Felbamate. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in epilepsy.
Felbamate is currently being developed as an antiepileptic agent. Although its mechanism of action has yet to be fully elucidated, felbamate appears to inhibit both the spread of seizures and increase seizure threshold in animal models. Data available in the clinical setting provide evidence that, at doses of up to 3600 mg/day as an adjunct to existing antiepileptic therapy or as monotherapy following substitution for other medications, the drug reduces the frequency of partial onset seizures in adult patients refractory to conventional antiepileptic treatments. Felbamate is also effective in the treatment of Lennox-Gastaut syndrome in children, a severe epilepsy which is usually refractory to antiepileptic agents. The effect of felbamate in the treatment of generalised tonic-clonic seizures in adults with partial onset seizures which are secondarily generalised is promising but requires clarification in large-scale trials. The most common adverse effects occurring during administration of felbamate are mild to moderate gastrointestinal (nausea, vomiting and anorexia) and central nervous system (headache, somnolence, diplopia, dizziness and insomnia) disturbances. Drug interactions with other antiepileptic agents may prove problematic in terms of adverse effects. Thus, at this stage of its development, the antiepileptic efficacy of felbamate in treatment-refractory patients with partial onset seizures and Lennox-Gastaut syndrome has been proven but efficacy in generalised tonic-clonic seizures requires further substantiation in large well controlled and well designed clinical trials. In addition, 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. The clinical implications of the drug interactions associated with felbamate also require more detailed investigation. These data will be awaited with interest and when available will help to place felbamate in perspective in the management of epilepsy.
Palmer
Katharine J
KJ
Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand.
McTavish
Donna
D
Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand.
D000293:Adolescent; D000328:Adult; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D004827:Epilepsy / Q000188:drug therapy*; D000078328:Felbamate; D006801:Humans; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011869:Radioligand Assay
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D000078328:Felbamate