From the Guidelines
Felbamate concentration fluctuations can cause significant morbidity and mortality due to breakthrough seizures or adverse effects, and thus, require careful management to maintain therapeutic levels. When considering the management of felbamate concentration fluctuations, several factors come into play, including dosing schedules, food interactions, and drug-drug interactions. According to the provided evidence, rifamycins can substantially decrease the concentrations of various drugs, including anticonvulsants like phenytoin and lamotrigine 1. Although felbamate is not directly mentioned in the table of clinically significant drug-drug interactions involving rifamycins, the principle of drug interactions affecting anticonvulsant levels is relevant. Key considerations for managing felbamate concentration fluctuations include:
- Consistent dosing schedules to maintain stable blood levels, given felbamate's relatively short half-life of 20-23 hours.
- Awareness of potential drug-drug interactions, particularly with other antiepileptic medications, which can alter felbamate concentrations.
- The importance of therapeutic drug monitoring to adjust dosages as needed and prevent adverse effects or breakthrough seizures.
- Consideration of individual variations in metabolism and the potential impact of hepatic impairment on drug clearance. Given the potential for significant morbidity and mortality associated with felbamate concentration fluctuations, therapeutic drug monitoring is recommended to ensure that felbamate levels remain within a therapeutic range. This approach allows for the adjustment of felbamate dosages in response to changes in the patient's regimen or clinical status, thereby minimizing the risk of adverse effects or therapeutic failure 1.
From the FDA Drug Label
Felbamate causes an increase in steady-state phenytoin plasma concentrations... Felbamate causes a decrease in the steady-state carbamazepine plasma concentrations and an increase in the steady-state carbamazepine epoxide plasma concentration. Felbamate causes an increase in steady-state valproate concentrations. Coadministration of felbamate with phenobarbital causes an increase in phenobarbital plasma concentrations Phenytoin causes an approximate doubling of the clearance of felbamate at steady-state and, therefore, the addition of phenytoin causes an approximate 45% decrease in the steady state trough concentrations of felbamate as compared to the same dose of felbamate given as monotherapy Carbamazepine causes an approximate 50% increase in the clearance of felbamate at steady-state and, therefore, the addition of carbamazepine results in an approximate 40% decrease in the steady-state trough concentrations of felbamate as compared to the same dose of felbamate given as monotherapy Available data suggest that there is no significant effect of valproate on the clearance of felbamate at steady-state. It appears that phenobarbital may reduce plasma felbamate concentrations
The fluctuations in felbamate concentration are caused by:
- Phenytoin: decreases felbamate concentration by approximately 45%
- Carbamazepine: decreases felbamate concentration by approximately 40%
- Valproate: has no significant effect on felbamate concentration
- Phenobarbital: may reduce felbamate concentration 2
From the Research
Felbamate Concentration Fluctuations
- Felbamate is an antiepileptic drug that has been shown to be effective in reducing the frequency of partial onset seizures in adult patients refractory to conventional antiepileptic treatments 3
- The drug has also been found to be effective in the treatment of Lennox-Gastaut syndrome in children, a severe epilepsy that is usually refractory to antiepileptic agents 3
- However, felbamate has been associated with a high risk of aplastic anemia and hepatotoxicity, and its use should be considered only for persons with intractable epilepsy under the care of a physician familiar with the drug 4, 5, 6
- The most common adverse effects occurring during administration of felbamate are mild to moderate gastrointestinal and central nervous system disturbances 3
- Drug interactions with other antiepileptic agents may prove problematic in terms of adverse effects, and a more comprehensive base of comparative clinical trials data is necessary to further clarify issues of relative efficacy and tolerability compared with other antiepileptic agents 3, 4
Factors Affecting Felbamate Concentration
- Felbamate may induce the metabolism of steroid oral contraceptives, and it also acts as a metabolic inhibitor 4
- The drug has a potential for significant side effects, and its use should be prescribed by physicians experienced in managing patients with complicated epilepsy 7
- A slower dose-escalation schedule and/or being more aggressive in decreasing co-medication may decrease the side effects experienced by patients taking felbamate 6