Version July 2025
The use of felbamate is associated with a marked increase in the incidence of aplastic anemia. Accordingly, felbamate should only be used in patients whose epilepsy is so severe that the risk of aplastic anemia is deemed acceptable in light of the benefits conferred by its use. Ordinarily, a patient should not be placed on and/or continued on felbamate without consideration of appropriate expert hematologic consultation.
Among felbamate-treated patients, aplastic anemia (pancytopenia in the presence of a bone marrow largely depleted of hematopoietic precursors) occurs at an incidence that may be more than a 100-fold greater than that seen in the untreated population (ie, 2 to 5 per million persons per year). The risk of death in patients with aplastic anemia generally varies as a function of its severity and etiology; 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 in the past.
There are too few felbamate-associated cases, and too little known about them to provide a reliable estimate of the syndrome's incidence or its case fatality rate or to identify the factors, if any, that might conceivably be used to predict who is at greater or lesser risk.
In managing patients on felbamate, the clinical manifestation of aplastic anemia may not be seen until after a patient has been taking felbamate for several months (eg, onset of aplastic anemia among felbamate-exposed patients for whom data are available has ranged from 5 to 30 weeks). However, the injury to bone marrow stem cells that is held to be ultimately responsible for the anemia may occur weeks to months earlier. Accordingly, patients who are discontinued from felbamate remain at risk for developing anemia for a variable, and unknown, period afterwards.
It is not known whether the risk of developing aplastic anemia changes with duration of exposure. Consequently, it is not safe to assume that a patient who has been on felbamate without signs of hematologic abnormality for long periods of time is without risk.
It is not known whether the dose of felbamate affects the incidence of aplastic anemia.
It is not known whether concomitant use of antiseizure drugs and/or other drugs affects the incidence of aplastic anemia.
Aplastic anemia typically develops without premonitory clinical or laboratory signs; the full blown syndrome presents with signs of infection, bleeding, or anemia. Accordingly, routine blood testing cannot be reliably used to reduce the incidence of aplastic anemia, but, it will, in some cases, allow the detection of the hematologic changes before the syndrome declares itself clinically. Discontinue felbamate if any evidence of bone marrow depression occurs.
Evaluation of postmarketing experience suggests that acute liver failure is associated with the use of felbamate. The reported rate in the United States has been approximately 6 cases of liver failure leading to death or transplant per 75,000 patient-years of use. This rate is an underestimate because of underreporting, and the true rate could be considerably greater than this. For example, if the reporting rate is 10%, the true rate would be 1 case per 1,250 patient-years of use.
Of the cases reported, approximately 67% resulted in death or liver transplantation, usually within 5 weeks of the onset of signs and symptoms of liver failure. The earliest onset of severe hepatic dysfunction followed subsequently by liver failure was 3 weeks after initiation of felbamate. Although some reports described dark urine and nonspecific prodromal symptoms (eg, anorexia, malaise, GI symptoms), in other reports it was not clear if any prodromal symptoms preceded the onset of jaundice.
It is not known whether the risk of developing hepatic failure changes with duration of exposure.
It is not known whether the dosage of felbamate affects the incidence of hepatic failure.
It is not known whether concomitant use of other AEDs and/or other drugs affects the incidence of hepatic failure.
Felbamate should not be prescribed for anyone with a history of hepatic dysfunction.
Treatment with felbamate should be initiated only in individuals without active liver disease and with normal baseline serum transaminases. It has not been proved that periodic serum transaminase testing will prevent serious injury, but it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspected drug enhances the likelihood for recovery. There is no information available that documents how rapidly patients can progress from normal liver function to liver failure, but other drugs known to be hepatotoxins can cause liver failure rapidly (eg, from normal enzymes to liver failure in 2 to 4 weeks). Accordingly, monitoring of serum transaminase levels (AST and ALT) is recommended at baseline and periodically thereafter. While more frequent monitoring increases the chances of early detection, the precise schedule for monitoring is a matter of clinical judgment.
