despite breast-feeding being continued in another infant. There are no data on the effects of carbamazepine on milk production.
Clinical studies of carbamazepine have not included sufficient numbers of geriatric subjects age 65 and over to determine whether they respond differently from younger adults. Other reported clinical experience has not identified differences in responses based on age alone. In general, dose selection for the geriatric adult should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. According to the Beers Criteria, antiepileptic drugs are considered potentially inappropriate medications (PIMs) in geriatric adults with a history of falls or fractures. Avoid those at risk except for treating seizure and mood disorders, since antiepileptic drugs can produce ataxia, impaired psychomotor function, syncope, and additional falls. If carbamazepine must be used, consider reducing the use of other CNS-active medications and implement strategies to reduce fall risk. Carbamazepine may also cause or exacerbate hyponatremia and SIADH and the older adult may be at increased risk for these conditions. Sodium concentrations should be closely monitored when starting or changing dosages. The U.S. Omnibus Budget Reconciliation Act (OBRA) regulates psychotropic medication use in residents of long-term care facilities (LTCFs). When carbamazepine is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt to taper the medication as outlined in the OBRA guidelines, unless a taper is clinically contraindicated. Dosages and durations of treatment used in the geriatric adult for such indications should be in accordance with prescribing labels, published literature recommendations, and expert guidelines.
Carbamazepine may be associated with reproductive risk. Discuss contraception requirements with the patient. Carbamazepine can reduce the effectiveness of hormonal contraceptives. Advise females of reproductive potential on the consistent use of effective nonhormonal contraception or barrier methods during carbamazepine therapy. Carbamazepine may also impair male fertility, which may result in infertility. Clinical studies have reported a reduction in semen quality in males of reproductive potential who received carbamazepine for treatment of epilepsy. Testicular atrophy and aspermatogenesis were observed in rats after repeat oral administration of carbamazepine at clinically relevant doses.
For the treatment of generalized tonic-clonic seizures or partial seizures:
Oral dosage (immediate-release tablets):
Adults: 200 mg PO twice daily, initially. Increase the dose by 200 mg/day weekly as needed. Max: 1,600 mg/day in 3 or 4 divided doses.
Adolescents 16 to 17 years: 200 mg PO twice daily, initially. Increase the dose by 200 mg/day weekly as needed. Max: 1,200 mg/day in 3 or 4 divided doses.
Children and Adolescents 12 to 15 years: 200 mg PO twice daily, initially. Increase the dose by 200 mg/day weekly as needed. Max: 1,000 mg/day in 3 or 4 divided doses.
Children 6 to 11 years: 100 mg PO twice daily, initially. Increase the dose by 100 mg/day weekly as needed. Max: 1,000 mg/day in 3 or 4 divided doses.
Children 1 to 5 years: 10 to 20 mg/kg/day PO in 2 or 3 divided doses, initially. Increase the dose weekly as needed. Max: 35 mg/kg/day in 3 or 4 divided doses. The safety of doses above 35 mg/kg/day has not been established.
Oral dosage (suspension):
Adults: 100 mg PO 4 times daily, initially. Increase the dose by 200 mg/day weekly as needed. Max: 1,600 mg/day in 3 or 4 divided doses.
Adolescents 16 to 17 years: 100 mg PO 4 times daily, initially. Increase the dose by 200 mg/day weekly as needed. Max: 1,200 mg/day in 3 or 4 divided doses.
Children and Adolescents 12 to 15 years: 100 mg PO 4 times daily, initially. Increase the dose by 200 mg/day weekly as needed. Max: 1,000 mg/day in 3 or 4 divided doses.
Children 6 to 11 years: 50 mg PO 4 times daily, initially. Increase the dose by 100 mg/day weekly as needed. Max: 1,000 mg/day in 3 or 4 divided doses.
Children 1 to 5 years: 10 to 20 mg/kg/day PO in 4 divided doses, initially. Increase the dose weekly as needed. Max: 35 mg/kg/day in 3 or 4 divided doses. The safety of doses above 35 mg/kg/day has not been established.
Oral dosage (extended-release tablets):
Adults: 200 mg PO twice daily, initially. Increase the dose by 200 mg/day weekly as needed. Max: 1,600 mg/day in 2 divided doses. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.
Adolescents 16 to 17 years: 200 mg PO twice daily, initially. Increase the dose by 200 mg/day weekly as needed. Max: 1,200 mg/day in 2 divided doses. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.
Children and Adolescents 12 to 15 years: 200 mg PO twice daily, initially. Increase the dose by 200 mg/day weekly as needed. Max: 1,000 mg/day in 2 divided doses. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.
Children 6 to 11 years: 100 mg PO twice daily, initially. Increase the dose by 100 mg/day weekly as needed. Max: 1,000 mg/day in 2 divided doses. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.
Oral dosage (extended-release capsules):
Adults: 200 mg PO twice daily, initially. Increase the dose by 200 mg/day weekly as needed. Max: 1,600 mg/day in 2 divided doses. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.
Adolescents 16 to 17 years: 200 mg PO twice daily, initially. Increase the dose by 200 mg/day weekly as needed. Max: 1,200 mg/day in 2 divided doses. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.
Children and Adolescents 12 to 15 years: 200 mg PO twice daily, initially. Increase the dose by 200 mg/day weekly as needed. Max: 1,000 mg/day in 2 divided doses. For conversion from immediate-release formulations, give the same total daily carbamazepine dose.
Children 1 to 12 years: Children taking immediate-release carbamazepine 400 mg/day or more can be converted to the same total daily dosage of the extended-release capsules using a twice-daily regimen. Optimal response is usually achieved at total doses less than 35 mg/kg/day. The safety of doses above 35 mg/kg/day has not been established.
For the treatment of neuropathic pain, including complex regional pain syndrome*, diabetic neuropathy*, and trigeminal neuralgia:
-for the treatment of complex regional pain syndrome*:
Oral dosage (immediate-release):
Adults: 200 mg PO 3 times daily. Alternately, 100 mg PO twice daily, initially; titrate dose to 600 to 800 mg/day.
-for the treatment of diabetic neuropathy*:
Oral dosage (immediate-release tablets):
Adults: 100 mg PO twice daily, initially. Titrate dose to 600 to 800 mg/day or until side effects are intolerable.
Oral dosage (suspension):
Adults: 50 mg PO 4 times daily, initially. Titrate dose to 600 to 800 mg/day or until side effects are intolerable.
-for the treatment of trigeminal neuralgia:
Oral dosage (immediate-release and extended-release tablets):
Adults: 100 mg PO twice daily, initially. Increase the dose by 200 mg/day as needed to achieve freedom from pain. Usual dose: 400 to 800 mg/day. Max: 1,200 mg/day. Attempt dose reduction or discontinuation at least once every 3 months.
Oral dosage (suspension):
Adults: 50 mg PO 4 times daily, initially. Increase the dose by 200 mg/day as needed to achieve freedom from pain. Usual dose: 400 to 800 mg/day. Max: 1,200 mg/day. Attempt dose reduction or discontinuation at least once every 3 months.
Oral dosage (extended-release capsules):
Adults: 200 mg PO once daily, initially. Increase the dose by 200 mg/day every 12 hours as needed to achieve freedom from pain. Usual dose: 400 to 800 mg/day. Max: 1,200 mg/day. Attempt dose reduction or discontinuation at least once every 3 months.
For the treatment of acute mania and mixed episodes associated with bipolar disorder (bipolar I disorder):
Oral dosage (extended-release capsules, Equetro):
Adults: 200 mg PO twice daily, initially. May increase the dose by 200 mg/day based on clinical response and tolerability. Max: 1,600 mg/day in 2 divided doses.
Oral dosage (immediate-release*):
Adults: 200 to 600 mg/day PO in 3 to 4 divided doses, initially. May increase the dose by up to 200 mg/day based on clinical response and tolerability. Usual dose: 1,000 mg/day. Dose range: 200 to 1,600 mg/day. Max: 1,600 mg/day.
Adolescents: 200 to 600 mg/day PO in 3 to 4 divided doses or alternately, 15 mg/kg/day PO in 3 divided doses, initially. May increase the dose by up to 200 mg/day based on clinical response and tolerability. Usual dose: 1,000 mg/day. Dose range: 200 to 1,600 mg/day. Max: 1,600 mg/day.
Children 6 to 12 years: 15 mg/kg/day PO in 3 divided doses, initially. Adjust dose to a serum carbamazepine concentration of 7 to 10 mcg/mL.
For the treatment of non-emergent behavioral or psychological symptoms of dementia* (BPSD):
Oral dosage (immediate-release):
Adults: Recommended starting dose is 50 mg PO twice daily, but if particularly frail, consider 25 mg PO twice daily. Titrate up to 100 mg PO twice daily on day 4, then to 150 mg PO twice daily on day 8. Max: 200 mg PO twice daily. Not a first-line treatment. Of anticonvulsant medications, carbamazepine has the most data supporting use for potential efficacy for BPSD after standard treatments (SSRIs, atypical antipsychotics) are not effective or not tolerated; potential for drug interactions and severe side effects must be considered before use.
For the treatment of persistent singultus (hiccups)*:
Oral dosage (regular-release tablets):
Adults: 200 mg PO three times per day provided relief of intractable hiccups secondary to new-onset multiple sclerosis.
For long-term prophylaxis of short-lasting short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT)*:
Oral dosage (regular-release tablets or suspension):
Adults: A limited number of case reports suggest doses of 600 to 1200 mg PO once daily may be effective. Some patients used carbamazepine in combination with other drugs including prednisolone or lamotrigine.
For the treatment of alcohol withdrawal*:
Oral dosage (immediate-release):
Adults: 200 mg PO every 8 hours or 400 mg PO every 12 hours, initially. Taper dose to 200 to 400 mg/day over 4 to 9 days.
Therapeutic Drug Monitoring:
-Usual adult therapeutic serum concentration is 4 to 12 mcg/mL.
-Monitoring serum carbamazepine concentrations may be useful for dose selection, minimizing toxicity, and verifying drug compliance, especially in clinical conditions in which alterations in carbamazepine metabolism can occur (e.g., drug interactions).
-If a satisfactory clinical response has not been achieved in pediatric patients, measure carbamazepine concentrations to determine whether they are in the therapeutic range.
Maximum Dosage Limits:
-Adults
1,200 mg/day PO for trigeminal neuralgia. In rare instances, 1,600 mg/day PO for epilepsy or bipolar disorder.
-Geriatric
1,200 mg/day PO for trigeminal neuralgia. In rare instances, 1,600 mg/day PO for epilepsy or bipolar disorder.
-Adolescents
16 to 17 years: 1,200 mg/day PO for epilepsy.
13 to 15 years: 1,000 mg/day PO for epilepsy.
-Children
6 to 12 years: 1,000 mg/day or 35 mg/kg/day PO for epilepsy.
1 to 5 years or younger: 35 mg/kg/day PO for epilepsy.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears no dosage adjustments are needed.
*non-FDA-approved indication
Abacavir; Dolutegravir; Lamivudine: (Major) When possible, avoid concurrent use of dolutegravir with carbamazepine in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with carbamazepine. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and carbamazepine is an inducer of CYP3A4.
Abemaciclib: (Major) Avoid coadministration of carbamazepine with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Abiraterone: (Major) Avoid coadministration of abiraterone with carbamazepine if possible due to decreased plasma concentrations of abiraterone. If concomitant use is unavoidable, increase the dosing frequency of abiraterone to twice daily. Reduce the dose back to the previous dose and frequency if carbamazepine is discontinued. Abiraterone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib and carbamazepine. If coadministration cannot be avoided, increase the acalabrutinib dose to 200 mg PO twice daily. Decreased acalabrutinib exposure may occur. Acalabrutinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. In healthy subjects, the Cmax and AUC values of acalabrutinib were decreased by 68% and 77%, respectively, when acalabrutinib was coadministered with another strong CYP3A4 inducer for 9 days.
Acetaminophen: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Aspirin: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Caffeine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with carbamazepine can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If carbamazepine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Carbamazepine is a strong inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Caffeine; Pyrilamine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Chlorpheniramine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Dextromethorphan: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Diphenhydramine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Guaifenesin; Phenylephrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Ibuprofen: (Moderate) Monitor carbamazepine concentrations closely during coadministration of ibuprofen; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of oxycodone as needed. If carbamazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Pamabrom; Pyrilamine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Phenylephrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetaminophen; Pseudoephedrine: (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Acetazolamide: (Minor) Acetazolamide can induce osteomalacia in patients being concomitantly treated with carbamazepine. Potential mechanisms for this interaction include an acetazolamide-induced increase in the urinary excretion of calcium and effects resulting from metabolic acidosis.
Adagrasib: (Major) Avoid concurrent use of adagrasib and carbamazepine due to the risk of decreased adagrasib exposure which may reduce its efficacy. The exposure of carbamazepine may also be increased. Adagrasib is a CYP3A substrate and strong CYP3A inhibitor and carbamazepine is a CYP3A substrate and strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced adagrasib exposure by more than 66%.
Adenosine: (Major) Carbamazepine increases the degree of heart block produced by adenosine. When used for supraventricular tachyarrhythmias in adults, reduce the initial adenosine dose to 3 mg. When possible, withhold carbamazepine for at least 5 half-lives before adenosine use for diagnostic imaging.
Afatinib: (Major) Increase the daily dose of afatinib by 10 mg as tolerated if the concomitant use with carbamazepine is necessary; resume the previous dose of afatinib 2 to 3 days after discontinuation of carbamazepine. Afatinib is a P-glycoprotein (P-gp) substrate and carbamazepine is a P-gp inducer; coadministration may decrease plasma concentrations of afatinib. Pre-treatment with another strong P-gp inducer decreased afatinib exposure by 34%.
Albendazole: (Minor) Enzyme-inducing antiepileptic drugs, such as carbamazepine, appear to induce the oxidative metabolism of albendazole. Notably, a significant reduction in the plasma concentration of the active albendazole sulfoxide metabolite may occur. Monitor patient clinical response closely during treatment.
Alfentanil: (Moderate) Monitor for reduced efficacy of alfentanil and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of alfentanil as needed. If carbamazepine is discontinued, consider a dose reduction of alfentanil and frequently monitor for signs or respiratory depression and sedation. Alfentanil is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease alfentanil levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Alosetron: (Minor) Alosetron is metabolized by CYP1A2 and CYP3A4. Carbamazepine can induce the activity of these enzymes and increase the metabolism of alosetron. Concomitant administration of carbamazepine and alosetron has not been evaluated.
Alpelisib: (Major) Avoid coadministration of alpelisib with carbamazepine due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer.
Alprazolam: (Moderate) Monitor for reduced efficacy of alprazolam and signs of benzodiazepine withdrawal if coadministration with carbamazepine is necessary. Alprazolam is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease alprazolam concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. The oral clearance of alprazolam (given in a 0.8 mg single dose) increased from 0.9 +/- 21 mL/minute/kg to 2.13 +/- 0.54 mL/minute/kg and the elimination half-life was shortened from 17.1 +/- 4.9 hours to 7.7 +/- 1.7 hours following administration of 300 mg per day carbamazepine for 10 days. However, the carbamazepine dose used in this study was low compared to the recommended doses (1000-1200 mg per day); the effect at usual carbamazepine doses is unknown.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Amiodarone: (Moderate) Monitor for a decrease in amiodarone efficacy and an increase in carbamazepine-related adverse reactions during concomitant use of amiodarone and carbamazepine. Monitor carbamazepine concentrations closely and adjust the dose as needed. Concomitant use may decrease amiodarone exposure and increase carbamazepine exposure. Amiodarone is a CYP3A substrate and weak CYP3A inhibitor and carbamazepine is a CYP3A substrate and strong CYP3A inducer.
Amitriptyline: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant carbamazepine use. Concomitant use may result in decreased tricyclic antidepressant exposure.
Amlodipine: (Moderate) Monitor carbamazepine concentrations and blood pressure closely during coadministration of amlodipine; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and strong inducer and amlodipine is CYP3A substrate and inhibitor. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Atorvastatin: (Moderate) Carbamazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates, such as atorvastatin. (Moderate) Monitor carbamazepine concentrations and blood pressure closely during coadministration of amlodipine; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and strong inducer and amlodipine is CYP3A substrate and inhibitor. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Benazepril: (Moderate) Monitor carbamazepine concentrations and blood pressure closely during coadministration of amlodipine; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and strong inducer and amlodipine is CYP3A substrate and inhibitor. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Celecoxib: (Moderate) Monitor carbamazepine concentrations and blood pressure closely during coadministration of amlodipine; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and strong inducer and amlodipine is CYP3A substrate and inhibitor. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Olmesartan: (Moderate) Monitor carbamazepine concentrations and blood pressure closely during coadministration of amlodipine; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and strong inducer and amlodipine is CYP3A substrate and inhibitor. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Valsartan: (Moderate) Monitor carbamazepine concentrations and blood pressure closely during coadministration of amlodipine; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and strong inducer and amlodipine is CYP3A substrate and inhibitor. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor carbamazepine concentrations and blood pressure closely during coadministration of amlodipine; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and strong inducer and amlodipine is CYP3A substrate and inhibitor. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine. (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Amobarbital: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concomitant use of omeprazole and carbamazepine as omeprazole exposure may be decreased, reducing its efficacy. Omeprazole is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. (Major) Coadministration of carbamazepine and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers. Additionally, carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Drugs known to inhibit CYP3A4, such as clarithromycin, may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely during coadministration; reduce carbamazepine doses may be necessary. Clarithromycin also inhibits epoxide hydrolase resulting in increased levels of the active metabolite carbamazepine 10, 11- epoxide, which may be more hepatotoxic than the parent drug. Several case reports have documented that clarithromycin can significantly decrease carbamazepine clearance, producing increases in the serum concentration of carbamazepine. Carbamazepine concentrations increased from 12 mcg/ml to 19.1 mcg/ml in a 17-year-old boy after 2 days of clarithromycin 250 mg PO bid. Patients should be monitored for carbamazepine toxicity if clarithromycin is added. Carbamazepine toxicity may be avoided if clarithromycin therapy is begun first and stabilized prior to beginning carbamazepine therapy, however, carbamazepine dosages may need to be increased if clarithromycin is subsequently discontinued.
Anagrelide: (Moderate) Anagrelide is partially metabolized by CYP1A2. Coadministration of anagrelide with drugs that induce CYP1A2, such as carbamazepine, could theoretically increase the elimination of anagrelide and decrease its efficacy. Patients should be monitored for changes in efficacy if these drugs are coadministered.
Apalutamide: (Moderate) Closely monitor carbamazepine levels if coadministration with apalutamide is necessary. Carbamazepine is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Inducers of CYP3A4 can increase the rate of carbamazepine metabolism and decrease carbamazepine levels.
Apixaban: (Major) Avoid the concomitant administration of apixaban and drugs that are both strong inducers of CYP3A4 and P-gp, such as carbamazepine. Concomitant administration of apixaban and carbamazepine results in decreased plasma concentrations of apixaban that may be insufficient to achieve the intended therapeutic effect.
Apremilast: (Major) The coadministration of apremilast and carbamazepine is not recommended. Apremilast is metabolized primarily by CYP3A4, with minor metabolism by CYP1A2. Carbamazepine is a strong CYP3A4 inducer and also induces CYP1A2. Coadministration of rifampin, another strong CYP3A4 inducer, with a single dose of apremilast resulted in a decrease in apremilast AUC and Cmax by 72% and 43%, respectively. A similar reduction in systemic exposure may be seen with coadministration of apremilast and carbamazepine which may result in a loss of efficacy of apremilast.
Aprepitant, Fosaprepitant: (Major) Avoid the concurrent use of carbamazepine with aprepitant, fosaprepitant due to substantially decreased exposure of aprepitant. If these drugs must be coadministered, monitor for a decrease in the efficacy of aprepitant as well as an increase in carbamazepine-related adverse effects for several days after administration of a multi-day aprepitant regimen. Carbamazepine is a strong CYP3A4 inducer and aprepitant is a CYP3A4 substrate. When a single dose of aprepitant (375 mg, or 3 times the maximum recommended dose) was administered on day 9 of a 14-day rifampin regimen (a strong CYP3A4 inducer), the AUC of aprepitant decreased approximately 11-fold and the mean terminal half-life decreased by 3-fold. Additionally, carbamazepine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may also increase plasma concentrations of carbamazepine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Major) Recommendations for managing aripiprazole and carbamazepine vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; carbamazepine is a strong CYP3A inducer. (Major) Recommendations for managing aripiprazole and carbamazepine vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), increase the 441 mg dose to 662 mg; no adjustments are necessary for other dosages. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; carbamazepine is a strong CYP3A inducer.
Armodafinil: (Moderate) Armodafinil is partially metabolized by CYP3A4 and combined use with CYP3A4 inducers such as carbamazepine may result in decreased armodafinil efficacy. In vitro data indicate that armodafinil is an inducer of CYP3A4. Therefore, decreased carbamazepine serum levels are possible during combined use with armodafinil. Clinically, be alert for increased sleepiness or other indicators of reduced armofafinil efficacy. The potential pharmacodynamic effects of combining armodafinil with anticonvulsant medications are unclear; however, should it be noted that other CNS stimulants (e.g., amphetamines) are known to lower the seizure threshold.
Artemether; Lumefantrine: (Contraindicated) Concomitant use of carbamazepine and artemether; lumefantrine is contraindicated. Carbamazepine is a substrate/inducer of CYP3A4 and both components of artemether; lumefantrine are substrates of this isoenzyme; therefore, coadministration may lead to decreased artemether; lumefantrine concentrations and possible reduction in antimalarial activity.
Artesunate: (Moderate) Monitor for a decrease in antimalarial efficacy if artesunate is coadministered with carbamazepine. Coadministration may decrease the exposure of the active metabolite of artesunate, dihydroartemisinin (DHA). DHA is a UGT substrate, and carbamazepine is a strong UGT inducer.
Asciminib: (Moderate) Monitor carbamazepine concentrations closely during coadministration of asciminib; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and asciminib is a CYP3A inhibitor.
Asenapine: (Moderate) Drugs that can cause significant CNS effects such as drowsiness and dizziness, such as carbamazepine, if used concomitantly with asenapine, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Carbamazepine has been tested and has been found to have no clinically significant pharmacokinetic interaction with asenapine; no dosage adjustment is necessary based on pharmacokinetics.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy. (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme.
Aspirin, ASA; Caffeine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer.
Aspirin, ASA; Omeprazole: (Major) Avoid concomitant use of omeprazole and carbamazepine as omeprazole exposure may be decreased, reducing its efficacy. Omeprazole is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of oxycodone as needed. If carbamazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Atazanavir: (Contraindicated) Atazanavir, with or without ritonavir, is contraindicated for use with carbamazepine. Concurrent administration may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduced antiretroviral efficacy and development of viral resistance. In addition, coadministration of atazanavir and ritonavir with carbamazepine could result in increased carbamazepine concentrations.
Atazanavir; Cobicistat: (Contraindicated) Atazanavir, with or without ritonavir, is contraindicated for use with carbamazepine. Concurrent administration may increase the metabolism of atazanavir and lead to decreased atazanavir concentrations resulting in reduced antiretroviral efficacy and development of viral resistance. In addition, coadministration of atazanavir and ritonavir with carbamazepine could result in increased carbamazepine concentrations. (Contraindicated) Coadministration of carbamazepine with cobicistat-containing regimens is contraindicated. If these drugs are used together, significant decreases in the plasma concentrations of the antiretrovirals may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. In addition, inhibition of CYP3A4 by cobicistat may result in elevated carbamazepine concentrations. Consider use of an alternative anticonvulsant or antiretroviral therapy.
Atenolol; Chlorthalidone: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Atogepant: (Major) Avoid use of atogepant and carbamazepine when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with carbamazepine. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Coadministration with a strong CYP3A inducer resulted in a 60% reduction in atogepant overall exposure and a 30% reduction in atogepant peak concentration.
Atorvastatin: (Moderate) Carbamazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates, such as atorvastatin.
Atracurium: (Moderate) Monitor for a more rapid recovery from neuromuscular blockade than expected during concurrent use of carbamazepine and atracurium. When administering neuromuscular blockade via continuous infusion, infusion rate requirements may be higher. Chronic carbamazepine administration may cause neuromuscular blockade resistance.
Auranofin: (Minor) Auranofin should be used cautiously in patients receiving carbamazepine, due to the potential for additive bone marrow/hematologic effects.
Avacopan: (Major) Avoid concomitant use of avacopan and carbamazepine due to the risk of decreased avacopan exposure which may reduce its efficacy. Carbamazepine exposure and the risk for carbamazepine-related adverse effects may also increase. Avacopan is a CYP3A substrate and weak CYP3A inhibitor; carbamazepine is a CYP3A substrate and strong CYP3A inducer. Concomitant use of another strong CYP3A inducer decreased avacopan overall exposure by 93%.
