Felbamate is well absorbed following oral administration, with bioavailability exceeding 90%. Felbamate is not extensively bound to plasma proteins, is about 40–50% eliminated via hepatic metabolism, and is about 50–60% excreted unchanged in the urine.

Felbamate is a low-extraction drug and is metabolized mainly by hydroxylation and conjugation.30-31

Effect of liver disease

Because felbamate is not extensively protein-bound, the free fraction is not significantly changed in liver disease. The effect of liver disease on the metabolism of felbamate is unknown. The mixture of renal and hepatic elimination may minimize the effect of liver disease. Patients with impairment of both kidney and liver function would be expected to have a reduced clearance of felbamate.

When felbamate was initially approved by the U.S. Food and Drug Administration (FDA), it was felt to be extremely well tolerated. However, after 100,000 patient exposures, the use of felbamate was associated with the occurrence of aplastic anemia and hepatotoxicity. These side effects are potentially fatal. Hepatotoxicity occurs less often than aplastic anemia. The incidence of hepatotoxicity with felbamate is felt to be comparable to the incidence with valproic acid. The patients developing hepatotoxicity were predominantly female, were equally divided between adult and pediatric patients, and had a broad range of time to presentation after starting felbamate therapy. The role of concomitant therapy with other drugs that may cause liver disease is unclear. A reactive metabolite, atropaldehyde, may be responsible for the hepatotoxicity. HLA studies may identify high risk patients.

Felbamate is still available, but the approval of other AEDs has relegated it to deep reserve status. It is unlikely that it would be used for patients with liver disease without careful consideration. Felbamate may be considered for patients who have failed other therapies. It is also useful in treating the Lennox-Gastaut syndrome.

Patients who start taking felbamate should be closely monitored for any signs of bone marrow suppression such as easy bruising, sore throat, or infections, and for the prodromal symptoms of liver disease, such as lethargy, dark urine, and jaundice.

Effect of GI disease

The effect of GI disease on the pharmacokinetics of felbamate is unknown.

Adapted from: Garnett WR. Gastrointestinal and hepatic disease. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;63-74. 
With permission from Elsevier (www.elsevier.com). 

Reviewed By: 
Steven C. Schachter, MD
Monday, March 1, 2004