Felbamate is an oral anticonvulsant agent. It is approved for the treatment of partial seizures in adults and Lennox-Gastaut syndrome in children and adults. It is chemically similar to meprobamate, an anxiolytic agent, but felbamate does not possess muscle-relaxant activity. Felbamate is effective as both add-on and monotherapy, has a broad spectrum of activity, and, at present, shows no teratogenicity in animal screening. Felbamate was approved by the FDA in July 1993. In 1994, the occurrence of aplastic anemia and later, acute hepatic failure, limited the use of felbamate to treatment of seizures refractory to other agents.
General Administration Information
NOTE: Felbamate should only be initiated or continued in the management of seizures when, in the physician's opinion, the patient's seizure disorder is refractory to alternative safer anticonvulsant therapy and is so severe that the benefit from therapy outweighs the risk of acute hepatic failure and aplastic anemia.
For storage information, see specific product information within the How Supplied section.
A MedGuide will be available that discusses the risk of suicidal thoughts and behaviors associated with the use of anticonvulsant medications.
Route-Specific Administration
Oral Administration
-Felbamate is administered orally.
Oral Solid Formulations:
-Tablets may be administered without regard to meals.
Oral Liquid Formulations:
-Shake the oral suspension well before using.
-The effect of food on GI absorption from the oral suspension has not been evaluated.
During monotherapy clinical trials in adults, anxiety was reported in 5.2% of patients receiving felbamate versus 2% of patients receiving valproate. During clinical trials assessing felbamate as adjunct therapy, the following psychiatric effects occurred in the felbamate group versus the placebo group, respectively: nervousness (7% vs 2.3%), anxiety (5.3% vs 4.7%), and depression (5.3% vs 0%). In children receiving felbamate as add-on therapy for Lennox-Gastaut Syndrome, the following psychiatric effects were reported in the felbamate group versus the placebo group, respectively: nervousness (16.1% vs 18.5%), abnormal thinking (6.5% vs 3.7%), and emotional lability (6.5% vs 0%). Psychiatric effects reported in at least 1% of patients receiving felbamate during other evaluations included agitation, psychological disturbance, and aggression. Hallucinations, euphoria, and suicide attempt were reported in 0.1-1% of patients. Anticonvulsants are thought to carry an increased risk of 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 (0.22%). 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. Depression has been reported during felbamate use in both adults and children. All patients beginning treatment with anticonvulsants or currently receiving such treatment should be closely monitored for emerging or worsening suicidal thoughts/behavior or depression. During post-market use, delusions, mania, paranoia, confusion, and psychosis have been reported; however, causality to the drug has not been established.
During monotherapy clinical trials in adults, the following adverse gastrointestinal (GI) effects were reported in patients receiving felbamate versus valproate, respectively: dyspepsia (8.6% vs 2%), vomiting (8.6% vs 2%), constipation (6.9% vs 2%), diarrhea (5.2% vs 0%), and weight loss (3.4% vs 0%). During clinical trials assessing felbamate as adjunct therapy, the following GI effects occurred in the felbamate group versus the placebo group, respectively: nausea (34.2% vs 2.3%), anorexia (19.3% vs 2.3%), vomiting (16.7% vs 4.7%), dyspepsia (12.3% vs 7%), constipation (11.4% vs 2.3%), diarrhea (5.3% vs 2.3%), abdominal pain (5.3% vs 0%), and xerostomia (2.6% vs 0%). In children receiving felbamate as add-on therapy for Lennox-Gastaut Syndrome, the following GI effects were reported in the felbamate group versus the placebo group, respectively: anorexia (54.8% vs 14.8%), vomiting (38.7% vs 14.8%), constipation (12.9% vs 0%), hiccups (9.7% vs 3.7%), nausea (6.5% vs 0%), dyspepsia (6.5% vs 3.7%), and weight loss (6.5% vs 0%). GI effects observed in 0.1-1% of patients during treatment with felbamate include esophagitis, appetite stimulation, and weight gain. Elevated GGT was a rare event (< 0.1%). During post-market use, GI bleeding, hyperammonemia, pancreatitis, hematemesis, gastritis, rectal hemorrhage, flatulence, gingival bleeding, acquired megacolon, ileus, GI obstruction, enteritis, ulcerative stomatitis, glossitis, dysphagia, peptic ulcer, gastric dilatation, and gastroesophageal reflux have been observed; however, a causal relationship to the drug has not been established.
