Drug information of Felbamate

Felbamate

Drug group: Anticonvulsants

Felbamate is an anticonvulsant drug used in the treatment of epilepsy . It is used to treat partial seizures (with and without generalization) in adults and partial and generalized seizures associated with Lennox-Gastaut syndrome in children.

 It has a weak inhibitory effect on GABA receptor binding sites.

Mechanism of effect

The mechanism by which felbamate exerts its anticonvulsant activity is unknown. In vitro receptor binding studies suggest that felbamate may be an antagonist at the strychnine-insensitive glycine-recognition site of the N-methyl-D-aspartate (NMDA) receptor-ionophore complex.

 Antagonism of the NMDA receptor glycine binding site may block the effects of the excitatory amino acids and suppress seizure activity. Animal studies indicate that felbamate may increase the seizure threshold and may decrease seizure spread. It is also indicated that felbamate has weak inhibitory effects on GABA-receptor binding, benzodiazepine receptor binding.

Pharmacodynamic

Receptor-binding studies in vitro indicate that felbamate has weak inhibitory effects on GABA-receptor binding, benzodiazepine receptor binding, and is devoid of activity at the MK-801 receptor binding site of the NMDA receptor-ionophore complex.

However, felbamate does interact as an antagonist at the strychnine-insensitive glycine recognition site of the NMDA receptor-ionophore complex.

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

Drug indications

Seizure Disorders

Dosage

Adult

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

Pediatric

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

Drug contraindications

liver failure

Alerts

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

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.

Points of recommendation

Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine (felbamate tablets) affects you.

Do not stop taking this medicine (felbamate tablets) all of a sudden without calling your doctor. You may have a greater risk of seizures. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.

Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.

Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking this medicine (felbamate tablets).

Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine (felbamate tablets) while you are pregnant.

Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Pregnancy level

C

Related drugs

Carbamazepine


Ask a Pharmacist


User's questions
    No comments yet.