Avanafil: (Major) Coadministration of avanafil with carbamazepine is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Avapritinib: (Major) Avoid coadministration of avapritinib with carbamazepine due to the risk of decreased avapritinib efficacy. Avapritinib is a CYP3A4 substrate and carbamazepine is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased the AUC and Cmax of avapritinib by 62% and 55%, respectively.
Axitinib: (Major) Avoid coadministration of axitinib with carbamazepine due to the risk of decreased efficacy of axitinib. Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Axitinib is a CYP3A4/5 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4/5 inducer significantly decreased the plasma exposure of axitinib in healthy volunteers.
Azathioprine: (Minor) Azathioprine should be used cautiously in patients receiving carbamazepine, due to the potential for additive bone marrow/hematologic effects.
Azelastine; Fluticasone: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of fluticasone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with fluticasone.
Azilsartan; Chlorthalidone: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Barbiturates: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy.
Bedaquiline: (Major) Avoid concurrent use of carbamazepine with bedaquiline. Carbamazepine may induce CYP3A4 metabolism resulting in decreased bedaquiline systemic exposure (AUC) and possibly reduced therapeutic effect.
Belumosudil: (Major) Increase the dosage of belumosudil to 200 mg PO twice daily when coadministered with carbamazepine; concomitant use may result in decreased belumosudil exposure and reduced belumosudil efficacy. Monitor carbamazepine concentrations closely during coadministration of belumosudil; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Belumosudil is a CYP3A4 substrate and a weak CYP3A inhibitor and carbamazepine is a strong CYP3A inducer and a CYP3A substrate. Coadministration with another strong CYP3A inducer decreased belumosudil exposure by 72% in healthy subjects.
Belzutifan: (Moderate) Monitor carbamazepine concentrations closely during coadministration of belzutifan; carbamazepine dose adjustments may be needed. Concomitant use may decrease carbamazepine concentrations. Carbamazepine is a CYP3A substrate and belzutifan is a CYP3A inducer.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Bendamustine: (Major) Consider the use of an alternative therapy if carbamazepine treatment is needed in patients receiving bendamustine. Carbamazepine may decrease bendamustine exposure, which may result in decreased efficacy. Bendamustine is a CYP1A2 substrate and carbamazepine is a CYP1A2 inducer.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with carbamazepine may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If concomitant use is necessary, consider increasing the benzhydrocodone dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Discontinuation of carbamazepine may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. If carbamazepine is discontinued, consider a benzhydrocodone dosage reduction and monitor patients for respiratory depression and sedation at frequent intervals. Benzhydrocodone is a prodrug of hydrocodone. Carbamazepine is a strong inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of hydrocodone. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Berotralstat: (Major) Avoid coadministration of berotralstat with carbamazepine. Concurrent use may decrease berotralstat exposure, leading to reduced efficacy. Concomitant use may also increase carbamazepine exposure and the risk for carbamazepine-related adverse effects. Berotralstat is a P-gp substrate and moderate CYP3A inhibitor; carbamazepine is a CYP3A substrate and P-gp inducer.
Betrixaban: (Major) Avoid the concomitant administration of betrixaban and carbamazepine. Concomitant administration of betrixaban and carbamazepine results in decreased plasma concentrations of betrixaban that may decrease efficacy. Betrixaban is a P-glycoprotein (P-gp) substrate and carbamazepine is a P-gp inducer.
Bexagliflozin: (Moderate) Monitor for a decrease in bexagliflozin efficacy during concomitant use of bexagliflozin and carbamazepine and adjust therapy as appropriate. Concomitant use may decrease bexagliflozin exposure. Bexagliflozin is a UGT substrate and carbamazepine is a UGT inducer.
Bicalutamide: (Major) Monitor for increased carbamazepine-related adverse reactions if coadministered with bicalutamide. Taking these drugs together may increase carbamazepine plasma concentrations, potentially resulting in adverse events. Bicalutamide is a weak CYP3A4 inhibitor; carbamazepine is a substrate of CYP3A4 with a narrow therapeutic index.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Administering tenofovir alafenamide with carbamazepine is not recommended. Consider use of an alternative anticonvulsant. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure. (Major) Consider an alternative anticonvulsant during treatment with bictegravir. Concomitant use of bictegravir and carbamazepine may result in decreased bictegravir plasma concentrations, which may result in the loss of therapeutic efficacy and development of resistance. Bictegravir is a substrate of CYP3A4; carbamazepine is a strong inducer of CYP3A4. In drug interaction studies, coadministration of bictegravir and carbamazepine decreased the mean AUC of bictegravir by approximately 54%.
Biotin: (Moderate) Carbamazepine use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like carbamazepine, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Minor) Monitor serum concentrations of carbamazepine when coadministered with systemic metronidazole. Concomitant use with metronidazole may increase the serum concentrations of carbamazepine; thereby, increasing the risk of side effects.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Monitor serum concentrations of carbamazepine when coadministered with systemic metronidazole. Concomitant use with metronidazole may increase the serum concentrations of carbamazepine; thereby, increasing the risk of side effects.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Blinatumomab: (Moderate) No drug interaction studies have been performed with blinatumomab. The drug may cause a transient release of cytokines leading to an inhibition of CYP450 enzymes. The interaction risk with CYP450 substrates is likely the highest during the first 9 days of the first cycle and the first 2 days of the second cycle. Monitor patients receiving concurrent CYP450 substrates that have a narrow therapeutic index (NTI) such as carbamazepine. The dose of the concomitant drug may need to be adjusted.
Bosentan: (Moderate) Monitor carbamazepine concentrations closely during coadministration of bosentan; carbamazepine dose adjustments may be needed. Concomitant use may decrease carbamazepine concentrations. Carbamazepine is a CYP3A substrate and bosentan is a CYP3A inducer.
Bosutinib: (Major) Avoid concomitant use of bosutinib, a CYP3A4 substrate, with a strong CYP3A4 inducer such as carbamazepine, as a large decrease in bosutinib plasma exposure may occur. Carbamazepine may interact with chemotherapeutic agents by different mechanisms. Although documentation of drug-drug interactions may not always be available, myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine. Clinicians should be alert to changes in the clinical effects of these agents. If coadministration is necessary, dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Brentuximab vedotin: (Moderate) Concomitant administration of brentuximab vedotin and carbamazepine may decrease the exposure of monomethyl auristatin E (MMAE), one of the 3 components released from brentuximab vedotin. MMAE is a CYP3A4 substrate and carbamazepine is a potent CYP3A4 inducer; therefore, the efficacy of brentuximab may be reduced.
Brexpiprazole: (Major) Because brexpiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the brexpiprazole dose be doubled over 1 to 2 weeks when a strong CYP3A4 inducer, such as carbamazepine, is added to brexpiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in brexpiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the brexpiprazole dose should be reduced to the original level over 1 to 2 weeks.
Brigatinib: (Major) Avoid coadministration of brigatinib with carbamazepine due to decreased plasma exposure to brigatinib which may result in decreased efficacy. Brigatinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased the AUC and Cmax of brigatinib by 80% and 60%, respectively.
Brivaracetam: (Moderate) Coadministration with carbamazepine may increase exposure to the active metabolite of carbamazepine, carbamazepine-epoxide, due to brivaracetam being a reversible inhibitor of epoxide hydrolase. During drug interaction studies, the carbamazepine-epoxide plasma concentration increased up to 198% with a brivaracetam dose of 100 mg twice daily. If tolerability issues arise during concomitant use, carbamazepine dose reduction should be considered. A 26% decrease in the plasma concentration of brivaracetam has also been observed during co-administration with carbamazepine. No dose adjustment is recommended for brivaracetam during concomitant carbamazepine therapy.
Brodalumab: (Moderate) If brodalumab is initiated or discontinued in a patient taking carbamazepine, monitor carbamazepine concentrations; carbamazepine dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during brodalumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as carbamazepine.
Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and carbamazepine are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; carbamazepine is a strong inducer of CYP3A4.
Bupivacaine Liposomal: (Minor) Bupivacaine is metabolized by CYP3A4. Carbamazepine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Bupivacaine: (Minor) Bupivacaine is metabolized by CYP3A4. Carbamazepine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Bupivacaine; Epinephrine: (Minor) Bupivacaine is metabolized by CYP3A4. Carbamazepine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and carbamazepine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; carbamazepine induces both hepatic isoenzymes. (Minor) Bupivacaine is metabolized by CYP3A4. Carbamazepine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Bupivacaine; Meloxicam: (Minor) Bupivacaine is metabolized by CYP3A4. Carbamazepine induces these isoenzymes and if given concurrently with bupivacaine may decrease the efficacy of bupivacaine.
Buprenorphine: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with carbamazepine is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If carbamazepine is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A4 substrate and carbamazepine is a CYP3A4 inducer.
Buprenorphine; Naloxone: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with carbamazepine is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If carbamazepine is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A4 substrate and carbamazepine is a CYP3A4 inducer.
Bupropion: (Moderate) Monitor for reduced bupropion efficacy during coadministration of carbamazepine as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose. Avoid concomitant use of combination dextromethorphan; bupropion and carbamazepine. Bupropion is a CYP2B6 substrate and carbamazepine is a strong CYP2B6 inducer. Concomitant use was observed to decrease bupropion overall exposure by 76% and dextromethorphan overall exposure by 64%.
Bupropion; Naltrexone: (Moderate) Monitor for reduced bupropion efficacy during coadministration of carbamazepine as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose. Avoid concomitant use of combination dextromethorphan; bupropion and carbamazepine. Bupropion is a CYP2B6 substrate and carbamazepine is a strong CYP2B6 inducer. Concomitant use was observed to decrease bupropion overall exposure by 76% and dextromethorphan overall exposure by 64%.
Buspirone: (Moderate) Monitor for decreased efficacy of buspirone if carbamazepine is added to a patient on a stable dosage of buspirone; a dose increase of buspirone may be needed to maintain anxiolytic activity. Buspirone is a sensitive CYP3A substrate and carbamazepine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased buspirone exposure by 89.6%.
Butalbital; Acetaminophen: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Butalbital; Acetaminophen; Caffeine: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy. (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy. (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer. (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy. (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer. (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme.
Cabotegravir: (Contraindicated) Coadministration of cabotegravir and carbamazepine is contraindicated due to the potential for significant decreases in the plasma concentrations of cabotegravir, which may result in potential loss of virologic response and development of resistance. Cabotegravir is a substrate for UGT1A1 and UGT1A9; carbamazepine is an inducer of UGT. Coadministration with another UGT inducer decreased cabotegravir exposure by 59%.
Cabotegravir; Rilpivirine: (Contraindicated) Coadministration of cabotegravir and carbamazepine is contraindicated due to the potential for significant decreases in the plasma concentrations of cabotegravir, which may result in potential loss of virologic response and development of resistance. Cabotegravir is a substrate for UGT1A1 and UGT1A9; carbamazepine is an inducer of UGT. Coadministration with another UGT inducer decreased cabotegravir exposure by 59%. (Contraindicated) Coadministration of carbamazepine and rilpivirine is contraindicated due to the potential for loss of virologic response and possible resistance to rilpivirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Rilpivirine is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
Cabozantinib: (Major) Avoid coadministration of cabozantinib with carbamazepine due to the risk of decreased cabozantinib exposure which could affect efficacy. If concomitant use is unavoidable, increase the dose of cabozantinib. For patients taking cabozantinib tablets, increase the dose of cabozantinib by 20 mg (e.g., 60 mg/day to 80 mg/day; 40 mg/day to 60 mg/day); the daily dose should not exceed 80 mg. For patients taking cabozantinib capsules, increase the dose of cabozantinib by 40 mg (e.g., 140 mg/day to 180 mg/day or 100 mg/day to 140 mg/day); the daily dose should not exceed 180 mg. Resume the cabozantinib dose that was used prior to initiating treatment with carbamazepine 2 to 3 days after discontinuation of carbamazepine. Cabozantinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased single-dose cabozantinib exposure by 77%.
Caffeine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme.
Caffeine; Sodium Benzoate: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme.
Canagliflozin: (Major) Increase the canagliflozin dose to 200 mg/day in persons who are tolerating canagliflozin 100 mg/day and receiving concomitant carbamazepine. The canagliflozin dose may be further increased to 300 mg/day for persons with an eGFR of 60 mL/minute/1.73 m2 or more who require additional glycemic control; consider adding another antihyperglycemic agent for persons with an eGFR less than 60 mL/minute/1.73 m2 who require additional glycemic control. Canagliflozin is an UGT1A9 and UGT2B4 substrate, and carbamazepine is an UGT inducer. Coadministration with a nonselective inducer of several UGT enzymes decreased canagliflozin exposure by 51%. This decrease in exposure may decrease canagliflozin efficacy.
Canagliflozin; Metformin: (Major) Increase the canagliflozin dose to 200 mg/day in persons who are tolerating canagliflozin 100 mg/day and receiving concomitant carbamazepine. The canagliflozin dose may be further increased to 300 mg/day for persons with an eGFR of 60 mL/minute/1.73 m2 or more who require additional glycemic control; consider adding another antihyperglycemic agent for persons with an eGFR less than 60 mL/minute/1.73 m2 who require additional glycemic control. Canagliflozin is an UGT1A9 and UGT2B4 substrate, and carbamazepine is an UGT inducer. Coadministration with a nonselective inducer of several UGT enzymes decreased canagliflozin exposure by 51%. This decrease in exposure may decrease canagliflozin efficacy.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Capivasertib: (Major) Avoid coadministration of capivasertib with carbamazepine due to decreased capivasertib exposure and risk of decreased efficacy. Concomitant use may also increase carbamazepine exposure and the risk for carbamazepine-related adverse effects. Capivasertib is a CYP3A substrate and weak CYP3A inhibitor; carbamazepine is a CYP 3A substrate and strong CYP3A inducer. Coadministration of another strong CYP3A inducer is predicted to decrease the capivasertib overall exposure by 70%.
Capmatinib: (Major) Avoid coadministration of capmatinib and carbamazepine due to the risk of decreased capmatinib exposure, which may reduce its efficacy. Capmatinib is a CYP3A substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased capmatinib exposure by 67%.
Capsaicin; Metaxalone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of carbamazepine and metaxalone. Concurrent use may result in additive CNS depression.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Concurrent use of cariprazine with CYP3A4 inducers, such as carbamazepine, has not been evaluated and is not recommended because the net effect on active drug and metabolites is unclear.
Caspofungin: (Major) Data suggest that coadministration of inducers or mixed inducers/inhibitors of hepatic drug clearance along with caspofungin may result in reduced caspofungin blood concentrations. The reductions may be clinically significant. According to the manufacturer, drugs that may lead to reductions in caspofungin concentrations include carbamazepine. For adult patients receiving carbamazepine, an increase in the caspofungin dose to 70 mg/day should be considered. For pediatric patients receiving carbamazepine, a daily dosage of 70 mg/m2, not to exceed 70 mg, should be considered.
Cefixime: (Moderate) Cefixime coadministered with carbamazepine has resulted in elevated carbamazepine concentrations according to postmarketing reports. Monitoring of carbamazepine plasma concentrations should be performed to detect any changes.
Celecoxib; Tramadol: (Major) Reserve concomitant use of tramadol and carbamazepine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required, and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Monitor for reduced efficacy of tramadol and signs of opioid withdrawal; consider increasing the dose of tramadol as needed. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death and/or decrease tramadol concentrations, which may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If carbamazepine is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Cenobamate: (Major) Increase the dosage of carbamazepine as needed when coadministered with cenobamate due to the potential for reduced efficacy of carbamazepine. Multiple doses of cenobamate decreased carbamazepine exposure by 23%.
Ceritinib: (Major) Avoid concomitant use of ceritinib with carbamazepine as ceritinib exposure may be decreased, which may reduce its efficacy; carbamazepine exposure may also increase. Ceritinib is a CYP3A4 substrate and a strong CYP3A4 inhibitor; carbamazepine is a CYP3A4 substrate with a narrow therapeutic index and a strong CYP3A4 inducer. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%.
Charcoal: (Major) Note that charcoal exerts a nonspecific effect, and many medications can be adsorbed by activated charcoal. Use of activated charcoal as a dietary supplement for flatulence or other purposes is likely to decrease the effectiveness of agents like carbamazepine.
Chlordiazepoxide: (Moderate) Hepatic inducers, such as carbamazepine, can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
Chlordiazepoxide; Amitriptyline: (Moderate) Hepatic inducers, such as carbamazepine, can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations. (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant carbamazepine use. Concomitant use may result in decreased tricyclic antidepressant exposure.
Chlordiazepoxide; Clidinium: (Moderate) Hepatic inducers, such as carbamazepine, can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
Chloroquine: (Moderate) Coadministration of chloroquine and carbamazepine may decrease exposure of chloroquine which may reduce its efficacy. Chloroquine may be an in vitro CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
Chlorothiazide: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor carbamazepine concentrations closely during coadministration of ibuprofen; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations.
Chlorthalidone: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Cimetidine: (Moderate) Monitor carbamazepine concentrations closely during coadministration of cimetidine; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A4 substrate and cimetidine is a CYP3A4 inhibitor.
Ciprofloxacin: (Moderate) Monitor carbamazepine concentrations closely during coadministration of ciprofloxacin; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A4 substrate and ciprofloxacin is a CYP3A4 inhibitor.
Cisapride: (Moderate) Cisapride is metabolized by the hepatic cytochrome P450 enzyme system, specifically the CYP3A4 isoenzyme. Inducers of CYP3A4, such as carbamazepine, may increase the clearance of cisapride.
Cisatracurium: (Moderate) Monitor for a more rapid recovery from neuromuscular blockade than expected during concurrent use of carbamazepine and cisatracurium. When administering neuromuscular blockade via continuous infusion, infusion rate requirements may be higher. Chronic carbamazepine administration may cause neuromuscular blockade resistance.
Cisplatin: (Moderate) Cisplatin may increase the rate of carbamazepine metabolism via CYP3A4 induction. Monitor the serum carbamazepine concentration if cisplatin is used concurrently. The carbamazepine dose may need to be increased.
Citalopram: (Moderate) Monitor for decreased efficacy of citalopram if coadministration with carbamazepine is necessary. Citalopram is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. In one study, coadministration with carbamazepine did not affect citalopram plasma concentrations, but increased clearance of citalopram with strong CYP3A4 inducers is possible.
Clarithromycin: (Major) Coadministration of carbamazepine and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers. Additionally, carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Drugs known to inhibit CYP3A4, such as clarithromycin, may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely during coadministration; reduce carbamazepine doses may be necessary. Clarithromycin also inhibits epoxide hydrolase resulting in increased levels of the active metabolite carbamazepine 10, 11- epoxide, which may be more hepatotoxic than the parent drug. Several case reports have documented that clarithromycin can significantly decrease carbamazepine clearance, producing increases in the serum concentration of carbamazepine. Carbamazepine concentrations increased from 12 mcg/ml to 19.1 mcg/ml in a 17-year-old boy after 2 days of clarithromycin 250 mg PO bid. Patients should be monitored for carbamazepine toxicity if clarithromycin is added. Carbamazepine toxicity may be avoided if clarithromycin therapy is begun first and stabilized prior to beginning carbamazepine therapy, however, carbamazepine dosages may need to be increased if clarithromycin is subsequently discontinued.
Clindamycin: (Moderate) Monitor for loss of clindamycin efficacy with coadministration of carbamazepine as concurrent use may decrease clindamycin exposure. Clindamycin is a CYP3A4 substrate; carbamazepine is a strong inducer of CYP3A4.
Clobazam: (Moderate) Carbamazepine induces CYP3A4 and clobazam is metabolized by CYP3A4; therefore, carbamazepine may potentially accelerate the hepatic metabolism of clobazam. Close monitoring of anticonvulsant efficacy and clinical effects is warranted.
Clofazimine: (Moderate) Monitor for increased toxicity of carbamazepine if used concomitantly with clofazimine. Concomitant use may increase the concentration of carbamazepine, increasing the risk of adverse effects. Carbamazepine is a CYP3A4 substrate that has a narrow therapeutic index; in vitro data suggest clofazimine inhibits CYP3A4.
Clomipramine: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant carbamazepine use. Concomitant use may result in decreased tricyclic antidepressant exposure.
Clonazepam: (Moderate) Monitor patients for decreased efficacy and a change in clonazepam dosage requirements when coadministered with carbamazepine. Clonazepam is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Clonazepam concentration decreases of approximately 38% have been reported when clonazepam is used with other strong CYP3A4 inducers.
Clorazepate: (Moderate) Carbamazepine is a hepatic inducers and can theoretically increase the clearance of clorazepate, leading to lower benzodiazepine concentrations.
Clozapine: (Major) Coadministration of clozapine, a CYP3A4 substrate, with a potent inducer of CYP3A4, such as carbamazepine, is not recommended. If coadministration is necessary, monitor for decreased effectiveness of clozapine and consider increasing the clozapine dose if necessary. If the inducer is discontinued, reduce the clozapine dose based on clinical response. Carbamazepine may also increase the metabolism of clozapine through induction of CYP1A2. Both agents have myelosuppressive properties; patients should be monitored for and instructed about symptoms of infection. Lastly, close monitoring is recommended when clozapine is administered to patients with a seizure disorder because clozapine lowers the seizure threshold. The effectiveness of carbamazepine in treating seizures may be reduced. Dosage adjustments may be necessary and close monitoring is warranted when carbamazepine is used with clozapine.
Cobicistat: (Contraindicated) Coadministration of carbamazepine with cobicistat-containing regimens is contraindicated. If these drugs are used together, significant decreases in the plasma concentrations of the antiretrovirals may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. In addition, inhibition of CYP3A4 by cobicistat may result in elevated carbamazepine concentrations. Consider use of an alternative anticonvulsant or antiretroviral therapy.
Codeine: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If carbamazepine is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Carbamazepine is a strong CYP3A4 inducer.
Colesevelam: (Moderate) Colesevelam may decrease the bioavailability of carbamazepine. To minimize potential for interactions, consider administering oral drugs with a narrow therapeutic index such as carbamazepine at least 1 hour before or at least 4 hours after colesevelam.
Colestipol: (Major) Concurrent administration of carbamazepine with colestipol results in a modest reduction in carbamazepine bioavailability. Although the reduction in carbamazepine bioavailability may not be clinically significant, staggering the times of administration of these agents should alleviate any drug interaction. In the same study, cholestyramine did not affect carbamazepine bioavailability.
Conivaptan: (Moderate) Monitor carbamazepine concentrations closely during coadministration of conivaptan; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and conivaptan is a CYP3A inhibitor.
Conjugated Estrogens: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination.
Conjugated Estrogens; Bazedoxifene: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Moderate) Bazedoxifene undergoes metabolism by UGT enzymes in the intestinal tract and liver. The metabolism of bazedoxifene may be increased by concomitant use of substances known to induce UGTs, such as carbamazepine. A reduction in bazedoxifene exposure may be associated with an increase risk of endometrial hyperplasia. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. In addition, in vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4, such as carbamazepine, may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile.
Conjugated Estrogens; Medroxyprogesterone: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Copanlisib: (Major) Avoid the concomitant use of copanlisib and carbamazepine; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate; carbamazepine is a strong CYP3A inducer. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of another strong CYP3A4 inducer in a drug interaction study in patients with cancer.
Crizotinib: (Major) Avoid coadministration of crizotinib with carbamazepine due to decreased crizotinib exposure; increased carbamazepine exposure may also occur. Both drugs are CYP3A substrates. Crizotinib is also a moderate CYP3A inhibitor and carbamazepine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the AUC of crizotinib at steady-state by 84%.
Cyclophosphamide: (Moderate) Monitor for cyclophosphamide-related adverse reactions if coadministration with carbamazepine is necessary. Chronic carbamazepine administration may increase the rate of metabolism and leukopenic activity of cyclophosphamide. Cyclophosphamide is an inactive prodrug that is converted to its active metabolite in part by CYP3A. Carbamazepine is a strong CYP3A4 inducer.
Cyclosporine: (Moderate) Carbamazepine can increase the clearance of cyclosporine by inducing cyclosporine metabolism.
Dabigatran: (Major) Avoid the concomitant administration of dabigatran and drugs that are strong inducers of P-gp, such as carbamazepine. Concomitant administration of dabigatran and carbamazepine results in decreased plasma concentrations of dabigatran that may be insufficient to achieve the intended therapeutic effect.
Dabrafenib: (Major) Use dabrafenib and carbamazepine together with caution; concentrations of either agent may be decreased resulting in loss of efficacy. Use of an alternate agent in place of carbamazepine is recommended. If concomitant use cannot be avoided, monitor patients for loss of carbamazepine efficacy. Carbamazepine is a CYP3A4 substrate and a strong CYP3A4 inducer; dabrafenib is a CYP3A4 substrate and a moderate CYP3A4 inducer. The AUC values of dabrafenib and its metabolite desmethyl-dabrafenib were decreased by 34% and 30%, respectively, when dabrafenib was coadministered with another strong CYP3A4 inducer for 10 days in a drug interaction study.
