Eslicarbazepine is an oral anticonvulsant indicated for monotherapy or adjunctive treatment of partial seizures. Eslicarbazepine acetate is a prodrug for eslicarbazepine (S-licarbazepine), which is the active metabolite of oxcarbazepine. In a pharmacokinetic study comparing eslicarbazepine acetate to oxcarbazepine, administration of eslicarbazepine acetate resulted in greater exposure to the eslicarbazepine metabolite and lower exposure to the R-licarbazepine and oxcarbazepine metabolites. This may correlate with improved tolerability of eslicarbazepine acetate compared with oxcarbazepine. Efficacy for monotherapy treatment was established in 2 dose-blinded historical control trials. Various exit criterion indicative of seizure activity occurred in approximately 13-44% of patients, where a pre-specified threshold below 65% defined efficacy. Efficacy for adjunctive treatment was established in clinical trials which enrolled patients with partial onset seizures who were not controlled with 1 to 3 concomitant antiepileptic drugs (AEDs). In these studies, eslicarbazepine resulted in a statistically significant reduction in seizure frequency compared with placebo. In addition, a reduction in seizure frequency of >= 50% was reported in statistically significantly more patients treated with eslicarbazepine compared with placebo. Eslicarbazepine is also under investigation as a possible treatment for bipolar disorder. Eslicarbazepine was FDA-approved in November 2013.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 3
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown. Eye/face and respiratory protection may be needed during preparation and administration.
Route-Specific Administration
Oral Administration
-May be taken with or without food.
-May be administered as a whole tablet or crushed.
In clinical trials of patients with partial-onset epilepsy, the rate of discontinuation was 14% for eslicarbazepine 800 mg/day, 25% for eslicarbazepine 1200 mg/day and 7% for placebo. Adverse reactions during titration occurred less frequently in patients who began therapy at an initial dose of 400 mg for 1 week and then increased to 800 mg compared to patients who initiated therapy at 800 mg.
Dose-dependent decreases in serum T3 and T4 (free and total) values have been observed in patients taking eslicarbazepine. However, these changes were not associated with other abnormal thyroid function tests suggesting hypothyroidism. Clinically evaluate abnormal thyroid function tests.
During clinical trials of eslicarbazepine as adjunctive therapy in adult epileptic patients, depression was reported in 1% of patients receiving eslicarbazepine 800 mg, 3% of patients receiving eslicarbazepine 1200 mg and in 2% of patients receiving placebo. Insomnia was reported at an incidence of 2% with both doses of eslicarbazepine compared with 1% with placebo. As with all anticonvulsants, use of eslicarbazepine is thought to carry an increased risk of new or worsened depression, suicidal ideation and behavior. An analysis by the FDA of previously gathered drug data showed that patients receiving anticonvulsants had approximately twice the risk of suicidal behavior or ideation (0.43%) as patients receiving placebo (0.24%). The relative risk for suicidality was higher in patients 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 should not preclude the possibility of an association to the drug since most studies included in the analysis did not continue beyond 24 weeks. All patients beginning treatment with anticonvulsants, including eslicarbazepine, or currently receiving such treatment should be closely monitored for emerging or worsening suicidal thoughts/behavior or depression. 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.
Stevens-Johnson Syndrome (SJS) has been reported with use of eslicarbazepine. In addition, serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and SJS, have been reported in patients using oxcarbazepine or carbamazepine which are chemically related to eslicarbazepine. The reporting rate of these reactions associated with oxcarbazepine use exceeds the background incidence rate estimates by a factor of 3-10-fold. Risk factors for development of serious dermatologic reactions with eslicarbazepine use are not known. Discontinue eslicarbazepine in patients who develop a dermatologic reaction, unless the reaction is clearly not drug-related. Do not use eslicarbazepine in patients who have had a prior dermatologic reaction with either oxcarbazepine or eslicarbazepine. In clinical trials of eslicarbazepine as adjunctive therapy in adult epileptic patients, rash (unspecified) was reported in 1% of patients treated with eslicarbazepine 800 mg, 3% of patients treated with 1200 mg and in 1% of patients on placebo.
Anaphylactoid reactions, including anaphylaxis and angioedema, have been reported rarely in patients taking eslicarbazepine. Anaphylaxis and angioedema involving laryngeal edema can be fatal. Other hypersensitivity reactions, which may present as multi-organ hypersensitivity reactions, also known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), may manifest in a variety of ways, and may include fever, hepatitis, nephritis, lymphadenopathy, rash, eosinophilia, other hematological abnormalities, myocarditis, or myositis. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. Evaluate patients who present with these signs immediately. Discontinue eslicarbazepine and do not resume therapy if an alternative etiology for the signs or symptoms of an anaphylactic-type reaction or DRESS cannot be established. Do not use eslicarbazepine in patients with prior anaphylactic-type reaction or DRESS with either oxcarbazepine or eslicarbazepine.
Gastrointestinal-related adverse events reported during clinical trials of eslicarbazepine in adult epileptic patients treated with eslicarbazepine 800 or 1200 mg compared with placebo include: nausea (10-16% vs. 5%), vomiting (6-10% vs. 3%), diarrhea (2-4% vs. 3%), constipation (2% vs. 1%), abdominal pain (2% vs. 1%), and gastritis (<= 2% vs. < 1%).
Clinically significant hyponatremia (typically sodium less than 125 mmol/L) may develop during treatment with eslicarbazepine. In clinical trials, hyponatremia occurred at an incidence of 2% in patients treated with eslicarbazepine 800 mg or 1,200 mg compared with less than 1% of placebo patients. At least 1 serum sodium of less than 125 mmol/L was reported in 1% of patients treated with eslicarbazepine 800 mg and 1.5% of those treated with 1,200 mg compared with none of the patients receiving placebo. In addition, a greater percentage of eslicarbazepine-treated patients experienced a decrease in serum sodium of more than 10 mmol/L compared to placebo (5.1% vs. 0.7%). The effects were dose-related and generally appeared within the first 8 weeks of therapy and sometimes as early as within 3 days. In some cases, serious, life-threatening complications were reported with eslicarbazepine-associated hyponatremia (as low as 112 mmol/L) including seizures, severe nausea/vomiting leading to dehydration, severe gait instability, and injury. Concurrent hypochloremia was also present in patients with hyponatremia. Cases of symptomatic hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been reported during postmarketing use. Dose reduction or discontinuation of therapy may be needed depending on the severity of hyponatremia. Once discontinued, serum sodium generally normalizes within a few days without additional treatment.
Dose-related increases in somnolence and fatigue-related adverse reactions were reported more frequently in patients treated with eslicarbazepine 800 mg and 1200 mg compared with placebo (16% and 28% vs. 13%). Specific adverse events reported with eslicarbazepine 800 mg and 1200 mg compared with placebo included: fatigue (4-7% vs. 4%), asthenia (2-3% vs. 2%), and drowsiness (11-18% vs. 8%). Malaise, hypersomnia, sedation, and lethargy were also reported as fatigue-related adverse reactions. Somnolence and fatigue-related adverse events were reported as serious and led to discontinuation more frequently in the eslicarbazepine group than with placebo.
Eslicarbazepine causes dose-related increases in adverse reactions related to dizziness and disturbance in gait and coordination. In clinical trials, these events were reported more frequently in patients receiving eslicarbazepine at doses of 800 mg and 1200 mg/day compared to placebo (26% and 38% vs. 12%). Specific adverse reactions reported with eslicarbazepine at doses of 800 mg and 1200 mg/day compared to placebo include dizziness (20-28% vs. 9%), ataxia (4-6% vs. 2%), vertigo (2-6% vs. < 1%), balance disorder (3% vs. < 1%), gait disturbance (2% vs. < 1%), and nystagmus (1-2% vs. < 1%). These events were reported as serious and led to discontinuation more frequently in the eslicarbazepine group than with placebo. In addition, these events occurred more frequently during dosage titration and in patients >= 60 years of age compared to younger adults. Nausea and vomiting also occurred with these events. The incidence of dizziness was greater with the concomitant use of eslicarbazepine and carbamazepine compared to the use of eslicarbazepine without carbamazepine (up to 37% vs. 19%, respectively). Consider dosage modifications of both eslicarbazepine and carbamazepine if these drugs are used concomitantly.
Dose-related increases in impaired cognition were reported more frequently in patients treated with eslicarbazepine 800 mg and 1200 mg compared with placebo (4% and 7% vs. 1%). Memory impairment was reported in 1% of patients treated with eslicarbazepine 800 mg and 2% of patients treated with eslicarbazepine 1200 mg compared with < 1% of patients on placebo. Other related adverse events leading to impaired cognition included disturbance in attention, amnesia, confusion, aphasia, speech disorder, slowness of thought, disorientation, and psychomotor impairment. These events led to discontinuation more frequently in the eslicarbazepine group than with placebo.
Dose-related changes in vision were reported more frequently in patients treated with eslicarbazepine compared with placebo (16% vs. 6%). Specific adverse events reported with eslicarbazepine 800 mg and 1200 mg/day compared with placebo include diplopia (9-11% vs. 2%), blurred vision (5-6% vs. 1%), and visual impairment (1-2% vs. 1%). These events were reported as serious and led to discontinuation more frequently in the eslicarbazepine group than with placebo. In addition, these events occurred more frequently during dosage titration and in patients >= 60 years of age compared to younger adults. The incidence of diplopia was greater with the concomitant use of eslicarbazepine and carbamazepine compared to the use of eslicarbazepine without carbamazepine (up to 16% vs. 6%, respectively).