Elevated hepatic enzymes occurred more frequently in patients receiving felbamate than placebo during monotherapy clinical trials in adults (5.2% vs. 2%) and adjunct therapy clinical trials in adults (3.5% vs. 0%). Increased SGOT was reported in at least 1% of patients receiving felbamate in other clinical trial evaluations. During postmarketing use, hepatitis, hepatic failure, and jaundice have been reported. Postmarketing experience suggests that the reported rate of hepatotoxicity is about 6 cases of hepatic failure leading to transplant or death per 75,000 patient years of use. However, due to factors such as underreporting, the actual rate may be considerably higher. About 67% of reported cases have resulted in liver transplantation or death. The earliest documented onset of severe hepatic dysfunction with subsequent liver failure has been 3 weeks. It is not known if the risk of developing hepatic failure is related to duration of exposure, dosage, or concomitant drug use. Patients receiving felbamate should be monitored for signs of hepatotoxicity, including periodic assessment of serum transaminase concentrations at baseline and at regular intervals according to clinical judgement. Felbamate should be discontinued if either serum AST or ALT concentrations become increased 2 or more times the upper limit of normal (ULN) or if clinical signs and symptoms suggest liver failure.
During clinical trials assessing felbamate as add-on therapy for Lennox-Gastaut Syndrome in children, the following adverse hematologic effects were reported (in the felbamate group vs. the placebo group, respectively): purpura (12.9% vs. 7.4%) and leukopenia (6.5% vs. 0%). During other clinical trial evaluation, lymphadenopathy, leukopenia, leukocytosis, thrombocytopenia, and granulocytopenia were observed infrequently (0.1% to 1%). Rare events (less than 0.1%) included a positive antinuclear factor test, qualitative platelet disorder, and agranulocytosis. During postmarketing use, increased and decreased prothrombin time, aplastic anemia, hypochromic anemia, pancytopenia, hemolytic-uremic syndrome, increased mean corpuscular volume with and without anemia, coagulation disorder, limb embolism, disseminated intravascular coagulation (DIC), eosinophilia, hemolytic anemia, and leukemia (i.e., myelogenous leukemia, lymphoma including T-cell and B-cell lymphoproliferative disorders) have been observed; however, a causal relationship to the drug has not been established. Although the actual incidence of aplastic anemia is unknown, it is estimated to occur at an incidence that may be more than 100-fold greater than that seen in the untreated population. Current estimates of the overall case fatality rate are in the range of 20% to 30%, but rates as high as 70% have been reported. Symptoms may not become evident until after the patient has been on felbamate for several months (range: 5 to 30 weeks). However, injury to bone marrow stem cells may occur weeks to months earlier. Therefore, patients are at risk for developing aplastic anemia for an unknown period of time following discontinuation of the drug. Aplastic anemia usually develops without pre-monitory clinical or laboratory signs. Although routine blood monitoring cannot be used as a reliable method to reduce the incidence of aplastic anemia, it may allow detection of changes in hematologic parameters prior to the onset of clinical symptoms of the condition. Felbamate should be discontinued if any evidence of bone marrow depression occurs.
During monotherapy clinical trials in adults, the following adverse dermatologic effects were reported in patients receiving felbamate versus valproate, respectively: acne vulgaris (3.4% vs 0%) and rash (unspecified) (3.4% vs 0%). During clinical trials assessing felbamate as adjunct therapy, rash occurred in 3.5% of patients in the felbamate group and 4.7% of patients in the placebo group. In children receiving felbamate as add-on therapy for Lennox-Gastaut Syndrome, rash was reported in 9.7% of patients in the felbamate group and 7.4% of patients in the placebo group. During other clinical trial evaluation, pruritus was observed in at least 1% of patients. Dermatologic effects observed in 0.1-1% of patients included urticaria and bullous rash. Buccal mucous membrane swelling and Stevens-Johnson syndrome were reported rarely (< 0.1%). During post-market use, drug-induced body odor, hyperhidrosis, lichen planus, livedo reticularis, alopecia, and toxic epidermal necrolysis have been observed; however, a causal relationship to the drug has not been established. Photosensitivity has been reported as an allergic reaction.
During monotherapy clinical trials in adults, the following centrally-mediated effects were reported in patients receiving felbamate versus valproate, respectively: insomnia (8.6% vs 4%) and headache (6.9% vs 18%). During clinical trials assessing felbamate as adjunct therapy, the following CNS effects occurred in the felbamate group versus the placebo group, respectively: headache (36.8% vs 9.3%), drowsiness (19.3% vs 7%), dizziness (18.4% vs 14%), insomnia (17.5% vs 7%), tremor (6.1% vs 2.3%), abnormal gait (5.3% vs 0%), paresthesias (3.5% vs 2.3%), ataxia (3.5% vs 0%), and stupor (2.6% vs 0%). In children receiving felbamate as add-on therapy for Lennox-Gastaut Syndrome, the following CNS effects were reported in the felbamate group versus the placebo group, respectively: drowsiness (48.4% vs 11.1%), insomnia (16.1% vs 14.8%), abnormal gait (9.7% vs 0%), headache (6.5% vs 18.5%), and ataxia (6.5% vs 3.7%). Migraine was observed in 0.1-1% of patients during other evaluations with felbamate. During post-market use, paralysis, mononeuritis, cerebrovascular disorder, cerebral edema, coma, encephalopathy, nystagmus, choreoathetosis, extrapyramidal disorder, dyskinesia, status epilepticus, dysarthria, apathy, and impaired concentration have been observed; however, a causal relationship to the drug has not been established.
