Felbamate
Felbamate is an anticonvulsant medication used primarily to treat seizures in patients with severe epilepsy syndromes, particularly Lennox-Gastaut syndrome and refractory partial seizures. While effective, its use is limited due to the risk of severe side effects, including aplastic anemia and liver toxicity.
Trade Names
Felbamate is marketed under the trade name Felbatol.
Chemical Properties
Chemical Structure: Felbamate is a dicarbamate derivative structurally related to meprobamate.
Molecular Formula: C₁₁H₁₄N₂O₄
Molecular Weight: 238.24 g/mol
Solubility: Felbamate is water-soluble and available in tablet and oral suspension forms.
Biochemical Properties
Mechanism of Action:
Modulation of NMDA (N-methyl-D-aspartate) receptors by selectively blocking the glycine site, reducing excitatory neurotransmission.
Potentiation of GABAergic (gamma-aminobutyric acid) inhibitory neurotransmission.
Inhibition of voltage-gated sodium channels, decreasing neuronal excitability.
Pharmacology
Administration: Felbamate is administered orally as tablets or as an oral suspension.
Bioavailability: It has high oral bioavailability (greater than 90%).
Metabolism: Felbamate is metabolized in the liver through hydroxylation and conjugation pathways, producing metabolites, some of which may contribute to its toxicity.
Half-Life: The half-life of Felbamate is approximately 20–23 hours, allowing twice-daily dosing.
Clinical Indications
Lennox-Gastaut Syndrome: Approved for use in treating this severe and treatment-resistant epilepsy syndrome, significantly to reduce drop attacks.
Refractory Partial Seizures: Used in patients who have not responded to other antiepileptic medications.
Off-Label: Occasionally considered for other severe epilepsy syndromes under careful monitoring.
Side Effects
Insomnia Nausea Vomiting Headache Dizziness Loss of appetite and weight loss
Aplastic Anemia: A rare but life-threatening reduction in bone marrow activity, necessitating regular blood count monitoring.
Hepatotoxicity: Risk of severe liver damage, requiring liver function tests at regular intervals.
Monitoring and Precautions
Hematological Monitoring: Regular, complete blood counts (CBC) are required to detect early signs of aplastic anemia.
Liver Function Tests: Periodic liver function tests are necessary to monitor for signs of hepatotoxicity.
Use in Pregnancy: The safety of Felbamate during pregnancy is not well established, so it is generally avoided unless no alternatives exist.
Drug Interactions: Felbamate can interact with other antiepileptic drugs, altering their metabolism. Adjustments to doses of co-administered medications such as phenytoin, carbamazepine, and valproate may be required.
Discontinuation: If Felbamate must be stopped, the dose should be tapered gradually to avoid withdrawal seizures.