Elevated hepatic enzymes, ranging from mild to moderate (> 3x the upper limit of normal (ULN)) with rare cases of concomitant hyperbilirubinemia (> 2x ULN) have been reported with eslicarbazepine use. Baseline measurement of LFTs are recommended. In general, the combination of transaminase elevations and elevated bilirubin without evidence of obstruction is an important predictor of severe liver injury. Discontinue eslicarbazepine in patients with jaundice or other evidence of significant liver injury (e.g., laboratory evidence).
Central nervous system-related adverse reactions reported in clinical trials in patients receiving eslicarbazepine 800 mg or 1200 mg/day compared with placebo include headache (13-15% vs. 9%), tremor (2-4% vs. 1%), and dysarthria (1-2% vs. 0%).
Cardiovascular-related disorders reported during clinical trials in patients receiving eslicarbazepine 800 mg or 1200 mg/day compared with placebo include peripheral edema (1-2% vs. 1%) and hypertension (1-2% vs. 1%). In addition, eslicarbazepine was associated with a slightly higher frequency of decreases in hemoglobin and hematocrit, hypercholesterolemia, hypertriglyceridemia, and increases in LDL and creatine phosphokinase compared with placebo.
Cough was reported at an incidence of 1-2% of eslicarbazepine-treated patients in clinical trials compared with 1% of placebo-treated patients.
Urinary tract infection (cystitis) was reported in 2% of patients receiving eslicarbazepine in clinical trials compared with 1% of patients receiving placebo.
Rare cases of pancytopenia, agranulocytosis, leukopenia, megaloblastic anemia, and thrombocytopenia have been reported during postmarketing use. Consider discontinuation of treatment if a hematologic event occurs.
In general, abrupt discontinuation of anticonvulsants may precipitate rebound seizures. Gradually withdraw eslicarbazepine because of the risk of seizures and status epilepticus. If withdrawal is needed because of a serious adverse reaction, rapid discontinuation can be considered. Physiological dependence or a withdrawal syndrome was observed in healthy volunteers who were maintained on eslicarbazepine 800 mg/day for 4 weeks before discontinuation. Visual analog scales for anxiety and nausea were increased in subjects who were maintained on eslicarbazepine vs. placebo. There was no significant difference in the maximum change from steady-state baseline in the Physician's Withdrawal Checklist (PWC-34) between the 2 groups during the 21-day discontinuation period.
Eslicarbazepine is contraindicated in patients with a history of eslicarbazepine hypersensitivity or oxcarbazepine hypersensitivity.
In general, abrupt discontinuation of anticonvulsants may precipitate rebound seizures. Gradually withdraw eslicarbazepine because of the risk of seizures and status epilepticus. If withdrawal is needed because of a serious adverse reaction, rapid discontinuation can be considered.
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.
Clinically significant hyponatremia (sodium < 125 mmol/L) may develop during treatment with eslicarbazepine. This is typically dose-related and appeared within the first 8 weeks of treatment and as early as after 3 days. Monitoring of sodium levels should be considered if eslicarbazepine is used with other medications known to decrease sodium levels or if symptoms possibly indicating hyponatremia develop (e.g., nausea, malaise, headache, lethargy, confusion, obtundation, or increase in seizure frequency or severity). Dosage adjustment or discontinuation may be needed depending on the severity of hyponatremia.
The clearance of eslicarbazepine is reduced in patients with renal impairment. Dosage adjustments are recommended in patients with moderate to severe renal impairment (i.e., CrCl < 50 mL/min).
Use caution in patients with hepatic disease. No dosage adjustments are needed in patients with mild to moderate hepatic impairment; however, eslicarbazepine has not been studied in patients with severe hepatic impairment and is therefore not recommended in this population. Baseline evaluations of liver laboratory tests are recommended.
Central nervous system effects, including somnolence and dizziness, are among the most frequently reported adverse effects of eslicarbazepine. Patients should be cautioned about engaging in tasks requiring mental alertness such as driving or operating machinery until they know how the drug will affect their cognition. Patients should also be informed about the additive central nervous system depressant effects of alcohol when used with anticonvulsants, acute ethanol intoxication should generally be avoided.
No adequate and well controlled studies have been conducted with eslicarbazepine in pregnant women. Although there are no clinical trials documenting its effect in pregnant women, results of some animal studies indicate that eslicarbazepine may be teratogenic in humans. The documented cases of human teratogenicity of a related compound, carbamazepine, support this theory. Therefore, eslicarbazepine should only be used during pregnancy if the benefits of treatment clearly outweigh the risks to the fetus. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to eslicarbazepine; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.
Eslicarbazepine is present in breast milk. The effects of eslicarbazepine are unknown. Consider the developmental and health benefits of breast-feeding along with the mothers clinical need for eslicarbazepine and any potential adverse effects on the breastfed infant. Previous American Academy of Pediatrics (AAP) recommendations consider the related drug, carbamazepine, to be usually compatible with breast-feeding; however, the AAP has not evaluated eslicarbazepine. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Use eslicarbazepine with caution in the geriatric adult due to the insufficient numbers of this population included during epilepsy trials. Dose adjustment is necessary if creatinine clearance (CrCl) is less than 50 mL/minute in any patient. According to the Beers Criteria, anticonvulsants are considered potentially inappropriate medications (PIMs) in geriatric adults with a history of falls or fractures; avoid in at-risk patients except for treating seizure and mood disorders, since anticonvulsants can produce ataxia, impaired psychomotor function, syncope, and additional falls. If eslicarbazepine must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk.
For monotherapy or adjunctive treatment of partial seizures:
NOTE: Eslicarbazepine is a prodrug for the active metabolite of oxcarbazepine and should therefore not be used as adjunctive therapy with oxcarbazepine.
Oral dosage:
Adults: Initially, 400 mg PO once daily. Treatment may be initiated at 800 mg PO once daily if the need for seizure reduction outweighs an increased risk of adverse reactions during initiation. Increase the dose in weekly increments of 400 to 600 mg based on clinical response and tolerability to the recommended maintenance dosage of 800 to 1,600 mg PO once daily. For monotherapy, consider the 800 mg PO once daily maintenance dose in patients who are unable to tolerate a 1,200 mg PO once daily dose. For adjunctive therapy, consider the 1,600 mg PO once daily maintenance dose in patients who do not achieve a satisfactory response with a 1,200 mg PO once daily dose. When discontinuing therapy, gradually withdraw eslicarbazepine because of the risk of seizures and status epilepticus.
Children and Adolescents 4 to 17 years weighing more than 38 kg: Initially, 400 mg PO once daily. Increase the dose in weekly increments of 400 mg based on clinical response and tolerability to the recommended maintenance dosage of 800 to 1,200 mg PO once daily. When discontinuing therapy, gradually withdraw eslicarbazepine because of the risk of seizures and status epilepticus.
Children and Adolescents 4 to 17 years weighing 32 to 38 kg: Initially, 300 mg PO once daily. Increase the dose in weekly increments of 300 mg based on clinical response and tolerability to the recommended maintenance dosage of 600 to 900 mg PO once daily. When discontinuing therapy, gradually withdraw eslicarbazepine because of the risk of seizures and status epilepticus.
Children and Adolescents 4 to 17 years weighing 22 to 31 kg: Initially, 300 mg PO once daily. Increase the dose in weekly increments of 300 mg based on clinical response and tolerability to the recommended maintenance dosage of 500 to 800 mg PO once daily. When discontinuing therapy, gradually withdraw eslicarbazepine because of the risk of seizures and status epilepticus.
Children and Adolescents 4 to 17 years weighing 11 to 21 kg: Initially, 200 mg PO once daily. Increase the dose in weekly increments of 200 mg based on clinical response and tolerability to the recommended maintenance dosage of 400 to 600 mg PO once daily. When discontinuing therapy, gradually withdraw eslicarbazepine because of the risk of seizures and status epilepticus.
Maximum Dosage Limits:
-Adults
1,600 mg/day PO.
-Geriatric
1,600 mg/day PO.
-Adolescents
weighing more than 38 kg: 1,200 mg/day PO.
weighing 32 to 38 kg: 900 mg/day PO.
weighing 22 to 31 kg: 800 mg/day PO.
-Children
4 to 12 years weighing more than 38 kg: 1,200 mg/day PO.
4 to 12 years weighing 32 to 38 kg: 900 mg/day PO.
4 to 12 years weighing 22 to 31 kg: 800 mg/day PO.
4 to 12 years weighing 11 to 21 kg: 600 mg/day PO.
1 to 3 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustments recommended for mild to moderate hepatic impairment. The effects of severe hepatic impairment have not been evaluated, therefore use in this population is not recommended.
Patients with Renal Impairment Dosing
CrCl >= 50 mL/min: No dosage adjustment needed.
CrCl < 50 mL/min: Reduce initial, titration, and maintenance dosages by 50%. May adjust titration and maintenance dosages according to clinical response.
*non-FDA-approved indication
Abemaciclib: (Major) Avoid coadministration of eslicarbazepine with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Coadministration with other moderate CYP3A inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 29% to 53%.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with eslicarbazepine 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 eslicarbazepine is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Eslicarbazepine is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with eslicarbazepine 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 eslicarbazepine 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. Eslicarbazepine is a moderate CYP3A4 inducer.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with eslicarbazepine 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 eslicarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer.
Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with eslicarbazepine is necessary; consider increasing the dose of oxycodone as needed. If eslicarbazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and eslicarbazepine is a moderate 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.
Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Amlodipine: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as amlodipine, may result in decreased serum concentrations of the substrates. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered with eslicarbazepine. Appropriate dose adjustments may be necessary.