During monotherapy clinical trials in adults, the following adverse respiratory effects were reported in patients receiving felbamate versus valproate, respectively: upper respiratory tract infection (8.6% vs 4%) and rhinitis (6.9% vs 0%). During clinical trials assessing felbamate as adjunct therapy, the following respiratory effects occurred in the felbamate group versus the placebo group, respectively: upper respiratory tract infection (5.3% vs 7%), sinusitis (3.5% vs 0%), and pharyngitis (2.6% vs 0%). In children receiving felbamate as add-on therapy for Lennox-Gastaut Syndrome, the following respiratory effects were reported in the felbamate group versus the placebo group, respectively: upper respiratory tract infection (45.2% vs 25.9%), pharyngitis (9.7% vs 3.7%), and cough (6.5% vs 0%). Respiratory depression, dyspnea, pneumonia, pneumonitis, hypoxia, epistaxis, pleural effusion, respiratory insufficiency, pulmonary hemorrhage, and asthma (bronchospasm) have been reported during post-market use; however, a causal relationship to the drug has not been established.
During monotherapy clinical trials in adults, the following adverse effects related to the special senses were reported in patients receiving felbamate versus valproate, respectively: diplopia (3.4% vs 4%) and otitis media (3.4% vs 0%). During clinical trials assessing felbamate as adjunct therapy, the following effects occurred in the felbamate group versus the placebo group, respectively: diplopia (6.1% vs 0%), dysgeusia (6.1% vs 0%), and visual impairment (5.3% vs 2.3%). In children receiving felbamate as add-on therapy for Lennox-Gastaut Syndrome, the following ophthalmic or otic effects were reported in the felbamate group versus the placebo group, respectively: otitis media (9.7% vs 0%) and miosis (6.5% vs 0). During post-market use, hemianopsia, decreased hearing, and conjunctivitis have been observed; however, a causal relationship to the drug has not been established.
During monotherapy clinical trials in adults, the following adverse genitourinary (GU) effects were reported in patients receiving felbamate versus valproate, respectively: urinary tract infection (3.4% vs 2%) and menstrual irregularity (intramenstrual bleeding 3.4% vs 0%). In children receiving felbamate as add-on therapy for Lennox-Gastaut Syndrome, urinary incontinence was reported in 6.5% of patients in the felbamate treatment group and 7.4% of patients in the placebo treatment group. During post-market use, menstrual disorder, acute renal failure (unspecified), hepatorenal syndrome, hematuria, urinary retention, nephrosis, vaginal bleeding, abnormal renal function (unspecified), dysuria, and placental disorder have been observed; however, a causal relationship to the drug has not been established.
During monotherapy clinical trials in adults, hyperphosphatemia was reported in 3.4% of patients receiving felbamate and no patients receiving valproate. During other evaluations, the following metabolic/nutritional effects were reported in 0.1-1% of patients receiving felbamate: hypokalemia, hyponatremia, increased LDH, increased alkaline phosphatase, and hypophosphatemia. Increased creatinine phosphokinase was reported rarely (< 0.1%). During post-market use, hypernatremia, hypoglycemia, SIADH, hypomagnesemia, dehydration, hyperglycemia, and hypocalcemia have been observed; however, a causal relationship to the drug has not been established.
During clinical trials assessing felbamate as adjunct therapy in adults, myalgia occurred in 2.6% of patients in the felbamate group and no patients in the placebo group. During other evaluations, dystonic reaction was reported in 0.1-1% of patients receiving felbamate. Arthralgia, myasthenia, involuntary muscle contractions, and rhabdomyolysis have been observed during post-market use; however, a causal relationship to the drug has not been established.
During clinical trial evaluation of felbamate, adverse cardiovascular effects including palpitations and sinus tachycardia were reported in at least 1% of patients. Supraventricular tachycardia (SVT) was reported rarely (< 0.1%). During post-market use, atrial fibrillation, atrial arrhythmia, cardiac arrest, torsade de pointes, heart failure, hypotension, hypertension, thrombophlebitis, ischemic necrosis, gangrene, peripheral ischemia, bradycardia, and Henoch-Schonlein purpura (vasculitis) have been observed; however, a causal relationship to the drug has not been established.