Daclatasvir: (Contraindicated) Concomitant use of daclatasvir with carbamazepine is contraindicated due to the potential for hepatitis C treatment failure. Coadministration may result in reduced systemic exposes to daclatasvir. Carbamazepine is a potent inducer of the hepatic isoenzyme CYP3A4; daclatasvir is a substrate of this isoenzyme.
Dalfopristin; Quinupristin: (Moderate) Dalfopristin; quinupristin is a major inhibitor of cytochrome P450 3A4 and may decrease the elimination of drugs metabolized by this enzyme including carbamazepine.
Danazol: (Moderate) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Danazol is known to inhibit CYP3A4 and may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations.
Dantrolene: (Moderate) Monitor carbamazepine concentrations closely during coadministration of dantrolene; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations.
Daprodustat: (Moderate) Monitor for a decrease in daprodustat efficacy during concomitant use of daprodustat and carbamazepine. Concomitant use may decrease daprodustat exposure. Daprodustat is a CYP2C8 substrate and carbamazepine is a CYP2C8 inducer.
Dapsone: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with carbamazepine is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and carbamazepine is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
Daridorexant: (Major) Avoid concomitant use of daridorexant and carbamazepine. Coadministration may decrease daridorexant exposure which may reduce its efficacy. Concomitant use may also increase carbamazepine concentrations. Daridorexant is a CYP3A substrate and inhibitor and carbamazepine is a CYP3A substrate and strong CYP3A inducer. Concomitant use of another strong CYP3A inducer decreased daridorexant overall exposure by over 50%.
Darolutamide: (Major) Avoid coadministration of darolutamide with carbamazepine due to the risk of decreased darolutamide plasma concentrations which may decrease efficacy. Carbamazepine is a P-glycoprotein (P-gp) inducer and a strong inducer of CYP3A4; darolutamide is a CYP3A4 substrate. Concomitant use with another combined P-gp and strong CYP3A4 inducer decreased the mean AUC and Cmax of darolutamide by 72% and 52%, respectively.
Darunavir: (Major) Closely monitor for carbamazepine toxicity during coadministration; clinical monitoring of carbamazepine concentrations with dosage titration if necessary is also warranted. Coadministration of darunavir and carbamazepine may result in increased carbamazepine concentrations. In drug interaction studies, the concentration of darunavir was unaffected during coadministration with carbamazepine.
Darunavir; Cobicistat: (Contraindicated) Coadministration of carbamazepine with cobicistat-containing regimens is contraindicated. If these drugs are used together, significant decreases in the plasma concentrations of the antiretrovirals may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. In addition, inhibition of CYP3A4 by cobicistat may result in elevated carbamazepine concentrations. Consider use of an alternative anticonvulsant or antiretroviral therapy. (Major) Closely monitor for carbamazepine toxicity during coadministration; clinical monitoring of carbamazepine concentrations with dosage titration if necessary is also warranted. Coadministration of darunavir and carbamazepine may result in increased carbamazepine concentrations. In drug interaction studies, the concentration of darunavir was unaffected during coadministration with carbamazepine.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Coadministration of carbamazepine with cobicistat-containing regimens is contraindicated. If these drugs are used together, significant decreases in the plasma concentrations of the antiretrovirals may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. In addition, inhibition of CYP3A4 by cobicistat may result in elevated carbamazepine concentrations. Consider use of an alternative anticonvulsant or antiretroviral therapy. (Major) Administering tenofovir alafenamide with carbamazepine is not recommended. Consider use of an alternative anticonvulsant. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure. (Major) Closely monitor for carbamazepine toxicity during coadministration; clinical monitoring of carbamazepine concentrations with dosage titration if necessary is also warranted. Coadministration of darunavir and carbamazepine may result in increased carbamazepine concentrations. In drug interaction studies, the concentration of darunavir was unaffected during coadministration with carbamazepine.
Dasatinib: (Major) Avoid coadministration of dasatinib and carbamazepine due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to carbamazepine with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
Deflazacort: (Major) Avoid concomitant use of deflazacort and carbamazepine. Concurrent use may significantly decrease concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A4 substrate; carbamazepine is a strong inducer of CYP3A4. Administration of deflazacort with multiple doses of rifampin (a strong CYP3A4 inducer) resulted in geometric mean exposures that were approximately 95% lower compared to administration alone.
Delavirdine: (Contraindicated) Coadministration of carbamazepine and delavirdine is contraindicated due to the potential for loss of virologic response and possible resistance to delavirdine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Delavirdine may also increase plasma concentrations of carbamazepine. Delavirdine and carbamazepine are both substrates of CYP3A4; however, carbamazepine is a potent CYP3A4 inducer while delavirdine is a potent CYP3A4 inhibitor.
Desipramine: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant carbamazepine use. Concomitant use may result in decreased tricyclic antidepressant exposure.
Desmopressin: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with water intoxication, hyponatremia, or SIADH including carbamazepine. The administration of carbamazepine prior to administration of desmopressin may act to reduce the duration of action of desmopressin. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia.
Desogestrel; Ethinyl Estradiol: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Dexamethasone: (Moderate) Monitor for decreased efficacy of both drugs if dexamethasone is coadministered with carbamazepine; dosage adjustments of either drug may be needed. Concomitant use may decrease the exposure of both drugs. Dexamethasone is a CYP3A substrate and weak CYP3A inducer; carbamazepine is a CYP3A substrate and strong CYP3A inducer.
Dexlansoprazole: (Moderate) Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Carbamazepine induces hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If carbamazepine and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
Dexmethylphenidate: (Minor) Psychostimulants, such as methylphenidate and its derivatives, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as carbamazepine. There are rare case reports of reduced methylphenidate concentrations occurring during the use of carbamazepine concurrently. The mechanism of the interaction is not clear as methylphenidate is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body. Interactions with other potent enzyme inducers have not been reported. Monitor for any changes in therapeutic effectiveness of either drug.
Dextromethorphan; Bupropion: (Moderate) Monitor for reduced bupropion efficacy during coadministration of carbamazepine as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose. Avoid concomitant use of combination dextromethorphan; bupropion and carbamazepine. Bupropion is a CYP2B6 substrate and carbamazepine is a strong CYP2B6 inducer. Concomitant use was observed to decrease bupropion overall exposure by 76% and dextromethorphan overall exposure by 64%.
Dextromethorphan; Quinidine: (Moderate) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Quinidine inhibits CYP3A4 and may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely if quinidine is added during carbamazepine therapy. It may be necessary to reduce the dose of carbamazepine in this situation.
Diazepam: (Moderate) Carbamazepine is a potent inducer of the hepatic isoenzyme CYP3A4, one of the pathways responsible for the hepatic metabolism of diazepam. Monitor closely for signs of reduced diazepam effects.
Dienogest; Estradiol valerate: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Diltiazem: (Major) Avoid coadministration of diltiazem and carbamazepine due to decreased plasma concentrations of diltiazem. Coadministration with another strong CYP3A4 inducer lowered diltiazem plasma concentrations to undetectable levels. Concomitant use has also resulted in a 40% to 72% increase in carbamazepine plasma concentration leading to toxicity in some cases. Diltiazem is a substrate and moderate inhibitor of CYP3A4 substrate and carbamazepine is a substrate and strong inducer of CYP3A4.
Diphenhydramine; Ibuprofen: (Moderate) Monitor carbamazepine concentrations closely during coadministration of ibuprofen; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations.
Disopyramide: (Moderate) Hepatic microsomal enzyme-inducing agents, such as carbamazepine, have the potential to accelerate the hepatic metabolism of disopyramide, a CYP3A4 substrate. Patients should be monitored for loss of disopyramide activity if carbamazepine is added. In addition, disopyramide doses may need to be reduced if acarbamazepine is stopped and disopyramide therapy is continued.
Docetaxel: (Major) Avoid coadministration of docetaxel with carbamazepine due to decreased plasma concentrations of docetaxel. Docetaxel is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with other strong CYP3A4 inducers increased docetaxel metabolism by 2.6-fold to 32-fold.
Dolutegravir: (Major) When possible, avoid concurrent use of dolutegravir with carbamazepine in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with carbamazepine. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and carbamazepine is an inducer of CYP3A4.
Dolutegravir; Lamivudine: (Major) When possible, avoid concurrent use of dolutegravir with carbamazepine in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with carbamazepine. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and carbamazepine is an inducer of CYP3A4.
Dolutegravir; Rilpivirine: (Contraindicated) Coadministration of carbamazepine and rilpivirine is contraindicated due to the potential for loss of virologic response and possible resistance to rilpivirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Rilpivirine is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. (Major) When possible, avoid concurrent use of dolutegravir with carbamazepine in integrase strand transfer inhibitor (INSTI)-experienced patients with INSTI-associated resistance substitutions or clinically suspected INSTI resistance. For treatment-naive or treatment-experienced, but INSTI-naive, adult and pediatric patients, the dose of dolutegravir should be increased to twice daily when administered with carbamazepine. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Dolutegravir is a CYP3A4 substrate and carbamazepine is an inducer of CYP3A4.
Donepezil: (Moderate) The elimination of donepezil may be increased by concurrent administration of certain in vitro inducers of the hepatic isoenzymes CYP2D6 and/or CYP3A4, including carbamazepine.
Donepezil; Memantine: (Moderate) The elimination of donepezil may be increased by concurrent administration of certain in vitro inducers of the hepatic isoenzymes CYP2D6 and/or CYP3A4, including carbamazepine.
Doravirine: (Contraindicated) Coadministration of carbamazepine and doravirine is contraindicated due to the potential for loss of virologic response and possible resistance to doravirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). If doravirine use is necessary, discontinue carbamazepine at least 4-weeks prior to initiation. Doravirine is a CYP3A4 substrate and carbamazepine is a potent CYP3A4 inducer.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Contraindicated) Coadministration of carbamazepine and doravirine is contraindicated due to the potential for loss of virologic response and possible resistance to doravirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). If doravirine use is necessary, discontinue carbamazepine at least 4-weeks prior to initiation. Doravirine is a CYP3A4 substrate and carbamazepine is a potent CYP3A4 inducer.
Doxepin: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant carbamazepine use. Concomitant use may result in decreased tricyclic antidepressant exposure.
Doxercalciferol: (Moderate) Hepatic enzyme inducers such as carbamazepine, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
Doxorubicin Liposomal: (Major) Avoid coadministration of doxorubicin with carbamazepine due to the risk for decreased doxorubicin plasma concentrations which may compromise the efficacy of chemotherapy. Doxorubicin is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Doxorubicin: (Major) Avoid coadministration of doxorubicin with carbamazepine due to the risk for decreased doxorubicin plasma concentrations which may compromise the efficacy of chemotherapy. Doxorubicin is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Doxycycline: (Moderate) Monitor for decreased efficacy of doxycycline if coadministered with carbamazepine. Carbamazepine may potentially accelerate the hepatic metabolism of doxycycline.
Dronabinol: (Moderate) Monitor for a decrease in dronabinol efficacy if coadministration with carbamazepine is necessary. Coadministration may decrease the exposure of dronabinol. Dronabinol is a CYP3A substrate; carbamazepine is a strong CYP3A inducer.
Dronedarone: (Major) The concomitant use of dronedarone and CYP3A4 inducers should be avoided. Dronedarone is metabolized by CYP3A. Carbamazepine induces CYP3A4. Coadministration of CYP3A4 inducers, such as carbamazepine, with dronedarone may result in reduced plasma concentration and subsequent reduced effectiveness of dronedarone therapy.
Drospirenone: (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Drospirenone; Estetrol: (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Drospirenone; Estradiol: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Drospirenone; Ethinyl Estradiol: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin). (Moderate) High doses of folate may cause decreased serum concentrations of carbamazepine resulting in a decrease in effectiveness and, possibly, an increase in the frequency of seizures in susceptible patients. In addition, L-methylfolate plasma levels may be decreased when administered with carbamazepine. Although no decrease in effectiveness of anticonvulsants has been reported with the concurrent use of L-methylfolate, caution still should be exercised with the coadministration of these agents and patients should be monitored closely for seizure activity.
Dupilumab: (Moderate) Coadministration of dupilumab may result in altered exposure to carbamazepine. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP450 enzymes could be normalized during dupilumab administration. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as carbamazepine. Monitor carbamazepine concentrations if dupilumab is initiated or discontinued in a patient taking carbamazepine; carbamazepine dose adjustments may be needed.
Duvelisib: (Major) Avoid coadministration of duvelisib with carbamazepine. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; carbamazepine is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Edoxaban: (Major) Avoid the concomitant administration of edoxaban and carbamazepine. Concomitant administration of edoxaban and carbamazepine results in decreased plasma concentrations of edoxaban that may be insufficient to achieve the intended therapeutic effect.
Efavirenz: (Major) Coadministration of carbamazepine and efavirenz is not recommended due to the potential for loss of virologic response and possible resistance to efavirenz or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Efavirenz may also decrease plasma concentrations of carbamazepine. Monitor carbamazepine and efavirenz concentration, or if possible, use an alternative anticonvulsant. In drug interaction studies, coadministration of carbamazepine and efavirenz resulted in a 27% decrease in carbamazepine AUC and a 36% decrease in the efavirenz AUC.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of carbamazepine and efavirenz is not recommended due to the potential for loss of virologic response and possible resistance to efavirenz or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Efavirenz may also decrease plasma concentrations of carbamazepine. Monitor carbamazepine and efavirenz concentration, or if possible, use an alternative anticonvulsant. In drug interaction studies, coadministration of carbamazepine and efavirenz resulted in a 27% decrease in carbamazepine AUC and a 36% decrease in the efavirenz AUC.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of carbamazepine and efavirenz is not recommended due to the potential for loss of virologic response and possible resistance to efavirenz or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Efavirenz may also decrease plasma concentrations of carbamazepine. Monitor carbamazepine and efavirenz concentration, or if possible, use an alternative anticonvulsant. In drug interaction studies, coadministration of carbamazepine and efavirenz resulted in a 27% decrease in carbamazepine AUC and a 36% decrease in the efavirenz AUC.
Elacestrant: (Major) Avoid concurrent use of elacestrant and carbamazepine due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Elagolix: (Moderate) Concomitant use of elagolix and carbamazepine may result in decreased concentrations of elagolix and/or carbamazepine; monitor for decreased efficacy of both drugs with coadministration. Elagolix is a CYP3A substrate and a weak to moderate inducer; carbamazepine is a strong inducer and substrate of CYP3A4.
Elagolix; Estradiol; Norethindrone acetate: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin). (Moderate) Concomitant use of elagolix and carbamazepine may result in decreased concentrations of elagolix and/or carbamazepine; monitor for decreased efficacy of both drugs with coadministration. Elagolix is a CYP3A substrate and a weak to moderate inducer; carbamazepine is a strong inducer and substrate of CYP3A4.
Elbasvir; Grazoprevir: (Contraindicated) Concurrent administration of elbasvir; grazoprevir with carbamazepine is contraindicated. Carbamazepine is a strong CYP3A inducer, while both elbasvir and grazoprevir are substrates of CYP3A. Use of these drugs together is expected to significantly decrease the plasma concentrations of both elbasvir and grazoprevir, and may result in decreased virologic response.
Elexacaftor; tezacaftor; ivacaftor: (Major) Coadministration of elexacaftor; tezacaftor; ivacaftor with carbamazepine is not recommended as concurrent use may decrease exposure of elexacaftor; tezacaftor; ivacaftor. Elexacaftor, tezacaftor, and ivacaftor are CYP3A4 substrates (ivacaftor is a sensitive CYP3A4 substrate). Carbamazepine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer significantly decreased ivacaftor exposure by 89%; elexacaftor and tezacaftor exposures are expected to also decrease during coadministration of strong CYP3A4 inducers. (Major) Coadministration of ivacaftor with carbamazepine is not recommended due to decreased plasma concentrations of ivacaftor. Ivacaftor is a sensitive CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer significantly decreased ivacaftor exposure by approximately 9-fold. (Major) Do not administer tezacaftor; ivacaftor and carbamazepine together; coadministration may reduce the efficacy of tezacaftor; ivacaftor. Exposure to ivacaftor is significantly decreased and exposure to tezacaftor may be reduced by the concomitant use of carbamazepine, a strong CYP3A inducer; both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate). Coadministration of ivacaftor with a strong CYP3A inducer decreased ivacaftor exposure 89%.
Eliglustat: (Major) Coadministration of eliglustat and carbamazepine significantly decreases eliglustat exposure and is not recommended in extensive, intermediate, or poor metabolizers of CYP2D6. Carbamazepine is a strong CYP3A inducer, and eliglustat is a CYP3A substrate.
Eltrombopag: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as carbamazepine, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Coadministration of carbamazepine with cobicistat-containing regimens is contraindicated. If these drugs are used together, significant decreases in the plasma concentrations of the antiretrovirals may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. In addition, inhibition of CYP3A4 by cobicistat may result in elevated carbamazepine concentrations. Consider use of an alternative anticonvulsant or antiretroviral therapy. (Major) Administering tenofovir alafenamide with carbamazepine is not recommended. Consider use of an alternative anticonvulsant. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure. (Major) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Carbamazepine induces the CYP3A4 metabolism of elvitegravir. Consider an alternative anticonvulsant when using elvitegravir. The combination product cobicistat; elvitegravir; emtricitabine; tenofovir is contraindicated in combination with carbamazepine as the concentrations of both elvitegravir and cobicistat may be significantly decreased.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Coadministration of carbamazepine with cobicistat-containing regimens is contraindicated. If these drugs are used together, significant decreases in the plasma concentrations of the antiretrovirals may occur, resulting in reduction of antiretroviral efficacy and development of viral resistance. In addition, inhibition of CYP3A4 by cobicistat may result in elevated carbamazepine concentrations. Consider use of an alternative anticonvulsant or antiretroviral therapy. (Major) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Carbamazepine induces the CYP3A4 metabolism of elvitegravir. Consider an alternative anticonvulsant when using elvitegravir. The combination product cobicistat; elvitegravir; emtricitabine; tenofovir is contraindicated in combination with carbamazepine as the concentrations of both elvitegravir and cobicistat may be significantly decreased.
Emapalumab: (Moderate) Monitor for decreased efficacy of carbamazepine and adjust the dose as needed during coadministration with emapalumab. Carbamazepine is a CYP3A4, CYP1A2, and CYP2C8 substrate with a narrow therapeutic index. Emapalumab may normalize CYP450 activity, which may decrease the efficacy of drugs that are CYP450 substrates due to increased metabolism.
Empagliflozin; Linagliptin: (Moderate) Monitor for a decrease in linagliptin efficacy during concomitant use of linagliptin and carbamazepine if coadministration is required. Concomitant use may decrease linagliptin exposure. Linagliptin is a CYP3A and P-gp substrate and carbamazepine is a strong CYP3A and P-gp inducer. Concomitant use with a strong CYP3A and P-gp inducer reduced linagliptin overall exposure by 0.6-fold.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor for a decrease in linagliptin efficacy during concomitant use of linagliptin and carbamazepine if coadministration is required. Concomitant use may decrease linagliptin exposure. Linagliptin is a CYP3A and P-gp substrate and carbamazepine is a strong CYP3A and P-gp inducer. Concomitant use with a strong CYP3A and P-gp inducer reduced linagliptin overall exposure by 0.6-fold.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Contraindicated) Coadministration of carbamazepine and rilpivirine is contraindicated due to the potential for loss of virologic response and possible resistance to rilpivirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Rilpivirine is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. (Major) Administering tenofovir alafenamide with carbamazepine is not recommended. Consider use of an alternative anticonvulsant. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Contraindicated) Coadministration of carbamazepine and rilpivirine is contraindicated due to the potential for loss of virologic response and possible resistance to rilpivirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Rilpivirine is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
Emtricitabine; Tenofovir alafenamide: (Major) Administering tenofovir alafenamide with carbamazepine is not recommended. Consider use of an alternative anticonvulsant. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Enasidenib: (Moderate) Monitor carbamazepine concentrations closely during coadministration of enasidenib; carbamazepine dose adjustments may be needed. Concomitant use may decrease carbamazepine concentrations. Carbamazepine is a CYP3A substrate and enasidenib is a CYP3A inducer.
Encorafenib: (Major) Avoid concomitant use of encorafenib and carbamazepine. Concurrent use may decrease the exposure of both drugs, which may reduce their efficacy. Both drugs are CYP3A substrates and strong CYP3A inducers.
Enteral Feedings: (Moderate) Concurrent enteral feedings appear to slow or impede the absorption of carbamazepine suspension from the GI tract. Where possible, hold continuous enteral feedings at least 15 minutes before and 15 minutes after the administration of a carbamazepine suspension dose. Flush enteral tubes with appropriate volumes of water or other compatible fluid before and after carbamazepine suspension administration.
Entrectinib: (Major) Avoid coadministration of entrectinib with carbamazepine due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the entrectinib AUC by 77% in a drug interaction study.
Enzalutamide: (Major) Avoid coadministration of carbamazepine with enzalutamide if possible due to decreased enzalutamide exposure which may compromise efficacy; carbamazepine plasma concentrations may also decrease. If concomitant use is unavoidable, increase the dose of enzalutamide from 160 mg to 240 mg once daily; the original dose of enzalutamide may be resumed when carbamazepine is discontinued. An increased dose of carbamazepine may also be necessary; monitor carbamazepine concentrations. Both enzalutamide and carbamazepine are substrates and strong inducers of CYP3A4. The composite AUC of enzalutamide plus N-desmethyl enzalutamide decreased by 37% in the presence of a strong CYP3A4 inducer. CYP3A4 inducers can decrease serum concentrations of carbamazepine and decrease its effectiveness.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Eravacycline: (Major) Increase the dose of eravacycline to 1.5 mg/kg IV every 12 hours when coadministered with a strong CYP3A4 inducer, such as carbamazepine. Concomitant use of strong CYP3A4 inducers decreases the exposure of eravacycline, which may reduce its efficacy. When eravacycline was administered with a strong CYP3A4/3A5 inducer, the eravacycline AUC was decreased by 35% and its clearance was increased by 54%.
Erdafitinib: (Major) Avoid coadministration of erdafitinib and carbamazepine due to the risk of decreased plasma concentrations of erdafitinib resulting in decreased efficacy. Erdafitinib is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Ergotamine; Caffeine: (Minor) Carbamazepine may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme.
Erlotinib: (Major) Avoid coadministration of erlotinib with carbamazepine if possible due to the risk of decreased erlotinib efficacy. If concomitant use is unavoidable, increase the dose of erlotinib in 50 mg increments at 2-week intervals as tolerated (maximum dose, 450 mg). Erlotinib is primarily metabolized by CYP3A4, and to a lesser extent by CYP1A2. Carbamazepine is a strong CYP3A4 inducer as well as a CYP1A2 inducer. Coadministration with another strong CYP3A4 inducer decreased erlotinib exposure by 58% to 80%.
Erythromycin: (Moderate) Monitor carbamazepine concentrations closely during coadministration of erythromycin; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and erythromycin is a CYP3A inhibitor.
Eslicarbazepine: (Major) Because carbamazepine and eslicarbazepine are chemically related, coadministration may result in an increased incidence of adverse reactions. In addition, carbamazepine reduces the plasma concentration of eslicarbazepine. Dosage adjustment of eslicarbazepine and carbamazepine may be necessary based on efficacy and tolerability.
Esomeprazole: (Major) Avoid concomitant use of esomeprazole and carbamazepine as esomeprazole exposure may be decreased, reducing its efficacy. Esomeprazole is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Estazolam: (Moderate) Carbamazepine is a hepatic inducer and can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism, possibly leading to reduced benzodiazepine concentrations.
Esterified Estrogens: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination.
Esterified Estrogens; Methyltestosterone: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination.
Estradiol: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination.
Estradiol; Levonorgestrel: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Estradiol; Norethindrone: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Estradiol; Norgestimate: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Estradiol; Progesterone: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Estrogens affected by CYP3A inducers: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination.
Estropipate: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination.
Eszopiclone: (Moderate) Potent inducers of CYP3A4, such as carbamazepine, may increase the rate of eszopiclone metabolism, resulting in decreased systemic eszopiclone concentrations.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression. (Moderate) Because of its primary CNS effect, caution should be used when carbamazepine is taken with other centrally acting drugs such as alcohol. The limited evidence from pharmacokinetic studies suggests that neither acute nor chronic alcohol use will significantly alter the pharmacokinetics of carbamazepine.
Ethinyl Estradiol; Norelgestromin: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Ethinyl Estradiol; Norethindrone Acetate: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Ethinyl Estradiol; Norgestrel: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Ethosuximide: (Moderate) Carbamazepine induces hepatic microsomal enzymes. Increased hepatic metabolism of ethosuximide leads to a decrease in its plasma concentration and a reduction in its half-life. To maintain a therapeutic dosage, serum concentrations of ethosuximide should be measured, especially if additional anticonvulsant therapy is added to or withdrawn from ethosuximide therapy.
