Felbamate in epilepsy therapy: evaluating the risks

Felbamate demonstrates a unique therapeutic profile and often results in seizure control when other agents fail. Its use has been associated with risks for aplastic anaemia and hepatic failure. A number of confounding factors makes the actual incidence rate for each adverse effect difficult to determine. However, certain risk factors are common in reported cases. In order to minimise the risk, at the present time, it is necessary to rely on the clinical profile of the patients reporting these adverse effects. The patient reporting aplastic anaemia is usually female, Caucasian, and an adult. The dose did not appear to be a factor and the time to onset of aplastic anaemia was less than 1 year for all patients. Concomitant medications and diseases may play an important role. Patients with reported aplastic anaemia generally had a history of a serious allergy or toxicity to other anticonvulsants and/or a background of having had a cytopenia due to other anticonvulsants, and a diagnosis or serological evidence of concomitant immune disorder. The demographics associated with hepatic failure are less well defined. Patients were also predominantly female, were equally divided among adult and paediatric patients, and had a broad range of time to presentation of hepatotoxicity following felbamate therapy. Concomitant medications again play an important role with, in this case, valproic acid (sodium valproate), phenytoin and carbamazepine being the most frequent. In 50% of the population, hepatic failure was not felt to be due to felbamate but associated with confounding factors including status epilepticus, paracetamol (acetaminophen) toxicity, hepatitis and shock liver. Initial research has failed to provide a diagnostic indicator. However, work on a potential intermediate felbamate metabolite has suggested the formation of a reactive aldehyde whose end products have been detected in the urine of felbamate treated patients. Until these data are confirmed, the medical history, clinical picture, and laboratory testing, should be used to identify patients at risk. The risks for toxicity with felbamate should be evaluated before starting treatment. In addition, liver function tests and complete blood count (CBC) prior to therapy and at clinically rational intervals should be conducted. Patients must be educated in the likely prodromal symptoms of potential marrow/liver toxicity. Felbamate is too valuable an anticonvulsant to be relegated to the therapeutic scrap heap. With monitoring, patient education, and continued research to further elucidate risk factors, felbamate can be a viable therapeutic agent for patients with epilepsy.