During monotherapy clinical trials in adults, the following general adverse effects were reported in patients receiving felbamate versus valproate, respectively: fatigue (6.9% vs 4%) and face edema (3.4% vs 0%). During clinical trials assessing felbamate as adjunct therapy, the following general effects occurred in the felbamate group versus the placebo group, respectively: fatigue (16.8% vs 7%), fever (2.6% vs 4.7%), and chest pain (unspecified) (2.6% vs 0%). In children receiving felbamate as add-on therapy for Lennox-Gastaut Syndrome, the following general effects were reported in the felbamate group versus the placebo group, respectively: fever (22.6% vs 11.1%), fatigue (9.7% vs 3.7%), and unspecified pain (6.5% vs 0%). During other evaluations, asthenia, malaise, and influenza-like syndrome were observed in at least 1% of patients. Anaphylactoid reactions and substernal chest pain were observed rarely (< 0.1%). General effects reported during post-market use include neoplasm, sepsis, L.E. syndrome, SIDS, sudden death, edema, hypothermia, rigors, and hyperpyrexia; however, a causal relationship to the drug has not been established.
There are no studies assessing the effects of felbamate in pregnant women; however, the following fetal disorders have been reported during post-market use of the drug: fetal death, microcephaly, genital malformation, anencephaly, and encephalocele. Physicians are advised to recommend that pregnant patients receiving felbamate enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry to provide information about the effects of in utero exposure to the drug.
Felbamate is contraindicated in patients with a felbamate or carbamate hypersensitivity. Patients sensitive to carbamate derivatives (e.g., meprobamate, carisoprodol) may also be sensitive to felbamate.
The use of felbamate is associated with a marked increase in the incidence of aplastic anemia (pancytopenia in the presence of a bone marrow largely depleted of hematologic precursor cells). Felbamate should only be used in patients with epilepsy that is so severe that the risk of aplastic anemia is acceptable in accordance with the benefits associated with felbamate use. A hematologic consultation is recommended to determine appropriateness of use prior to treatment. Among felbamate-treated patients, aplastic anemia occurs at an incidence that may be more than 100-fold greater than that seen in the untreated population (e.g., 2 to 5 cases per million persons per year). Cases of aplastic anemia may be fatal and fatalities are dependent on the severity and etiology of the presentation, but typically are in the range of 20 to 30%, and may be as high as 70%. Too little is known about felbamate-induced aplastic anemia to determine fatality percentages or which patients are more at risk for this serious adverse reaction. Clinical manifestations may not be present for several months after therapy is initiated; where data are available the onset has ranged from 5 to 30 weeks after the start of therapy. Bone marrow stem cell changes may occur weeks to months earlier than clinical presentation. Patients who are discontinued off the drug therefore remain at risk for aplastic anemia for an unknown time after drug discontinuation. It is not known if the duration of felbamate exposure or the dose used influences the risk for aplastic anemia. It is also not known if concurrent therapies may influence this risk. Clinical signs and symptoms may include infection, bleeding, or anemia. Routine laboratory testing of the blood cannot be reliably used to reduce the incidence of aplastic anemia. Felbamate is contraindicated in patients with a history of any hematological disease (e.g., leukopenia, neutropenia, agranulocytosis, bone marrow suppression, thrombocytopenia, anemia, aplastic anemia, or other hematological disease because of the potential increased risk of hematologic toxicity. A baseline CBC with platelets and reticulocytes should be obtained, as well as routine laboratory monitoring throughout treatment. Felbamate should be discontinued if signs and symptoms of hematologic abnormalities or any sign of bone marrow depression occurs. Patients who are discontinued from felbamate remain at risk for developing anemia for an uncertain length of time.
Felbamate is contraindicated in patients with current or previous hepatic disease (e.g., hepatic failure, hepatitis, jaundice). The drug may cause hepatotoxicity and hepatic failure. In September 1994, the manufacturer issued a letter stating 8 cases of acute hepatic failure, including 4 deaths, were associated with the use of felbamate. It is thought that hepatic failure in felbamate-treated patients greatly exceeds that which occurs in the general population. Therefore, it is recommended that felbamate only be used in patients with severe epilepsy for which the benefits of the drug outweigh the risks of hepatic failure and other toxicities. It is unknown if pre-existing hepatic disease increases the risk of felbamate-induced hepatotoxicity. It is not known if other risk factors exist, such as dose, concurrent use of other medications, or length of therapy. Therefore, all patients receiving felbamate should be monitored for signs of hepatotoxicity. Monitoring should include baseline liver function tests (i.e., ALT, AST, bilirubin), and periodically thereafter. While frequent monitoring of liver function tests may increase the likelihood of early detection, the precise schedule for monitoring is a matter of clinical judgement. Patients should be advised to be alert for signs of liver dysfunction (jaundice, anorexia, gastrointestinal complaints, malaise, etc.) and to report them to their doctor immediately if they should occur. Felbamate should be discontinued if either serum AST or ALT levels become increased 2- or more times the upper limit of normal (ULN), or if clinical signs and symptoms suggest liver failure. Any patient withdrawn from the drug for liver injury are considered at increased risk for such problems if the drug is re-introduced. Do not restart felbamate in these patients.
