Felbamate drug data and news

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Cognitive Side Effects of Antiepileptic Drugs in Children  Oct 3, 2005
Felbamate (Felbatol) was the first of the new generation AEDs to be introduced to the US market, but the development of idiosyncratic aplastic anemia and ... - Psychiatric Times,

Many meds don't mix with the sun  Sep 21, 2005
Anticonvulsants: Carbamaze-pine (Tegretol), felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), oxcarbazepine (Trileptal), topiramate (Topamax ... - Pioneer Press,

Drug interactions with the pill  Aug 31, 2005
Tegretol), phenytoin (Dilantin), phenobarbital, primidone (Mysoline), ethosuximide (Zarontin), oxcarbazepine (Trileptal), felbamate (Felbatol) and topiramate ... - Rochester Democrat and Chronicle,

Taking liver-taxing drugs calls for periodic testing  Apr 5, 2005
Celebrex), dapsone, diclofenac (Voltaren, Arthrotec), efavirenz (Sustiva), ethotoin (Peganone), ethosuximide (Zarontin), felbamate (Felbatol), fenofibrate ... - Contra Costa Times,

Taking liver-taxing drugs calls for periodic testing  Apr 5, 2005
Celebrex), dapsone, diclofenac (Voltaren, Arthrotec), efavirenz (Sustiva), ethotoin (Peganone), ethosuximide (Zarontin), felbamate (Felbatol), fenofibrate ... - Contra Costa Times,

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:

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.