Felbatol
Felbatol - General Information
Felbatol 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.
Pharmacology of Felbatol
Felbatol is an antiepileptic indicated as monotherapy or as an adjunct to other anticonvulsants for the treatment of partial seizures resulting from epilepsy. 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.
Felbatol for patients
Patient Information:
Felmabate can cause severe blood abnormality, hepatic failure and other fatal
conditions. Talk about the risks and side effects with your doctor before taking it.
Do not stop the medication without consulting your doctor. Finish the medication
even if you feel better.
Felbatol Interactions
The drug interaction data described in this section were obtained from controlled clinical trials and studies involving otherwise healthy adults with epilepsy.
Use in Conjunction with Other Antiepileptic Drugs:
The addition of Felbatol to antiepileptic drugs (AEDs) affects the steady-state plasma concentrations of AEDs. The net effect of these interactions is summarized in the following table:
| AED | AED | Felbatol |
| Coadministered | Concentration | Concentration |
| Phenytoin | Ó | ¯ |
| Valproate | Ó | «** |
| Carbamazepine (CBZ) | ¯ | ¯ |
| *CBZ epoxide | Ó | |
| Phenobarbital | Ó | ¯ |
|
*Not administered, but an active metabolite of carbamazepine.
|
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|
**No significant effect. |
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Specific Effects of Felbatol on Other Antiepileptic Drugs
Phenytoin: Felbatol causes an increase in steady-state phenytoin plasma concentrations. In 10 otherwise healthy subjects with epilepsy ingesting phenytoin, the steadystate trough (Cmin) phenytoin plasma concentration was 17±5 micrograms/mL. The steady-state Cmin increased to 21±5 micrograms/mL when 1200 mg/day of felbamate was coadministered. Increasing the felbamate dose to 1800 mg/day in six of these subjects increased the steady-state phenytoin Cmin to 25±7 micrograms/mL. In order to maintain phenytoin levels, limit adverse experiences, and achieve the felbamate dose of 3600 mg/day, a phenytoin dose reduction of approximately 40% was necessary for eight of these 10 subjects.
In a controlled clinical trial, a 20% reduction of the phenytoin dose at the initiation of Felbatol therapy resulted in phenytoin levels comparable to those prior to Felbatol administration.
Carbamazepine: Felbatol causes a decrease in the steady-state carbamazepine plasma concentrations and an increase in the steady-state carbamazepine epoxide plasma concentration. In nine otherwise healthy subjects with epilepsy ingesting carbamazepine, the steady-state trough (Cmin) carbamazepine concentration was 8±2 micrograms/mL. The carbamazepine steady-state Cmin decreased 31% to 5±1 micrograms/mL when felbamate (3000 mg/day, divided into three doses) was coadministered. Carbamazepine epoxide steady-state Cmin concentrations increased 57% from 1.0±0.3 to 1.6±0.4 micrograms/mL with the addition of felbamate.
In clinical trials, similar changes in carbamazepine and carbamazepine epoxide were seen.
Valproate: Felbatol causes an increase in steady-state valproate concentrations. In four subjects with epilepsy ingesting valproate, the steady-state trough (Cmin) valproate plasma concentration was 63±16 micrograms/mL. The steady-state Cmin increased to 78±14 micrograms/mL when 1200 mg/day of felbamate was coadministered. Increasing the felbamate dose to 2400 mg/day increased the steadystate valproate Cmin to 96±25 micrograms/mL. Corresponding values for free valproate Cmin concentrations were 7±3, 9±4, and 11±6 micrograms/mL for 0, 1200, and 2400 mg/day Felbatol, respectively. The ratios of the AUCs of unbound valproate to the AUCs of the total valproate were 11.1 %, 13.0%, and 11.5%, with coadministration of 0, 1200, and 2400 mg/day of Felbatol, respectively. This indicates that the protein binding of valproate did not change appreciably with increasing doses of Felbatol
Phenobarbital: Coadministration of felbamate with phenobarbital causes an increase in phenobarbital plasma concentrations, In 12 otherwise healthy male volunteers ingesting phenobarbital, the steady-state trough (Cmin) phenobarbital concentration was 14.2 micrograms/mL. The steady-state Cmin concentration increased to 17.8 micrograms/mL when 2400 mg/day of felbamate was coadministered for one week.