Use felbamate with caution in patients with pre-existing renal impairment, particularly renal failure. The half-life of the drug is prolonged and clearance reduced. Dosage adjustments are recommended.
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 (0.43%) as patients receiving placebo (0.24%), corresponding to an estimated 2.1 per 1000 (95% CI: 0.7-4.2) more patients in the drug treatment groups who experienced suicidal behavior or ideation. 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 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. Anticonvulsants such as felbamate should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose.
There are no studies in pregnant women to determine the effect of felbamate on the fetus. It is not teratogenic in animal models. However, in rats, there was a decrease in pup weight and an increase in pup deaths during the post-birth lactation period; the cause for these deaths is not known. In addition, as a result of the synthesis process, felbamate could contain small amounts of two known animal carcinogens, the genotoxic compound ethyl carbamate (urethane) and the non-genotoxic compound methyl carbamate. The serious toxicities of felbamate, such as aplastic anemia, would also warrant that felbamate be used during pregnancy only if clearly needed. The effect of felbamate on labor and delivery in humans is unknown. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to felbamate; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.
According to the manufacturer, felbamate is excreted into breast milk, but its effects on the infant are unknown. In rats, there was a decrease in pup weight and an increase in pup deaths during lactation; the reason for the deaths is not determined. Because of the serious toxicities associated with the drug, including aplastic anemia and hepatic failure, breast-feeding should generally be avoided during treatment with felbamate. Consider the benefits of breast-feeding, the risk of potential drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding baby experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
The safety and efficacy of felbamate in children, other than those with Lennox-Gastaut syndrome, have not been studied. The drug is not recommended for children under the age of 2 years or in infants.
Abrupt discontinuation of felbamate can precipitate seizures.
Clinical studies for felbamate did not include sufficient numbers of geriatric adults 65 years of age and older to determine whether they respond differently than younger adults. Other reported clinical experience has not identified differences in responses. In general, dosage selection for geriatric patients should be cautious, usually starting at the low end of the dosing range. According to the Beers Criteria, anticonvulsants such as felbamate are considered potentially inappropriate medications (PIMs) in geriatric adults with a history of falls or fractures; avoid in these patient populations, except for treating seizure and mood disorders, since anticonvulsants can produce ataxia, impaired psychomotor function, syncope, and additional falls. If felbamate must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement strategies to reduce fall risk.
For the treatment of partial seizures with or without generalization in adults:
NOTE: Felbamate has not been systematically studied as initial monotherapy.
Oral dosage-Monotherapy:
Adults and Adolescents > 14 years: 1200 mg/day PO in 3-4 divided doses. Increase dose in 600 mg increments every 2 weeks to 2400 mg/day PO based on clinical response. Doses may be increased to 3600 mg/day PO if clinically indicated. Previously untreated patients should be titrated under close clinical supervision.
Oral dosage-Conversion to Monotherapy:
Adults and Adolescents > 14 years: Initiate at 1200 mg/day PO in 3-4 divided doses. Upon initiation of felbamate therapy, reduce the dosage of other antiepileptic drugs (AEDs) by one-third (1/3). At week 2, increase felbamate dose to 2400 mg/day PO while decreasing the other AEDs dose by an additional one-third of the original dose. At week 3, increase the dose of felbamate to 3600 mg/day PO given in divided doses and continue to reduce the dose of the other AEDs as clinically indicated.
Oral dosage-Adjunctive Therapy:
Adults and Adolescents > 14 years: Add felbamate at 1200 mg/day PO in 3-4 divided doses and reduce the dose of other AEDs by 20-30%. The dosage reduction of other AEDs will help maintain plasma concentrations and reduce side effects of concurrent phenytoin, valproic acid, or carbamazepine and its metabolites. Serum concentrations of other anticonvulsants should be obtained and dosage adjustments made as necessary. Increase felbamate dosage by 1200 mg/day increments at weekly intervals to a maximum of 3600 mg/day PO given in divided doses.
For the treatment of partial and generalized seizures associated with Lennox-Gastaut syndrome in children:
Oral dosage-Adjunctive Therapy:
Adolescents and Children 2 - 14 years: Add felbamate at 15 mg/kg/day PO in 3-4 divided doses while reducing doses of other AEDs by 20-30%. The dosage reduction of other AEDs will help maintain plasma concentrations and reduce side effects of concurrent phenytoin, valproic acid, or carbamazepine and its metabolites. Serum concentrations of other anticonvulsants should be obtained and dosage adjustments made as necessary. Increase felbamate dosage by 15 mg/kg/day increments at weekly intervals to 45 mg/kg/day PO. Maximum dosage is 3600 mg/day.
Maximum Dosage Limits:
-Adults
3600 mg/day PO.
-Elderly
3600 mg/day PO.
-Adolescents
3600 mg/day PO.