Discontinue felbamate if serum AST or serum ALT levels become increased at least 2 times the upper limit of normal, or if clinical signs and symptoms suggest liver failure. Patients who develop evidence of hepatocellular injury while taking felbamate and are withdrawn from the drug for any reason should be presumed to be at increased risk for liver injury if felbamate is reintroduced. Accordingly, such patients should not be considered for re-treatment.
Note: Not for use as first-line therapy; use only in patients with severe epilepsy and/or inadequate response to alternative treatment due to risk of aplastic anemia and/or liver failure.
Focal (partial) onset seizures, adjunctive therapy: Oral: Initial: 1.2 g/day in 3 to 4 divided doses; may increase in increments of 1.2 g/day at weekly intervals based on response and tolerability to a maximum of 3.6 g/day in divided doses (Ref).
Focal (partial) onset seizures, monotherapy: Oral: Initial: 1.2 g/day in 3 to 4 divided doses; may increase in increments of 600 mg/day at 2-week intervals to 2.4 g/day based on response and tolerability; may further increase as needed to a maximum of 3.6 g/day in divided doses (Ref).
Conversion to monotherapy: Oral: Initiate at 1.2 g/day in 3 to 4 divided doses; reduce the dosage of the concomitant antiseizure medication(s) by 33% at the initiation of felbamate therapy; at week 2, increase the felbamate dosage to 2.4 g/day while reducing the dosage of the other antiseizure medication(s) up to an additional 33% of their original dosage; at week 3, increase the felbamate dosage up to 3.6 g/day and continue to reduce the dosage of the other antiseizure medication(s) as clinically indicated.
Discontinuation of therapy: In chronic therapy, unless safety concerns require more rapid withdrawal, withdraw gradually (eg, increments of 300 to 600 mg every week) to minimize the potential of increased seizure frequency or status epilepticus (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Adjunctive therapy with medications that affect felbamate plasma concentrations, especially antiseizure drugs, may warrant further reductions in felbamate daily doses in patients with kidney dysfunction.
Altered kidney function (Ref):
CrCl >50 mL/minute: No dosage adjustment necessary.
CrCl 10 to 50 mL/minute: Initial and maintenance doses: Administer 50% to 75% of usual indication-specific dose.
CrCl <10 mL/minute: Initial and maintenance doses: Administer 50% of usual indication-specific dose.
Hemodialysis, intermittent (thrice weekly): Likely to be significantly removed by hemodialysis (low protein binding, small Vd) (Ref): Dose as for CrCl <10 mL/minute (Ref).
Peritoneal dialysis: Dose as for CrCl <10 mL/minute (Ref).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, seizure control) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, CNS effects) due to drug accumulation is important.
Some degree of removal is likely based on pharmacokinetic characteristics (has not been studied). Reduce initial dose to 50% of usual indication-specific dose; titrate cautiously based on patient response and tolerability (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, seizure control) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, CNS effects) due to drug accumulation is important.
Some degree of removal is likely based on pharmacokinetic characteristics (has not been studied). Reduce initial doses by 50% of usual indication-specific dose; titrate cautiously based on patient response and tolerability (Ref).
Use is contraindicated in patients with a history of hepatic dysfunction.
Refer to adult dosing.
(For additional information see "Felbamate: Pediatric drug information")
Note: Not recommended for first-line therapy; reserve for refractory clinical situations (failed other therapies) and where benefits exceed hematologic (aplastic anemia) and hepatotoxicity risks (Ref).
Lennox-Gastaut syndrome; adjunctive therapy: Children and Adolescents 2 to 14 years: Oral: Initial: 15 mg/kg/day in 3 or 4 divided doses; increase dose by 15 mg/kg/day increments at weekly intervals; maximum daily dose: 45 mg/kg/day or 3,600 mg/day whichever is less. Note: At initiation of felbamate, decrease dose of concomitant carbamazepine, phenytoin, phenobarbital, or valproic acid by 20% to 33%. Further dosage reductions may be necessary as dose of felbamate is increased.