Ethotoin: (Moderate) Monitor carbamazepine and phenytoin concentrations closely during coadministration; dose adjustments may be needed. Concomitant use may decrease carbamazepine or phenytoin concentrations. Carbamazepine is a CYP3A4 substrate and CYP2C9 and CYP2C19 inducer. Hydantoins are CYP2C9 and CYP2C19 substrates and strong CYP3A inducers.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Etonogestrel: (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Etonogestrel; Ethinyl Estradiol: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Etravirine: (Major) Avoid concomitant use of carbamazepine and etravirine due to the potential for decreased plasma concentrations of etravirine, leading to a reduction of antiretroviral efficacy and the potential development of antiretroviral drug resistance. Decreased exposure to carbamazepine may also occur. Etravirine is a CYP3A, CYP2C9, and CYP2C19 substrate and moderate CYP3A inducer; carbamazepine is a CYP3A substrate and CYP2C9, CYP2C19, and strong CYP3A inducer.
Everolimus: (Major) Avoid coadministration of everolimus with carbamazepine due to the risk of decreased efficacy of everolimus. If concomitant use is unavoidable, coadministration requires a dose increase for some indications and close monitoring for others. For oncology indications and tuberous sclerosis complex (TSC)-associated renal angiomyolipoma, double the daily dose using increments of 5 mg or less; multiple increments may be required. For patients with TSC-associated subependymal giant cell astrocytoma (SEGA) and TSC-associated partial-onset seizures, assess the everolimus whole blood trough concentration 2 weeks after initiation of carbamazepine and adjust the dose as necessary to remain in the recommended therapeutic range. Also closely monitor everolimus whole blood trough concentrations in patients receiving everolimus for either kidney or liver transplant and adjust the dose as necessary to remain in the recommended therapeutic range. Everolimus is a sensitive CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC of everolimus by 63%. For indications where everolimus trough concentrations are monitored, the addition of a second strong CYP3A4 inducer in a patient already receiving treatment with a strong CYP3A4 inducer may not require additional dose modification.
Exemestane: (Major) If coadministration of exemestane with carbamazepine is necessary, increase the dose of exemestane to 50 mg once daily after a meal. Exemestane is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exemestane exposure by 54%.
Ezetimibe; Simvastatin: (Minor) Carbamazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates, including simvastatin.
Fedratinib: (Major) Avoid coadministration of fedratinib with carbamazepine as concurrent use may decrease fedratinib exposure which may result in decreased therapeutic response. Fedratinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration of fedratinib with another strong CYP3A4 inducer decreased the overall exposure of fedratinib by 81%.
Felbamate: (Moderate) Concurrent administration of felbamate and other antiepileptic drugs results in changes in serum concentrations of both felbamate and the antiepileptic drugs. Felbamate causes a decrease in the steady-state plasma concentration of carbamazepine but increases concentrations of carbamazepine epoxide, a carbamazepine metabolite.
Felodipine: (Moderate) Carbamazepine induces CYP3A4 and may significantly enhance the hepatic metabolism of felodipine. Higher doses of felodipine may be necessary in epileptic patients receiving carbamazepine.
Fenfluramine: (Major) Avoid concurrent use of fenfluramine and carbamazepine due to the risk of decreased fenfluramine plasma concentrations, which may reduce its efficacy. If concomitant use is necessary, monitor for decreased efficacy and consider increasing fenfluramine dose as needed. If carbamazepine is discontinued during fenfluramine maintenance treatment, consider gradual reduction in the fenfluramine dosage to the dose administered prior to carbamazepine initiation. Fenfluramine is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concurrent use of carbamazepine is necessary. If carbamazepine is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like carbamazepine with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Fexinidazole: (Major) Avoid concurrent use of fexinidazole and carbamazepine. Coadministration may increase the risk for fexinidazole-related adverse effects including QT prolongation as well as increase carbamazepine concentrations. Carbamazepine may enhance the conversion of fexinidazole to its active metabolites. Higher metabolite concentrations have been associated with increased risk of QT prolongation. Fexinidazole is converted to its active metabolites via CYP3A and is also a CYP3A inhibitor; carbamazepine is a CYP3A substrate and strong CYP3A inducer.
Finasteride; Tadalafil: (Major) Avoid coadministration of tadalafil with carbamazepine in patients with pulmonary hypertension due to decreased plasma concentrations of tadalafil. In patients with erectile dysfunction and/or benign prostatic hyperplasia, consider the potential for loss of efficacy of tadalafil during concurrent administration of carbamazepine due to reduced tadalafil exposure. Tadalafil is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased tadalafil exposure by 88%.
Finerenone: (Major) Avoid concurrent use of finerenone and carbamazepine due to the risk for decreased finerenone exposure which may reduce its efficacy. Finerenone is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased overall exposure to finerenone by 90%.
Flibanserin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and carbamazepine, a strong CYP3A4 inducer, is not recommended.
Fluconazole: (Moderate) Monitor carbamazepine concentrations closely during coadministration of fluconazole; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and fluconazole is a CYP3A inhibitor.
Flucytosine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants, including carbamazepine.
Flurazepam: (Moderate) Monitor patients for decreased efficacy of flurazepam if coadministration with carbamazepine is necessary. Concurrent use may decrease flurazepam exposure. Flurazepam is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Fluticasone: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of fluticasone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with fluticasone.
Fluticasone; Salmeterol: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of fluticasone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with fluticasone.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of fluticasone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with fluticasone.
Fluticasone; Vilanterol: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of fluticasone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with fluticasone.
Fluvoxamine: (Moderate) Carbamazepine is metabolized by CYP3A4 and fluvoxamine is known to inhibit this enzyme. Serum carbamazepine concentrations should be monitored closely if fluvoxamine is added during carbamazepine therapy. It may be necessary to reduce the dose of carbamazepine in this situation. At least one case is noted where carbamazepine serum concentrations increased substantially when fluvoxamine was added, accompanied by signs of carbamazepine toxicity.
Fomepizole: (Minor) Carbabamezapine may decrease the actions of Fomepizole via induction of the CYP450 hepatic enzyme system. This interaction has not been studied, and its clinical significance has not been established.
Food: (Major) Advise patients to avoid cannabis use during carbamazepine treatment. Concomitant use may decrease the concentration of some cannabinoids and alter their effects. The cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concomitant use of a cannabinoid product containing THC and CBD at an approximate 1:1 ratio with another strong CYP3A inducer decreased THC, 11-OH-THC, and CBD peak exposures by 36%, 87%, and 52% respectively.
Fosamprenavir: (Moderate) Monitor for decreased efficacy of fosamprenavir during coadministration of carbamazepine. Additionally, monitor carbamazepine concentrations closely as increased side effects may occur; dose adjustments may be needed. Concomitant use may result in decreased plasma concentrations of fosamprenavir and increased carbamazepine concentrations. Fosamprenavir is a CYP3A substrate and moderate CYP3A inhibitor; carbamazepine is a CYP3A substrate and strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the fosamprenavir overall exposure by 82%.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Fosphenytoin: (Moderate) Monitor carbamazepine and phenytoin concentrations closely during coadministration; dose adjustments may be needed. Concomitant use may decrease carbamazepine or phenytoin concentrations. Carbamazepine is a CYP3A4 substrate and CYP2C9 and CYP2C19 inducer. Hydantoins are CYP2C9 and CYP2C19 substrates and strong CYP3A inducers.
Fostamatinib: (Major) Avoid the concomitant use of fostamatinib with carbamazepine. Concomitant use of fostamatinib with a strong CYP3A4 inducer decreases exposure to the major active metabolite, R406. R406 is extensively metabolized by CYP3A4; carbamazepine is a strong CYP3A4 inducer. Concomitant use of fostamatinib with another strong CYP3A4 inducer decreased R406 AUC by 75% and Cmax by 59%.
Fostemsavir: (Contraindicated) Concomitant use of fostemsavir and carbamazepine is contraindicated. Use of these drugs together may significantly decrease the plasma concentrations of temsavir, the active moiety of fostemsavir, thereby increasing the risk for HIV treatment failure or development of viral resistance. Temsavir is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
Fruquintinib: (Major) Avoid coadministration of fruquintinib with carbamazepine due to decreased fruquintinib exposure and risk of decreased efficacy. Fruquintinib is a CYP3A substrate; carbamazepine is a strong CYP3A inducer. Coadministration of a strong CYP3A inducer decreased fruquintinib exposure by 65%.
Futibatinib: (Major) Avoid concurrent use of futibatinib and carbamazepine. Concomitant use may decrease futibatinib exposure, which may reduce its efficacy. Futibatinib is a substrate of CYP3A and P-gp; carbamazepine is a dual P-gp and strong CYP3A inducer. Coadministration with another dual P-gp and strong CYP3A inducer decreased futibatinib exposure by 64%.
Ganaxolone: (Major) Avoid concurrent use of ganaxolone and carbamazepine due to the risk of decreased ganaxolone efficacy. If concomitant use is unavoidable, consider increasing ganaxolone dose without exceeding the maximum daily dose. Ganaxolone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ganaxolone overall exposure by 68%.
Gefitinib: (Major) Increase the dose of gefitinib to 500 mg PO once daily if coadministration with carbamazepine is necessary. If carbamazepine is discontinued, gefitinib at a dose of 250 mg once daily may be resumed 7 days later. Gefitinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer reduced gefitinib exposure by 83%.
Gemfibrozil: (Moderate) Use carbamazepine and gemfibrozil together with caution. Carbamazepine is a substrate of CYP2C8, and gemfibrozil is a strong CYP2C8 inhibitor. Coadministration may result in a significant increase in carbamazepine exposure. A dose reduction of carbamazepine may be required if used concomitantly with gemfibrozil.
Gilteritinib: (Major) Avoid coadministration of gilteritinib and carbamazepine due to the potential for decreased gilteritinib exposure and risk of decreased efficacy. Gilteritinib is a P-gp and CYP3A4 substrate; carbamazepine is a combined P-gp and strong CYP3A4 inducer. Coadministration of another combined P-gp and strong CYP3A4 inducer decreased the gilteritinib AUC by 70% in a drug interaction study.
Givosiran: (Major) Avoid concomitant use of givosiran and carbamazepine due to the risk of increased carbamazepine-related adverse reactions. If use is necessary, consider reducing the carbamazepine dose. Carbamazepine is a CYP1A2 substrate. Givosiran may moderately reduce hepatic CYP1A2 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway.
Glasdegib: (Major) Avoid coadministration of glasdegib and carbamazepine due to the potential for decreased glasdegib exposure and risk of decreased efficacy. Glasdegib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the glasdegib AUC by 70% in a drug interaction study.
Glecaprevir; Pibrentasvir: (Major) Coadministration of glecaprevir with carbamazepine is not recommended due to the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A4 and P-glycoprotein (P-gp); carbamazepine is a CYP3A4/P-gp inducer. In drug interaction studies, coadministration of carbamazepine with glecaprevir resulted in a 66% decrease in the AUC of glecaprevir. (Major) Coadministration of pibrentasvir with carbamazepine is not recommended due to the potential loss of efficacy of pibrentasvir. Pibrentasvir is a substrate of P-glycoprotein (P-gp); carbamazepine is an inducer of P-gp. Coadministration may decrease plasma concentrations of pibrentasvir. In drug interaction studies, coadministration of carbamazepine with pibrentasvir resulted in a 51% decrease in the AUC of pibrentasvir.
Glycerol Phenylbutyrate: (Moderate) Monitor carbamazepine concentrations closely during coadministration of glycerol phenylbutyrate; carbamazepine dose adjustments may be needed. Concomitant use may decrease carbamazepine concentrations. Carbamazepine is a CYP3A substrate and glycerol phenylbutyrate is a CYP3A inducer.
Grapefruit juice: (Moderate) Grapefruit juice has been shown to increase carbamazepine peak and trough serum concentrations and the AUC by up to 40 percent. Grapefruit juice contains a compound that inhibits CYP3A4 in enterocytes. Increased sedation or other side effects may be possible. It is recommended that patients not significantly alter their grapefruit ingestion while taking carbamazepine.
Green Tea: (Minor) Some, but not all, green tea products contain caffeine. Medications that may induce caffeine metabolism via induction of the hepatic CYP1A2 isoenzyme include carbamazepine.
Guanfacine: (Major) Carbamazepine can significantly decrease guanfacine plasma concentrations; guanfacine dosage adjustment is recommended. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, doubling the recommended dose of guanfacine should be considered. If carbamazepine is added in a patient already receiving guanfacine, this escalation should occur over 1 to 2 weeks. If carbamazepine is discontinued, decrease the guanfacine ER dosage back to the recommended dose over 1 to 2 weeks. Specific recommendations for immediate-release (IR) guanfacine are not available. Guanfacine is primarily metabolized by CYP3A4, and carbamazepine is a strong CYP3A4 inducer.
Guanidine: (Minor) Bone marrow suppression is associated with guanidine therapy. Avoid concomitant use of other drugs known to cause bone marrow suppression such as carbamazepine.
Haloperidol: (Major) Carbamazepine may potentially accelerate the hepatic metabolism of haloperidol. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with haloperidol.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
Hydantoins: (Moderate) Monitor carbamazepine and phenytoin concentrations closely during coadministration; dose adjustments may be needed. Concomitant use may decrease carbamazepine or phenytoin concentrations. Carbamazepine is a CYP3A4 substrate and CYP2C9 and CYP2C19 inducer. Hydantoins are CYP2C9 and CYP2C19 substrates and strong CYP3A inducers.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with carbamazepine can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If carbamazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. (Moderate) Monitor carbamazepine concentrations closely during coadministration of ibuprofen; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations.
Hydroxychloroquine: (Moderate) Monitor for a decrease in hydroxychloroquine and carbamazepine efficacy if coadministration is necessary. Antiepileptic drug activity may be impaired if coadministered with hydroxychloroquine and concomitant use may decrease exposure of hydroxychloroquine. Hydroxychloroquine is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Ibrexafungerp: (Major) Avoid concurrent administration of ibrexafungerp with carbamazepine. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Ibrutinib: (Major) Avoid the concomitant use of ibrutinib and carbamazepine; ibrutinib plasma concentrations may decrease. Ibrutinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ibrutinib exposure by more than 10-fold.
Ibuprofen: (Moderate) Monitor carbamazepine concentrations closely during coadministration of ibuprofen; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations.
Ibuprofen; Famotidine: (Moderate) Monitor carbamazepine concentrations closely during coadministration of ibuprofen; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations.
Ibuprofen; Oxycodone: (Moderate) Monitor carbamazepine concentrations closely during coadministration of ibuprofen; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of oxycodone as needed. If carbamazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor carbamazepine concentrations closely during coadministration of ibuprofen; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations.
Idelalisib: (Contraindicated) Avoid concomitant use of idelalisib, a CYP3A4 substrate, with a strong CYP3A4 inducer such as carbamazepine, as idelalisib exposure may be significantly reduced and efficacy compromised. Additionally, idelalisib is a strong CYP3A inhibitor while carbamazepine is a CYP3A substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Avoid concomitant use of idelalisib and carbamazepine.
Ifosfamide: (Moderate) Closely monitor for increased ifosfamide-related toxicities (e.g., neurotoxicity, nephrotoxicity) if coadministration with carbamazepine is necessary; consider adjusting the dose of ifosfamide as clinically appropriate. Ifosfamide is metabolized to its active alkylating metabolites by CYP3A4; carbamazepine is a strong CYP3A4 inducer. Concomitant use may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde.
Iloperidone: (Moderate) In vitro studies indicate that CYP3A4 is involved in the metabolism of iloperidone. In theory, potent inducers of CYP3A4 such as carbamazepine may increase the elimination of iloperidone.
Imatinib: (Major) Avoid coadministration of imatinib and carbamazepine if possible due to the risk for decreased imatinib concentrations and increased carbamazepine concentrations. If concomitant use is necessary, increase the dose of imatinib by at least 50%, carefully monitoring clinical response; imatinib doses up to 1,200 mg per day (600 mg twice daily) have been given to patients receiving concomitant strong CYP3A4 inducers. Additionally, monitor carbamazepine concentrations closely as carbamazepine dosage adjustments may be needed. Imatinib is a CYP3A4 substrate and moderate CYP3A inhibitor; carbamazepine is a CYP3A substrate and strong CYP3A inducer. Coadministration with another strong CYP3A4 inducer increased imatinib clearance by 3.8-fold, which significantly decreased the mean Cmax and AUC of imatinib.
Imipramine: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant carbamazepine use. Concomitant use may result in decreased tricyclic antidepressant exposure.
Indinavir: (Major) Anticonvulsants, such as carbamazepine, may increase the metabolism of indinavir and lead to decreased efficacy. Treatment failures have been reported with protease inhibitors when carbamazepine was used concomitantly. In addition, indinavir is a potent CYP3A inibitor and coadministration may result in increased serum concentrations of carbamazepine. The appropriate drug-dose adjustments necessary to ensure optimum levels of both antiretroviral and anticonvulsant drugs are unknown. If indinavir and carbamazepine are coadministered, the patient should be observed for changes in the clinical efficacy of the antiretroviral regimen or carbamazepine toxicity.
Infigratinib: (Major) Avoid concurrent use of infigratinib and carbamazepine. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Infigratinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC of infigratinib by 56%.
Iptacopan: (Moderate) Monitor for a decrease in iptacopan efficacy during concomitant use of iptacopan and carbamazepine; discontinue use of carbamazepine if loss of efficacy of iptacopan is evident. Concomitant use may decrease iptacopan exposure. Iptacopan is a CYP2C8 substrate and carbamazepine is a CYP2C8 inducer.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Irinotecan Liposomal: (Major) Avoid administration of carbamazepine during treatment with irinotecan and for at least 2 weeks prior to starting therapy unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates. Carbamazepine is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers substantially reduced exposure to irinotecan or SN-38 in both adult and pediatric patients. An appropriate starting dose for patients taking irinotecan with strong CYP3A4 inducers has not been defined.
Irinotecan: (Major) Avoid administration of carbamazepine during treatment with irinotecan and for at least 2 weeks prior to starting therapy unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates. Carbamazepine is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers substantially reduced exposure to irinotecan or SN-38 in both adult and pediatric patients. An appropriate starting dose for patients taking irinotecan with strong CYP3A4 inducers has not been defined.
Isavuconazonium: (Contraindicated) Concomitant use of isavuconazonium with carbamazepine is contraindicated due to the potential for decreased isavuconazole serum concentrations and treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; carbamazepine is a strong inducer of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inducers is contraindicated. There was a 97% decrease in isavuconazole serum concentrations when coadministered with rifampin, another strong CYP3A4 inducer. Elevated carbamazepine concentrations would also be expected with coadministration, as carbamazepine is a substrate and isavuconazole is a moderate inhibitor of CYP3A4.
Isocarboxazid: (Contraindicated) Carbamazepine is contraindicated for use with monoamine oxidase inhibitors (MAOIs), because of a possible increased risk of serotonin syndrome and/or hypertensive crisis. Due to the risk of serotonin syndrome, carbamazepine is contraindicated for use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing treatment with an MAOI. Conversely, MAOIs should not be initiated within 14 days of stopping carbamazepine. Monitor blood pressure and for serotonin-related side effects during therapy transitions.
Isoflurane: (Moderate) Caution is advised with the concomitant use of isoflurane and carbamazepine as concurrent use may increase the risk of hepatotoxicity.
Isoniazid, INH: (Moderate) Isoniazid is known to increase carbamazepine exposure. Measure carbamazepine concentrations prior to coadministration with isoniazid. Monitor for evidence of carbamazepine toxicity during concurrent use and adjust the carbamazepine dose as necessary.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of carbamazepine. Carbamazepine dosages may need to be adjusted while the patient is receiving rifampin. (Moderate) Isoniazid is known to increase carbamazepine exposure. Measure carbamazepine concentrations prior to coadministration with isoniazid. Monitor for evidence of carbamazepine toxicity during concurrent use and adjust the carbamazepine dose as necessary.
Isoniazid, INH; Rifampin: (Major) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of carbamazepine. Carbamazepine dosages may need to be adjusted while the patient is receiving rifampin. (Moderate) Isoniazid is known to increase carbamazepine exposure. Measure carbamazepine concentrations prior to coadministration with isoniazid. Monitor for evidence of carbamazepine toxicity during concurrent use and adjust the carbamazepine dose as necessary.
Isradipine: (Moderate) Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that induce CYP3A4, such as carbamazepine, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine.
Istradefylline: (Major) Avoid coadministration of istradefylline with carbamazepine as istradefylline exposure and efficacy may be reduced. Additionally, taking these drugs together may increase carbamazepine plasma concentrations, potentially resulting in adverse events. Carbamazepine is a substrate of CYP3A4 with a narrow therapeutic index and a strong inducer. Istradefylline administered as 40 mg daily is a weak CYP3A4 inhibitor. Istradefylline exposure was decreased by 81% when administered with a strong inducer in a drug interaction study. There was no effect on drug exposure when istradefylline 20 mg daily was coadministered with a sensitive CYP3A4 substrate.
Itraconazole: (Major) Use of carbamazepine is not recommended for 2 weeks before, during, or for 2 weeks after itraconazole therapy due to the potential for increased carbamazepine and decreased itraconazole exposure. If concurrent use is unavoidable, an increased dose of itraconazole and a decreased dose of carbamazepine may be necessary. Itraconazole is a strong CYP3A4 inhibitor and substrate; carbamazepine is a strong CYP3A4 inducer and substrate.
Ivabradine: (Major) Avoid coadministration of ivabradine and carbamazepine. Ivabradine is primarily metabolized by CYP3A4; carbamazepine induces CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure.
Ivacaftor: (Major) Coadministration of ivacaftor with carbamazepine is not recommended due to decreased plasma concentrations of ivacaftor. Ivacaftor is a sensitive CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer significantly decreased ivacaftor exposure by approximately 9-fold.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with carbamazepine due to decreased plasma concentrations of ivosidenib. Ivosidenib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer is predicted to decrease ivosidenib exposure at steady-state by 33%.
Ixabepilone: (Major) Avoid concurrent use of ixabepilone and carbamazepine due to decreased plasma concentrations of ixabepilone, which may reduce its efficacy. If concomitant use is unavoidable, gradually increase the dose of ixabepilone as tolerated from 40 mg/m2 to 60 mg/m2 and infuse over 4 hours; monitor carefully for ixabepilone-related toxicities. Ixabepilone is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased ixabepilone exposure by 43%.
Ixazomib: (Major) Avoid the concomitant use of ixazomib and carbamazepine; ixazomib levels may be significantly decreased and its efficacy reduced. Ixazomib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. In subjects who received ixazomib with another strong CYP3A4 inducer, the ixazomib Cmax and AUC values were decreased by 54% and 74%, respectively.
Ketoconazole: (Major) Avoid carbamazepine for 2 weeks prior to and during treatment with ketoconazole. Concomitant use may decrease exposure of ketoconazole and reduce its efficacy. The exposure of carbamazepine may also be increased. If coadministration cannot be avoided, monitor for decreased efficacy of ketoconazole and monitor carbamazepine concentrations closely for increased toxicity; adjust dosage for both drugs as clinically indicated. Ketoconazole is a CYP3A substrate and strong CYP3A inhibitor; carbamazepine is a CYP3A substrate and strong CYP3A inducer.
Ketorolac: (Moderate) Monitor for increased seizures during concomitant use of carbamazepine and ketorolac. Sporadic cases of seizures have been reported during coadministration of ketorolac and antiepileptic drugs like carbamazepine.
Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., carbamazepine), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lamotrigine: (Major) Adjustments in lamotrigine escalation and maintenance dose regimens are necessary with concomitant carbamazepine use. Monitoring lamotrigine plasma concentrations may be indicated, particularly during dosage adjustments. Lamotrigine is metabolized predominantly by glucuronic acid conjugation, and carbamazepine induces glucuronidation. During concurrent use of lamotrigine with carbamazepine, lamotrigine steady-state concentration decreased by approximately 40%. Lamotrigine may increase the concentration of the 10, 11-epoxide metabolite of carbamazepine; small studies have demonstrated mixed results when evaluating carbamazepine-epoxide concentrations in the presence of lamotrigine. Limited data suggest that there is a higher incidence of dizziness, diplopia, ataxia, and blurred vision in patients receiving lamotrigine with carbamazepine than in patients receiving lamotrigine with other AEDs; the mechanism of the interaction is not known.