-Children
>= 2 years: 3600 mg/day PO.
< 2 years: Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
The manufacturer advises to avoid use of felbamate in patients with pre-existing hepatic disease.
Patients with Renal Impairment Dosing
In the renally-impaired, starting and maintenance doses should be reduced by 50% (manufacturers recommendation).
*non-FDA-approved indication
Alprazolam: (Moderate) Concomitant administration of alprazolam with CNS-depressant drugs, including anticonvulsants, can potentiate the CNS effects of either agent.
Amitriptyline: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Amoxapine: (Moderate) Amoxapine, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as felbamate, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.
Belzutifan: (Moderate) Monitor for anemia and hypoxia if concomitant use of felbamate 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 felbamate is a CYP2C19 inhibitor.
Bupropion: (Major) Bupropion should not be used by patients taking anticonvulsants for seizures because it may decrease the seizure threshold. Bupropion may also interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function.
Bupropion; Naltrexone: (Major) Bupropion should not be used by patients taking anticonvulsants for seizures because it may decrease the seizure threshold. Bupropion may also interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function.
Carbamazepine: (Moderate) Concurrent administration of felbamate and other antiepileptic drugs results in changes in serum concentrations of both felbamate and the antiepileptic drugs. Felbamate causes a decrease in the steady-state plasma concentration of carbamazepine but increases concentrations of carbamazepine epoxide, a carbamazepine metabolite.
Carisoprodol: (Minor) Carisoprodol is extensively metabolized and is a significant substrate of CYP2C19 isoenzymes. Theoretically, CY2C19 inhibitors, such as felbamate, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects.
Chlordiazepoxide; Amitriptyline: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Chlorpromazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Citalopram: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with felbamate, 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.
Clobazam: (Moderate) A dosage reduction of clobazam may be necessary during co-administration of felbamate. Metabolism of N-desmethylclobazam, the active metabolite of clobazam, occurs primarily through CYP2C19 and felbamate is an inhibitor of CYP2C19. Extrapolation from pharmacogenomic data indicates that concurrent use 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. It should be noted that results of a population pharmacokinetic analysis showed that concurrent use of felbamate and clobazam did not significantly alter the kinetics of clobazam or its active metabolite at steady-state.
Clomipramine: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Clopidogrel: (Major) Felbamate may reduce the antiplatelet activity of clopidogrel by inhibiting clopidogrel's metabolism to its active metabolite. Use clopidogrel and felbamate together with caution and monitor for reduced efficacy of clopidogrel. Clopidogrel requires hepatic biotransformation via 2 cytochrome dependent oxidative steps; the CYP2C19 isoenzyme is involved in both steps. Felbamate is a potent inhibitor of CYP2C19.
Codeine; Phenylephrine; Promethazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Codeine; Promethazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Colesevelam: (Moderate) Colesevelam may decrease the bioavailability or felbamate if coadministered. To minimize potential for interactions, consider administering oral anticonvulsants such as felbamate at least 1 hour before or at least 4 hours after colesevelam.
Conjugated Estrogens: (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Conjugated Estrogens; Bazedoxifene: (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Conjugated Estrogens; Medroxyprogesterone: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Deferiprone: (Major) Avoid concomitant use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis, such as felbamate; however, if this is not possible, closely monitor the absolute neutrophil count and interrupt deferiprone therapy if neutropenia develops.
Desipramine: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Desogestrel; Ethinyl Estradiol: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Dextromethorphan; Bupropion: (Major) Bupropion should not be used by patients taking anticonvulsants for seizures because it may decrease the seizure threshold. Bupropion may also interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function.
Dienogest; Estradiol valerate: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Doxepin: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Drospirenone: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
Drospirenone; Estetrol: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Drospirenone; Estradiol: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Drospirenone; Ethinyl Estradiol: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Elagolix; Estradiol; Norethindrone acetate: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Escitalopram: (Moderate) The plasma concentration of escitalopram, a CYP2C19 substrate, may be increased when administered concurrently with felbamate, a CYP2C19 inhibitor. If these drugs are used together, monitor for escitalopram-associated adverse reactions.
Esomeprazole: (Minor) Felbamate may inhibit the CYP2C19 isoenzyme, leading to increased plasma levels of drugs that are substrates for the CYP2C19 isoenzyme, such as esomeprazole.
Esterified Estrogens: (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Esterified Estrogens; Methyltestosterone: (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Estradiol: (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Estradiol; Levonorgestrel: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Estradiol; Norethindrone: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Estradiol; Norgestimate: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Estradiol; Progesterone: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Estrogens: (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Estropipate: (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Ethinyl Estradiol; Norelgestromin: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Ethinyl Estradiol; Norgestrel: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Ethotoin: (Moderate) Hydantoins are hepatic enzyme inducers and thus may accelerate the metabolism of several other anticonvulsants, including felbamate.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Etonogestrel: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
Etonogestrel; Ethinyl Estradiol: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Fluphenazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Fosphenytoin: (Moderate) Hydantoins are hepatic enzyme inducers and thus may accelerate the metabolism of several other anticonvulsants, including felbamate.