Partial seizures, adjunctive therapy: Adolescents ≥14 years: Oral: Initial: 1,200 mg/day in 3 or 4 divided doses; increase dose in 1,200 mg/day increments at weekly intervals; maximum daily dose: 3,600 mg/day. Note: At initiation of felbamate, decrease dose of concomitant carbamazepine, phenytoin, phenobarbital, or valproic acid by 20%. Further dosage reductions may be necessary as dose of felbamate is increased.
Partial seizures, monotherapy:
Adolescents ≥14 years: Oral:
Initial: 1,200 mg/day in divided doses 3 or 4 times daily; titrate previously untreated patients under close clinical supervision, increasing the dose in 600 mg/day increments every 2 weeks to 2,400 mg/day based on clinical response and thereafter to 3,600 mg/day if clinically indicated.
Conversion to monotherapy: Initial: 1,200 mg/day in divided doses 3 or 4 times daily, reduce the dosage of the concomitant antiseizure medication(s) by 33% at the initiation of felbamate therapy; at week 2, increase felbamate daily dose to 2,400 mg/day in divided doses while reducing the dosage of the other antiseizure medication(s) up to an additional 33% of their original dose; at week 3, increase the felbamate dosage up to a maximum daily dose: 3,600 mg/day and continue to reduce the dosage of the other antiseizure medication(s) as clinically indicated.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Any signs/symptoms of aplastic anemia (infection, anemia, bleeding): Discontinue therapy.
Children ≥2 years and Adolescents: Oral: Reduce initial and maintenance doses by 50%; adjunctive therapy with medications that affect felbamate plasma concentrations, especially antiseizure medications, may warrant further reductions in felbamate daily doses in patients with renal dysfunction.
Children ≥2 years and Adolescents:
Baseline: Use is contraindicated in patients with hepatic impairment.
Hepatotoxicity during therapy: If AST or ALT ≥2 × ULN or signs and symptoms of liver dysfunction (failure): Discontinue therapy.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children and adults unless otherwise indicated.
1% to 10%:
Cardiovascular: Palpitations (≥1%), tachycardia (≥1%)
Dermatologic: Acne vulgaris (adults: 3%), bullous rash (≤1%), pruritus (≥1%), skin rash (adults: 3%), urticaria (≤1%)
Endocrine & metabolic: Hypokalemia (≤1%), hyponatremia (≤1%), hypophosphatemia (adults: 3%), increased lactate dehydrogenase (≤1%), intermenstrual bleeding (adults: 3%), weight gain (≥1%), weight loss (adults: 3%)
Gastrointestinal: Constipation (adults: 7%), diarrhea (adults: 5%), dyspepsia (adults: 9%), esophagitis (≤1%), increased appetite (≤1%), vomiting (9%)
Genitourinary: Urinary tract infection (adults: 3%)
Hematologic & oncologic: Granulocytopenia (≤1%), leukocytosis (≤1%), leukopenia (≤1%), lymphadenopathy (≤1%), thrombocytopenia (≤1%)
Hepatic: Increased serum alanine aminotransferase (adults: 5%), increased serum alkaline phosphatase (≤1%), increased serum aspartate aminotransferase (≥1%)
Hypersensitivity: Facial edema (adults: 3%)
Nervous system: Aggressive behavior (≥1%), agitation (≥1%), anxiety (adults: 5%), asthenia (≥1%), euphoria (≤1%), fatigue (adults: 7%), hallucination (≤1%), headache (adults: 7%), insomnia (adults: 9%), malaise (≥1%), migraine (≤1%), psychological disorder (≥1%), suicidal tendencies (≤1%)
Neuromuscular & skeletal: Dystonia (≤1%)
Ophthalmic: Diplopia (adults: 3%)
Respiratory: Flu-like symptoms (≥1%), rhinitis (adults: 7%), upper respiratory infection (adults: 9%)
<1%:
Cardiovascular: Substernal pain, supraventricular tachycardia
Dermatologic: Skin photosensitivity, Stevens-Johnson syndrome
Gastrointestinal: Buccal mucous membrane swelling
Hematologic & oncologic: Agranulocytosis, platelet disorder, positive ANA titer
Hepatic: Increased gamma-glutamyl transferase
Hypersensitivity: Nonimmune anaphylaxis
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen
Frequency not defined: Gastrointestinal: Anorexia, nausea
Postmarketing (may include combination therapy):