Amlodipine; Atorvastatin: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as amlodipine, may result in decreased serum concentrations of the substrates. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered with eslicarbazepine. Appropriate dose adjustments may be necessary. (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as atorvastatin, may result in decreased serum concentrations of the substrate. Monitor for decreased efficacy of atorvastatin if coadministered with eslicarbazepine. Adjust the dose of atorvastatin if clinically significant alterations in serum lipids are noted.
Amlodipine; Benazepril: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as amlodipine, may result in decreased serum concentrations of the substrates. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered with eslicarbazepine. Appropriate dose adjustments may be necessary.
Amlodipine; Celecoxib: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as amlodipine, may result in decreased serum concentrations of the substrates. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered with eslicarbazepine. Appropriate dose adjustments may be necessary.
Amlodipine; Olmesartan: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as amlodipine, may result in decreased serum concentrations of the substrates. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered with eslicarbazepine. Appropriate dose adjustments may be necessary.
Amlodipine; Valsartan: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as amlodipine, may result in decreased serum concentrations of the substrates. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered with eslicarbazepine. Appropriate dose adjustments may be necessary.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as amlodipine, may result in decreased serum concentrations of the substrates. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered with eslicarbazepine. Appropriate dose adjustments may be necessary.
Amobarbital: (Major) Barbiturates may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. An increased dose of eslicarbazepine may be necessary if these drugs are coadministered.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of eslicarbazepine 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. (Moderate) Eslicarbazepine may inhibit the CYP2C19-mediated and induce the CYP3A4-mediated metabolism of omeprazole; both enzymes are involved in the metabolism of proton pump inhibitors (PPIs). It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and PPIs. If eslicarbazepine and PPI must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
Amphetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
Amphetamine; Dextroamphetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
Amphetamines: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
Aprepitant, Fosaprepitant: (Major) Use caution if eslicarbazepine and aprepitant are used concurrently and monitor for a possible decrease in the efficacy of aprepitant. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Eslicarbazepine is a moderate 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. The manufacturer of aprepitant recommends avoidance of administration with strong CYP3A4 inducers, but does not provide guidance for weak-to-moderate inducers.
Aripiprazole: (Moderate) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as aripiprazole, may result in decreased serum concentrations of the substrate. Monitor for decreased efficacy of aripiprazole if coadministered with eslicarbazepine. Dosage adjustments of aripirazole may be necessary. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Artemether; Lumefantrine: (Major) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Both components of artemether; lumefantrine are substrates of the CYP3A4 isoenzyme; therefore, coadministration may lead to decreased artemether; lumefantrine concentrations. Concomitant use warrants caution due to a possible reduction in antimalarial activity.
Aspirin, ASA; Butalbital; Caffeine: (Major) Barbiturates may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. An increased dose of eslicarbazepine may be necessary if these drugs are coadministered.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with eslicarbazepine 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 eslicarbazepine 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. Eslicarbazepine is a moderate CYP3A4 inducer. (Minor) Eslicarbazepine may inhibit the CYP2C19-mediated metabolism of carisoprodol resulting in increased concentrations of carisoprodol. Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. The formation of meprobamate (active metabolite of carisoprodol) is catalyzed by CYP2C19. CYP2C19 inhibitors such as eslicarbazepine could increase carisoprodol plasma concentrations and decrease meprobamate concentrations, with potential for enhanced CNS depressant effects. The full pharmacological impact of these potential alterations of exposures in terms of either efficacy or safety of carisoprodol is unknown.
Aspirin, ASA; Omeprazole: (Moderate) Eslicarbazepine may inhibit the CYP2C19-mediated and induce the CYP3A4-mediated metabolism of omeprazole; both enzymes are involved in the metabolism of proton pump inhibitors (PPIs). It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and PPIs. If eslicarbazepine and PPI must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with eslicarbazepine is necessary; consider increasing the dose of oxycodone as needed. If eslicarbazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and eslicarbazepine is a moderate 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: (Major) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as atazanavir, may result in decreased serum concentrations of the substrate. Monitor for decreased efficacy of atazanavir if coadministered with eslicarbazepine.
Atazanavir; Cobicistat: (Major) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration may result in significant decreases in the plasma concentrations of the CYP3A4 substrates, cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Consider use of an alternative anticonvulsant. (Major) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as atazanavir, may result in decreased serum concentrations of the substrate. Monitor for decreased efficacy of atazanavir if coadministered with eslicarbazepine.
Atogepant: (Major) Avoid use of atogepant and eslicarbazepine 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 eslicarbazepine. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
Atorvastatin: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as atorvastatin, may result in decreased serum concentrations of the substrate. Monitor for decreased efficacy of atorvastatin if coadministered with eslicarbazepine. Adjust the dose of atorvastatin if clinically significant alterations in serum lipids are noted.
Avacopan: (Major) Avoid concomitant use of avacopan and eslicarbazepine due to the risk of decreased avacopan exposure which may reduce its efficacy. Avacopan is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
Avapritinib: (Major) Avoid coadministration of avapritinib with eslicarbazepine due to the risk of decreased avapritinib efficacy. Avapritinib is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer is predicted to decrease the AUC and Cmax of avapritinib by 62% and 55%, respectively.
Axitinib: (Major) Avoid coadministration of axitinib with eslicarbazepine if possible 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 eslicarbazepine is a moderate CYP3A4 inducer.
Barbiturates: (Major) Barbiturates may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. An increased dose of eslicarbazepine may be necessary if these drugs are coadministered.
Bedaquiline: (Major) Avoid concurrent use of eslicarbazepine with bedaquiline. Eslicarbazepine is a CYP3A4 inducer, which may result in decreased bedaquiline systemic exposure (AUC) and possibly reduced therapeutic effect.
Belzutifan: (Moderate) Monitor for anemia and hypoxia if concomitant use of eslicarbazepine with belzutifan is necessary due to increased plasma exposure of belzutifan which may increase the incidence and severity of adverse reactions. Reduce the dose of belzutifan as recommended if anemia or hypoxia occur. Belzutifan is a CYP2C19 substrate and eslicarbazepine is a CYP2C19 inhibitor.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with eslicarbazepine 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 eslicarbazepine may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. If eslicarbazepine is discontinued, consider a benzhydrocodone dosage reduction and monitor patients for respiratory depression and sedation at frequent intervals. Benzhydrocodone is a prodrug of hydrocodone. Eslicarbazepine is an inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of hydrocodone.
Benzphetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
Brigatinib: (Major) Avoid coadministration of brigatinib with eslicarbazepine due to decreased plasma exposure to brigatinib which may result in decreased efficacy. If concomitant use is unavoidable, after 7 days of concomitant treatment with eslicarbazepine, increase the dose of brigatinib as tolerated in 30 mg increments to a maximum of twice the original brigatinib dose. After discontinuation of eslicarbazepine, resume the brigatinib dose that was tolerated prior to initiation of eslicarbazepine. Brigatinib is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease the AUC of brigatinib by approximately 50%.
Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and eslicarbazepine 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; eslicarbazepine is a moderate inducer of CYP3A4.
Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and eslicarbazepine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; eslicarbazepine induces CYP3A4.
Buprenorphine: (Moderate) Close monitoring of the patient is recommended if a CYP3A4 inducer, such as eslicarbazepine, is used with a CYP3A4 substrate, such as buprenorphine. Moderate to strong CYP3A4 inducers may increase the hepatic metabolism of buprenorphine, which may lead to opiate withdrawal or inadequate pain control. This interaction is most significant if the enzyme-inducing agent is added after buprenorphine therapy has begun. Buprenorphine doses may need to be increased if a CYP3A4 inducer is added. Conversely, buprenorphine doses may need to be decreased if the CYP3A4 inducer discontinued. The effect of CYP3A4 inducers on buprenorphine implants has not been studied.
Buprenorphine; Naloxone: (Moderate) Close monitoring of the patient is recommended if a CYP3A4 inducer, such as eslicarbazepine, is used with a CYP3A4 substrate, such as buprenorphine. Moderate to strong CYP3A4 inducers may increase the hepatic metabolism of buprenorphine, which may lead to opiate withdrawal or inadequate pain control. This interaction is most significant if the enzyme-inducing agent is added after buprenorphine therapy has begun. Buprenorphine doses may need to be increased if a CYP3A4 inducer is added. Conversely, buprenorphine doses may need to be decreased if the CYP3A4 inducer discontinued. The effect of CYP3A4 inducers on buprenorphine implants has not been studied.
Butalbital; Acetaminophen: (Major) Barbiturates may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. An increased dose of eslicarbazepine may be necessary if these drugs are coadministered.
Butalbital; Acetaminophen; Caffeine: (Major) Barbiturates may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. An increased dose of eslicarbazepine may be necessary if these drugs are coadministered.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Barbiturates may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. An increased dose of eslicarbazepine may be necessary if these drugs are coadministered. (Moderate) Concomitant use of codeine with eslicarbazepine 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 eslicarbazepine 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. Eslicarbazepine is a moderate CYP3A4 inducer.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Barbiturates may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. An increased dose of eslicarbazepine may be necessary if these drugs are coadministered. (Moderate) Concomitant use of codeine with eslicarbazepine 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 eslicarbazepine 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. Eslicarbazepine is a moderate CYP3A4 inducer.
Cabotegravir; Rilpivirine: (Contraindicated) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. CYP3A4 is primarily responsible for the metabolism of rilpivirine. The related anticonvulsants, carbamazepine and oxcarbazepine are contraindicated in combination with rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine. Although not specifically mentioned by the manufacturer of rilpivirine, it may be prudent to avoid coadministration of eslicarbazepine and rilpivirine given the potential for an interaction based on the pharmacokinetic parameters of the drugs.