Guanidine: (Minor) Bone marrow suppression is associated with guanidine therapy. Avoid concomitant use of other drugs known to cause bone marrow suppression such as felbamate.
Hydantoins: (Moderate) Hydantoins are hepatic enzyme inducers and thus may accelerate the metabolism of several other anticonvulsants, including felbamate.
Hydroxychloroquine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as felbamate. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
Imipramine: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Isocarboxazid: (Moderate) Additive CNS depression is possible if MAOIs and felbamate are coadministered. MAOIs can also cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required.
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., felbamate), 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.
Leuprolide; Norethindrone: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
Levonorgestrel: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
Levonorgestrel; Ethinyl Estradiol: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Lisdexamfetamine: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use lisdexamfetamine with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.
Maprotiline: (Major) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients carefully.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with felbamate due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 substrate and felbamate is a moderate CYP2C19 inhibitor.
Medroxyprogesterone: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
Mefloquine: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration is recommended. Patients may also experience additive sedation or dizziness, or changes in moods and behaviors.
Methsuximide: (Moderate) Monitor concentrations of N-desmethylmethsuximide in patients treated with methsuximide and felbamate. Dosage adjustment of methsuximide may be required. Concomitant use of felbamate and methsuximide may result in increased plasma concentrations of N-desmethylmethsuximide. The cause of the increase in N-desmethylmethsuximide concentrations is not known.
Molindone: (Moderate) Consistent with the pharmacology of molindone, additive effects may occur with other CNS active drugs such as anticonvulsants. In addition, seizures have been reported during the use of molindone, which is of particular significance in patients with a seizure disorder receiving anticonvulsants. Adequate dosages of anticonvulsants should be continued when molindone is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either molindone or the anticonvulsant.
Monoamine oxidase inhibitors: (Moderate) Additive CNS depression is possible if MAOIs and felbamate are coadministered. MAOIs can also cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required.
Naproxen; Esomeprazole: (Minor) Felbamate may inhibit the CYP2C19 isoenzyme, leading to increased plasma levels of drugs that are substrates for the CYP2C19 isoenzyme, such as esomeprazole.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Norethindrone: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
Norethindrone; Ethinyl Estradiol: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Norgestimate; Ethinyl Estradiol: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Norgestrel: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
Nortriptyline: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Perphenazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Perphenazine; Amitriptyline: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Phenelzine: (Moderate) Additive CNS depression is possible if MAOIs and felbamate are coadministered. MAOIs can also cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required.
Phenobarbital: (Moderate) Concurrent administration of felbamate and other antiepileptic drugs results in changes in serum concentrations of both felbamate and the antiepileptic drugs. Felbamate increases the steady-state serum concentrations of phenobarbital.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Concurrent administration of felbamate and other antiepileptic drugs results in changes in serum concentrations of both felbamate and the antiepileptic drugs. Felbamate increases the steady-state serum concentrations of phenobarbital.
Phenothiazines: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Phenytoin: (Moderate) Hydantoins are hepatic enzyme inducers and thus may accelerate the metabolism of several other anticonvulsants, including felbamate.
Prochlorperazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Progesterone: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
Progestins: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary.
Promethazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Promethazine; Dextromethorphan: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Promethazine; Phenylephrine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Protriptyline: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Relugolix; Estradiol; Norethindrone acetate: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Segesterone Acetate; Ethinyl Estradiol: (Major) Based on very limited data, it appears felbamate can accelerate the clearance of the estrogen component of some oral contraceptives. Patients who experience breakthrough bleeding while receiving these drugs together should notify their prescribers. An alternate or additional form of contraception should be used during concomitant treatment. Additionally, patients taking non-oral combination contraceptives or estrogens or progestins for hormone replacement therapy may also experience reduced clinical efficacy; dosage adjustments may be necessary. (Major) Estrogens and progestins are both susceptible to drug interactions with hepatic enzyme inducing drugs. Estrogens are metabolized by CYP3A4. Anticonvulsants that stimulate the activity of this enzyme include: barbiturates (including primidone), carbamazepine, felbamate, oxcarbazepine, phenytoin or fosphenytoin (and possibly ethotoin), and topiramate. The anticonvulsants mentioned may cause oral contraceptive failure, especially when low-dose estrogen regimens (e.g., ethinyl estradiol is < 50 mcg/day) are used. Epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism and the higher risk for oral contraceptive failure. During oral contraceptive failure, the additive effects could potentially heighten the risk of neural tube defects in pregnancy. Women on OCs and enzyme-inducing anticonvulsant medications concurrently should report breakthrough bleeding to their prescribers. Oral contraceptive formulations containing higher dosages of ethinyl estradiol (i.e., 50 mcg ethinyl estradiol) may be needed to increase contraceptive efficacy. It may be prudent for some women who receive OCs concurrently with enzyme-inducing anticonvulsants to use an additional contraceptive method to protect against unwanted pregnancy. Higher dosages of oral contraceptives (e.g., ethinyl estradiol >= 50 mcg/day) or a second contraceptive method are typically suggested if women use an enzyme-inducing anti-epileptic drug or a barbiturate. Proper intake of folic acid should also be ensured.