Cardiovascular: Atrial arrhythmia, atrial fibrillation, bradycardia, edema, flushing, heart failure, hypertension, hypotension, ischemic changes (necrosis), limb embolism, livedo reticularis, peripheral ischemia, thrombophlebitis, torsades de pointes
Dermatologic: Alopecia, body odor, diaphoresis, gangrene of skin and/or subcutaneous tissues, lichen planus, toxic epidermal necrolysis
Endocrine & metabolic: Dehydration, hyperammonemia, hyperglycemia, hypernatremia, hypocalcemia, hypoglycemia, hypomagnesemia, menstrual disease, SIADH
Gastrointestinal: Aphthous stomatitis, dysphagia, enteritis, flatulence, gastric dilation, gastric ulcer, gastritis, gastroesophageal reflux disease, gastrointestinal hemorrhage, gingival hemorrhage, glossitis, hematemesis, intestinal obstruction, non-Hirschsprung megacolon, pancreatitis, rectal hemorrhage
Genitourinary: Dysuria, hematuria, urinary retention, urolithiasis (Sparagana 2001), vaginal hemorrhage
Hematologic & oncologic: Anemia, aplastic anemia, decreased prothrombin time, disorder of hemostatic components of blood, disseminated intravascular coagulation, eosinophilia, hemolytic anemia, hemolytic-uremic syndrome, Henoch-Schönlein purpura, hypochromic anemia, leukemia (including myeloid leukemia), lymphoproliferative disorders (T cell and B cell), malignant lymphoma, neoplasm, pancytopenia, prolonged prothrombin time
Hepatic: Hepatic failure, hepatitis, hepatorenal syndrome, jaundice
Infection: Sepsis
Nervous system: Apathy, brain edema, cerebrovascular disease, choreoathetosis, coma, confusion, delusions, dysarthria, encephalopathy, extrapyramidal reaction, hypothermia, lack of concentration, manic reaction, myasthenia, neuritis (mononeuritis), paralysis, paranoid ideation, psychosis, rigors, status epilepticus
Neuromuscular & skeletal: Arthralgia, dyskinesia, Lambert-Eaton syndrome, muscle spasm, rhabdomyolysis
Ophthalmic: Conjunctivitis, hemianopia, nystagmus disorder
Otic: Hearing loss
Renal: Acute kidney injury, nephrosis
Respiratory: Asthma, dyspnea, epistaxis, hypoxia, pleural effusion, pneumonia, pneumonitis, pulmonary hemorrhage, respiratory depression
Miscellaneous: Hyperpyrexia
Hypersensitivity to felbamate, carbamates, or any component of the formulation; history of any blood dyscrasia or hepatic dysfunction
Concerns related to adverse effects:
• Aplastic anemia: Felbamate is associated with a significant increased risk of aplastic anemia. Risk may be more than 100-fold greater than in untreated population. Current estimates of fatality are 20% to 30%, but higher rates (up to 70%) have been reported in the past. Aplastic anemia can develop at any point during therapy and for an unknown period of time after discontinuation of therapy. It is not known if dose, duration of therapy, or concomitant medication use affects risk. Routine blood monitoring may be helpful in detecting hematologic changes before any clinical onset of signs/symptoms of the disease; however, aplastic anemia often develops without any prior indication or warnings. Discontinue use if any evidence of bone-marrow suppression occurs.
• Hepatic failure: Felbamate has been associated with rare cases of hepatic failure (estimated >6 cases per 75,000 patients per year). Of the cases reported in the literature, 67% have resulted in fatality or liver transplant. Onset may or may not be preceded by prodromal symptoms. It is not known whether dose, duration of therapy, or concomitant medication use affects risk. Monitoring of serum transaminases has not been demonstrated to prevent serious hepatic injury, however, early diagnosis and drug withdrawal may improve the likelihood of recovery. Obtain baseline transaminase levels and periodically thereafter; discontinue use if transaminase levels increase to ≥2 times the ULN or with signs/symptoms suggesting hepatic failure. Therapy should not be initiated or reintroduced in patients with evidence of hepatic damage or who discontinue use for any reason.
