Felbamate (marketed under the brand nameFelbatol byMedPointe) is ananticonvulsant[1] used in the treatment ofepilepsy. It is used to treatpartial seizures[2][3] (with and without generalization) in adults and partial and generalized seizures associated withLennox–Gastaut syndrome in children. However, an increased risk of potentially fatalaplastic anemia and/orliver failure limit the drug's usage to severe refractory epilepsy.
Felbamate has been proposed to have a unique dual mechanism of action as a positive modulator ofGABAA receptors[4][5] and as a blocker ofNMDA receptors, particularly isoforms containing theNR2B subunit.[6][7][8][9] Although it is clear that felbamate does cause pharmacological inhibition of NMDA receptors, the relevance of NMDA receptor blockade as a strategy for the treatment of human epilepsy has been questioned.[10] Therefore, the importance of the effects of felbamate on NMDA receptors to its therapeutic action in epilepsy is uncertain.
August 1993. Felbamate was approved for partial seizures with and without secondary generalization in adults and for Lennox–Gastaut Syndrome, a serious form of childhood epilepsy. Over the following year 150,000 people were started on felbamate therapy and a third of these became established.
August 1, 1994. It was urgently withdrawn after 10 cases of aplastic anemia.[11] A "Dear Doctor" letter was sent to 240,000 physicians.
September 27, 1994. Felbamate had a limited redemption in another "Dear Doctor" letter sent to 260,000 physicians. It was recommended that the drug remain available only for patients with severe epilepsy for whom the benefits outweigh the risks, and that changes be made to the product's labelling to reflect the newly recognized risk.[12] This redemption came with an additional warning since there had been 10 cases acute liver failure (4 of which were fatal). At this point, 10,000 to 12,000 people remained on the drug.
Adverse reactions include decreased appetite, vomiting,insomnia, nausea, dizziness, somnolence, and headache. Many patients report increased alertness with the drug.Two rare but very serious effects includeaplastic anemia and serious liver damage. The risk of aplastic anemia is between 1:3,600 and 1:5,000, of which 30% of cases are fatal. The risk of liver damage is between 1:24,000 to 1:34,000, of which 40% of cases are fatal.[citation needed]
Felbamate is aninhibitor ofCYP2C19 - an enzyme involved in themetabolism of several commonly used medications.[13] Felbamate interacts with several other AEDs, includingphenytoin,valproate, andcarbamazepine; dosage adjustments may be necessary to avoid adverse effects. Concomitant administration of felbamate and carbamazepine decreases blood levels of both drugs, while increasing the level ofcarbamazepine-10,11 epoxide, the activemetabolite of carbamazepine.[14]
^Rho JM, Donevan SD, Rogawski MA (Feb 1994). "Mechanism of Action of the Anticonvulsant Felbamate: Opposing Effects onN-Methyl-D-aspartate and Gamma-Aminobutyric Acid A Receptors".Annals of Neurology.35 (2):229–34.doi:10.1002/ana.410350216.PMID8109904.S2CID33913077.