Terbinafine: (Moderate) Caution is advised when administering terbinafine with felbamate. 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; felbamate is an inducer of CYP3A4 and an inhibitor of CYP2C19. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
Thioridazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Tranylcypromine: (Moderate) Additive CNS depression is possible if MAOIs and felbamate are coadministered. MAOIs can also cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required.
Tretinoin, ATRA: (Moderate) Felbamate may increase the CYP450 metabolism of tretinoin, ATRA, potentially resulting in decreased plasma concentrations of tretinoin, ATRA. Monitor for decreased clinical effects of tretinoin, ATRA while receiving concomitant therapy.
Tricyclic antidepressants: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Trifluoperazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Trimipramine: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when a TCA is used concurrently.
Valproic Acid, Divalproex Sodium: (Moderate) Felbamate has been shown to increase valproic acid serum concentrations, however the magnitude of this effect varies. Felbamate may interfere with valproic acid metabolism and should be administered cautiously to patients receiving valproic acid.
Vasopressin, ADH: (Moderate) Monitor hemodynamics and adjust the dose of vasopressin as needed when used concomitantly with drugs suspected of causing syndrome of inappropriate antidiuretic hormone (SIADH), such as felbamate. Use together may increase the pressor and antidiuretic effects of vasopressin.
Voriconazole: (Minor) Voriconazole is a primary substrate of the CYP2C19 isoenzyme, and also is metabolized to a lesser extent by CYP3A4 and CYP2C9. Theoretically, CYP2C19 inhibitors, such as felbamate, may result in elevated voriconazole serum concentrations when coadministered. Felbamate is known to induce CYP3A4 as well as inhibit CYP2C19, so the net effect of this drug on voriconazole metabolism is not certain.
Zonisamide: (Moderate) Concomitant use of zonisamide with felbamate may increase the risks of hyperammonemia and encephalopathy. Monitor serum ammonia concentrations if signs or symptoms of encephalopathy occur. Hyperammonemia resulting from zonisamide resolves when zonisamide is discontinued and may resolve or decrease in severity with a decrease of the daily dose.
The exact mechanism by which felbamate exerts its anticonvulsant activity is unknown. One possible mechanism involves N-methyl-D-aspartate (NMDA) receptors present in the central nervous system. Seizures are believed to be initiated and propagated by stimulation of the NMDA receptor, which may be regulated by activation of a receptor-gated calcium ion channel. These channels are regulated by the amino acid glycine. The binding of glycine to the NMDA receptor causes an increase in the frequency of NMDA receptor-mediated channel opening, which is important in the initiation and propagation of seizures. It is believed that felbamate antagonizes the effects of glycine by binding to the glycine-binding site of the NMDA receptor, thereby increasing the seizure threshold and preventing the spread of seizures. Felbamate does have relatively weak carbonic anhydrase inhibitory activity. Felbamate has no effect on benzodiazepine receptors, no interaction with GABA-A receptors, and no enhancement of GABA-induced chloride influx.
Felbamate is administered orally. The therapeutic range has not been established. Plasma protein binding ranges from 25-35%. About 15% of a dose is metabolized to agents that have insignificant anticonvulsant activity. Most (40-50%) of the administered dose is present in the urine unchanged, and 40% is recovered in the urine as unidentified metabolites and conjugates. Less than 5% of an orally administered dose is recovered in the feces. The plasma half-life of felbamate is 13-23 hours and is not changed after multiple doses.
Affected cytochrome P450 isoenzymes: CYP2C19, CYP3A4
Felbamate inhibits CYP2C19 and induces CYP3A4.
-Route-Specific Pharmacokinetics
Oral Route
Absorption of felbamate after oral administration is approximately 90% and is not affected by food. It is similar for both the tablets and suspension. Time to peak serum concentration is 1-6 hours.
-Special Populations
Renal Impairment
Felbamate's single dose monotherapy pharmacokinetic parameters were evaluated in 12 otherwise healthy individuals with renal impairment. There was a 40-50% reduction in total body clearance and 9-15 hours prolongation of half-life in renally impaired subjects compared to adults with normal renal function. Reduced felbamate clearance and a longer half-life were associated with diminishing renal function. Dosage adjustments are recommended.