• Suicidal ideation: Pooled analysis of trials involving various antiseizure medications (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify health care provider immediately if symptoms occur.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; half-life is increased.
Concurrent drug therapy issues:
• Sedatives: CNS effects may be potentiated when used with other sedative drugs or ethanol.
Other warnings/precautions:
• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Suspension, Oral:
Felbatol: 600 mg/5 mL (237 mL [DSC], 946 mL [DSC])
Generic: 600 mg/5 mL (5 mL [DSC], 237 mL, 240 mL, 473 mL, 946 mL)
Tablet, Oral:
Felbatol: 400 mg, 600 mg [scored]
Generic: 400 mg, 600 mg
Yes
Suspension (Felbamate Oral)
600 mg/5 mL (per mL): $0.63 - $2.71
Tablets (Felbamate Oral)
400 mg (per each): $2.95 - $9.23
600 mg (per each): $3.83 - $10.57
Tablets (Felbatol Oral)
400 mg (per each): $18.52
600 mg (per each): $21.23
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
A patient “informed consent” form should be completed and signed by the patient and physician. Copies are available from MEDA Pharmaceuticals by calling 800-526-3840.
Administer with or without food. Shake suspension prior to use.
Oral: May be administered without regard to meals; shake suspension well before use
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM263034.pdf, must be dispensed with this medication.
Focal (partial)-onset seizures (monotherapy or adjunctive therapy): Monotherapy or adjunctive therapy in the treatment of focal (partial)-onset seizures (with and without generalization) in adults and adolescents ≥14 years of age.
Lennox-Gastaut syndrome: Adjunctive therapy in the treatment of focal (partial)-onset and generalized seizures associated with Lennox-Gastaut syndrome in children.
Limitations of use: Not for use as first-line therapy; use only in patients with severe epilepsy and/or inadequate response to alternative treatment due to risk of aplastic anemia and/or liver failure.
Substrate of CYP2E1 (Minor), CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C19 (Weak);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
CarBAMazepine: May decrease serum concentration of Felbamate. Felbamate may decrease serum concentration of CarBAMazepine. Felbamate may increase active metabolite exposure of CarBAMazepine. Specifically, concentrations of the carbamazepine epoxide metabolite may be increased. Management: Initiate felbamate at typical doses (1,200 mg/day in 3 or 4 divided doses for adults and children 14 years of age or older; 15 mg/kg/day in 3 or 4 divided doses in children 2 to 14 years of age) while reducing the carbamazepine dose by 20%. Risk D: Consider Therapy Modification
CloBAZam: CYP2C19 Inhibitors (Weak) may increase serum concentration of CloBAZam. CYP2C19 Inhibitors (Weak) may increase active metabolite exposure of CloBAZam. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Felbamate. Risk C: Monitor
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Fosphenytoin: May decrease serum concentration of Felbamate. Felbamate may increase serum concentration of Fosphenytoin. Management: Initiate felbamate at typical doses (1,200 mg/day in 3 or 4 divided doses for adults and children 14 years of age or older; 15 mg/kg/day in 3 or 4 divided doses in children 2 to 14 years of age) while reducing the fosphenytoin dose by 20%. Risk D: Consider Therapy Modification
Hormonal Contraceptives: Felbamate may decrease serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing felbamate to ensure contraceptive reliability. Risk D: Consider Therapy Modification
Mavacamten: CYP2C19 Inhibitors (Weak) may increase serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a weak CYP2C19 inhibitor, and reduce the mavacamten dose by one dose level if initiating a weak CYP2C19 inhibitor. Avoid initiating weak CYP2C19 inhibitors in patients on mavacamten 2.5 mg/day. Risk D: Consider Therapy Modification
Mefloquine: May decrease therapeutic effects of Antiseizure Agents. Mefloquine may decrease serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider Therapy Modification