Effects of Other Antiepileptic Drugs on Felbatol
Phenytoin: Phenytoin causes an approximate doubling of the clearance of Felbatol (felbamate) at steady state and, therefore, the addition of phenytoin causes an approximate 45% decrease in the steady-state trough concentrations of Felbatol as compared to the same dose of Felbatol given as monotherapy.
Carbamazepine: Carbamazepine causes an approximate 50% increase in the clearance of Felbatol at steady state and, therefore, the addition of carbamazepine results in an approximate 40% decrease in the steady-state trough concentrations of Felbatol as compared to the same dose of Felbatol given as monotherapy.
Valproate: Available data suggest that there is no significant effect of valproate on the clearance of Felbatol at steady state, Therefore, the addition of valproate is not expected to cause a clinically important effect on Felbatol (felbamate) plasma concentrations.
Phenobarbital: It appears that phenobarbital may reduce plasma felbamate concentrations. Steady-state plasma felbamate concentrations were found to be 29% lower than the mean concentrations of a group of newly diagnosed subjects with epilepsy also receiving 2400 mg of felbamate a day.
Effects of Antacids on Felbatol
The rate and extent of absorption of a 2400 mg dose of Felbatol as monotherapy given as tablets was not affected when coadministered with antacids.
Effects of Erythromycin on Felbatol
The coadministration of erythromycin (1000 mg/day) for 10 days did not alter the pharmacokinetic parameters of Cmax, Cmin, AUC, CI/kg or tmax at felbamate daily doses of 3000 or 3600 mg/day in 10 otherwise healthy subjects with epilepsy.
Effects of Felbatol on Low-Dose Combination Oral Contraceptives
A group of 24 nonsmoking, healthy white female volunteers established on an oral contraceptive regimen containing 30 mg ethinyl estradiol and 75 mg gestodene for at least 3 months received 2400 mg/day of felbamate from midcycle (day 15) to midcycle (day 14) of two consecutive oral contraceptive cycles. Felbamate treatment resulted in a 42% decrease in the gestodene AUC 0-24, but no clinically relevant effect was observed on the pharmacokinetic parameters of ethinyl estradiol. No volunteer showed hormonal evidence of ovulation, but one volunteer reported intermenstrual bleeding during felbamate treatment.
Felbatol Contraindications
Felbatol is contraindicated in patients with known hypersensitivity to Felbatol, its ingredients, or known sensitivity to other carbamates. It should not be used in patients with a history of any blood dyscrasia or hepatic dysfunction.
Additional information about Felbatol
Felbatol Indication: For use only in those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia and/or liver failure is deemed acceptable in light of the benefits conferred by its use.
Mechanism Of Action: The mechanism by which felbamate exerts its anticonvulsant activity is unknown, but in animal test systems designed to detect anticonvulsant activity, felbamate has properties in common with other marketed anticonvulsants. 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.
Drug Interactions: Carbamazepine Decreased effect of both products
Divalproex sodium Felbatol increases the effect of valproate
Ethotoin Increased phenytoin levels and decreased felbamate levels
Fosphenytoin Increased phenytoin levels and decreased felbamate levels
Mephenytoin Increased phenytoin levels and decreased felbamate levels
Phenytoin Increased phenytoin levels and decreased felbamate levels
Phenobarbital Felbatol increases the effect and toxicity of phenobarbital/primidone
Primidone Felbatol increases the effect and toxicity of phenobarbital/primidone
Quinupristin This combination presents an increased risk of toxicity
Food Interactions: Taking it after a meal may reduce the incidence of adverse effects.
Generic Name: Felbamate
Synonyms: Not Available
Drug Category: Antiepileptic Agents; Anticonvulsants; Neuroprotective Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Felbamate: Felbamyl; Felbatol; Taloxa;
Absorption: >90%
Toxicity (Overdose): LD50=5000 mg/kg (Orally in rats)
Protein Binding: 20-36%
Biotransformation: Hepatic
Half Life: 20-23 hours
Dosage Forms of Felbatol: Tablet Oral
Suspension Oral
Chemical IUPAC Name: (3-carbamoyloxy-2-phenylpropyl) carbamate
Chemical Formula: C11H14N2O4
Felbamate on Wikipedia: https://en.wikipedia.org/wiki/Felbamate
Organisms Affected: Humans and other mammals
