Felbamate aplastic anemia

Felbamate, a new anticonvulsant, has beneficial effects in partial and secondarily generalized seizures.lt can reduce symptoms in Lennox-Gastaut syndrome. However an association with aplastic anemia reduces its usefulness and Lennox-Gastaut syndrome is considered to be its only indication. 

Felbamate (Felbatol) was introduced with the expectation that it would become a major drug in the treatment of epilepsy. Felbamate exhibited few manifestations of serious toxicity in early clinical trials. Soon after its introduction, however, it became apparent that its use was associated with a high incidence of aplastic anemia. Consequently, felbamate is indicated only for patients whose epilepsy is so severe that the risk of aplastic anemia is considered acceptable. 

Felbamate has been approved and marketed in the USA and in some European countries. Although it is effective in some patients with partial seizures, the drug causes aplastic anemia and severe hepatitis at unexpectedly high rates and has been relegated to the status of a third-line drug for refractory cases. 

Hypersusceptibility reactions can involve any system, but they most often affect the skin, leading to drug withdrawal in up to 20% of patients. Aplastic anemia and hepatotoxicity have drastically curtailed the use of felbamate. 

Felbamate is a broad-spectrum antiepileptic drug, whose use has been drastically curtailed owing to the risks of aplastic anemia and hepatotoxicity. 

Of 34 cases of aplastic anemia (mean age 41 years, mean time of felbamate exposure 154 days), 20 occurred in combination with other compounds implicated as a possible cause of aplastic anemia and 5 occurred concurrently with viral infections (7). Although 5 patients were taking felbamate monotherapy, 13 of the 34 suffered from autoimmune disease, and 1 was receiving cytostatic therapy. Past allergic or toxic reactions to other anticonvulsants were reported by 65% of the patients and blood dyscrasias by 45%, while 32% had serological evidence of a previous immune disorder. Eight of nine patients tested had experienced at least one episode of aplastic anemia associated with HLA antigens. 

Because felbamate-induced aplastic anemia might be linked to the formation of atropaldehyde, a urine screening test has been developed that indirectly assesses the formation of this toxic metabolite (8). The risk of serious toxicity may also be related to HLA status, and HLA typing is being performed in patients entered in the manufacturer s felbamate registry. The potential value of these tests in reducing the risk of toxicity remains to be established. 

Pennell PB, OgaUy MS, Macdonald RL. Aplastic anemia in a patient receiving felbamate for complex partial seizures. Neurology 1995 45(3 Pt l) 456-60. 

Kaufman DW, Kelly JP, Anderson T, Harmon DC, Shapiro S. Evaluation of case reports of aplastic anemia among patients treated with felbamate. Epilepsia 1997 38(12) 1265-9. 

Felbamate. Felbamate is an adjuvant anticonvulsant, containing the warning that its use is associated with a marked increase in the incidence of aplastic anemia and that patients being started on the drug should have liver function tests performed before therapy is initiated. Animal studies have revealed a statistically significant increase in hepatic cell adenomas in high dose studies (18). It is postulated that this cancer was induced by toxic by-products urethane and methyl carbamate. Felbamate is not recommended as first-line therapy and is indicated for those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia or liver failure is deemed acceptable in light of the benefits provided by its use. 

Felbamate, proprietary name Felhatol, was approved for primary or adjunctive therapy of partial seizures. Its use is limited to those patients who fail other drug treatments, because felbamate carries with it a substantial risk of aplastic anemia and hver failure that is not related to the blood level. Biweekly monitoring of complete blood count, serum ammotransferases, and bilirubin is recommended to detect early onset of these side effects. Felbamate is particularly effective in control of Lennox-Gastaut syndrome. 

Disadvantages. The use of felbamate is limited by the association with aplastic anemia and hepatotoxicity, as well as multiple drug interactions. 

Felbamate Blocks Na+ and Ca2+ channels blocks glutamate receptors Partial seizures, Lennox-Gastaut Syndrome, myoclonic (adjunct) Aplastic anemia, acute liver failure 1 i... 

Felbamate (Felbatol) is a dicarbamate that was approved by the FDA for partial seizures in 1993. An association between felbamate and aplastic anemia in at least 10 cases resulted in a recommendation by the FDA and the manufacturer for the immediate withdrawal of most patients from treatment with this drug. 

Felbamate is a dicarbamate that is structurally similar to the antianxiety drug meprobamate. It was approved by the U.S. FDA for antiseizure use in 1993. Following the occurrence of rare cases of aplastic anemia and of severe hepatotoxicity associated with the use of felbamate during early 1994, however, a black box warning was added to the drug s package insert (53). 

Felbamate has exhibited the rare occurrence of aplastic anemia and of severe hepatotoxicity, which may be associated with the... 

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