MetyraPONE: Coadministration of Antiseizure Agents and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider Therapy Modification
Mianserin: May decrease therapeutic effects of Antiseizure Agents. Risk C: Monitor
Orlistat: May decrease serum concentration of Antiseizure Agents. Risk C: Monitor
PHENobarbital: May decrease serum concentration of Felbamate. Felbamate may increase serum concentration of PHENobarbital. Management: Initiate felbamate at typical doses (1,200 mg/day in 3 or 4 divided doses for adults and children 14 years of age or older; 15 mg/kg/day in 3 or 4 divided doses in children 2 to 14 years of age) while reducing the phenobarbital dose by 20%. Risk D: Consider Therapy Modification
Phenytoin: Felbamate may increase serum concentration of Phenytoin. Phenytoin may decrease serum concentration of Felbamate. Management: Initiate felbamate at typical doses (1,200 mg/day in 3 or 4 divided doses for adults and children 14 years of age or older; 15 mg/kg/day in 3 or 4 divided doses in children 2 to 14 years of age) while reducing the phenytoin dose by 20%. Risk D: Consider Therapy Modification
Primidone: Felbamate may increase active metabolite exposure of Primidone. Specifically, phenobarbital concentrations may increase. Primidone may decrease serum concentration of Felbamate. Management: Initiate felbamate at typical doses (1,200 mg/day in 3 or 4 divided doses for adults and children 14 years of age or older; 15 mg/kg/day in 3 or 4 divided doses in children 2 to 14 years of age) while reducing the primidone dose by 20%. Risk D: Consider Therapy Modification
Ulipristal: Felbamate may decrease serum concentration of Ulipristal. Risk X: Avoid
Valproic Acid and Derivatives: Felbamate may increase serum concentration of Valproic Acid and Derivatives. Management: Initiate felbamate at typical doses (1,200 mg/day in 3 or 4 divided doses for adults and children 14 years of age or older; 15 mg/kg/day in 3 or 4 divided doses in children 2 to 14 years of age) while reducing the valproate product dose by 20%. Risk D: Consider Therapy Modification
Vasopressin: Drugs Suspected of Causing SIADH may increase therapeutic effects of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor
Tablet: Food does not affect absorption. Management: Administer without regard to meals.
Postmarketing case reports in humans include fetal death, genital malformation, anencephaly, encephalocele, and placental disorder.
Patients exposed to felbamate during pregnancy are encouraged to enroll themselves into the North American Antiepileptic Drug (AED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.
Felbamate is excreted in breast milk. Until additional data is available, breastfeeding is not recommended (Bar-Oz 2000; Hägg 2000).
Serum levels of concomitant antiseizure therapy; LFTs (baseline, every 2 weeks after therapy initiation for the first 6 to 12 months of therapy, periodically thereafter); CBC (baseline, every 2 weeks for the first 6 to 12 months of therapy, periodically thereafter, and for a significant period after discontinuation); suicidality (eg, suicidal thoughts, depression, behavioral changes) (Abou-Khalil 2016; Pellock 2006; manufacturer's labeling).
While not entirely known, felbamate likely possesses multiple mechanisms of action, including NMDA antagonism, calcium and sodium channel inhibition, and potentiation of GABA response (Abou-Khalil 2016; White 1999; manufacturer’s labeling).
Absorption: Rapid and almost complete; food has no effect upon the tablet's absorption (Patsalos 2018; manufacturer’s labeling).
Distribution: Vd: 0.7 to 0.91 L/kg (Patsalos 2018).
Protein binding: 22% to 48 % (Patsalos 2017), primarily to albumin.
Half-life elimination: 20 to 23 hours (average); prolonged by 9 to 15 hours in patients with renal impairment.
Bioavailability: >90% (Patsalos 2018).
Time to peak, serum: 2 to 6 hours (Patsalos 2018).
Excretion: Urine (40% to 50% as unchanged drug, 40% as inactive metabolites).
Clearance: Decreased in renal impairment (40% to 50%). Clearance faster in children than adults (20% to 65%) (Perucca 2006), particularly younger children (Carmant 1994).
Children 2 to 9 years: 61.3 ± 8.2 mL/kg/hour.
Children 10 to 12 years: 34.3 ± 4.3 mL/kg/hour.