Lansoprazole: (Moderate) Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Carbamazepine induces hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If carbamazepine and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Coadministration of carbamazepine and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers. Additionally, carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Drugs known to inhibit CYP3A4, such as clarithromycin, may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely during coadministration; reduce carbamazepine doses may be necessary. Clarithromycin also inhibits epoxide hydrolase resulting in increased levels of the active metabolite carbamazepine 10, 11- epoxide, which may be more hepatotoxic than the parent drug. Several case reports have documented that clarithromycin can significantly decrease carbamazepine clearance, producing increases in the serum concentration of carbamazepine. Carbamazepine concentrations increased from 12 mcg/ml to 19.1 mcg/ml in a 17-year-old boy after 2 days of clarithromycin 250 mg PO bid. Patients should be monitored for carbamazepine toxicity if clarithromycin is added. Carbamazepine toxicity may be avoided if clarithromycin therapy is begun first and stabilized prior to beginning carbamazepine therapy, however, carbamazepine dosages may need to be increased if clarithromycin is subsequently discontinued. (Moderate) Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Carbamazepine induces hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If carbamazepine and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
Lapatinib: (Major) Avoid coadministration of lapatinib with carbamazepine due to decreased plasma concentrations of lapatinib. If concomitant use is unavoidable, gradually titrate the dose of lapatinib from 1,250 mg per day to 4,500 mg per day in patients receiving concomitant capecitabine (HER2-positive metastatic breast cancer), and from 1,500 mg per day to 5,500 mg per day in patients receiving concomitant aromatase inhibitor therapy (HR-positive, HER2-positive breast cancer) based on tolerability. If carbamazepine is discontinued, reduce lapatinib to the indicated dose. Lapatinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with carbamazepine decreased lapatinib exposure by 72%.
Larotrectinib: (Major) Avoid coadministration of larotrectinib with carbamazepine due to decreased larotrectinib exposure and risk of decreased efficacy. If coadministration cannot be avoided, double the larotrectinib dose. If carbamazepine is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of carbamazepine. Larotrectinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the larotrectinib AUC by 81% in a drug interaction study.
Ledipasvir; Sofosbuvir: (Major) Avoid coadministration of ledipasvir with carbamazepine. Taking these drugs together may decrease ledipasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of sofosbuvir with inducers of P-glycoprotein (P-gp), such as carbamazepine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy.
Lefamulin: (Major) Avoid coadministration of lefamulin with carbamazepine unless the benefits outweigh the risks as concurrent use may decrease lefamulin exposure and efficacy. Lefamulin is a CYP3A4 and P-gp substrate; carbamazepine is a P-gp and strong CYP3A4 inducer. Coadministration of a combined P-gp and strong CYP3A4 inducer decreased the mean AUC of oral and intravenous lefamulin by 72% and 28%, respectively.
Lemborexant: (Major) Avoid coadministration of lemborexant and carbamazepine as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Additive CNS effects are also possible; monitor for sedation or other potential impairment.
Lenacapavir: (Contraindicated) Concurrent use of lenacapavir and carbamazepine is contraindicated due to the risk of decreased lenacapavir exposure which may result in loss of therapeutic effect and development of resistance. The exposure of carbamazepine may also be increased. Lenacapavir is a CYP3A substrate and moderate CYP3A inhibitor and carbamazepine is a CYP3A substrate and strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced lenacapavir overall exposure by 84%.
Leniolisib: (Major) Avoid concomitant use of leniolisib and carbamazepine. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Letermovir: (Major) Concurrent administration of letermovir and carbamazepine is not recommended. Use of these drugs together may decrease letermovir plasma concentrations, resulting in a potential loss of letermovir efficacy. Letermovir is a substrate of UDP-glucuronosyltransferase 1A1/3 (UGT1A1/3) and P-glycoprotein (P-gp). Carbamazepine is a strong inducer of UGTA1 and P-gp. Also, plasma concentrations of carbamazepine could be increased when administered concurrently with letermovir. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. Carbamazepine is metabolized by CYP3A4. Letermovir is a moderate inhibitor of CYP3A4; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Leuprolide; Norethindrone: (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Levamlodipine: (Moderate) Monitor carbamazepine concentrations and blood pressure closely during coadministration of amlodipine; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and strong inducer and amlodipine is CYP3A substrate and inhibitor. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Levetiracetam: (Moderate) Closely monitor patients for signs or symptoms of carbamazepine toxicity, such as vision changes, unstable gait, ataxia, dizziness, nausea, or vomiting during coadministration of carbamazepine and levetiracetam. Carbamazepine toxicity, unrelated to elevated concentrations of carbamazepine or the epoxide, may occur when levetiracetam is added to carbamazepine therapy. The interaction appears to be pharmacodynamic in nature rather than pharmacokinetic. Toxicity was reversed when the dose of carbamazepine was reduced.
Levoketoconazole: (Major) Avoid carbamazepine for 2 weeks prior to and during treatment with ketoconazole. Concomitant use may decrease exposure of ketoconazole and reduce its efficacy. The exposure of carbamazepine may also be increased. If coadministration cannot be avoided, monitor for decreased efficacy of ketoconazole and monitor carbamazepine concentrations closely for increased toxicity; adjust dosage for both drugs as clinically indicated. Ketoconazole is a CYP3A substrate and strong CYP3A inhibitor; carbamazepine is a CYP3A substrate and strong CYP3A inducer.
Levomefolate: (Moderate) High doses of folate may cause decreased serum concentrations of carbamazepine resulting in a decrease in effectiveness and, possibly, an increase in the frequency of seizures in susceptible patients. In addition, L-methylfolate plasma levels may be decreased when administered with carbamazepine. Although no decrease in effectiveness of anticonvulsants has been reported with the concurrent use of L-methylfolate, caution still should be exercised with the coadministration of these agents and patients should be monitored closely for seizure activity.
Levonorgestrel: (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Levonorgestrel; Ethinyl Estradiol: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Levothyroxine: (Minor) Use carbamazepine and thyroid hormones together with caution. Carbamazepine may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations. Carbamazepine reduces serum protein binding of levothyroxine, and total and free-T4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Monitor thyroid hormone parameters.
Levothyroxine; Liothyronine (Porcine): (Minor) Use carbamazepine and thyroid hormones together with caution. Carbamazepine may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations. Carbamazepine reduces serum protein binding of levothyroxine, and total and free-T4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Monitor thyroid hormone parameters.
Levothyroxine; Liothyronine (Synthetic): (Minor) Use carbamazepine and thyroid hormones together with caution. Carbamazepine may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations. Carbamazepine reduces serum protein binding of levothyroxine, and total and free-T4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Monitor thyroid hormone parameters.
Lidocaine: (Moderate) Concomitant use of systemic lidocaine and carbamazepine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; carbamazepine induces both hepatic isoenzymes.
Lidocaine; Epinephrine: (Moderate) Concomitant use of systemic lidocaine and carbamazepine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; carbamazepine induces both hepatic isoenzymes.
Lidocaine; Prilocaine: (Moderate) Concomitant use of systemic lidocaine and carbamazepine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; carbamazepine induces both hepatic isoenzymes.
Linagliptin: (Moderate) Monitor for a decrease in linagliptin efficacy during concomitant use of linagliptin and carbamazepine if coadministration is required. Concomitant use may decrease linagliptin exposure. Linagliptin is a CYP3A and P-gp substrate and carbamazepine is a strong CYP3A and P-gp inducer. Concomitant use with a strong CYP3A and P-gp inducer reduced linagliptin overall exposure by 0.6-fold.
Linagliptin; Metformin: (Moderate) Monitor for a decrease in linagliptin efficacy during concomitant use of linagliptin and carbamazepine if coadministration is required. Concomitant use may decrease linagliptin exposure. Linagliptin is a CYP3A and P-gp substrate and carbamazepine is a strong CYP3A and P-gp inducer. Concomitant use with a strong CYP3A and P-gp inducer reduced linagliptin overall exposure by 0.6-fold.
Linezolid: (Major) Carbamazepine is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if carbamazepine could cause decreases in linezolid exposure if coadministered. Additionally, linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor; therefore, linezolid has the potential for interaction with carbamazepine. Carbamazepine, a dibenazepine-related drug, should not be coadministered with MAO inhibitors. Hypertensive crises, seizures, coma, or circulatory collapse may occur in patients receiving this combination. MAOIs should be discontinued for a minimum of 14 days or longer if the clinical situation permits, before administering carbamazepine.
Liothyronine: (Minor) Use carbamazepine and thyroid hormones together with caution. Carbamazepine may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations. Carbamazepine reduces serum protein binding of levothyroxine, and total and free-T4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Monitor thyroid hormone parameters.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Lithium: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium carbamazepine. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and carbamazepine is contraindicated; concurrent use may decrease lonafarnib exposure, which may reduce its efficacy. The exposure of carbamazepine may also be increased, increasing the risk for carbamazepine-related adverse reactions. Lonafarnib is a sensitive CYP3A4 substrate and strong CYP3A4 inhibitor; carbamazepine is a CYP3A4 substrate and strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the exposure of lonafarnib by 98%.
Lopinavir; Ritonavir: (Major) Avoid concomitant use of lopinavir; ritonavir and carbamazepine. If concomitant use is necessary, do not use once daily dosing of lopinavir; ritonavir. Concomitant use may decrease lopinavir plasma concentrations, resulting in reduced efficacy. Lopinavir is a CYP3A substrate and carbamazepine is a CYP3A inducer. (Major) Avoid concomitant use of ritonavir and carbamazepine. Concomitant use may increase carbamazepine exposure, resulting in toxicity and/or decrease ritonavir exposure, resulting in reduced efficacy. If concomitant use is necessary, monitor for reduced virologic response and for carbamazepine toxicity; a carbamazepine dose reduction may be needed. Ritonavir is a CYP3A and P-gp substrate and CYP3A inducer; carbamazepine is a CYP3A and P-gp inducer.
Lorlatinib: (Contraindicated) Coadministration of lorlatinib with carbamazepine is contraindicated due to the risk of severe hepatotoxicity as well as decreased lorlatinib exposure which may reduce its efficacy. Discontinue carbamazepine for 3 plasma half-lives prior to initiating therapy with lorlatinib. Lorlatinib is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased lorlatinib exposure by 85% and caused severe (grade 3 or 4) hepatotoxicity in 83% of patients.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Lovastatin: (Minor) Carbamazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates, such as lovastatin. Monitor for potential reduced cholesterol-lowering efficacy when these drugs are co-administered with HMG-CoA reductase inhibitors which are metabolized by CYP3A4.
Loxapine: (Moderate) Coadministration of carbamazepine and loxapine may result in increased serum concentrations of the active metabolite of carbamazepine, carbamazepine10,11-epoxide. Carbamazepine is metabolized to carbamazepine 10,11-epoxide by human microsomal epoxide hydrolase and loxapine inhibits of human microsomal epoxide hydrolase. In addition, loxapine lowers the seizure threshold. Seizures have been reported in patients receiving loxapine at antipsychotic dose levels, and may occur in epileptic patients even with maintenance of routine anticonvulsant drug therapy. Monitor carbamazepine serum concentrations and adjust the dose accordingly during concomitant use.
Lumacaftor; Ivacaftor: (Major) Coadministration of ivacaftor with carbamazepine is not recommended due to decreased plasma concentrations of ivacaftor. Ivacaftor is a sensitive CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer significantly decreased ivacaftor exposure by approximately 9-fold. (Major) Concomitant use of carbamazepine and lumacaftor; ivacaftor is not recommended. Carbamazepine may decrease the therapeutic effect of lumacaftor; ivacaftor by significantly decreasing the systemic exposure of ivacaftor. Lumacaftor; ivacaftor may also decrease the therapeutic effect of carbamazepine. Carbamazepine is a substrate and potent inducer of CYP3A. Ivacaftor is a substrate of CYP3A and lumacaftor is a potent inducer of CYP3A. Although the enzyme induction effects of lumacaftor are already accounted for in fixed-combination dosing, ivacaftor exposure is further decreased when given together with other CYP3A inducers. In pharmacokinetic studies, coadministration of lumacaftor; ivacaftor with rifampin, another potent CYP3A inducer, decreased ivacaftor exposure by 57%, with minimal effect on the exposure of lumacaftor.
Lumacaftor; Ivacaftor: (Major) Concomitant use of carbamazepine and lumacaftor; ivacaftor is not recommended. Carbamazepine may decrease the therapeutic effect of lumacaftor; ivacaftor by significantly decreasing the systemic exposure of ivacaftor. Lumacaftor; ivacaftor may also decrease the therapeutic effect of carbamazepine. Carbamazepine is a substrate and potent inducer of CYP3A. Ivacaftor is a substrate of CYP3A and lumacaftor is a potent inducer of CYP3A. Although the enzyme induction effects of lumacaftor are already accounted for in fixed-combination dosing, ivacaftor exposure is further decreased when given together with other CYP3A inducers. In pharmacokinetic studies, coadministration of lumacaftor; ivacaftor with rifampin, another potent CYP3A inducer, decreased ivacaftor exposure by 57%, with minimal effect on the exposure of lumacaftor.
Lumateperone: (Major) Avoid coadministration of lumateperone and carbamazepine as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration of lumateperone with a strong CYP3A4 inducer decreased lumateperone overall exposure by greater than 30-fold.
Lurasidone: (Contraindicated) Concurrent use of lurasidone with strong CYP3A4 inducers, such as carbamazepine, is contraindicated. Lurasidone is primarily metabolized by CYP3A4. Decreased blood concentrations of lurasidone are expected when the drug is co-administered with inducers of CYP3A4.
Lurbinectedin: (Major) Avoid coadministration of lurbinectedin and carbamazepine due to the risk of decreased lurbinectedin exposure which may reduce its efficacy. Lurbinectedin is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Macimorelin: (Major) Discontinue carbamazepine and allow a sufficient washout period to pass before administering macimorelin. Use of these drugs together can significantly decrease macimorelin plasma concentrations, and may result in a false positive test for growth hormone deficiency. No drug-drug interaction studies have been conducted; however, macimorelin is primarily metabolized by CYP3A4 and carbamazepine is a strong CYP3A4 inducer.
Macitentan; Tadalafil: (Major) Avoid coadministration of tadalafil with carbamazepine in patients with pulmonary hypertension due to decreased plasma concentrations of tadalafil. In patients with erectile dysfunction and/or benign prostatic hyperplasia, consider the potential for loss of efficacy of tadalafil during concurrent administration of carbamazepine due to reduced tadalafil exposure. Tadalafil is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased tadalafil exposure by 88%.
Maprotiline: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Maraviroc: (Major) Coadministration of maraviroc, a CYP3A/P-glycoprotein (P-gp) substrate, and carbamazepine, a strong CYP3A inducer and P-gp inducer, without a concomitant strong CYP3A inhibitor may decrease maraviroc concentrations, therefore, the adult maraviroc dose should be increased to 600 mg PO twice daily when coadministered with carbamazepine without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and carbamazepine is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. If the patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of the inducer; overall, increased maraviroc concentrations are expected.
Maribavir: (Major) Increase maribavir dose to 800 mg PO twice daily when coadministered with carbamazepine. Coadministration may decrease maribavir exposure resulting in reduced virologic response. Additionally, monitor carbamazepine concentrations closely during coadministration as concomitant use may increase carbamazepine exposure; carbamazepine dose adjustments may be needed. Maribavir is a CYP3A substrate and weak CYP3A inhibitor; carbamazepine is a CYP3A substrate and strong CYP3A inducer.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with carbamazepine due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure and may decrease carbamazepine concentrations. Mavacamten is a CYP2C19 substrate and substrate and inducer of CYP3A and carbamazepine is a moderate inducer of CYP2C19 and substrate and strong inducer of CYP3A. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Mebendazole: (Moderate) Carbamazepine may potentially accelerate the hepatic metabolism of mebendazole. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with mebendazole.
Medroxyprogesterone: (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Mefloquine: (Moderate) Carbamazepine induces CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and anticonvulsants may also result in lower than expected carbamazepine anticonvulsant concentrations and loss of seizure control. Monitoring of the carbamazepine serum concentration is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Melatonin: (Moderate) Potent CYP1A2 inducers, such as carbamazepine, may reduce plasma concentrations of melatonin and reduce melatonin efficacy. Melatonin is primarily metabolized by CYP1A2, with lesser contributions by CYP1A1, CYP2C9 and CYP2C19. Because carbamazepine exhibits central nervous system (CNS) effects, such as drowsiness in some patients, additive CNS effects may occur if melatonin is taken. Be alert for any changes in anticonvulsant control, unusual impairment of attention, memory and coordination, over-sedation, CNS effects, or sleep-related behaviors. Patients reporting unusual moods or behaviors likely should discontinue use of melatonin.
Meropenem: (Moderate) Monitor carbamazepine concentrations closely during coadministration of meropenem; carbamazepine dose adjustments may be needed. Concomitant use may decrease carbamazepine concentrations. Carbamazepine is a CYP3A substrate and meropenem is a CYP3A inducer.
Meropenem; Vaborbactam: (Moderate) Monitor carbamazepine concentrations closely during coadministration of meropenem; carbamazepine dose adjustments may be needed. Concomitant use may decrease carbamazepine concentrations. Carbamazepine is a CYP3A substrate and meropenem is a CYP3A inducer.
Metaxalone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of carbamazepine and metaxalone. Concurrent use may result in additive CNS depression.
Metformin; Repaglinide: (Major) Coadministration of carbamazepine and repaglinide may decrease the serum concentration of repaglinide; if coadministration is necessary, a dose increase of repaglinide may be required and an increased frequency of glucose monitoring is recommended. Carbamazepine is a potent CYP3A4 inducer and repaglinide is a CYP3A4 substrate. Monitor for the possibility of reduced effectiveness of repaglinide and possible symptoms indicating hyperglycemia.
Methadone: (Moderate) Monitor for reduced efficacy of methadone and signs of opioid withdrawal if coadministration with carbamazepine is necessary. Consider increasing the dose of methadone as needed. If carbamazepine is discontinued, consider a dose reduction of methadone and frequently monitor for signs of respiratory depression and sedation. Methadone is a substrate of CYP3A, CYP2B6, CYP2C19, CYP2C9, and CYP2D6; carbamazepine is a CYP3A, CYP2B6, CYP2C19, and CYP2C9 inducer. Concomitant use can decrease methadone exposure resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Methazolamide: (Minor) Methazolamide can induce osteomalacia in patients being concomitantly treated with carbamazepine. Potential mechanisms for this interaction include an methazolamide-induced increase in the urinary excretion of calcium and effects resulting from metabolic acidosis.
Methohexital: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy.
Methsuximide: (Moderate) Methsuximide is an inducer of the hepatic CYP3A4 isoenzyme and can increase the rate of carbamazepine metabolism, leading to subtherapeutic carbamazepine plasma concentrations. Also, methsuximide can be potentially affected by carbamazepine enzyme induction. Decreased methsuximide concentrations may occur.
Methylergonovine: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and carbamazepine. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Methylphenidate Derivatives: (Minor) Psychostimulants, such as methylphenidate and its derivatives, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as carbamazepine. There are rare case reports of reduced methylphenidate concentrations occurring during the use of carbamazepine concurrently. The mechanism of the interaction is not clear as methylphenidate is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body. Interactions with other potent enzyme inducers have not been reported. Monitor for any changes in therapeutic effectiveness of either drug.
Methylphenidate: (Minor) Psychostimulants, such as methylphenidate and its derivatives, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as carbamazepine. There are rare case reports of reduced methylphenidate concentrations occurring during the use of carbamazepine concurrently. The mechanism of the interaction is not clear as methylphenidate is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body. Interactions with other potent enzyme inducers have not been reported. Monitor for any changes in therapeutic effectiveness of either drug.
Methylprednisolone: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of methylprednisolone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with methylprednisolone.
Metolazone: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Metreleptin: (Moderate) Upon initiation or discontinuation of metreleptin in a patient receiving carbamazepine, drug concentration monitoring should be performed and the carbamazepine dosage adjusted as needed. Leptin is a cytokine and may have the potential to alter the formation of cytochrome P450 (CYP450) enzymes. The effect of metreleptin on CYP450 enzymes may be clinically relevant for CYP450 substrates with a narrow therapeutic index, such as carbamazepine.
Metronidazole: (Minor) Monitor serum concentrations of carbamazepine when coadministered with systemic metronidazole. Concomitant use with metronidazole may increase the serum concentrations of carbamazepine; thereby, increasing the risk of side effects.
Mexiletine: (Moderate) Carbamazepine induces the hepatic metabolism of other drugs, and should be used cautiously with mexiletine. Conversely, mexiletine doses may need to be reduced if a hepatic enzyme inducer is stopped while mexiletine therapy continues.
Midazolam: (Moderate) Carbamazepine is a potent inducer of the hepatic isoenzyme CYP3A4, one of the pathways responsible for the hepatic metabolism of midazolam. Patients receiving carbamazepine may require higher doses of midazolam to achieve the desired clinical effect.
Midostaurin: (Major) Avoid the concomitant use of midostaurin and carbamazepine as midostaurin exposure may be decreased, which may reduce its efficacy. Midostaurin is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased the exposure of midostaurin and its metabolites CGP62221 and CGP52421 by 96%, 92%, and 59%, respectively.
Mifepristone: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of carbamazepine. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving carbamazepine. Monitor carbamazepine concentrations closely during coadministration of mifepristone; carbamazepine dose adjustments may be needed. Coadministration may decrease mifepristone exposure reducing efficacy and may increase carbamazepine concentrations. Mifepristone is a substrate and strong inhibitor of CYP3A; carbamazepine is a substrate and strong inducer of CYP3A.
Mirtazapine: (Moderate) As carbamazepine is known to induce CYP1A2 and CYP3A4, serum concentrations of mirtazapine may be decreased because of CYP enzyme induction. Increased dosages of mirtazapine may be needed.
Mitapivat: (Major) Avoid coadministration of mitapivat with carbamazepine due to decreased mitapivat efficacy. Coadministration decreases mitapivat and carbamazepine concentrations. Mitapivat is a CYP3A substrate and inducer and carbamazepine is a CYP3A substrate and strong inducer. Coadministration with another strong CYP3A inducer decreased mitapivat overall exposure by 91% to 95%.
Mitotane: (Major) Use caution if mitotane and carbamazepine are used concomitantly, and monitor for decreased efficacy of carbamazepine and a possible change in dosage requirements. Carbamazepine dosages may need to be adjusted while the patient is receiving mitotane. Mitotane is a strong CYP3A4 inducer and carbamazepine is a CYP3A4 substrate in vitro; coadministration may result in decreased plasma concentrations of carbamazepine.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and carbamazepine. Coadministration may decrease mobocertinib exposure resulting in decreased efficacy. Concomitant use may also decrease carbamazepine concentrations. Mobocertinib is a CYP3A substrate and weak CYP3A inducer; carbamazepine is a CYP3A substrate and strong CYP3A inducer. Use of a strong CYP3A inducer is predicted to decrease the overall exposure of mobocertinib and its active metabolites by 92%.
Modafinil: (Moderate) Modafinil is partially metabolized by CYP3A4 and combined use with CYP3A4 inducers such as carbamazepine may result in decreased modafinil efficacy. In vitro data indicate that modafinil is an inducer of CYP3A4. Therefore, decreased carbamazepine serum levels are possible. Clinically, be alert for increased sleepiness or other indicators of reduced mofafinil efficacy. The potential pharmacodynamic effects of combining modafinil with anticonvulsant medications are unclear; however, should it be noted that other CNS stimulants (e.g., amphetamines) are known to lower the seizure threshold.
Molindone: (Major) Increased CNS depressant effects can occur during combined use of carbamazepine and molindone. Decreased anticonvulsant efficacy is a possibility when some antipsychotic agents, such as molindone, are administered to patients with a seizure disorder, because some of these drugs lower the seizure threshold. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with molindone.
Monoamine oxidase inhibitors: (Contraindicated) Carbamazepine is contraindicated for use with monoamine oxidase inhibitors (MAOIs), because of a possible increased risk of serotonin syndrome and/or hypertensive crisis. Due to the risk of serotonin syndrome, carbamazepine is contraindicated for use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing treatment with an MAOI. Conversely, MAOIs should not be initiated within 14 days of stopping carbamazepine. Monitor blood pressure and for serotonin-related side effects during therapy transitions.
Montelukast: (Minor) Carbamazepine may reduce the systemic exposure of montelukast. However, dosage adjustment is not likely to be needed. If used together, the manufacturer recommends monitoring for proper montelukast effectiveness as a precaution. Carbamazepine is a strong CYP3A inducer. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4.
Naldemedine: (Major) Avoid coadministration of naldemedine with strong CYP3A4 inducers. Naldemedine is metabolized primarily by the CYP3A enzyme system. Strong CYP3A4 inducers, such as carbamazepine, significantly decrease plasma naldemedine concentrations and may decrease the efficacy of naldemedine treatment.
Naloxegol: (Major) Coadministration of naloxegol with carbamazepine is not recommended due to the potential for decreased naloxegol efficacy. Naloxegol is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased naloxegol exposure by 89%.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with carbamazepine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A and CYP2C8 substrate and carbamazepine is a strong CYP3A inducer and a CYP2C8 inducer.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and carbamazepine as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and carbamazepine is a strong CYP3A and P-gp inducer.