Capivasertib: (Major) Avoid coadministration of capivasertib with eslicarbazepine due to decreased capivasertib exposure and risk of decreased efficacy. Capivasertib is a CYP3A substrate; eslicarbazepine is a moderate CYP3A inducer. Coadministration of another moderate CYP3A inducer is predicted to decrease the capivasertib overall exposure by 60%.
Capmatinib: (Major) Avoid coadministration of capmatinib and eslicarbazepine due to the risk of decreased capmatinib exposure, which may reduce its efficacy. Capmatinib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased capmatinib exposure by 44%.
Carbamazepine: (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.
Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Concurrent use of cariprazine with CYP3A4 inducers, such as eslicarbazepine, has not been evaluated and is not recommended because the net effect on active drug and metabolites is unclear.
Carisoprodol: (Minor) Eslicarbazepine may inhibit the CYP2C19-mediated metabolism of carisoprodol resulting in increased concentrations of carisoprodol. Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. The formation of meprobamate (active metabolite of carisoprodol) is catalyzed by CYP2C19. CYP2C19 inhibitors such as eslicarbazepine could increase carisoprodol plasma concentrations and decrease meprobamate concentrations, with potential for enhanced CNS depressant effects. The full pharmacological impact of these potential alterations of exposures in terms of either efficacy or safety of carisoprodol is unknown.
Chlordiazepoxide; Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with eslicarbazepine 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 eslicarbazepine 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. Eslicarbazepine is a moderate CYP3A4 inducer.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with eslicarbazepine 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 eslicarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer.
Citalopram: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with eslicarbazepine, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.
Clarithromycin: (Major) Coadministration of eslicarbazepine 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.
Clobazam: (Moderate) Eslicarbazepine may inhibit the CYP2C19-mediated metabolism of clobazam resulting in increased concentrations of clobazam. Metabolism of the active metabolite of clobazam occurs primarily through CYP2C19. Extrapolation of pharmacogenomic data indicates that concurrent administration of clobazam with moderate or potent inhibitors of CYP2C19 may result in up to a 5-fold increase in exposure to N-desmethylclobazam. Adverse effects, such as sedation, lethargy, ataxia, or insomnia may be potentiated. A dosage reduction of clobazam may be necessary during co-administration of eslicarbazepine.
Clomipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Clopidogrel: (Moderate) Monitor for reduced clopidogrel efficacy during concomitant use of eslicarbazepine. Clopidogrel is primarily metabolized to its active metabolite by CYP2C19; eslicarbazepine is a CYP2C19 inhibitor.
Clozapine: (Moderate) Eslicarbazepine is an inducer of CYP3A4, one of the isoenzymes reponsible for the metabolism of clozapine. According to the manufacturer of clozapine, patients receiving clozapine in combination with a weak to moderate CYP3A4 inducer should be monitored for loss of effectiveness. Consideration should be given to increasing the clozapine dose if necessary. If the inducer is discontinued, monitor for adverse reactions, and consider reducing the clozapine dose if necessary. In addition, clozapine can lower the seizure threshold, potentially reducing the effectiveness of eslicarbazepine in treating seizures. Monitor for increased seizure activity during concurrent use.
Cobicistat: (Major) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration may result in significant decreases in the plasma concentrations of the CYP3A4 substrates, cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Consider use of an alternative anticonvulsant.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with eslicarbazepine due to decreased cobimetinib efficacy. Cobimetinib is a CYP3A substrate in vitro, and eslicarbazepine is a moderate inducer of CYP3A. Based on simulations, cobimetinib exposure would decrease by 73% when coadministered with a moderate CYP3A inducer.
Codeine: (Moderate) Concomitant use of codeine with eslicarbazepine 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 eslicarbazepine 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. Eslicarbazepine is a moderate CYP3A4 inducer.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with eslicarbazepine 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 eslicarbazepine 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. Eslicarbazepine is a moderate CYP3A4 inducer.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with eslicarbazepine 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 eslicarbazepine 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. Eslicarbazepine is a moderate CYP3A4 inducer.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with eslicarbazepine 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 eslicarbazepine 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. Eslicarbazepine is a moderate CYP3A4 inducer.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with eslicarbazepine 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 eslicarbazepine 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. Eslicarbazepine is a moderate CYP3A4 inducer.
Cyclosporine: (Moderate) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as cyclosporine, may result in decreased serum concentrations of the substrate. Cyclosporine concentrations should be monitored closely to avoid loss of clinical efficacy until a new steady-state cyclosporine concentration is achieved when eslicarbazepine is added to an existing cyclosporine regimen; conversely, if eslicarbazepine is discontinued, cyclosporine concentrations could increase.
Daclatasvir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as eslicarbazepine. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Dapsone: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with eslicarbazepine is necessary. Dapsone is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Daridorexant: (Major) Avoid concomitant use of daridorexant and eslicarbazepine. Coadministration may decrease daridorexant exposure which may reduce its efficacy. Daridorexant is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Concomitant use of another moderate CYP3A inducer decreased daridorexant overall exposure by over 50%.
Darunavir: (Major) Plasma concentrations of darunavir may be reduced if administered concurrently with eslicarbazepine, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Consider use of an alternative anticonvulsant. In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Darunavir is a substrate of CYP3A4.
Darunavir; Cobicistat: (Major) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration may result in significant decreases in the plasma concentrations of the CYP3A4 substrates, cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Consider use of an alternative anticonvulsant. (Major) Plasma concentrations of darunavir may be reduced if administered concurrently with eslicarbazepine, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Consider use of an alternative anticonvulsant. In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Darunavir is a substrate of CYP3A4.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration may result in significant decreases in the plasma concentrations of the CYP3A4 substrates, cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Consider use of an alternative anticonvulsant. (Major) Plasma concentrations of darunavir may be reduced if administered concurrently with eslicarbazepine, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Consider use of an alternative anticonvulsant. In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Darunavir is a substrate of CYP3A4.
Deflazacort: (Major) Avoid concomitant use of deflazacort and eslicarbazepine. Concurrent use may significantly decrease concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A4 substrate; eslicarbazepine is a moderate 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.
Desipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Desogestrel; Ethinyl Estradiol: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Dextroamphetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
Dienogest; Estradiol valerate: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Dolutegravir; Rilpivirine: (Contraindicated) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. CYP3A4 is primarily responsible for the metabolism of rilpivirine. The related anticonvulsants, carbamazepine and oxcarbazepine are contraindicated in combination with rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine. Although not specifically mentioned by the manufacturer of rilpivirine, it may be prudent to avoid coadministration of eslicarbazepine and rilpivirine given the potential for an interaction based on the pharmacokinetic parameters of the drugs.
Donepezil: (Moderate) The elimination of donepezil may be increased by concurrent administration of moderate to strong inducers of CYP3A4, such as carbamazepine, eslicarbazepine, or oxcarbazepine. The clinical effect of this interaction on the efficacy of donepezil has not been determined. Observe patients for evidence of reduced donepezil efficacy if these agents are prescribed concurrently.
Donepezil; Memantine: (Moderate) The elimination of donepezil may be increased by concurrent administration of moderate to strong inducers of CYP3A4, such as carbamazepine, eslicarbazepine, or oxcarbazepine. The clinical effect of this interaction on the efficacy of donepezil has not been determined. Observe patients for evidence of reduced donepezil efficacy if these agents are prescribed concurrently.
Doravirine: (Moderate) Concurrent administration of doravirine and eslicarbazepine may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Concurrent administration of doravirine and eslicarbazepine may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer.
Doxepin: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Doxorubicin Liposomal: (Major) Avoid coadministration of doxorubicin with eslicarbazepine due to decreased doxorubicin plasma concentrations. Doxorubicin is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Inducers of CYP3A may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy.
Doxorubicin: (Major) Avoid coadministration of doxorubicin with eslicarbazepine due to decreased doxorubicin plasma concentrations. Doxorubicin is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Inducers of CYP3A may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with eslicarbazepine is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; eslicarbazepine is a moderate inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Dronedarone: (Major) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as dronedarone, may result in decreased serum concentrations of the substrate. The concomitant use of dronedarone and CYP3A4 inducers should be avoided.
Drospirenone: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Drospirenone; Estetrol: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Drospirenone; Estradiol: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Drospirenone; Ethinyl Estradiol: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Duvelisib: (Major) Avoid concomitant use of duvelisib with eslicarbazepine. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When eslicarbazepine has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with eslicarbazepine. Duvelisib is a CYP3A substrate; eslicarbazepine is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Elacestrant: (Major) Avoid concurrent use of elacestrant and eslicarbazepine due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Elagolix; Estradiol; Norethindrone acetate: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Elbasvir; Grazoprevir: (Major) If possible, avoid concurrent administration of elbasvir with eslicarbazepine. Eslicarbazepine is a moderate CYP3A inducer, while elbasvir is a substrate of CYP3A. Use of these drugs together is expected to decrease the plasma concentrations of elbasvir, and may result in decreased virologic response. (Major) If possible, avoid concurrent administration of grazoprevir with eslicarbazepine. Eslicarbazepine is a moderate CYP3A inducer, while grazoprevir is a substrate of CYP3A. Use of these drugs together is expected to decrease the plasma concentrations of grazoprevir, and may result in decreased virologic response.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration may result in significant decreases in the plasma concentrations of the CYP3A4 substrates, cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Consider use of an alternative anticonvulsant. (Major) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of elvitegravir, may result in significant decreases in the plasma concentrations of the CYP3A4 substrate, elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Consider use of an alternative anticonvulsant.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration may result in significant decreases in the plasma concentrations of the CYP3A4 substrates, cobicistat, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Consider use of an alternative anticonvulsant. (Major) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of elvitegravir, may result in significant decreases in the plasma concentrations of the CYP3A4 substrate, elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Consider use of an alternative anticonvulsant.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Contraindicated) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. CYP3A4 is primarily responsible for the metabolism of rilpivirine. The related anticonvulsants, carbamazepine and oxcarbazepine are contraindicated in combination with rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine. Although not specifically mentioned by the manufacturer of rilpivirine, it may be prudent to avoid coadministration of eslicarbazepine and rilpivirine given the potential for an interaction based on the pharmacokinetic parameters of the drugs.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Contraindicated) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. CYP3A4 is primarily responsible for the metabolism of rilpivirine. The related anticonvulsants, carbamazepine and oxcarbazepine are contraindicated in combination with rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine. Although not specifically mentioned by the manufacturer of rilpivirine, it may be prudent to avoid coadministration of eslicarbazepine and rilpivirine given the potential for an interaction based on the pharmacokinetic parameters of the drugs.
