Felbamate
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Felbamate
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| Systematic (IUPAC) name | |
| trideca-1,3,11-trien-5,7,9-triyne | |
| Identifiers | |
| CAS number | |
| ATC code | N03 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C11H14N2O4 |
| Mol. mass | 238.24 |
| Pharmacokinetic data | |
| Bioavailability | > 90% |
| Metabolism | Hepatic |
| Half life | 20-23 hours |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
C (USA) |
| Legal status |
Unscheduled |
| Routes | Oral |
Felbamate (marketed under the brand name Felbatol by MedPointe) is an anticonvulsant drug[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 drugs usage to severe refractory epilepsy.
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[edit] Mechanism of action
As with most anticonvulsants, the precise mechanism is unknown.
It has an effect on GABA receptor binding sites.[4]
It may also work as a NMDA receptor antagonist.[5]
[edit] Approval history
[edit] United States
- 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 It was urgently withdrawn after 10 cases of aplastic anemia.[6] A "Dear Doctor" letter was sent to 240,000 physicians.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.[7] 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.
[edit] United Kingdom
- The drug is only available on a limited named-patient basis.
[edit] Indications and usage
- 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.
[edit] Dosing
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
[edit] 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 hepatic (liver) failure. The risk of aplastic anemia is between 1:3,600 and 1:5,000, of which 30% of cases are fatal. The risk of hepatic failure is between 1:24,000 to 1:34,000, of which 40% of cases are fatal.
[edit] Drug interactions
Felbamate is an inhibitor of CYP2C19, an isoenzyme of the cytochrome P450 system involved in the metabolism of several commonly used medications.[8] 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.[9]
[edit] References
- ^ Rho JM, Donevan SD, Rogawski MA (March 1997). "Barbiturate-like actions of the propanediol dicarbamates felbamate and meprobamate". J. Pharmacol. Exp. Ther. 280 (3): 1383–91. PMID 9067327. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9067327.
- ^ Leppik IE, Dreifuss FE, Pledger GW, et al (November 1991). "Felbamate for partial seizures: results of a controlled clinical trial". Neurology 41 (11): 1785–9. PMID 1944909.
- ^ Devinsky O, Faught RE, Wilder BJ, et al (March 1995). "Efficacy of felbamate monotherapy in patients undergoing presurgical evaluation of partial seizures". Epilepsy Res. 20 (3): 241–6. PMID 7796796. http://linkinghub.elsevier.com/retrieve/pii/092012119400084A.
- ^ Kume A, Greenfield LJ, Macdonald RL, Albin RL (June 1996). "Felbamate inhibits [3Ht-butylbicycloorthobenzoate (TBOB) binding and enhances Cl- current at the gamma-aminobutyric AcidA (GABAA) receptor]". J. Pharmacol. Exp. Ther. 277 (3): 1784–92. PMID 8667250. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8667250.
- ^ Prous Science: Molecule of the Month January 2005
- ^ "www.fda.gov". Retrieved on 2008-11-15.
- ^ "www.fda.gov". Retrieved on 2008-11-15.
- ^ Flockhart DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. Retrieved on December 25, 2008.
- ^ Curry WJ, Kulling DL (February 1998). "Newer antiepileptic drugs: gabapentin, lamotrigine, felbamate, topiramate and fosphenytoin". Am Fam Physician 57 (3): 513–20. PMID 9475899. http://www.aafp.org/afp/980201ap/curry.html.
[edit] External links
- 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
- MedPonte Pharmaceuticals
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