Naproxen; Esomeprazole: (Major) Avoid concomitant use of esomeprazole and carbamazepine as esomeprazole exposure may be decreased, reducing its efficacy. Esomeprazole is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Nefazodone: (Contraindicated) Coadministration of carbamazepine and nefazodone is contraindicated; use together may result in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect. Nefazodone may also increase plasma concentrations of carbamazepine. Nefazodone and carbamazepine are both substrates of CYP3A4; however, carbamazepine is a strong CYP3A4 inducer while nefazodone is a strong CYP3A4 inhibitor.
Nelfinavir: (Major) Anticonvulsants, such as carbamazepine, may increase the metabolism of nelfinavir and lead to decreased efficacy. Treatment failures have been reported with protease inhibitors when carbamazepine was used concomitantly. In addition, nelfinavir is a potent CYP3A inibitor and coadministration may result in increased serum concentrations of carbamazepine. The appropriate drug-dose adjustments necessary to ensure optimum levels of both antiretroviral and anticonvulsant drugs are unknown. If nelfinavir and carbamazepine are coadministered, the patient should be observed for changes in the clinical efficacy of the antiretroviral regimen or carbamazepine toxicity.
Neratinib: (Major) Avoid concomitant use of carbamazepine with neratinib due to decreased efficacy of neratinib. Neratinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased neratinib exposure by 87%, while exposure to active metabolites M6 and M7 were reduced by 37% to 49%. Concomitant use with other strong inducers of CYP3A4 may also decrease neratinib concentrations.
Netupitant, Fosnetupitant; Palonosetron: (Major) Netupitant is mainly metabolized by CYP3A4. Avoid coadministration of netupitant in patients who are chronically using a strong CYP3A4 inducer, such as carbamazepine. A strong CYP3A inducer can decrease the efficacy of netupitant by substantially reducing plasma concentrations of netupitant. In addition, netupitant is a moderate inhibitor of CYP3A4 and the plasma concentrations of medications that are primarily metabolized through CYP3A4, such as carbamazepine, can increase with coadministration; the inhibitory effect on CYP3A4 can last for multiple days.
Nevirapine: (Major) Coadministration of carbamazepine and nevirapine is not recommended due to the potential for loss of virologic response and possible resistance to nevirapine. Nevirapine may also decrease plasma concentrations of carbamazepine. If concurrent use is necessary, monitor carbamazepine concentrations and virologic response. Nevirapine is a CYP3A substrate and weak CYP3A inducer; carbamazepine is a CYP3A substrate and strong CYP3A inducer.
Niacin, Niacinamide: (Moderate) Niacin may inhibit the CYP3A4 metabolism of carbamazepine, resulting in elevated carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored if niacin is added during carbamazepine therapy. It may be necessary to reduce the dose of carbamazepine.
Nicardipine: (Moderate) Carbamazepine may induce the hepatic metabolism of calcium-channel blockers by the CYP3A4 isoenzyme; which reduces the oral bioavailability of the calcium channel blockers by increasing their presystemic clearance.
NIFEdipine: (Major) Avoid coadministration of nifedipine with carbamazepine and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and carbamazepine is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and carbamazepine; significantly decreased nilotinib exposure and reduced nilotinib efficacy may occur. Nilotinib is a CYPA4 substrate and carbamazepine is a strong CYP3A4 inducer. In a drug interaction study, coadministration with another strong CYP3A4 inducer decreased nilotinib exposure by approximately 80%.
Nimodipine: (Moderate) Limited data suggest that nimodipine may potentiate the effects of carbamazepine. Patients receiving nimodipine with carbamazepine should be monitored for adverse affects and the dosages of the anticonvulsants should be adjusted accordingly. Serum concentrations of carbamazepine may be helpful in guiding dosage adjustments as peak carbamazepine serum concentrations were increased when given concomitantly with nimodipine. In addition, in epileptic patients taking carbamazepine and/or phenytoin with or without other enzyme-inducing anticonvulsants, there is a 7-fold decrease in the AUC of nimodipine due to hepatic enzyme induction.
Nintedanib: (Major) Avoid the use of carbamazepine with nintedanib, as carbamazepine is expected to decrease the exposure of nintedanib and compromise its efficacy. Carbamazepine is a potent P-glycoprotein (P-gp) and CYP3A4 inducer; nintedanib is a P-gp substrate and a minor substrate of CYP3A4. In drug interaction studies, administration of a dual P-gp and CYP3A4 inducer with nintedanib decreased the AUC of nintedanib by 50%.
Niraparib; Abiraterone: (Major) Avoid coadministration of abiraterone with carbamazepine if possible due to decreased plasma concentrations of abiraterone. If concomitant use is unavoidable, increase the dosing frequency of abiraterone to twice daily. Reduce the dose back to the previous dose and frequency if carbamazepine is discontinued. Abiraterone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased abiraterone exposure by 55%.
Nirmatrelvir; Ritonavir: (Contraindicated) Ritonavir-boosted nirmatrelvir is contraindicated for use within 2 weeks of administering carbamazepine; consider an alternative COVID-19 therapy. Coadministration may decrease nirmatrelvir exposure resulting in reduced virologic response. The risk for reduced efficacy may persist following carbamazepine discontinuation. Nirmatrelvir is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. (Major) Avoid concomitant use of ritonavir and carbamazepine. Concomitant use may increase carbamazepine exposure, resulting in toxicity and/or decrease ritonavir exposure, resulting in reduced efficacy. If concomitant use is necessary, monitor for reduced virologic response and for carbamazepine toxicity; a carbamazepine dose reduction may be needed. Ritonavir is a CYP3A and P-gp substrate and CYP3A inducer; carbamazepine is a CYP3A and P-gp inducer.
Nirogacestat: (Major) Avoid concomitant use of nirogacestat and carbamazepine. Concurrent use may decrease nirogacestat exposure which may reduce its efficacy. Concomitant use may also increase carbamazepine exposure and the risk for carbamazepine-related adverse effects. Nirogacestat is a CYP3A substrate and moderate CYP3A inhibitor; carbamazepine is a CYP3A substrate and strong CYP3A inducer. Concomitant with another strong CYP3A inducer is predicted to reduce nirogacestat overall exposure by 85%.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with carbamazepine due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Norethindrone: (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Norethindrone; Ethinyl Estradiol: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Norgestimate; Ethinyl Estradiol: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Norgestrel: (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Nortriptyline: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant carbamazepine use. Concomitant use may result in decreased tricyclic antidepressant exposure.
Odevixibat: (Moderate) Monitor carbamazepine concentrations closely during coadministration of odevixibat; carbamazepine dose adjustments may be needed. Concomitant use may decrease carbamazepine concentrations. Carbamazepine is a CYP3A substrate and odevixibat is a weak CYP3A inducer.
Olanzapine: (Moderate) Monitor for reduced olanzapine efficacy; dosage adjustments might be necessary in some patients for whom carbamazepine treatment is medically necessary. Carbamazepine (200 mg BID) increases olanzapine clearance by approximately 50% via potent induction of CYP1A2. Higher daily doses of carbamazepine may cause an even greater increase in olanzapine clearance. In addition, additive CNS effects (e.g., sedation) may occur, and antipsychotic therapy may also reduce the seizure threshold in some patients.
Olanzapine; Fluoxetine: (Moderate) Monitor for reduced olanzapine efficacy; dosage adjustments might be necessary in some patients for whom carbamazepine treatment is medically necessary. Carbamazepine (200 mg BID) increases olanzapine clearance by approximately 50% via potent induction of CYP1A2. Higher daily doses of carbamazepine may cause an even greater increase in olanzapine clearance. In addition, additive CNS effects (e.g., sedation) may occur, and antipsychotic therapy may also reduce the seizure threshold in some patients.
Olanzapine; Samidorphan: (Major) Avoid the concurrent use of samidorphan and carbamazepine; decreased samidorphan exposure and loss of efficacy may occur. Samidorphan is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Concomitant use of another strong CYP3A inducer reduced samidorphan exposure by 73%. (Moderate) Monitor for reduced olanzapine efficacy; dosage adjustments might be necessary in some patients for whom carbamazepine treatment is medically necessary. Carbamazepine (200 mg BID) increases olanzapine clearance by approximately 50% via potent induction of CYP1A2. Higher daily doses of carbamazepine may cause an even greater increase in olanzapine clearance. In addition, additive CNS effects (e.g., sedation) may occur, and antipsychotic therapy may also reduce the seizure threshold in some patients.
Olaparib: (Major) Avoid coadministration of olaparib with carbamazepine due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and carbamazepine is a strong CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with another strong CYP3A inducer decreased the olaparib Cmax by 71% and the AUC by 87%.
Oliceridine: (Moderate) Monitor for reduced efficacy of oliceridine and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of oliceridine as needed. If carbamazepine is discontinued, consider a dose reduction of oliceridine and frequently monitor for signs of respiratory depression and sedation. Oliceridine is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease the plasma concentrations of oliceridine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor carbamazepine concentrations and blood pressure closely during coadministration of amlodipine; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and strong inducer and amlodipine is CYP3A substrate and inhibitor. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine. (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Olutasidenib: (Major) Avoid concurrent use of olutasidenib and carbamazepine due to the risk of decreased olutasidenib exposure which may reduce its efficacy. The exposure of carbamazepine may also be reduced. Olutasidenib is a CYP3A substrate and CYP3A inducer; carbamazepine is a CYP3A substrate and strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced olutasidenib exposure by approximately 80%.
Omaveloxolone: (Major) Avoid concurrent use of omaveloxolone and carbamazepine. Concurrent use may decrease omaveloxolone exposure which may reduce its efficacy. The exposure of carbamazepine may also be decreased. Omaveloxolone is a CYP3A substrate and weak CYP3A inducer and carbamazepine is a CYP3A substrate and strong CYP3A inducer.
Omeprazole: (Major) Avoid concomitant use of omeprazole and carbamazepine as omeprazole exposure may be decreased, reducing its efficacy. Omeprazole is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid concomitant use of omeprazole and carbamazepine as omeprazole exposure may be decreased, reducing its efficacy. Omeprazole is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. (Moderate) Inducers of the hepatic CYP3A4 isoenzyme, such as rifabutin, can increase the rate of carbamazepine metabolism, leading to subtherapeutic carbamazepine plasma concentrations.
Omeprazole; Sodium Bicarbonate: (Major) Avoid concomitant use of omeprazole and carbamazepine as omeprazole exposure may be decreased, reducing its efficacy. Omeprazole is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Oritavancin: (Moderate) Avoid use of oritavancin with drugs that have a narrow therapeutic window, such as carbamazepine. Carbamazepine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of carbamazepine may be reduced if these drugs are administered concurrently. Monitor for lack of carbamazepine efficacy.
Osilodrostat: (Major) Monitor cortisol concentration and patient's signs and symptoms during coadministration of osilodrostat and carbamazepine. Concurrent use may decrease osilodrostat exposure and reduce its efficacy; an increase in osilodrostat dose may be necessary. After discontinuation of carbamazepine, monitor cortisol concentration and patient's signs and symptoms; a reduction in osilodrostat dose may be needed. Osilodrostat is a CYP3A4 and CYP2B6 substrate and carbamazepine is a strong CYP3A4 inducer and also induces CYP2B6.
Osimertinib: (Major) Avoid coadministration of carbamazepine with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If carbamazepine is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Ospemifene: (Moderate) Coadministration of carbamazepine and ospemifene may decrease the systemic exposure of ospemifene, which may decrease the clinical effect of ospemifene. Ospemifene is a substrate of CYP3A4, CYP2C9, and CYP2C19, and carbamazepine is an inducer of CYP2C9 and a strong inducer of CYP3A4. Similar enzyme inducers decreased the systemic exposure of ospemifene by 58%.
Oxcarbazepine: (Moderate) Monitor MHD, the active metabolite of oxcarbazepine, concentrations during oxcarbazepine dosage titration if carbamazepine and oxcarbazepine are used concurrently. A dose adjustment of oxcarbazepine may be required after initiation, dosage modification, or discontinuation of carbamazepine. Coadministration of carbamazepine (400 to 2,000 mg/day) with oxcarbazepine (900 mg/day) decreased MHD concentrations by 40%. Strong CYP3A4 inducers or UGT inducers have been shown to decrease plasma concentrations of MHD. Carbamazepine is a strong CYP3A4 inducer and a UGT inducer.
Oxybutynin: (Minor) Monitor for signs and symptoms of carbamazepine toxicity during concomitant oxybutynin use. In a single case report, concomitant use of oxybutynin with carbamazepine (and dantrolene) was associated with vomiting, drowsiness, confusion, unsteadiness, slurred speech and nystagmus, suggestive of carbamazepine toxicity.
Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of oxycodone as needed. If carbamazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Paclitaxel: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with carbamazepine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A and CYP2C8 substrate and carbamazepine is a strong CYP3A inducer and a CYP2C8 inducer.
Pacritinib: (Contraindicated) Concurrent use of pacritinib with carbamazepine is contraindicated due to decreased pacritinib exposure which may impair efficacy. Carbamazepine exposure may also increase. Pacritinib is a CYP3A substrate and weak inhibitor. Carbamazepine is a strong CYP3A inducer and a CYP3A4 substrate. Coadministration with another strong CYP3A inducer decreased pacritinib exposure by 87%.
Palbociclib: (Major) Avoid coadministration of carbamazepine with palbociclib due to decreased palbociclib exposure which may compromise efficacy. Palbociclib is a CYP3A substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased palbociclib exposure by 85% after a single dose.
Paliperidone: (Major) It may be necessary to increase the dose of oral paliperidone during coadministration of a strong inducer of both CYP3A4 and P-gp, such as carbamazepine. Conversely, a reduction in oral paliperidone dose may be needed upon discontinuation of the inducer. Avoid using a strong inducer of CYP3A4 and/or P-gp if possible during the 1-month injectable dosing interval of Invega Sustenna or the 3-month injectable dosing interval of Invega Trinza. If use of a strong inducer is required in patients receiving injectable paliperidone, consider management with oral paliperidone. Paliperidone is a P-gp substrate, with minor contributions in metabolism by CYP3A4 and CYP2D6. Coadministration of oral paliperidone (6 mg/day) and carbamazepine (200 mg twice daily) resulted in a 37% decrease in paliperidone Cmax and AUC during one study, primarily via an increase in paliperidone renal clearance. A minor decrease in the amount of unchanged paliperidone in the urine suggested only minimal effects from changes in CYP activity or paliperidone bioavailability.
Palovarotene: (Major) Avoid concomitant use of palovarotene and carbamazepine. Concurrent use may decrease palovarotene exposure which may reduce its efficacy. Palovarotene is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced palovarotene overall exposure by 11%.
Pancuronium: (Moderate) Monitor for a more rapid recovery from neuromuscular blockade than expected during concurrent use of carbamazepine and pancuronium. When administering neuromuscular blockade via continuous infusion, infusion rate requirements may be higher. Chronic carbamazepine administration may cause neuromuscular blockade resistance.
Panobinostat: (Major) Avoid the concomitant use of panobinostat and carbamazepine; panobinostat levels may be significantly decreased and its efficacy reduced. Carbamazepine is a strong CYP3A4 inducer and panobinostat is a CYP3A4 substrate. Using a physiologically-based pharmacokinetic model, the systemic exposure was estimated to be decreased by 70% when a strong CYP3A inducer was co-administered with panobinostat.
Paricalcitol: (Moderate) Antiepileptic drugs can increase the metabolism of endogenous vitamin D, thereby lowering serum concentrations and decreasing its activity. In addition, carbamazepine is a CYP3A4 inducer and thus may further lower serum concentrations of paricalcitol. Dosage adjustments of paricalcitol may be required.
Pazopanib: (Major) Avoid administering pazopanib in patients who require chronic treatment with a strong CYP3A4 inducer, such as carbamazepine. The concomitant use of pazopanib, a weak CYP3A4 inhibitor and a substrate for CYP3A4 and P-glycoprotein (P-gp), and carbamazepine, a strong CYP3A4 inducer and a P-gp inducer, may result in altered pazopanib and/or carbamazepine concentrations.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and carbamazepine due to the risk of decreased pemigatinib exposure which may reduce its efficacy. Pemigatinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased pemigatinib exposure by 85%.
Pentobarbital: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy.
Perampanel: (Major) Start perampanel at a higher initial dose of 4 mg once daily at bedtime when using concurrently with carbamazepine due to a potential reduction in perampanel plasma concentration. If introduction or withdrawal of carbamazepine occurs during perampanel therapy, closely monitor patient response; a dosage adjustment may be necessary. Carbamazepine is a strong CYP3A4 inducer, and perampanel is a CYP3A4 substrate. Steady state administration of carbamazepine 300 mg twice daily with a single dose of perampanel 2 mg reduced the Cmax of perampanel by 26% and AUC by 67%. The half-life of perampanel decreased from 56.8 hours to 25 hours.
Perindopril; Amlodipine: (Moderate) Monitor carbamazepine concentrations and blood pressure closely during coadministration of amlodipine; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and strong inducer and amlodipine is CYP3A substrate and inhibitor. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Perphenazine; Amitriptyline: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant carbamazepine use. Concomitant use may result in decreased tricyclic antidepressant exposure.
Pexidartinib: (Major) Avoid coadministration of pexidartinib with carbamazepine as concurrent use may decrease pexidartinib exposure which may result in decreased therapeutic response. Additionally, both pexidartinib and carbamazepine may cause hepatotoxicity and should be avoided in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease. Pexidartinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased pexidartinib exposure by 65%.
Phenelzine: (Contraindicated) Carbamazepine is contraindicated for use with monoamine oxidase inhibitors (MAOIs), because of a possible increased risk of serotonin syndrome and/or hypertensive crisis. Due to the risk of serotonin syndrome, carbamazepine is contraindicated for use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing treatment with an MAOI. Conversely, MAOIs should not be initiated within 14 days of stopping carbamazepine. Monitor blood pressure and for serotonin-related side effects during therapy transitions.
Phenobarbital: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy.
Phentermine; Topiramate: (Moderate) A topiramate dosage adjustment may be needed during concomitant carbamazepine use. Concomitant administration of topiramate with carbamazepine resulted in a clinically significant decrease (40%) in plasma topiramate concentrations.
Phenytoin: (Moderate) Monitor carbamazepine and phenytoin concentrations closely during coadministration; dose adjustments may be needed. Concomitant use may decrease carbamazepine or phenytoin concentrations. Carbamazepine is a CYP3A4 substrate and CYP2C9 and CYP2C19 inducer. Hydantoins are CYP2C9 and CYP2C19 substrates and strong CYP3A inducers.
Pimavanserin: (Major) Because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends avoiding concomitant use of pimavanserin with strong CYP3A4 inducers, such as carbamazepine. Strong inducers of CYP3A4 reduce pimavanserin exposure, potentially decreasing the effectiveness of pimavanserin.
Pirtobrutinib: (Major) Avoid concurrent use of pirtobrutinib and carbamazepine due to the risk of decreased pirtobrutinib exposure which may reduce its efficacy. The exposure of carbamazepine may also be increased. Pirtobrutinib is a CYP3A substrate and CYP3A inhibitor and carbamazepine is a CYP3A substrate and strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced pirtobrutinib overall exposure by 71%.
Pitolisant: (Major) Monitor for loss of pitolisant efficacy after initiation of carbamazepine. Increase to double the original daily dose of pitolisant over 7 days in patients stable on 8.9 mg or 17.8 mg once daily (i.e., 17.8 mg or 35.6 mg, respectively). Decrease the pitolisant dose by half if carbamazepine is discontinued. Pitolisant is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration of strong CYP3A4 inducers decreases pitolisant exposure by 50%.
Polatuzumab Vedotin: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of carbamazepine due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; carbamazepine is a strong CYP3A4 inducer. Strong CYP3A4 inducers are predicted to decrease the exposure of MMAE by 63%.
Pomalidomide: (Minor) A decrease in pomalidomide exposure occurred when pomalidomide and carbamazepine were administered together in a drug interaction study. Pomalidomide is a substrate of CYP3A4 and CYP1A2 and carbamazepine is a strong CYP3A4 and moderate CYP1A2 inducer. In healthy male volunteers, the pomalidomide AUC value was decreased by 20% (90% CI, 13% to 27%) when pomalidomide was co-administered with carbamazepine. The authors did not consider this to be a clinically significant reduction, however it may be prudent to monitor for reduced efficacy of pomalidomide if coadministered with carbamazepine.
Ponatinib: (Major) Avoid coadministration of ponatinib with carbamazepine due to decreased plasma concentrations of ponatinib. If concomitant use is unavoidable, monitor for reduced efficacy of ponatinib. Ponatinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased ponatinib exposure by 62%.
Ponesimod: (Major) Avoid concurrent use of ponesimod and carbamazepine and monitor for decreased ponesimod efficacy if use is necessary. Ponesimod is a CYP3A and an UGT1A1 substrate and carbamazepine is a strong CYP3A inducer and an UGT1A1 inducer that may decrease ponesimod exposure.
Porfimer: (Major) Avoid coadministration of porfimer with carbamazepine due to the risk of increased photosensitivity. All patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like carbamazepine may increase the risk of a photosensitivity reaction.
Posaconazole: (Major) Posaconazole and carbamazepine should be coadministered with caution due to an increased potential for adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of carbamazepine. Further, carbamazepine is an inducer of the drug efflux protein, P-glycoprotein, for which posaconazole is a substrate. This complex interaction may cause alterations in the serum concentrations of both posaconazole and carbamazepine, ultimately resulting in an increased risk of adverse events. Monitor carbamazepine serum concentrations, and adjust the carbamazepine dose as needed.
Pralsetinib: (Major) Avoid coadministration of carbamazepine with pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is unavoidable, double the current dose of pralsetinib starting on day 7 of coadministration. After carbamazepine has been discontinued for at least 14 days, resume the pralsetinib dose taken prior to initiating carbamazepine. Pralsetinib is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the pralsetinib AUC by 68%.
Praziquantel: (Contraindicated) Concomitant use of praziquantel and carbamazepine is contraindicated due to the risk of decreased praziquantel exposure which may reduce its efficacy. Praziquantel is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. In a crossover study with a 2-week washout period, administration of praziquantel followed by another strong CYP3A inducer resulted in undetectable plasma concentrations of praziquantel in 7 out of 10 subjects. When praziquantel was administered 2 weeks after discontinuation of the strong inducer, the mean praziquantel AUC was 23% lower than when praziquantel was given alone.
Prednisolone: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of prednisolone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with prednisolone.
Prednisone: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of prednisone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with prednisone.
Pretomanid: (Major) Avoid coadministration of pretomanid with carbamazepine as concurrent use may decrease pretomanid exposure which may lead to decreased efficacy; concurrent use may also increase the risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications. Pretomanid is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased pretomanid exposure by 66%.
Primidone: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy.
Progesterone: (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Progestins: (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Protriptyline: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant carbamazepine use. Concomitant use may result in decreased tricyclic antidepressant exposure.
Pyrimethamine: (Moderate) Pyrimethamine should be used cautiously in patients receiving carbamazepine, due to the potential for additive bone marrow/hematologic effects.
Quazepam: (Moderate) Carbamazepine is a hepatic inducer and can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism, leading to lower benzodiazepine concentrations.
Quetiapine: (Major) Increase the dose of quetiapine by up to 5-fold if coadministered with carbamazepine. Coadministration may significantly decrease quetiapine exposure leading to reduced efficacy as well as increase concentrations of the carbamazepine active metabolite, carbamazepine-10,11 epoxide. If carbamazepine is discontinued, reduce the quetiapine dose to the original level in 7 to 14 days. Quetiapine is a sensitive CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased the mean oral clearance of quetiapine by 5-fold. Quetiapine also inhibits epoxide hydrolase.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Quinidine: (Moderate) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Quinidine inhibits CYP3A4 and may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely if quinidine is added during carbamazepine therapy. It may be necessary to reduce the dose of carbamazepine in this situation.
Quinine: (Major) If concomitant administration of carbamazepine and quinine cannot be avoided, frequently monitor carbamazepine concentration. Also, monitor closely for increased carbamazepine-associated adverse events such as excessive drowsiness, loss of balance or difficulty walking straight, severe headaches, blurred or double vision, vomiting, or nystagmus. A single quinine 600 mg dose increased the mean plasma Cmax and AUC of carbamazepine by 56% and 104%, respectively, in 8 healthy subjects. In addition, carbamazepine is a CYP3A4 inducer and may decrease plasma quinine concentrations.
Quizartinib: (Major) Avoid concomitant use of carbamazepine with quizartinib due to the risk of decreased quizartinib exposure which may reduce its efficacy. Quizartinib is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Rabeprazole: (Moderate) Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and proton pump inhibitors (PPIs). Carbamazepine induces hepatic cytochrome P-450 enzymes, including those responsible for the metabolism of PPIs. A reduction in PPI concentrations may increase the risk of gastrointestinal (GI) adverse events such as GI bleeding. If carbamazepine and PPIs must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy.