Entrectinib: (Major) Avoid coadministration of entrectinib with eslicarbazepine due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Erdafitinib: (Major) If coadministration of erdafitinib and eslicarbazepine is necessary at the initiation of erdafitinib therapy, increase the dose of erdafitinib to 9 mg once daily. Erdafitinib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced erdafitinib overall exposure by 45%.
Erlotinib: (Moderate) There may be a risk of reduced erlotinib efficacy when coadministered with eslicarbazepine; however, the risk has not been clearly defined. If coadministration is necessary, consider increasing the erlotinib dose by 50 mg increments at 2-week intervals as tolerated, to a maximum of 450 mg. Erlotinib is a CYP3A4 substrate, and eslicarbazepine is a moderate CYP3A4 inducer.
Escitalopram: (Moderate) The plasma concentration of escitalopram, a CYP2C19 and CYP3A4 substrate, may be altered when administered concurrently with eslicarbazepine, a CYP2C19 inhibitor and CYP3A4 inducer. Because escitalopram is extensively metabolized by both CYP2C19 and CYP3A4, the outcome of the interaction is unpredictable. If these drugs are used together, monitor for reduced efficacy of escitalopram as well as escitalopram-associated adverse reactions.
Esomeprazole: (Moderate) Eslicarbazepine may inhibit the CYP2C19-mediated and induce the CYP3A4-mediated metabolism of esomeprazole; both enzymes are involved in the metabolism of esomeprazole. It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and PPIs. If eslicarbazepine and PPI must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
Estradiol; Levonorgestrel: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Estradiol; Norethindrone: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Estradiol; Norgestimate: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Ethinyl Estradiol; Norelgestromin: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Ethinyl Estradiol; Norgestrel: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Etonogestrel; Ethinyl Estradiol: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate if coadministration with eslicarbazepine is necessary. The dose of everolimus may need to be increased. Everolimus is a sensitive CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer. Coadministration with CYP3A4 inducers may increase the metabolism of everolimus and decrease everolimus blood concentrations.
Exemestane: (Moderate) Use caution if coadministration of exemestane with eslicarbazepine is necessary, and monitor for a possible decrease in the efficacy of exemestane. Exemestane is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer. In a pharmacokinetic interaction study (n = 10) with a strong CYP3A4 inducer, rifampicin (600 mg daily for 14 days), the mean Cmax and AUC of exemestane (single dose) decreased by 41% and 54%, respectively. The manufacturer of exemestane recommends a dose increase when concomitant use with a strong CYP3A4 inducer is necessary; recommendations are not available for moderate CYP3A4 inducers.
Ezetimibe; Simvastatin: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as simvastatin, may result in decreased serum concentrations of the substrate. Monitor for decreased efficacy of simvastatin if coadministered with eslicarbazepine. Adjust the dose of simvastatin if clinically significant alterations in serum lipds are noted.
Fedratinib: (Major) Avoid coadministration of fedratinib with eslicarbazepine as concurrent use may decrease fedratinib exposure which may result in decreased therapeutic response. Fedratinib is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer. Coadministration of fedratinib with another moderate CYP3A4 inducer decreased the overall exposure of fedratinib by 47%.
Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concurrent use of eslicarbazepine is necessary. If eslicarbazepine is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like eslicarbazepine 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.
Finerenone: (Major) Avoid concurrent use of finerenone and eslicarbazepine due to the risk for decreased finerenone exposure which may reduce its efficacy. Finerenone is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased overall exposure to finerenone by 80%.
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 CYP3A4 inducers, such as eslicarbazepine, is not recommended.
Fosamprenavir: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with eslicarbazepine. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
Fosphenytoin: (Major) Phenytoin (and fosphenytoin) may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. An increased dose of eslicarbazepine may be necessary if these drugs are coadministered. In addition, eslicarbazepine may inhibit the CYP2C19-mediated metabolism of phenytoin resulting in increased concentrations of phenytoin. Monitor phenytoin plasma concentrations if coadministered with eslicarbazepine and adjust the dose of phenytoin or fosphenytoin based on clinical response and serum concentration.
Fruquintinib: (Major) Avoid coadministration of fruquintinib with eslicarbazepine if possible due to decreased fruquintinib exposure and risk of decreased efficacy. If concomitant use of fruquintinib and eslicarbazepine is necessary, monitor for decreased efficacy. Fruquintinib is a CYP3A substrate; eslicarbazepine is a strong CYP3A inducer. Coadministration of a moderate CYP3A inducer is predicted to decrease fruquintinib exposure by 32%.
Ganaxolone: (Major) Avoid concurrent use of ganaxolone and eslicarbazepine 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 eslicarbazepine is a moderate CYP3A4 inducer.
Glasdegib: (Major) Avoid coadministration of glasdegib and eslicarbazepine due to the potential for decreased glasdegib exposure and risk of decreased efficacy. If concurrent use cannot be avoided, increase the glasdegib dosage (i.e., from 100 mg PO daily to 200 mg PO daily; or from 50 mg PO daily to 100 mg PO daily). Resume the previous dose of glasdegib after eslicarbazepine has been discontinued for 7 days. Glasdegib is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer was predicted to decrease the glasdegib AUC value by 55%.
Guanfacine: (Major) Eslicarbazepine may significantly decrease guanfacine plasma concentrations. 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 eslicarbazepine is added in a patient already receiving guanfacine, this escalation should occur over 1 to 2 weeks. If eslicarbazepine 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 eslicarbazepine is a moderate CYP3A4 inducer.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with eslicarbazepine 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 eslicarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with eslicarbazepine 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 eslicarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with eslicarbazepine 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 eslicarbazepine is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer.
Hydrocortisone: (Moderate) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Hydrocodone is metabolized by CYP3A4. Coadministration may cause increased clearance of hydrocodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to hydrocodone. Monitor the patient for reduced efficacy of hydrocodone. A higher hydrocodone dose may be needed if used with eslicarbazepine.
Hydroxychloroquine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as eslicarbazepine. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
Ibrexafungerp: (Major) Avoid concurrent administration of ibrexafungerp with eslicarbazepine. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
Ibrutinib: (Moderate) Use ibrutinib and eslicarbazepine together with caution; decreased ibrutinib levels may occur resulting in reduced ibrutinib efficacy. Monitor patients for signs of decreased ibrutinib efficacy if these agents are used together. Ibrutinib is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A inducer. Simulations suggest that coadministration with a moderate CYP3A4 inducer may decrease ibrutinib exposure by 3-fold.
Ibuprofen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with eslicarbazepine is necessary; consider increasing the dose of oxycodone as needed. If eslicarbazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and eslicarbazepine is a moderate 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.
Ifosfamide: (Moderate) Closely monitor for increased ifosfamide-related toxicities (e.g., neurotoxicity, nephrotoxicity) if coadministration with eslicarbazepine is necessary; consider adjusting the dose of ifosfamide as clinically appropriate. Ifosfamide is metabolized to its active alkylating metabolites by CYP3A4; eslicarbazepine is a moderate CYP3A4 inducer. Concomitant use may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde.
Imipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Infigratinib: (Major) Avoid concurrent use of infigratinib and eslicarbazepine. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Infigratinib is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer.
Isavuconazonium: (Major) Concomitant use of isavuconazonium with eslicarbazepine may result in decreased serum concentrations of isavuconazonium and the potential for treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of the hepatic isoenzyme CYP3A4; eslicarbazepine is an inducer of this enzyme. Caution and close monitoring for decreased antifungal efficacy are advised if these drugs are used together.
Isocarboxazid: (Contraindicated) MAOIs should not be coadministered at the same time with eslicarbazepine, a dibenzazepine-related drug. Hypertensive crises, seizures, coma, or circulatory collapse may occur in patients receiving this combination. At least 7 days should elapse between discontinuation of eslicarbazepine and initiation of an MAOI. MAOIs should be discontinued for a minimum of 14 days or longer if the clinical situation permits, before administering eslicarbazepine. When starting MAOI therapy after discontinuing eslicarbazepine, it is advised to begin the MAOI at one-half the normal starting dosage for at least the first week of therapy. Carefully monitor the patient. Watch carefully for other effects besides effects on blood pressure, such as sedation, confusion, and increased CNS depression. If eslicarbazepine is used for the treatment of epilepsy, be aware that MAOI effects can include lowering of seizure threshold in some patients.
