Dosing and uses of Felbatol (felbamate)
Adult dosage forms and strengths
tablets
- 400 mg
- 600 mg
oral suspension
- 600 mg/5 mL
Seizures
Monotherapy
- 1200 mg/day PO divided q6-8hr initially; titrate previously untreated patients with caution, increasing the dose in 600 mg increments q2weeks to 2400 mg/day based on clinial response and thereafter to 3600 mg/day if necessary
Conversion to monotherapy
- Initial: 1200 mg/day PO divided q6-8hr; reduce dose of concomitant anticonvulsant(s) by 33% at initiation of felbamate therapy
- Week 2: Increase felbamate dose to 2400 mg/day while reducing the dosage of other anticonvulsant(s) up to an additional 33% of original dosage
- Week 3: Increase felbamate dose up to 3600 mg/day and continue to reduce dosage of other anticonvulsant(s) as clinically indicated
Adjunctive therapy
- Initial: 1200 mg/day PO divided q6-8hr; increase by 1200 mg/day once per week up to 3600 mg/day PO divided q6-8hr
- Decrease concomitant dose of carbamazepine, phenytoin, phenobarbital, or valproic acid by 20 % when intiating felbamate dosing; as felbamate dose is increased, further dosage reductions of concomitant anticonvulsant therapies may be necessary
Renal Impairment
Decreased intial and maintenance doses by 50%
Hepatic Impairment
Contraindicated
Pediatric dosage forms and strengths
tablets
- 400 mg
- 600 mg
oral suspension
- 600 mg/5mL
Seizures
<14 years: Safety and efficacy not established
>14 years:
Monotherapy
- 1200 mg/day PO divided q6-8hr initially; titrate previously untreated patients with caution, increasing the dose in 600 mg increments q2weeks to 2400 mg/day based on clinial response and thereafter to 3600 mg/day if necessary
Conversion to monotherapy
- Initial: 1200 mg/day PO divided q6-8hr; reduce dose of concomitant anticonvulsant(s) by 33% at initiation of felbamate therapy
- Week 2: Increase felbamate dose to 2400 mg/day while reducing the dosage of other anticonvulsant(s) up to an additional 33% of original dosage
- Week 3: Increase felbamate dose up to 3600 mg/day and continue to reduce dosage of other anticonvulsant(s) as clinically indicated
Adjunctive therapy
- Initial: 1200 mg/day PO divided q6-8hr; increase by 1200 mg/day once per week up to 3600 mg/day PO divided q6-8hr
- Decrease concomitant dose of carbamazepine, phenytoin, phenobarbital, or valproic acid by 20 % when intiating felbamate dosing; as felbamate dose is increased, further dosage reductions of concomitant anticonvulsant therapies may be necessary
Lennox-Gastaut Adjunctive Therapy
<2 years
- Safety and efficacy not established
2-14 years
- Initial: 15 mg/kg/day PO divided q6-8hr
- May increase to by 15 mg/kg/day qWeek to 45 mg/kg/day
- Decrease concomitant dose of carbamazepine, phenytoin, phenobarbital, or valproic acid by 20 % when intiating felbamate dosing; as felbamate dose is increased, further dosage reductions of concomitant anticonvulsant therapies may be necessary
Felbatol (felbamate) adverse (side) effects
>10%
Adjunctive therapy
- Nausea (34.2%)
- Vomiting (16.7%)
- Constipation (11.4%)
- Dyspepsia (12.3%)
- Anorexia (19.3%)
- Dyspepsia (12.3%)
Lennox-Gastaut
- Anorexia (55%)
- Somnolence (48%)
- URI (46-50%)
- Vomiting (39%)
- Nervousness (16-20%)
- Insomnia (16.1%)
- Purpura (11-15%)
- Fever (22.6%)
- Constipation (12.9%)
1-10%
Monotherapy
- Acne (3.4%)
- Anxiety (5.2%)
- Constipation (6.9%)
- Diarrhea (5.2%)
- Diplopia (3.4%)
- Dyspepsia (8.6%)
- Face edema (3.4%)
- Fatigue (6.9%)
- Headache (6.9%)
- Insomnia (8.6%)
- Intramenstrual bleeding (3.4%)
- Otitis media (3.4%)
- Rash (3.4%)
- Urinary tract infection (3.4%)
- Vomiting (8.6%)
Adjunctive therapy
- Abdominal pain (5.3%)
- Abnormal gait (5.3%)
- Anxiety (5.3%)
- Ataxia (3.5%)
- Depression (5.3%)
- Increased ALT (3.5%)
- Diarrhea (5.3%)
- Dry mouth (2.6%)
- Diplopia (6-10%)
- Paresthesia (3.5%)
- Pharyngitis (2.6%)
- Stupor (2.6%)
- Sinusitis (2-5%)
- Tremor (6.1%)
- Upper respiratory infection (5.3%)
Lennox-Gastaut
- Abnormal gait (9.7%)
- Abnormal thoughts (6.5%)
- Ataxia (6.5%)
- Dyspepsia (6.5%)
- Emotional lability (6.5%)
- Fatigue (9.7%)
- Headache (6.5%)
- Hiccup (9.7%)
- Leukopenia (6.5%)
- Miosis (6.5%)
- Nausea (6.5%)
- Coughing (6.5%)
- Pain (6.5%)
- Pharyngitis (9.7%)
- Otitis media (6-10%)
<1%
Atrial arrhythmia
Bradycardia
Hypotension
Thrombophlebitis
Cerebral edema
Coma
Alopecia
Jaundice
Hepatic failure
Rigors
Rhabdomyolysis
Warnings
Black box warnings
Aplastic anemia associated with felbamate use. Risk 100-fold in felbamate-treated patients compared with untreated population.
May be fatal. Use only in patients with severe epilepsy in whom risk of aplastic anemia is acceptable.
Acute liver failure reported with use; initiate use in patients with normal liver function.
Contraindications
Hypersensitivity to carbamates; history of blood dyscrasia, hepatic impairment
Cautions
Increased risk of suicidal behavior reported with anticonvulsant use; monitor patients for changes in behavior that might indicate suicidal behavior
Associated with increased incidence of aplastic anemia and acute hepatic failure , use only when alternative therapy is unsuitable and benefits outweigh risks
Use caution in renal impairment
Not for use as first line therapy in epilepsy; for use when benefits outweigh risks
Do not discontinue therapy abruptly
Pregnancy and lactation
Pregnancy category: C
Lactation: Excreted in milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Felbatol (felbamate)
Mechanism of action
Mechanism of action is unknown. Has weak inhibitory effects on GABA-receptor binding and benzodiazepine receptor binding.
Pharmacokinetics
Half-Life: 20-23 hr
Peak Plasma: 17-49 mcg/mL (dose-dependent)
Peak serum time: 3-5 hr
Bioavailability: High
Protein bound: 22-25%
Vd: 756 mL/kg
Metabolism: Liver
Metabolites: Inactive
Total body clearance: 26 mL/hr/kg (single dose); 30 mL/hr/kg (mult. doses)
Excretion: Urine (80-90%)
Enzyme induced: CYP3A4
Enzyme inhibited: hepatic CYP2C19