Raltegravir: (Major) Coadministration of carbamazepine with raltegravir is not recommended. Raltegravir is a substrate of uridine diphosphate glucuronosyltransferase (UGT) 1A1; carbamazepine is a strong UGT1A1 inducer. Although not specifically studied with carbamazepine, other strong UGT1A1 inducers have been shown to decrease plasma concentrations of raltegravir, which may lead to HIV treatment failure or to the development of viral resistance.
Ramelteon: (Moderate) Efficacy of ramelteon may be reduced when it is used in combination with strong CYP1A2 enzyme inducers such as carbamazepine.
Ranolazine: (Contraindicated) Ranolazine is contraindicated in patients receiving drugs known to be CYP3A inducers including carbamazepine. Induction of CYP3A metabolism could lead to decreased ranolazine plasma concentrations and decreased efficacy. In addition, carbamazepine may increase the absorption of ranolazine via induction of P-glycoprotein transport.
Rasagiline: (Major) The manufacturer of carbamazepine contraindicates concurrent use with monoamine oxidase inhibitors (MAOIs) or use within 14 days of MAOI discontinuation. Carbamazepine is structurally related to tricyclics, an antidepressant class which may cause serotonin syndrome (characterized by hyperthermia, diaphoresis, shivering, tremor, myoclonus, seizures, ataxia, delirium, restlessness) when administered with MAOIs. Although rasagiline differs from other MAOIs because it is MAO-B selective at recommended doses, it may be advisable to avoid co-administration with carbamazepine until specific information becomes available about the safety of this combination. It should be noted that CYP1A2 is the major hepatic enzyme responsible for the metabolism of rasagiline, and carbamazepine is an inducer of the isoenzyme. The efficacy of rasagiline may be diminished during combined use with carbamazepine.
Red Yeast Rice: (Moderate) Since certain red yeast rice products (i.e., pre-2005 Cholestin formulations) contain lovastatin, clinicians should use red yeast rice cautiously in combination with drugs known to interact with lovastatin. CYP3A4 inducers can theoretically reduce the effectiveness of HMG-CoA reductase activity via induction of CYP3A4 metabolism. Examples of CYP3A4 inducers include carbamazepine.
Regorafenib: (Major) Avoid coadministration of regorafenib with carbamazepine due to decreased plasma concentrations of regorafenib and increased plasma concentrations of the M-5 active metabolite, which may lead to decreased efficacy. Regorafenib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the mean AUC of regorafenib by 50% and increased the mean AUC of M-5 by 264%; no change in the mean AUC of M-2 was observed.
Relugolix: (Major) Avoid concurrent use of relugolix and carbamazepine. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If carbamazepine is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-gp and CYP3A substrate and carbamazepine is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%.
Relugolix; Estradiol; Norethindrone acetate: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin). (Major) Avoid concurrent use of relugolix and carbamazepine. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If carbamazepine is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-gp and CYP3A substrate and carbamazepine is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%.
Repaglinide: (Major) Coadministration of carbamazepine and repaglinide may decrease the serum concentration of repaglinide; if coadministration is necessary, a dose increase of repaglinide may be required and an increased frequency of glucose monitoring is recommended. Carbamazepine is a potent CYP3A4 inducer and repaglinide is a CYP3A4 substrate. Monitor for the possibility of reduced effectiveness of repaglinide and possible symptoms indicating hyperglycemia.
Repotrectinib: (Major) Avoid coadministration of repotrectinib with carbamazepine due to decreased repotrectinib exposure and risk of decreased efficacy. Concomitant use may also decrease carbamazepine exposure. Repotrectinib is a CYP3A substrate and moderate CYP3A inducer; carbamazepine is a CYP3A substrate and strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased repotrectinib overall exposure by 92%.
Ribociclib: (Major) Avoid coadministration of carbamazepine with ribociclib due to decreased ribociclib exposure resulting decreased efficacy; carbamazepine exposure may also increase. Ribociclib is a CYP3A4 substrate and strong inhibitor. Carbamazepine is a CYP3A4 substrate and strong inducer. Coadministration with another strong CYP3A4 inducer decreased ribociclib exposure in healthy subjects by 89%.
Ribociclib; Letrozole: (Major) Avoid coadministration of carbamazepine with ribociclib due to decreased ribociclib exposure resulting decreased efficacy; carbamazepine exposure may also increase. Ribociclib is a CYP3A4 substrate and strong inhibitor. Carbamazepine is a CYP3A4 substrate and strong inducer. Coadministration with another strong CYP3A4 inducer decreased ribociclib exposure in healthy subjects by 89%.
Rifabutin: (Moderate) Inducers of the hepatic CYP3A4 isoenzyme, such as rifabutin, can increase the rate of carbamazepine metabolism, leading to subtherapeutic carbamazepine plasma concentrations.
Rifampin: (Major) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of carbamazepine. Carbamazepine dosages may need to be adjusted while the patient is receiving rifampin.
Rifapentine: (Moderate) Monitor carbamazepine concentrations closely during coadministration of rifapentine; carbamazepine dose adjustments may be needed. Concomitant use may decrease carbamazepine concentrations. Carbamazepine is a CYP3A4 substrate and rifapentine is a CYP3A4 inducer.
Rilpivirine: (Contraindicated) Coadministration of carbamazepine and rilpivirine is contraindicated due to the potential for loss of virologic response and possible resistance to rilpivirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Rilpivirine is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury and decreased riluzole efficacy during coadministration of riluzole and carbamazepine. Concomitant use may increase the risk for hepatotoxicity and may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and carbamazepine is a CYP1A2 inducer.
Rimegepant: (Major) Avoid coadministration of rimegepant with carbamazepine; concurrent use may significantly decrease rimegepant exposure which may result in loss of efficacy. Rimegepant is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration of rimegepant with another strong CYP3A4 inducer decreased rimegepant exposure by 80%.
Riociguat: (Major) Strong inducers of CYP3A (e.g., rifampin, phenytoin, carbamazepine, phenobarbital or St. John's Wort) may significantly reduce riociguat exposure. Dosage adjustment recommendations are not available when strong CYP3A inducers are co-administered with riociguat.
Ripretinib: (Major) Avoid coadministration of ripretinib with carbamazepine. Coadministration may decrease the exposure of ripretinib and its active metabolite (DP-5439), which may decrease ripretinib anti-tumor activity. Ripretinib and DP-5439 are metabolized by CYP3A4 and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased ripretinib exposure by 61% and decreased DP-5439 exposure by 57%.
Risperidone: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and carbamazepine and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Concomitant use reduced risperidone overall exposure by 50%.
Ritlecitinib: (Moderate) Monitor for a decrease in ritlecitinib efficacy and increased carbamazepine concentrations during concomitant use of ritlecitinib and carbamazepine. Concomitant use may decrease ritlecitinib exposure and increase carbamazepine exposure. Ritlecitinib is a CYP3A substrate and moderate CYP3A inhibitor and carbamazepine is a CYP3A substrate and strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced ritlecitinib overall exposure by 44%.
Ritonavir: (Major) Avoid concomitant use of ritonavir and carbamazepine. Concomitant use may increase carbamazepine exposure, resulting in toxicity and/or decrease ritonavir exposure, resulting in reduced efficacy. If concomitant use is necessary, monitor for reduced virologic response and for carbamazepine toxicity; a carbamazepine dose reduction may be needed. Ritonavir is a CYP3A and P-gp substrate and CYP3A inducer; carbamazepine is a CYP3A and P-gp inducer.
Rivaroxaban: (Major) Avoid the concomitant administration of rivaroxaban and drugs that are both strong inducers of CYP3A4 and P-gp, such as carbamazepine. Concomitant administration of rivaroxaban and carbamazepine results in decreased plasma concentrations of rivaroxaban that may be insufficient to achieve the intended therapeutic effect. In a drug interaction study, coadministration of rivaroxaban 20 mg single dose with food with a drug that is a combined P-glycoprotein and strong CYP3A4 inducer led to approximate decreases of 50% and 22% in rivaroxaban AUC and Cmax, respectively. Similar decreases in pharmacodynamic effects were also observed.
Rocuronium: (Moderate) Monitor for a more rapid recovery from neuromuscular blockade than expected during concurrent use of carbamazepine and rocuronium. When administering neuromuscular blockade via continuous infusion, infusion rate requirements may be higher. Chronic carbamazepine administration may cause neuromuscular blockade resistance.
Roflumilast: (Major) Coadministration of carbamazepine and roflumilast is not recommended, as significantly reduced systemic exposure to roflumilast is expected. Carbamazepine is a strong CYP3A4 inducer; roflumilast is a CYP3A4 substrate. In pharmacokinetic study, administration of a single dose of roflumilast in patients receiving another strong CYP3A4 inducer, rifampicin, resulted in decreased roflumilast Cmax and AUC, as well as increased Cmax and decreased AUC of the active metabolite roflumilast N-oxide.
Rolapitant: (Major) Avoid the use of rolapitant with chronic administration of carbamazepine. Rolapitant is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. When another strong CYP3A4 inducer, rifampin (600 mg once daily), was administered for 7 days before and 7 days after a single dose of rolapitant (180 mg), the mean Cmax and AUC of rolapitant were decreased by 30% and 85%, respectively; additionally, the mean half-life decreased from 176 hours to 41 hours. Significantly reduced plasma concentrations and decreased half-life can decrease the efficacy of rolapitant.
Romidepsin: (Major) The concomitant use of romidepsin, a CYP3A4 substrate, and carbamazepine, a strong CYP3A4 inducer, may result in significantly altered romidepsin plasma exposure. Therefore, avoid using romidepsin with potent CYP3A4 inducers if possible.
Ropinirole: (Moderate) Carbamazepine induces cytochrome P450 CYP1A2 isoenzymes, which can potentially lead to decreased plasma concentrations of CYP1A2 substrates, such as ropinirole. If these drugs are coadministered, adjustment of ropinirole dose may be required. Decreased anticonvulsant efficacy is a possibility when some antipsychotic or antidepressant agents are administered to patients with a seizure disorder, because some of these drugs lower the seizure threshold. Clinical documentation of interactions is not always available. Clinicians should be alert to altered effects of any of these agents. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Rosiglitazone: (Moderate) Monitor for a decrease in rosiglitazone efficacy during concomitant use with carbamazepine; adjust the dose of rosiglitazone based on clinical response. Coadministration may decrease the exposure of rosiglitazone. Rosiglitazone is a CYP2C8 substrate and carbamazepine is a CYP2C8 inducer.
Rucaparib: (Moderate) Monitor carbamazepine concentrations closely during coadministration of rucaparib; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A4 substrate and rucaparib is a CYP3A4 inhibitor.
Rufinamide: (Moderate) Rufinamide is metabolized by carboxylesterases. The clearance of rufinamide may be increased due to induction of carboxylesterases by carbamazepine.
Ruxolitinib: (Moderate) Monitor patients frequently and adjust the ruxolitinib dose based on safety and efficacy if coadministered with carbamazepine; decreased ruxolitinib exposure is possible. Ruxolitinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration of another strong CYP3A4 inducer decreased ruxolitinib Cmax and AUC by 32% and 61%, respectively. The relative exposure to ruxolitinib's active metabolites increased approximately 100%.
Saquinavir: (Major) Carbamazepine increases the metabolism of the protease inhibitors, including saquinavir, and may lead to decreased efficacy of these medications. An alternative anticonvulsant should be considered when possible. Treatment failures have been reported with other protease inhibitors when carbamazepine was used concomitantly. In addition, saquinavir boosted with ritonavir is a potent CYP3A inibitor and coadministration may result in increased serum concentrations of carbamazepine. The appropriate drug-dose adjustments necessary to ensure optimum levels of both antiretroviral drugs and carbamazepine are unknown. If used concomitantly, the patient should be observed for changes in the clinical efficacy of the antiretroviral regimen or carbamazepine toxicity.
Sarilumab: (Moderate) Monitor carbamazepine concentrations and watch for decreased efficacy of carbamazepine if coadministration with sarilumab is necessary; adjust carbamazepine dosage as necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as carbamazepine, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Carbamazepine is a substrate of both CYP1A2 and CYP3A4 and a narrow therapeutic index drug.
Secobarbital: (Moderate) Barbiturates can accelerate hepatic metabolism of carbamazepine due to induction of hepatic microsomal enzyme activity. Carbamazepine serum concentrations should be monitored closely if a barbiturate is added or discontinued during therapy.
Secukinumab: (Moderate) If secukinumab is initiated or discontinued in a patient taking carbamazepine, monitor carbamazepine concentrations; carbamazepine dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as carbamazepine. These interactions remain theoretical. Results from a drug-drug interaction study in subjects with moderate to severe psoriasis showed no clinically relevant interaction for drugs metabolized by CYP3A4.
Segesterone Acetate; Ethinyl Estradiol: (Major) Advise patients taking estrogen hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens containing a minimum of 30 mcg of ethinyl estradiol or equivalent may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase estrogen elimination. (Major) Advise patients taking progestin hormones for contraception to consider an alternate or additional form of contraception, such as nonhormonal and/or barrier methods, during and for at least 1 month following discontinuation of carbamazepine. Higher-dose hormonal regimens may also be considered. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on carbamazepine, with dose adjustments made based on clinical efficacy. Progestins are CYP3A substrates and carbamazepine is a strong CYP3A inducer. Concurrent administration may increase progestin elimination. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Selegiline: (Contraindicated) Carbamazepine is contraindicated for use with selegiline, an inhibitor of monoamine oxidase type B, because of a possible increased risk of serotonin syndrome and/or hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with carbamazepine. After stopping treatment with carbamazepine, a time period equal to 4 to 5 half-lives of carbamazepine or any active metabolite should elapse before starting therapy with selegiline. When used with selegiline transdermal, carbamazepine has been shown to significantly elevate selegiline levels, which may increase the risk of a hypertensive crisis.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and carbamazepine due to the risk of decreased selpercatinib exposure which may reduce its efficacy. The exposure of carbamazepine may also be increased. Selpercatinib is a CYP3A4 substrate and is also a weak CYP3A4 and moderate CYP2C8 inhibitor. Carbamazepine is a CYP3A4 and CYP2C8 substrate and strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased selpercatinib exposure by 87%.
Selumetinib: (Major) Avoid coadministration of selumetinib and carbamazepine due to the risk of decreased selumetinib exposure which may reduce its efficacy. Selumetinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased selumetinib exposure by 51%.
Semaglutide: (Moderate) Consider increased clinical or laboratory monitoring for carbamazepine if administered with oral semaglutide as the oral absorption of carbamazepine may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications, particularly those with a narrow therapeutic index. Be sure to administer oral semaglutide as directed, separately from other oral medications. This interaction does not occur with subcutaneous semaglutide.
Serdexmethylphenidate; Dexmethylphenidate: (Minor) Psychostimulants, such as methylphenidate and its derivatives, may lower the seizure threshold, thereby reducing the efficacy of anticonvulsants such as carbamazepine. There are rare case reports of reduced methylphenidate concentrations occurring during the use of carbamazepine concurrently. The mechanism of the interaction is not clear as methylphenidate is metabolized primarily to ritalinic acid by nonmicrosomal hydrolytic esterases that are widely distributed throughout the body. Interactions with other potent enzyme inducers have not been reported. Monitor for any changes in therapeutic effectiveness of either drug.
Sevoflurane: (Moderate) Caution is advised with the concomitant use of sevoflurane and carbamazepine as concurrent use may increase the risk of hepatotoxicity.
Sildenafil: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with carbamazepine is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and carbamazepine is a strong CYP3A inducer. Concomitant administration of strong CYP3A inducers is expected to substantially decrease plasma concentrations of sildenafil.
Siltuximab: (Moderate) Monitor carbamazepine concentrations and watch for decreased efficacy of carbamazepine if coadministration with siltuximab is necessary; adjust carbamazepine dosage as necessary. Inhibition of IL-6 signaling by siltuximab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as carbamazepine, may have fluctuations in drug levels and therapeutic effect when siltuximab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping siltuximab. In vitro, siltuximab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Carbamazepine is a substrate of both CYP1A2 and CYP3A4 and a narrow therapeutic index drug.
Simvastatin: (Minor) Carbamazepine, which is a CYP3A4 inducer, may decrease the efficacy of HMG-Co-A reductase inhibitors which are CYP3A4 substrates, including simvastatin.
Siponimod: (Moderate) Concomitant use of siponimod and carbamazepine is not recommended for patients with CYP2C9*1/*3 and *2/*3 genotypes due to a significant decrease in siponimod exposure. Use of siponimod with carbamazepine is not recommended in any patient if they are also receiving a moderate CYP2C9 inducer. Siponimod is a CYP2C9 and CYP3A substrate; carbamazepine is a strong CYP3A inducer. Coadministration with a moderate CYP2C9/strong CYP3A dual inducer decreased siponimod exposure by 57%.
Sirolimus: (Major) Avoid concomitant use of sirolimus and carbamazepine as use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A and P-gp substrate and carbamazepine is a strong CYP3A and P-gp inducer. Concomitant use of another strong CYP3A and P-gp inducer decreased sirolimus overall exposure by 82%.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor carbamazepine concentrations closely during coadministration of taurursodiol; carbamazepine dose adjustments may be needed. Concomitant use may decrease carbamazepine concentrations. Carbamazepine is a CYP3A substrate and taurursodiol is a CYP3A inducer.
Sofosbuvir: (Major) Avoid coadministration of sofosbuvir with inducers of P-glycoprotein (P-gp), such as carbamazepine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy.
Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of sofosbuvir with inducers of P-glycoprotein (P-gp), such as carbamazepine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp) and CYP 3A4 and 2B6 isoenzymes, such as carbamazepine. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is metabolized by P-gp and CYP3A4 and 2B6.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of sofosbuvir with inducers of P-glycoprotein (P-gp), such as carbamazepine. Taking these drugs together may decrease sofosbuvir plasma concentrations, potentially resulting in loss of antiviral efficacy. (Major) Avoid coadministration of velpatasvir with inducers of P-glycoprotein (P-gp) and CYP 3A4 and 2B6 isoenzymes, such as carbamazepine. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is metabolized by P-gp and CYP3A4 and 2B6. (Major) Avoid coadministration of voxilaprevir with inducers of P-glycoprotein (P-gp) and CYP3A4, such as carbamazepine. Taking these drugs together may significantly decrease voxilaprevir plasma concentrations, potentially resulting in loss of antiviral efficacy. Voxilaprevir is metabolized by P-gp and CYP3A4.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and carbamazepine; sonidegib exposure may be significantly decreased and its efficacy reduced. Sonidegib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the geometric mean Cmax and AUC of sonidegib by 54% and 72%, respectively.
Sorafenib: (Major) Avoid coadministration of sorafenib with carbamazepine due to decreased plasma concentrations of sorafenib. Sorafenib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased sorafenib exposure by 37%.
Sotagliflozin: (Moderate) Monitor for a decrease in sotagliflozin efficacy during concomitant use of sotagliflozin and carbamazepine and adjust therapy as appropriate. Concomitant use may decrease sotagliflozin exposure. Sotagliflozin is a UGT substrate and carbamazepine is a UGT inducer. Concomitant use with another UGT inducer reduced sotagliflozin overall exposure by 45%.
Sotorasib: (Major) Avoid concurrent use of sotorasib and carbamazepine. Coadministration may decrease sotorasib exposure resulting in decreased efficacy. Concomitant use may also decrease carbamazepine concentrations. Sotorasib is a CYP3A4 substrate and moderate CYP3A4 inducer; carbamazepine is a CYP3A4 substrate and strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC of sotorasib by 51%.
Sparsentan: (Major) Avoid concomitant use of sparsentan and carbamazepine due to the risk for decreased sparsentan exposure which may reduce its efficacy. Sparsentan is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer is predicted to decrease sparsentan overall exposure by 47%.
Spironolactone: (Moderate) Monitor carbamazepine concentrations closely during coadministration of spironolactone; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and spironolactone is a CYP3A inhibitor.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor carbamazepine concentrations closely during coadministration of spironolactone; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and spironolactone is a CYP3A inhibitor. (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
St. John's Wort, Hypericum perforatum: (Moderate) Monitor carbamazepine concentrations closely during coadministration of St. John's Wort; carbamazepine dose adjustments may be needed. Concomitant use may decrease carbamazepine concentrations. Carbamazepine is a CYP3A4 substrate and St. John's Wort is a CYP3A4 inducer.
Stiripentol: (Major) Avoid coadministration of stiripentol with carbamazepine. If concurrent use is necessary, increase the dose of stiripentol; consider a dose adjustment of carbamazepine. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy; carbamazepine exposure may be altered resulting in an increased risk of adverse reactions and/or decreased efficacy. Stiripentol is metabolized by CYP3A4, CYP1A2, and CYP2C19; carbamazepine is a strong inducer of CYP3A4, and an inducer of CYP1A2 and CYP2C19. Carbamazepine is a CYP1A2, CYP3A4, CYP2C8, and P-gp substrate. In vitro data predicts inhibition or induction of CYP1A2, CYP3A4, and CYP2C8 and inhibition of P-gp by stiripentol potentially resulting in clinically significant interactions.
Streptogramins: (Moderate) Dalfopristin; quinupristin is a major inhibitor of cytochrome P450 3A4 and may decrease the elimination of drugs metabolized by this enzyme including carbamazepine.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if carbamazepine must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with carbamazepine is necessary; consider increasing the dose of sufentanil injection as needed. If carbamazepine is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Sunitinib: (Major) Avoid coadministration of carbamazepine with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
Suvorexant: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with carbamazepine is necessary. Suvorexant is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%.
Tacrolimus: (Moderate) Carbamazepine induces CYP3A enzymes and may decrease tacrolimus whole blood concentrations. Monitoring of whole blood concentrations and appropriate dosage adjustments of tacrolimus are recommended when carbamazepine and tacrolimus are used concomitantly.
Tadalafil: (Major) Avoid coadministration of tadalafil with carbamazepine in patients with pulmonary hypertension due to decreased plasma concentrations of tadalafil. In patients with erectile dysfunction and/or benign prostatic hyperplasia, consider the potential for loss of efficacy of tadalafil during concurrent administration of carbamazepine due to reduced tadalafil exposure. Tadalafil is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased tadalafil exposure by 88%.
Tamoxifen: (Major) Avoid coadministration of carbamazepine with tamoxifen due to decreased exposure to tamoxifen which may affect efficacy. Tamoxifen is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the AUC and Cmax of tamoxifen by 86% and 55%, respectively.
Tasimelteon: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as carbamazepine, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Carbamazepine also induces CYP1A2, a secondary metabolic pathway of tasimelteon.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with carbamazepine as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer.
Teduglutide: (Moderate) Teduglutide may increase absorption of carbamazepine because of it's pharmacodynamic effect of improving intestinal absorption. Careful monitoring and possible dose adjustment of cabamazepine is recommended.
Telmisartan; Amlodipine: (Moderate) Monitor carbamazepine concentrations and blood pressure closely during coadministration of amlodipine; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and strong inducer and amlodipine is CYP3A substrate and inhibitor. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Telotristat Ethyl: (Moderate) Monitor carbamazepine concentrations closely during coadministration of telotristat; carbamazepine dose adjustments may be needed. Concomitant use may decrease carbamazepine concentrations. Carbamazepine is a CYP3A4 substrate and telotristat is a CYP3A4 inducer.
Temsirolimus: (Major) Avoid coadministration of temsirolimus with carbamazepine due to the risk of decreased plasma concentrations of the primary active metabolite of temsirolimus (sirolimus). If concomitant use is unavoidable, consider increasing the dose of temsirolimus from 25 mg per week up to 50 mg per week. If carbamazepine is discontinued, decrease the dose of temsirolimus to the dose used before initiation of carbamazepine. Temsirolimus is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer had no significant effect on the AUC or Cmax of temsirolimus, but decreased the AUC and Cmax of the active metabolite, sirolimus, by 56% and 65%, respectively.
Tenofovir Alafenamide: (Major) Administering tenofovir alafenamide with carbamazepine is not recommended. Consider use of an alternative anticonvulsant. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
Tenofovir Alafenamide: (Major) Administering tenofovir alafenamide with carbamazepine is not recommended. Consider use of an alternative anticonvulsant. Taking these drugs together is expected to decrease tenofovir plasma concentrations, which may increase the potential for resistance and HIV treatment failure.
Tezacaftor; Ivacaftor: (Major) Coadministration of ivacaftor with carbamazepine is not recommended due to decreased plasma concentrations of ivacaftor. Ivacaftor is a sensitive CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer significantly decreased ivacaftor exposure by approximately 9-fold. (Major) Do not administer tezacaftor; ivacaftor and carbamazepine together; coadministration may reduce the efficacy of tezacaftor; ivacaftor. Exposure to ivacaftor is significantly decreased and exposure to tezacaftor may be reduced by the concomitant use of carbamazepine, a strong CYP3A inducer; both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate). Coadministration of ivacaftor with a strong CYP3A inducer decreased ivacaftor exposure 89%.