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., eslicarbazepine), 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: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as eslicarbazepine. Concomitant use of eslicarbazepine with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Lansoprazole: (Moderate) Eslicarbazepine may inhibit the CYP2C19-mediated and induce the CYP3A4-mediated metabolism of lansoprazole; both enzymes are involved in the metabolism of proton pump inhibitors (PPIs). It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and PPIs. If eslicarbazepine and PPI must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Coadministration of eslicarbazepine 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. (Moderate) Eslicarbazepine may inhibit the CYP2C19-mediated and induce the CYP3A4-mediated metabolism of lansoprazole; both enzymes are involved in the metabolism of proton pump inhibitors (PPIs). It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and PPIs. If eslicarbazepine and PPI must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
Larotrectinib: (Major) Avoid concurrent use of larotrectinib and eslicarbazepine due to the risk of decreased larotrectinib exposure which may reduce its efficacy. If concomitant use is necessary, double the dose of larotrectinib and monitor response. If eslicarbazepine is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of eslicarbazepine. Larotrectinib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease larotrectinib exposure by 72%.
Lefamulin: (Major) Avoid coadministration of lefamulin with eslicarbazepine unless the benefits outweigh the risks as concurrent use may decrease lefamulin exposure and efficacy. Lefamulin is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer.
Lemborexant: (Major) Avoid coadministration of lemborexant and eslicarbazepine as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer.
Lenacapavir: (Major) Avoid concurrent use of lenacapavir and eslicarbazepine due to the risk of decreased lenacapavir exposure which may result in loss of therapeutic effect and development of resistance. Lenacapavir is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced lenacapavir overall exposure by 56%.
Leniolisib: (Major) Avoid concomitant use of leniolisib and eslicarbazepine. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Leuprolide; Norethindrone: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Levamlodipine: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as amlodipine, may result in decreased serum concentrations of the substrates. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered with eslicarbazepine. Appropriate dose adjustments may be necessary.
Levonorgestrel: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Levonorgestrel; Ethinyl Estradiol: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Lidocaine: (Moderate) Concomitant use of systemic lidocaine and eslicarbazepine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; eslicarbazepine induces CYP3A4.
Lidocaine; Epinephrine: (Moderate) Concomitant use of systemic lidocaine and eslicarbazepine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; eslicarbazepine induces CYP3A4.
Lidocaine; Prilocaine: (Moderate) Concomitant use of systemic lidocaine and eslicarbazepine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; eslicarbazepine induces CYP3A4.
Lisdexamfetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and eslicarbazepine is contraindicated; concurrent use may decrease lonafarnib exposure, which may reduce its efficacy. Lonafarnib is a sensitive CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer.
Lopinavir; Ritonavir: (Major) Concurrent administration of eslicarbazepine with ritonavir may result in decreased plasma concentrations of ritonavir. Eslicarbazepine is an inducer of the hepatic isoenzyme CYP3A4; ritonavir is metabolized by this enzyme. Caution and close monitoring for decreased antiviral efficacy are advised if these drugs are administered together.
Lorlatinib: (Major) Avoid concomitant use of lorlatinib and eslicarbazepine due to decreased plasma concentrations of lorlatinib, which may reduce its efficacy. If concomitant use is necessary, increase the dose of lorlatinib to 125 mg PO once daily. Lorlatinib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Administration with another moderate CYP3A inducer decreased lorlatinib exposure by 23%.
Lovastatin: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as lovastatin, may result in decreased serum concentrations of the substrate. Monitor for decreased efficacy of lovastatin if coadministered with eslicarbazepine. Adjust the dose of lovastatin if clinically significant alterations in serum lipds are noted.
Lumateperone: (Major) Avoid coadministration of lumateperone and eslicarbazepine as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer.
Lurasidone: (Moderate) Because lurasidone is primarily metabolized by CYP3A4, decreased plasma concentrations of lurasidone may occur when the drug is co-administered with inducers of CYP3A4 such as eslicarbazepine. Concurrent use of lurasidone and eslicarbazepine may lead to a decrease in efficacy of lurasidone. If lurasidone is used with a moderate CYP3A4 inducer, it may be necessary to increase the lurasidone dose after chronic treatment (7 days or more).
Maraviroc: (Moderate) Use caution if coadministration of maraviroc with eslicarbazepine is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and eslicarbazepine is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with eslicarbazepine due to risk for reduced mavacamten efficacy. There is also risk for increased adverse reactions due to mavacamten. Concomitant use may increase or decrease mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and eslicarbazepine is a weak CYP2C19 inhibitor and moderate CYP3A inducer. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall exposure by 48%.
Methamphetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
Methohexital: (Major) Barbiturates may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. An increased dose of eslicarbazepine may be necessary if these drugs are coadministered.
Mitapivat: (Major) Avoid coadministration of mitapivat with eslicarbazepine, if possible, due to decreased mitapivat efficacy. Coadministration decreases mitapivat concentrations. If concomitant use is necessary, up-titration of mitapivat may be required. Monitor hemoglobin and titrate the mitapivat dose based on response; do not exceed 100 mg PO twice daily. Mitapivat is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased mitapivat overall exposure by 55% to 60%.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and eslicarbazepine. Coadministration may decrease mobocertinib exposure resulting in decreased efficacy. Mobocertinib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Use of a moderate CYP3A inducer is predicted to decrease the overall exposure of mobocertinib and its active metabolites by 58%.
Monoamine oxidase inhibitors: (Contraindicated) MAOIs should not be coadministered at the same time with eslicarbazepine, a dibenzazepine-related drug. Hypertensive crises, seizures, coma, or circulatory collapse may occur in patients receiving this combination. At least 7 days should elapse between discontinuation of eslicarbazepine and initiation of an MAOI. MAOIs should be discontinued for a minimum of 14 days or longer if the clinical situation permits, before administering eslicarbazepine. When starting MAOI therapy after discontinuing eslicarbazepine, it is advised to begin the MAOI at one-half the normal starting dosage for at least the first week of therapy. Carefully monitor the patient. Watch carefully for other effects besides effects on blood pressure, such as sedation, confusion, and increased CNS depression. If eslicarbazepine is used for the treatment of epilepsy, be aware that MAOI effects can include lowering of seizure threshold in some patients.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with eslicarbazepine is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer.
Nanoparticle Albumin-Bound Sirolimus: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with eslicarbazepine. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
Naproxen; Esomeprazole: (Moderate) Eslicarbazepine may inhibit the CYP2C19-mediated and induce the CYP3A4-mediated metabolism of esomeprazole; both enzymes are involved in the metabolism of esomeprazole. It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and PPIs. If eslicarbazepine and PPI must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
Neratinib: (Major) Avoid concomitant use of eslicarbazepine with neratinib due to decreased efficacy of neratinib. Neratinib is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer. Simulations using physiologically based pharmacokinetic (PBPK) models suggest that another moderate CYP3A4 inducer may decrease neratinib exposure by 52%.
Nirmatrelvir; Ritonavir: (Major) Concurrent administration of eslicarbazepine with ritonavir may result in decreased plasma concentrations of ritonavir. Eslicarbazepine is an inducer of the hepatic isoenzyme CYP3A4; ritonavir is metabolized by this enzyme. Caution and close monitoring for decreased antiviral efficacy are advised if these drugs are administered together. (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of eslicarbazepine is necessary. Concomitant use of nirmatrelvir and eslicarbazepine may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
Nirogacestat: (Major) Avoid concomitant use of nirogacestat and eslicarbazepine. Concurrent use may decrease nirogacestat exposure which may reduce its efficacy. Nirogacestat is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer is predicted to reduce nirogacestat overall exposure by 67%.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with eslicarbazepine due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and eslicarbazepine is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Norethindrone: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Norethindrone; Ethinyl Estradiol: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Norgestimate; Ethinyl Estradiol: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Norgestrel: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Nortriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Olaparib: (Major) Avoid coadministration of olaparib with eslicarbazepine due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as amlodipine, may result in decreased serum concentrations of the substrates. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered with eslicarbazepine. Appropriate dose adjustments may be necessary.
Olutasidenib: (Major) Avoid concurrent use of olutasidenib and eslicarbazepine due to the risk of decreased olutasidenib exposure which may reduce its efficacy. Olutasidenib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
Omaveloxolone: (Major) Avoid concurrent use of omaveloxolone and eslicarbazepine. Concurrent use may decrease omaveloxolone exposure which may reduce its efficacy. Omaveloxolone is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
Omeprazole: (Moderate) Eslicarbazepine may inhibit the CYP2C19-mediated and induce the CYP3A4-mediated metabolism of omeprazole; both enzymes are involved in the metabolism of proton pump inhibitors (PPIs). It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and PPIs. If eslicarbazepine and PPI must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Eslicarbazepine may inhibit the CYP2C19-mediated and induce the CYP3A4-mediated metabolism of omeprazole; both enzymes are involved in the metabolism of proton pump inhibitors (PPIs). It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and PPIs. If eslicarbazepine and PPI must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
Omeprazole; Sodium Bicarbonate: (Moderate) Eslicarbazepine may inhibit the CYP2C19-mediated and induce the CYP3A4-mediated metabolism of omeprazole; both enzymes are involved in the metabolism of proton pump inhibitors (PPIs). It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and PPIs. If eslicarbazepine and PPI must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
Oral Contraceptives: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Oxcarbazepine: (Contraindicated) Eslicarbazepine is a prodrug for the active metabolite of oxcarbazepine and should therefore not be used as adjunctive therapy with oxcarbazepine.
Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with eslicarbazepine is necessary; consider increasing the dose of oxycodone as needed. If eslicarbazepine is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and eslicarbazepine is a moderate 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.
