Felbamate (marketed under the brand name Felbatol by MedPointe) is an anticonvulsant
Mechanism of action
Felbamate has been proposed to have a unique dual mechanism of action as a positive modulator of
GABAA receptor and as a blocker of
, particularly isoforms containing the NR2B subunit.
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.
Therefore, the importance of the effects of felbamate on NMDA receptors to its therapeutic action in epilepsy is uncertain.
Approval history
United States
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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.
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August 1, 1994. It was urgently withdrawn after 10 cases of aplastic anemia.
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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.
United Kingdom
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The drug is only available on a limited named-patient basis.
Indications and usage
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Adults: Monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization.
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Children: Adjunctive therapy in the treatment of partial and generalized seizures associated with Lennox-Gastaut syndrome.
Dosing
Felbamate is available in tablets (400 mg and 600 mg) and as a peach-coloured oral suspension (600 mg/5 mL).
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Adults (≥ 14 years): begin with 1,200 mg daily given every 6 to 8 hours
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Children (2–14 years): 15 to 45 mg per kg per day given every 6 to 8 hours
Side effects
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 include
aplastic 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.
Drug interactions
Felbamate is an
enzyme inhibitor of CYP2C19 - an enzyme involved in the
drug metabolism of several commonly used medications.
[ Retrieved on December 25, 2008.] Felbamate interacts with several other AEDs, including
phenytoin,
valproate, and
carbamazepine; 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 of
carbamazepine-10,11 epoxide, the active
metabolite of carbamazepine.
History
Felbamate was discovered by
Frank Berger at
Carter-Wallace.
External links
