Felbamate

Felbamate

Clinical data
Trade names	Felbatol
AHFS/Drugs.com	Monograph
MedlinePlus	a606011
Routes of administration	By mouth (tablets, oral suspension)
ATC code	N03AX10 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	>90%
Metabolism	Hepatic
Elimination half-life	20–23 hours
Identifiers
IUPAC name (3-carbamoyloxy-2-phenylpropyl) carbamate
CAS Number	25451-15-4 Y
PubChem CID	3331
IUPHAR/BPS	5473
DrugBank	DB00949 Y
ChemSpider	3214 Y
UNII	X72RBB02N8
KEGG	D00536 Y
ChEBI	CHEBI:4995 Y
ChEMBL	ChEMBL1094 Y
CompTox Dashboard (EPA)	DTXSID9023041
ECHA InfoCard	100.042.714
Chemical and physical data
Formula	C11H14N2O4
Molar mass	238.243 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(N)OCC(c1ccccc1)COC(N)=O
InChI InChI=1S/C11H14N2O4/c12-10(14)16-6-9(7-17-11(13)15)8-4-2-1-3-5-8/h1-5,9H,6-7H2,(H2,12,14)(H2,13,15) Y Key:WKGXYQFOCVYPAC-UHFFFAOYSA-N Y
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Felbamate (marketed under the brand name Felbatol by MedPointe) is an anticonvulsant^[1] used in the treatment of epilepsy. It is used to treat partial seizures^[2][3] (with and without generalization) in adults and partial and generalized seizures associated with Lennox–Gastaut syndrome in children. However, an increased risk of potentially fatal aplastic anemia and/or liver 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 of GABA_A receptors^[4][5] and as a blocker of NMDA receptors, particularly isoforms containing the NR2B 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 It was urgently withdrawn after 10 cases of aplastic anemia.^[11] A "Dear Doctor" letter was sent to 240,000 physicians.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.

• The drug is only available on a limited named-patient basis.

• Adults: Monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization.
• Children: Adjunctive therapy in the treatment of partial and generalized seizures associated with Lennox-Gastaut syndrome.

Felbamate is available in tablets (400 mg and 600 mg) and as a peach-coloured oral suspension (600 mg/5 mL).

• Adults (≥ 14 years): begin with 1,200 mg daily given every 6 to 8 hours
• Children (2–14 years): 15 to 45 mg per kg per day given every 6 to 8 hours

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. ^{[citation needed]}

Felbamate is an inhibitor of CYP2C19 - an enzyme involved in the metabolism of several commonly used medications.^[13] 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.^[14]

Felbamate was discovered by Frank Berger at Wallace Laboratories.^[15]

• Felbatol: Prescribing Information
• RxList: Felbamate contains extensive information including the patient warning and a sample consent form.
• Hard Choices with Felbamate
• Newer Antiepileptic Drugs: Gabapentin, Lamotrigine, Felbamate, Topiramate and Fosphenytoin Archived 2011-09-27 at the Wayback Machine
• MedPonte Pharmaceuticals