Pacritinib: (Major) Avoid concurrent use of pacritinib with eslicarbazepine due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
Palovarotene: (Major) Avoid concomitant use of palovarotene and eslicarbazepine. Concurrent use may decrease palovarotene exposure which may reduce its efficacy. Palovarotene is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and eslicarbazepine due to the risk of decreased pemigatinib exposure which may reduce its efficacy. Pemigatinib is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease pemigatinib exposure by more than 50%.
Pentobarbital: (Major) Barbiturates may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. An increased dose of eslicarbazepine may be necessary if these drugs are coadministered.
Perampanel: (Major) Start perampanel at a higher initial dose of 4 mg once daily at bedtime when using concurrently with eslicarbazepine due to a potential reduction in perampanel plasma concentration. If introduction or withdrawal of eslicarbazepine occurs during perampanel therapy, closely monitor patient response; a dosage adjustment may be necessary. Eslicarbazepine is a CYP3A4 inducer, and perampanel is a CYP3A4 substrate.
Perindopril; Amlodipine: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as amlodipine, may result in decreased serum concentrations of the substrates. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered with eslicarbazepine. Appropriate dose adjustments may be necessary.
Perphenazine; Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Phenelzine: (Contraindicated) MAOIs should not be coadministered at the same time with eslicarbazepine, a dibenzazepine-related drug. Hypertensive crises, seizures, coma, or circulatory collapse may occur in patients receiving this combination. At least 7 days should elapse between discontinuation of eslicarbazepine and initiation of an MAOI. MAOIs should be discontinued for a minimum of 14 days or longer if the clinical situation permits, before administering eslicarbazepine. When starting MAOI therapy after discontinuing eslicarbazepine, it is advised to begin the MAOI at one-half the normal starting dosage for at least the first week of therapy. Carefully monitor the patient. Watch carefully for other effects besides effects on blood pressure, such as sedation, confusion, and increased CNS depression. If eslicarbazepine is used for the treatment of epilepsy, be aware that MAOI effects can include lowering of seizure threshold in some patients.
Phenobarbital: (Major) Barbiturates may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. An increased dose of eslicarbazepine may be necessary if these drugs are coadministered.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Barbiturates may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. An increased dose of eslicarbazepine may be necessary if these drugs are coadministered.
Phenytoin: (Moderate) An increased dose of eslicarbazepine may be necessary if these drugs are coadministered. Phenytoin may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. In addition, eslicarbazepine may inhibit the CYP2C19-mediated metabolism of phenytoin resulting in increased concentrations of phenytoin. Monitor phenytoin plasma concentrations if coadministered with eslicarbazepine and adjust the dose of phenytoin based on clinical response and serum concentration.
Pimavanserin: (Major) Because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends avoiding concomitant use of pimavanserin with moderate CYP3A4 inducers, such as eslicarbazepine. Moderate inducers of CYP3A4 can reduce pimavanserin exposure, potentially decreasing the effectiveness of pimavanserin.
Pirtobrutinib: (Major) Avoid concurrent use of pirtobrutinib and eslicarbazepine due to the risk of decreased pirtobrutinib exposure which may reduce its efficacy. If concomitant use is necessary, an empiric pirtobrutinib dosage increase is required. If the current dosage is 200 mg once daily, increase the dose to 300 mg; if the current dosage is 50 mg or 100 mg once daily, increase the dose by 50 mg. Pirtobrutinib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Concomitant use with other moderate CYP3A inducers reduced pirtobrutinib overall exposure by 27% and 49%.
Pralsetinib: (Major) Avoid concurrent use of eslicarbazepine and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Praziquantel: (Major) Avoid concomitant use of praziquantel and eslicarbazepine. Concurrent use may decrease praziquantel exposure which may reduce its efficacy. If concomitant use is necessary, monitor for reduced response to praziquantel. Praziquantel is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. When praziquantel was administered after 13 days of treatment with a moderate CYP3A inducer, the mean praziquantel AUC was 77% lower than when praziquantel was given alone.
Pretomanid: (Major) Avoid coadministration of pretomanid with eslicarbazepine as concurrent use may decrease pretomanid exposure which may lead to decreased efficacy. Pretomanid is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased pretomanid exposure by 35%.
Primidone: (Major) Barbiturates may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. An increased dose of eslicarbazepine may be necessary if these drugs are coadministered.
Protriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Quetiapine: (Moderate) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4 thereby having the potential to lower the plasma levels of medications metabolized through these pathways. The effectiveness of CNS medications such as quetiapine could theoretically be decreased.
Quizartinib: (Major) Avoid concomitant use of eslicarbazepine with quizartinib due to the risk of decreased quizartinib exposure which may reduce its efficacy. Quizartinib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the quizartinib overall exposure by 90%.
Rabeprazole: (Moderate) Eslicarbazepine may inhibit the CYP2C19-mediated and induce the CYP3A4-mediated metabolism of rabeprazole; both enzymes are involved in the metabolism of proton pump inhibitors (PPIs). It is unclear that the theoretical interaction would result in a net increase or decrease in PPI action. Some manufacturers recommend avoiding the coadministration of hepatic cytochrome P-450 enzyme inducers and PPIs. If eslicarbazepine and PPI must be used together, monitor the patient closely for signs and symptoms of GI bleeding or other signs and symptoms of reduced PPI efficacy, or for signs of PPI side effects.
Ranolazine: (Contraindicated) Ranolazine is contraindicated in patients receiving drugs known to be CYP3A inducers. In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Although not specifically mentioned by the manufacturer, coadministration of ranolazine with eslicarbazepine may result in decreased ranolazine plasma concentrations and decreased efficacy.
Relugolix; Estradiol; Norethindrone acetate: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Repotrectinib: (Major) Avoid coadministration of repotrectinib with eslicarbazepine due to decreased repotrectinib exposure and risk of decreased efficacy. Repotrectinib is a CYP3A substrate; eslicarbazepine is a moderate CYP3A inducer.
Rilpivirine: (Contraindicated) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. CYP3A4 is primarily responsible for the metabolism of rilpivirine. The related anticonvulsants, carbamazepine and oxcarbazepine are contraindicated in combination with rilpivirine. Coadministration may result in decreased rilpivirine serum concentrations, which could cause impaired virologic response to rilpivirine. Although not specifically mentioned by the manufacturer of rilpivirine, it may be prudent to avoid coadministration of eslicarbazepine and rilpivirine given the potential for an interaction based on the pharmacokinetic parameters of the drugs.
Rimegepant: (Major) Avoid coadministration of rimegepant with eslicarbazepine; concurrent use may significantly decrease rimegepant exposure which may result in loss of efficacy. Rimegepant is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer.
Ripretinib: (Major) Avoid coadministration of ripretinib with eslicarbazepine. If concomitant use is unavoidable, increase the frequency of ripretinib dosing from 150 mg once daily to 150 mg twice daily; monitor for clinical response and tolerability. Resume once daily dosing of ripretinib 14 days after discontinuation of eslicarbazepine. Coadministration is predicted to 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 CYP3A and eslicarbazepine is a moderate CYP3A inducer. Drug interaction modeling studies suggest coadministration with a moderate CYP3A inducer may decrease ripretinib exposure by 56%.
Ritonavir: (Major) Concurrent administration of eslicarbazepine with ritonavir may result in decreased plasma concentrations of ritonavir. Eslicarbazepine is an inducer of the hepatic isoenzyme CYP3A4; ritonavir is metabolized by this enzyme. Caution and close monitoring for decreased antiviral efficacy are advised if these drugs are administered together.
Rivaroxaban: (Minor) Coadministration of rivaroxaban and eslicarbazepine may result in decreased rivaroxaban exposure and may decrease the efficacy of rivaroxaban. Eslicarbazepine is an inducer of CYP3A4, and rivaroxaban is a substrate of CYP3A4. If these drugs are administered concurrently, monitor the patient for signs of lack of efficacy of rivaroxaban.
Secobarbital: (Major) Barbiturates may induce the metabolism of eslicarbazepine resulting in decreased plasma concentrations of and potentially reduced efficacy of eslicarbazepine. An increased dose of eslicarbazepine may be necessary if these drugs are coadministered.
Segesterone Acetate; Ethinyl Estradiol: (Major) Coadministration of eslicarbazepine with oral contraceptives may result in contraceptive failure. Coadministration of eslicarbazepine and ethinyl estradiol and levonorgestrel has resulted in decreased plasma concentrations of these hormones. Instruct females of child-bearing potential to use additional or non-hormonal contraception during therapy with eslicarbazepine and after treatment has been discontinued for at least one menstrual cycle.
Selegiline: (Contraindicated) Eslicarbazepine is a prodrug of carbamazepine, which is contraindicated for use with selegiline because of a possible increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with eslicarbazepine. After stopping treatment with eslicarbazepine, a time period equal to 4 to 5 half-lives of the active moiety carbamazepine should elapse before starting therapy with selegiline.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and eslicarbazepine due to the risk of decreased selpercatinib exposure which may reduce its efficacy. Selpercatinib is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer. Coadministration with other moderate CYP3A4 inducers is predicted to decrease selpercatinib exposure by 40% to 70%.
Selumetinib: (Major) Avoid coadministration of selumetinib and eslicarbazepine due to the risk of decreased selumetinib exposure which may reduce its efficacy. Selumetinib is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease selumetinib exposure by 38%.
Simvastatin: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as simvastatin, may result in decreased serum concentrations of the substrate. Monitor for decreased efficacy of simvastatin if coadministered with eslicarbazepine. Adjust the dose of simvastatin if clinically significant alterations in serum lipds are noted.