Theophylline, Aminophylline: (Major) Aminophylline is expected to decrease plasma concentrations of carbamazepine via 3A4 induction. Also, aminophylline is primarily metabolized in the liver by the CYP1A2 isoenzyme. Carbamazepine can stimulate the hepatic metabolism of aminophylline if used concurrently. Aminophylline doses may need to be increased if carbamazepine is added. More importantly, serious aminophylline toxicity can result if carbamazepine is discontinued and the dose of aminophylline is not correspondingly decreased. (Major) Theophylline is expected to decrease plasma concentrations of carbamazepine via 3A4 induction. Theophylline is primarily metabolized in the liver by the CYP1A2 isoenzyme. Carbamazepine can stimulate the hepatic metabolism of theophylline if used concurrently. Theophylline doses may need to be increased if carbamazepine is added. More importantly, serious theophylline toxicity can result if carbamazepine is discontinued and the dose of theophylline is not correspondingly decreased.
Thiazide diuretics: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Thiotepa: (Major) Avoid the concomitant use of thiotepa and carbamazepine if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Consider an alternative agent with no or minimal potential to induce CYP3A4. If coadministration is necessary, monitor patients for signs and symptoms of thiotepa toxicity. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; carbamazepine is a strong CYP3A4 inducer.
Thiothixene: (Major) Thiothixene, when used concomitantly with carbamazepine, can increase CNS depression and lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when thiothixene is added; monitor for loss of seizure control or the need for dosage adjustments of either the neuroleptic or the anticonvulsant. In addition, carbamazepine is a potent inducer of the cytochrome P-450 mixed-function hepatic oxidase system, and can reduce plasma concentrations of thiothixene to undetectable levels. If thiothixene and carbamazepine must be used together, then dosage adjustments of thiothixene may be required.
Thyroid hormones: (Minor) Use carbamazepine and thyroid hormones together with caution. Carbamazepine may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations. Carbamazepine reduces serum protein binding of levothyroxine, and total and free-T4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Monitor thyroid hormone parameters.
Ticagrelor: (Major) Avoid the concomitant use of ticagrelor and strong CYP3A4 inducers, such as carbamazepine. Ticagrelor is a substrate of CYP3A4/5 and concomitant use with carbamazepine substantially decreases ticagrelor exposure which may decrease the efficacy of ticagrelor.
Tipranavir: (Major) Carbamazepine increases the metabolism of the protease inhibitors and may lead to decreased efficacy of these medications. Coadministration of tipranavir with carbamazepine is expected to result in decreased tipranavir concentrations, an alternative anticonvulsant should be considered when possible. Treatment failures have been reported with other protease inhibitors when carbamazepine was used concomitantly. In addition, tipranavir boosted with ritonavir is a potent CYP3A inibitor and coadministration may result in increased serum concentrations of carbamazepine. The appropriate drug-dose adjustments necessary to ensure optimum levels of both antiretroviral drugs and carbamazepine are unknown. If used concomitantly, the patient should be observed for changes in the clinical efficacy of the antiretroviral regimen or carbamazepine toxicity.
Tirzepatide: (Moderate) Consider increased clinical or laboratory monitoring for carbamazepine if administered with tirzepatide as the oral absorption of carbamazepine may be altered. Tirzepatide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications, particularly those with a narrow therapeutic index.
Tivozanib: (Major) Avoid concomitant use of tivozanib with carbamazepine due to decreased plasma concentrations of tivozanib, which may reduce its efficacy. Tivozanib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the overall exposure of tivozanib by 52%.
Tocilizumab: (Moderate) Monitor carbamazepine concentrations and watch for decreased efficacy of carbamazepine if coadministration with tocilizumab is necessary; adjust carbamazepine dosage as necessary. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as carbamazepine, may have fluctuations in drug levels and therapeutic effect when tocilizumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Carbamazepine is a substrate of both CYP1A2 and CYP3A4 and narrow therapeutic index drug.
Tofacitinib: (Major) Coadministration of tofacitinib and carbamazepine is not recommended due to the potential for a loss of response or reduced clinical response to tofacitinib. Tofacitinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Tofacitinib exposure is decreased when coadministered with strong CYP3A4 inducers. In one study, the mean AUC and Cmax of tofacitinib were decreased by 84% and 74%, respectively when administered with another strong CYP3A4 inducer.
Tolvaptan: (Major) Avoid concurrent use of tolvaptan and carbamazepine due to the risk for decreased tolvaptan plasma concentrations and reduced efficacy. Tolvaptan is a sensitive CYP3A substrate and carbamazepine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased tolvaptan exposure by 85%.
Topiramate: (Moderate) A topiramate dosage adjustment may be needed during concomitant carbamazepine use. Concomitant administration of topiramate with carbamazepine resulted in a clinically significant decrease (40%) in plasma topiramate concentrations.
Toremifene: (Major) Avoid coadministration of carbamazepine with toremifene due to decreased plasma concentrations of toremifene which may result in decreased efficacy. Toremifene is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with strong CYP3A4 inducers lowers steady-state serum concentrations of toremifene.
Trabectedin: (Major) Avoid the concomitant use of trabectedin with carbamazepine due to the risk of decreased trabectedin exposure. Trabectedin is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased the systemic exposure of a single dose of trabectedin by 31% compared to a single dose of trabectedin given alone.
Tramadol: (Major) Reserve concomitant use of tramadol and carbamazepine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required, and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Monitor for reduced efficacy of tramadol and signs of opioid withdrawal; consider increasing the dose of tramadol as needed. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death and/or decrease tramadol concentrations, which may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If carbamazepine is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Tramadol; Acetaminophen: (Major) Reserve concomitant use of tramadol and carbamazepine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required, and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Monitor for reduced efficacy of tramadol and signs of opioid withdrawal; consider increasing the dose of tramadol as needed. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death and/or decrease tramadol concentrations, which may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If carbamazepine is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. (Minor) Carbamazepine may potentially accelerate the hepatic metabolism of acetaminophen. In addition, due to enzyme induction, carbamazepine may increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolite, NAPQI. Clinicians should be alert to decreased effect of acetaminophen. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Trandolapril; Verapamil: (Moderate) Monitor blood pressure and heart rate if coadministration of verapamil with carbamazepine is necessary. Additionally, monitor carbamazepine concentrations closely during coadministration; carbamazepine dose adjustments may be needed. Concomitant use may decrease exposure of verapamil and increase exposure of carbamazepine. Verapamil is a CYP3A substrate and moderate CYP3A inhibitor; carbamazepine is a CYP3A substrate and strong CYP3A inducer.
Tranylcypromine: (Contraindicated) Carbamazepine is contraindicated for use with monoamine oxidase inhibitors (MAOIs), because of a possible increased risk of serotonin syndrome and/or hypertensive crisis. Due to the risk of serotonin syndrome, carbamazepine is contraindicated for use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing treatment with an MAOI. Conversely, MAOIs should not be initiated within 14 days of stopping carbamazepine. Monitor blood pressure and for serotonin-related side effects during therapy transitions.
Trazodone: (Moderate) Consider increasing the trazodone dose based on therapeutic response when coadministered with carbamazepine. Concurrent use may decrease trazodone exposure. Trazodone is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration with other strong CYP3A4 inducers decreased the exposure of trazodone compared to the use of trazodone alone.
Tretinoin, ATRA: (Moderate) Concurrent use of hepatic cytochrome P450 inducers, such as carbamazepine, with oral tretinoin therapy may result in significant decreases in serum tretinoin levels. Patients should be closely monitored for decreased clinical effects of tretinoin while receiving concomitant therapy. Also monitor for potential additive side effects, such as risk of infection.
Triamcinolone: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of triamcinolone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with triamcinolone.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Triazolam: (Moderate) Monitor for withdrawal symptoms or lack of triazolam efficacy if coadministration with carbamazepine is necessary. Consider appropriate dose adjustment of triazolam if clinically indicated. Triazolam is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Tricyclic antidepressants: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant carbamazepine use. Concomitant use may result in decreased tricyclic antidepressant exposure.
Trimipramine: (Moderate) Monitor for loss of tricyclic antidepressant efficacy during concomitant carbamazepine use. Concomitant use may result in decreased tricyclic antidepressant exposure.
Trofinetide: (Moderate) Monitor carbamazepine concentrations closely during coadministration of trofinetide; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and trofinetide is a CYP3A inhibitor.
Tucatinib: (Major) Avoid coadministration of tucatinib and carbamazepine due to the risk of decreased tucatinib exposure which may reduce its efficacy. Tucatinib is a CYP3A4 and CYP2C8 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with a strong CYP3A4/moderate CYP2C8 inducer decreased tucatinib exposure by 50%.
Ubrogepant: (Major) Avoid the coadministration of ubrogepant and carbamazepine as concurrent use may decrease ubrogepant exposure and reduce the efficacy. Ubrogepant is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer resulted in an 80% reduction in ubrogepant exposure.
Ulipristal: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and carbamazepine is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
Upadacitinib: (Major) Coadministration of upadacitinib with carbamazepine is not recommended as upadacitinib exposure may be decreased leading to reduced therapeutic effect. Upadacitinib is CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Concurrent use of a strong CYP3A4 inducer decreased upadacitinib exposure by 61%.
Valbenazine: (Major) Co-administration of strong CYP3A4 inducers, such as carbamazepine, and valbenazine, a CYP3A4 substrate, is not recommended. Strong CYP3A4 inducers can decrease systemic exposure of valbenazine and its active metabolite compared to the use of valbenazine alone. Reduced exposure of valbenazine and its active metabolite may reduce efficacy.
Valproic Acid, Divalproex Sodium: (Moderate) Carbamazepine induces hepatic microsomal enzyme activity and can increase the clearance of valproic acid (or divalproex) and decrease valproic acid serum concentrations, an interaction that is clinically significant in practice and may result in reduction in valproic acid efficacy. Clearance of valproic acid may double. Valproic acid may also decrease the metabolism of the active metabolite of carbamazepine, carbamazepine10,11-epoxide, by inhibition of epoxide hydrolase, which is the enzyme responsible for converting carbamazepine10,11-epoxide to an inactive end metabolite. Carbamazepine10,11-epoxide is more hepatotoxic than the parent drug and can be especially problematic for children, causing vomiting and tiredness. Carbamazepine-10,11-epoxide serum concentrations have been elevated by 45% when coadministered with valproate. Careful monitoring of both valproic acid and carbamazepine serum concentrations, along with the patient's clinical response may be necessary when one agent is added to the other.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant use of carbamazepine and thiazide diuretics due to additive risk of developing hyponatremia.
Vandetanib: (Major) Avoid coadministration of vandetanib with carbamazepine due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Vasopressin, ADH: (Minor) Carbamazepine may cause additive hyponatremia or antidiuretic effects when combined with vasopressin, ADH.
Vecuronium: (Moderate) Monitor for a more rapid recovery from neuromuscular blockade than expected during concurrent use of carbamazepine and vecuronium. When administering neuromuscular blockade via continuous infusion, infusion rate requirements may be higher. Chronic carbamazepine administration may cause neuromuscular blockade resistance.
Vemurafenib: (Major) Avoid the concomitant use of vemurafenib and carbamazepine; significantly decreased vemurafenib exposure may occur resulting in reduced vemurafenib efficacy. Consider the use of an alternative agent. If use with carbamazepine cannot be avoided, increase the vemurafenib dose by 240 mg (as tolerated). If carbamazepine is discontinued, the previous (lower) vemurafenib dose may be resumed 2 weeks after the last carbamazepine dose. Vemurafenib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. In a drug interaction study, the vemurafenib AUC value decreased by 40% (90% CI, 24% to 53%) when a single 960-mg vemurafenib dose was administered with another strong CYP3A4 inducer; the vemurafenib Cmax was not changed.
Venetoclax: (Major) Avoid the concomitant use of venetoclax and carbamazepine; venetoclax levels may be significantly decreased and its efficacy reduced. Venetoclax is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Consider alternative agents. In a drug interaction study in healthy subjects (n = 10), the venetoclax Cmax and AUC values were decreased by 42% and 71%, respectively, following the co-administration of multiple doses of a strong CYP3A4 inducer.
Verapamil: (Moderate) Monitor blood pressure and heart rate if coadministration of verapamil with carbamazepine is necessary. Additionally, monitor carbamazepine concentrations closely during coadministration; carbamazepine dose adjustments may be needed. Concomitant use may decrease exposure of verapamil and increase exposure of carbamazepine. Verapamil is a CYP3A substrate and moderate CYP3A inhibitor; carbamazepine is a CYP3A substrate and strong CYP3A inducer.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with carbamazepine is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like carbamazepine may increase the risk of a photosensitivity reaction.
Vilazodone: (Moderate) Consider increasing the dose of vilazodone up to 2-fold over 1 to 2 weeks (maximum, 80 mg per day) based on clinical response if coadministration with carbamazepine is necessary for more than 14 days. After discontinuation of carbamazepine, resume the previous vilazodone dose over 1 to 2 weeks. Vilazodone is primarily metabolized by CYP3A4 and carbamazepine is a strong CYP3A4 inducer. Decreased plasma concentrations of vilazodone are expected if vilazodone is used concomitantly with strong CYP3A4 inducers.
Viloxazine: (Moderate) Monitor carbamazepine concentrations closely during coadministration of viloxazine; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A4 substrate and viloxazine is a CYP3A4 inhibitor.
Vincristine Liposomal: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 such as carbamazepine may increase the metabolism of vincristine and decrease the efficacy of drug. In addition, myelosuppressive antineoplastic agents possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution.
Vincristine: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 such as carbamazepine may increase the metabolism of vincristine and decrease the efficacy of drug. In addition, myelosuppressive antineoplastic agents possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution.
Vitamin B Complex Supplements: (Moderate) Carbamazepine use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like carbamazepine, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly. (Moderate) Niacin may inhibit the CYP3A4 metabolism of carbamazepine, resulting in elevated carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored if niacin is added during carbamazepine therapy. It may be necessary to reduce the dose of carbamazepine.
Voclosporin: (Major) Avoid coadministration of voclosporin with carbamazepine. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Vonoprazan: (Major) Avoid concomitant use of vonoprazan and carbamazepine due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Concomitant use may also increase carbamazepine concentrations. Vonoprazan is a CYP3A substrate and weak CYP3A inhibitor and carbamazepine is a CYP3A substrate and strong CYP3A inducer. Vonoprazan exposures are predicted to be 80% lower when coadministered with a strong CYP3A4 inducer.
Vonoprazan; Amoxicillin: (Major) Avoid concomitant use of vonoprazan and carbamazepine due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Concomitant use may also increase carbamazepine concentrations. Vonoprazan is a CYP3A substrate and weak CYP3A inhibitor and carbamazepine is a CYP3A substrate and strong CYP3A inducer. Vonoprazan exposures are predicted to be 80% lower when coadministered with a strong CYP3A4 inducer.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of vonoprazan and carbamazepine due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Concomitant use may also increase carbamazepine concentrations. Vonoprazan is a CYP3A substrate and weak CYP3A inhibitor and carbamazepine is a CYP3A substrate and strong CYP3A inducer. Vonoprazan exposures are predicted to be 80% lower when coadministered with a strong CYP3A4 inducer. (Major) Coadministration of carbamazepine and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers. Additionally, carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Drugs known to inhibit CYP3A4, such as clarithromycin, may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely during coadministration; reduce carbamazepine doses may be necessary. Clarithromycin also inhibits epoxide hydrolase resulting in increased levels of the active metabolite carbamazepine 10, 11- epoxide, which may be more hepatotoxic than the parent drug. Several case reports have documented that clarithromycin can significantly decrease carbamazepine clearance, producing increases in the serum concentration of carbamazepine. Carbamazepine concentrations increased from 12 mcg/ml to 19.1 mcg/ml in a 17-year-old boy after 2 days of clarithromycin 250 mg PO bid. Patients should be monitored for carbamazepine toxicity if clarithromycin is added. Carbamazepine toxicity may be avoided if clarithromycin therapy is begun first and stabilized prior to beginning carbamazepine therapy, however, carbamazepine dosages may need to be increased if clarithromycin is subsequently discontinued.
Vorapaxar: (Major) Avoid coadministration of vorapaxar and carbamazepine. Decreased serum concentrations of vorapaxar and thus decreased efficacy are possible when vorapaxar, a CYP3A4 substrate, is coadministered with carbamazepine, a strong CYP3A inducer.
Voriconazole: (Contraindicated) Coadministration of carbamazepine and voriconazole is contraindicated due to the potential for decreased exposure to voriconazole; increased exposure to carbamazepine may also occur. Voriconazole is a CYP3A and CYP2C9 substrate and strong CYP3A inhibitor; carbamazepine is a CYP3A substrate and CYP2C9 and strong CYP3A4 inducer.
Vortioxetine: (Major) Vortioxetine is extensively metabolized by CYP isoenzymes, primarily CYP2D6 and by CYP3A4 and other isoenzymes to a lesser extent. Therefore, the manufacturer recommends that the practitioner consider an increase in dose of vortioxetine when a strong CYP inducer, such as carbamazepine, is co-administered for more than 14 days. In such cases, the maximum recommended dose of vortioxetine should not exceed three times the original dose. When the inducer is discontinued, the dose of vortioxetine should be reduced to the original level within 14 days.
Voxelotor: (Major) Avoid coadministration of voxelotor and carbamazepine as concurrent use may decrease voxelotor exposure and lead to reduced efficacy. If coadministration is unavoidable, increase voxelotor dosage to 2,500 mg PO once daily in patients 12 years and older. In patients 4 to 11 years old, weight-based dosage adjustments are recommended; consult product labeling for specific recommendations. Additionally, monitor carbamazepine concentrations closely during coadministration as exposure may be increased; dose adjustments may be needed. Voxelotor is a substrate of CYP3A and moderate CYP3A inhibitor; carbamazepine is a CYP3A substrate and strong CYP3A inducer. Coadministration of voxelotor with a strong CYP3A inducer is predicted to decrease voxelotor exposure by up to 40%.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with carbamazepine is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Carbamazepine is a CYP1A2, CYP2C9, and strong CYP3A4 inducer and the enantiomers of warfarin are CYP1A2/CYP2C9/CYP3A4 substrates. If carbamazepine is discontinued, dosage reductions of warfarin may be necessary.
Zafirlukast: (Moderate) In vitro data indicate that zafirlukast inhibits the CYP2C9 and CYP3A4 isoenzymes at concentrations close to the clinically achieved total plasma concentrations. Until more clinical data are available, zafirlukast should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as carbamazepine.
Zaleplon: (Moderate) Monitor for decreased efficacy when zaleplon is coadministered with carbamazepine due to decreased zaleplon exposure. Zaleplon is partially metabolized by CYP3A4; carbamazepine is a strong CYP3A4 inducer. Consider using an alternative non-CYP3A4 substrate hypnotic in patients taking strong CYP3A4 inducers. Coadministration with another strong CYP3A4 inducer reduced zaleplon exposure by approximately 80%.
Zanubrutinib: (Major) Avoid the concomitant use of zanubrutinib and carbamazepine. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with another strong CYP3A4 inducer.
Ziprasidone: (Moderate) Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with ziprasidone. Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. The concurrent use of ziprasidone with carbamazepine, a potent CYP3A4 inducer, causes a 35% decrease in the AUC of ziprasidone. Decreased anticonvulsant efficacy is a possibility when some antipsychotic or antidepressant agents are administered to patients with a seizure disorder, because some of these drugs lower the seizure threshold.
Zolpidem: (Major) Concurrent use of zolpidem with potent CYP3A4 inducers, such as carbamazepine, should be avoided if possible because decreased plasma concentrations of zolpidem are possible and efficacy may be reduced. CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism, and there is evidence of significant decreases in systemic exposure and pharmacodynamics effects of zolpidem during co-administration of rifampin, a potent CYP3A4 inducer.
Zonisamide: (Moderate) Zonisamide is metabolized by hepatic cytochrome P450 enzyme 3A4. Carbamazepine is an inducer of CYP3A4 and can reduce the systemic exposure to zonisamide by increasing the metabolism of the drug.
Zuranolone: (Major) Avoid concomitant use of zuranolone and carbamazepine. Concurrent use may decrease zuranolone exposure which may reduce its efficacy. Zuranolone is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced zuranolone overall exposure by 85%.
Anticonvulsant properties of carbamazepine are not fully understood. Carbamazepine blocks use-dependent sodium channels, inhibiting sustained repetitive firing. Like phenytoin, carbamazepine reduces post-tetanic potentiation of synaptic transmission in the spinal cord. This effect may explain its ability to limit the spread of seizures. Individual patient response to carbamazepine is variable. Pain relief is believed to be associated with blockade of synaptic transmission in the trigeminal nucleus. Carbamazepine is a complex drug that also possesses anticholinergic, central antidiuretic (syndrome of inappropriate antidiuretic hormone, SIADH), antiarrhythmic, muscle relaxant, antidepressant (possibly through blockade of norepinephrine release), sedative, and neuromuscular-blocking properties. Carbamazepine is a potent enzyme inducer and can induce its own metabolism.
Carbamazepine is administered orally. Carbamazepine is 76% bound to plasma proteins. The CSF/serum ratio is 0.22, similar to the 24% unbound carbamazepine in serum. Carbamazepine is metabolized in the liver. CYP3A4 is the major isoform responsible for the formation of carbamazepine-10,11-epoxide; human microsomal epoxide hydrolase is the enzyme responsible for the formation of the 10,11-transdiol derivative from carbamazepine-10,11-epoxide. Because carbamazepine induces its own metabolism, the half-life is also variable. Autoinduction is completed after 3 to 5 weeks of a fixed dosing regimen. Initial half-life values are 25 to 65 hours, decreasing to 12 to 17 hours on repeated doses. Carbamazepine is excreted in the urine and feces; after administration of radiolabeled carbamazepine, 72% of the administered radioactivity was found in the urine, largely composed of hydroxylated and conjugated metabolites with only 3% unchanged carbamazepine, and 28% in the feces.
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, P-gp, UGT
CYP3A4 is the major enzyme responsible for the metabolism of carbamazepine to carbamazepine 10,11-epoxide with CYP2C8 playing a minor role. Carbamazepine is a strong CYP3A4 inducer, with auto-induction also occurring through CYP3A4. Carbamazepine is also an inducer of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, P-gp, and UGT.
-Route-Specific Pharmacokinetics
Oral Route
Absorption of carbamazepine from the GI tract is slow and variable. In clinical studies, carbamazepine suspension, conventional tablets, and extended-release tablets delivered equivalent amounts of drug to the systemic circulation. However, the suspension was absorbed somewhat faster, and the extended-release tablet slightly slower, than the conventional tablet. Bioavailability is roughly 85%. Plasma concentrations peak within 4 to 5 hours after administration of the immediate-release tablets and within 1.5 hours after administration of suspension. A Cmax of 11 +/- 2.5 mcg/mL was attained approximately 6 hours after chronic administration of the extended-release capsules (800 mg every 12 hours). In comparison, a Cmax of 1.9 +/- 0.3 mcg/mL was attained in 19 +/- 7 hours after a single 200 mg dose. Administration of the extended-release capsules with a high fat meal did not alter the AUC or half-life, and steady-state Cmax values were within the therapeutic concentration range. In a fasting state, the pharmacokinetic profiles of extended-release capsules were similar when administered by sprinkling the contents over applesauce or as an intact capsule. Serum concentrations of 4 to 12 mcg/mL are considered to be therapeutic in the treatment of seizure disorders. Several days of therapy may be required to reach steady-state concentrations. Carbamazepine extended-release capsules or tablets taken every 12 hours provide steady-state plasma concentrations similar to immediate-release tablets given every 6 hours.
-Special Populations
Hepatic Impairment
The effect of hepatic impairment on the pharmacokinetics of carbamazepine is not known. Carbamazepine is primarily metabolized by the liver.
Renal Impairment
The effect of renal impairment on the pharmacokinetics of carbamazepine is not known.
Pediatrics
The pharmacokinetic parameters of carbamazepine are similar in children and in adults. However, there is a poor correlation between plasma concentrations of carbamazepine and dose in children. Carbamazepine (CBZ) is more rapidly metabolized to carbamazepine-10,11-epoxide (CBZ-E), the active metabolite, in younger age groups than in adults. In children younger than 15 years, there is an inverse relationship of the CBZ-E/CBZ ratio and increasing age (in a single report from 0.44 in infants younger than 1 year to 0.18 in children 10 to 15 years).
Gender Differences
No difference in the mean AUC and Cmax of carbamazepine and the active metabolite, carbamazepine-10,11-epoxide, was found between males and females.
Ethnic Differences
The effects of race on carbamazepine pharmacokinetics have not been systematically evaluated.
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