Siponimod: (Moderate) Concomitant use of siponimod and eslicarbazepine is not recommended for patients with CYP2C9*1/*3 and *2/*3 genotypes due to a significant decrease in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer. Across different CYP2C9 genotypes, a moderate CYP3A4 inducer decreased the exposure of siponimod by up to 52% according to in silico evaluation.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of eslicarbazepine. Concomitant use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of velpatasvir with eslicarbazepine. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; eslicarbazepine is an inducer of CYP3A4.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of velpatasvir with eslicarbazepine. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; eslicarbazepine is an inducer of CYP3A4. (Major) Avoid coadministration of voxilaprevir (a CYP3A4 substrate) with moderate to strong inducers of CYP3A4, such as eslicarbazepine. Taking these drugs together may significantly decrease voxilaprevir plasma concentrations, potentially resulting in loss of antiviral efficacy.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and eslicarbazepine; sonidegib levels may be significantly decreased and its efficacy reduced. Sonidegib is a CYP3A4 substrate and eslicarbazepine is a CYP3A4 inducer in vitro. Physiologic-based pharmacokinetics (PBPK) simulations indicate that a moderate CYP3A4 inducer would decrease the sonidegib AUC by 56% if administered for 14 days and by 69% if the moderate CYP3A inducer is administered for more than 14 days.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if eslicarbazepine must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with eslicarbazepine is necessary; consider increasing the dose of sufentanil injection as needed. If eslicarbazepine 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 eslicarbazepine is a moderate 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.
Tacrolimus: (Moderate) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Tacrolimus is a CYP3A4 substrate. Eslicarbazepine may potentially accelerate the hepatic metabolism of tacrolimus. Clinicians should be alert to decreased effectiveness of tacrolimus; dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Tasimelteon: (Moderate) Caution is recommended during concurrent use of tasimelteon and eslicarbazepine. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inducers, such as eslicarbazepine, may reduce the efficacy of tasimelteon.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with eslicarbazepine as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer.
Telmisartan; Amlodipine: (Minor) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as amlodipine, may result in decreased serum concentrations of the substrates. Monitor for potential reduced cholesterol-lowering and hypotensive efficacy when these drugs are coadministered with eslicarbazepine. Appropriate dose adjustments may be necessary.
Terbinafine: (Moderate) Caution is advised when administering terbinafine with eslicarbazepine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; eslicarbazepine is an inducer of CYP3A4 and an inhibitor of CYP2C19. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
Tranylcypromine: (Contraindicated) MAOIs should not be coadministered at the same time with eslicarbazepine, a dibenzazepine-related drug. Hypertensive crises, seizures, coma, or circulatory collapse may occur in patients receiving this combination. At least 7 days should elapse between discontinuation of eslicarbazepine and initiation of an MAOI. MAOIs should be discontinued for a minimum of 14 days or longer if the clinical situation permits, before administering eslicarbazepine. When starting MAOI therapy after discontinuing eslicarbazepine, it is advised to begin the MAOI at one-half the normal starting dosage for at least the first week of therapy. Carefully monitor the patient. Watch carefully for other effects besides effects on blood pressure, such as sedation, confusion, and increased CNS depression. If eslicarbazepine is used for the treatment of epilepsy, be aware that MAOI effects can include lowering of seizure threshold in some patients.
Tricyclic antidepressants: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Trimipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Ubrogepant: (Major) Increase the initial and second dose of ubrogepant to 100 mg if coadministered with eslicarbazepine as concurrent use may decrease ubrogepant exposure and reduce its efficacy. Ubrogepant is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer.
Ulipristal: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and eslicarbazepine is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
Venetoclax: (Major) Avoid the concomitant use of venetoclax and eslicarbazepine; venetoclax levels may be decreased and its efficacy reduced. Venetoclax is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer. Consider alternative agents. In a drug interaction study (n = 11), 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. Use of venetoclax with a moderate CYP3A4 inducer has not been evaluated.
Vincristine Liposomal: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including eslicarbazepines. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Vincristine: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including eslicarbazepines. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Voclosporin: (Major) Avoid coadministration of voclosporin with eslicarbazepine. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Vonoprazan: (Major) Avoid concomitant use of vonoprazan and eslicarbazepine due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer.
Vonoprazan; Amoxicillin: (Major) Avoid concomitant use of vonoprazan and eslicarbazepine due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of vonoprazan and eslicarbazepine due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer. (Major) Coadministration of eslicarbazepine 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.
Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and eslicarbazepine. Decreased serum concentrations of vorapaxar and thus decreased efficacy are possible when vorapaxar, a CYP3A4 substrate, is coadministered with eslicarbazepine, a CYP3A inducer.
Voxelotor: (Major) Avoid coadministration of voxelotor and eslicarbazepine as concurrent use may decrease voxelotor exposure and lead to reduced efficacy. If coadministration is unavoidable, increase voxelotor dosage to 2,000 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. Voxelotor is a substrate of CYP3A; eslicarbazepine is a moderate CYP3A inducer. Coadministration of voxelotor with a moderate CYP3A inducer is predicted to decrease voxelotor exposure by up to 24%.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with eslicarbazepine is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Eslicarbazepine is a moderate CYP3A4 inducer and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zanubrutinib: (Major) Avoid concurrent use of zanubrutinib and eslicarbazepine due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if eslicarbazepine is discontinued. Zanubrutinib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Ziprasidone: (Moderate) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Ziprasidone is partially metabolized via the hepatic CYP3A4 isoenzyme. A decrease in ziprasidone plasma levels could potentially occur if the drug is used concurrently with eslicarbazepine.
Zolpidem: (Moderate) It is advisable to closely monitor for reductions in zolpidem efficacy during co-administration of moderate CYP3A4 inducers, such as eslicarbazepine. 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.
Eslicarbazepine acetate is a voltage-gated sodium channel (VGSC) blocker. Like most anticonvulsants, the exact mechanism of action of eslicarbazepine acetate as an antiepileptic drug is unknown. In vitro studies indicate that eslicarbazepine and its metabolites competitively interact with site 2 of the inactivated state of VGSC, inhibiting sustained repetitive neuronal firing. Eslicarbazepine has a much higher affinity for the inactivated state of VGSC than the resting state, suggesting an enhanced inhibitory selectivity for rapidly firing neurons over those displaying normal activity. Eslicarbazepine does not appear to interact with benzodiazepine, GABA, and glutamate receptors.
Eslicarbazepine acetate is administered orally. Plasma protein binding is relatively low (less than 40%) and independent of concentration. Eslicarbazepine acetate is rapidly metabolized to the primary active metabolite eslicarbazepine via hydrolytic first-pass metabolism. The metabolites are primarily renally excreted unchanged and as glucuronide conjugates. In healthy subjects with normal renal function, the renal clearance of eslicarbazepine is substantially lower than glomerular filtration rate (approximately 20 mL/minute vs. 80 to 120 mL/minute, respectively), suggesting that renal tubular reabsorption occurs. The apparent plasma half-life in epileptic patients was 13 to 20 hours.
Affected cytochrome P450 isoenzymes: CYP2C19, CYP3A4
In in vitro studies, eslicarbazepine acetate was found to be a moderate inhibitor of CYP2C19 and an inducer of CYP3A4. No clinically relevant inhibitory effects were noted on CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, and CYP3A4. In studies with eslicarbazepine in fresh human hepatocytes, there was no induction of enzymes involved in glucuronidation and sulfation of 7-hydroxy-coumarin. A mild activation of UGT1A1-mediated glucuronidation was observed in human hepatic microsomes. Eslicarbazepine does not appear to undergo autoinduction.
-Route-Specific Pharmacokinetics
Oral Route
After oral administration, peak plasma concentrations are reached within 1 to 4 hours while steady state levels are attained within 4 to 5 days of once daily dosing. Food has no effect on the pharmacokinetics of eslicarbazepine.
-Special Populations
Hepatic Impairment
The pharmacokinetics of eslicarbazepine are not affected by mild to moderate hepatic impairment but have not been studied in severe hepatic dysfunction. According to the manufacturer, eslicarbazepine should not be used in patients with severe hepatic dysfunction.
Renal Impairment
The clearance of eslicarbazepine is decreased in patients with renal impairment. After a single 800 mg dose, the extent of systemic absorption of eslicarbazepine was increased by 62% in patients with mild renal impairment (CrCl 50 to 80 mL/minute), by 2-fold in patients with moderate renal impairment (CrCl 30 to 49 mL/minute) and by 2.5-fold in patients with severe renal impairment (CrCl less than 30 mL/minute) compared to healthy subjects. Dosage adjustments are recommended in patients with CrCl less than 50 mL/minute. Repeated hemodialysis removed eslicarbazepine acetate metabolites from systemic circulation in patients with end stage renal disease.
Pediatrics
The pharmacokinetics of eslicarbazepine in children and adolescents are linear and dose-proportional in the dose range of 5 to 30 mg/kg/day. Peak plasma concentrations occur at 1 to 3 hours post-dose. Similar to adults, eslicarbazepine acetate is rapidly metabolized to eslicarbazepine in all pediatric age groups. Body weight significantly correlates with the clearance of eslicarbazepine in pediatric patients; clearance increases with an increase in body weight. During a population pharmacokinetic analysis in pediatric patients (ages 4 to 17), the eslicarbazepine half-life was 10 to 16 hours and steady state plasma concentrations were obtained after 4 to 5 days of once daily dosing. The pharmacokinetics of eslicarbazepine in pediatric patients are similar when used as monotherapy or as adjunctive therapy for the treatment of partial-onset seizures.