Felbamate drug interactions

Egnell, A.-C., Houston, B. and Boyer, S. (2003) in vivo CYP3A4 heteroactivation is a possible mechanism for the drug interaction between felbamate and carbamazepine. The Journal of Pharmacology and Experimental Therapeutics, 305, 1251-1262. 

Drug interactions involving AEDs are shown in Table 52-5. Phenobarbital, phoiytom, primidone and carbamazepine are potent inducers of cytochrome P450 (CYP450), epoxide hydrolase, and uridine diphosphate gjucuronosyltransferase enzyme systems. Valproic acid inhibits many hepatic enzjrme systems and displaces some drugs from plasma albumin. Felbamate and topiramate can act as inducers with some isoforms and inhibitors with others. 

Drug Interactions. Felbamate inhibits the clearance and increases the serum concentration of phenytoin, valproic acid, and phenobar-bital. The concentration of carbamazepine decreases in patients on concmrent therapy with felbamate secondary to enzyme induction however, the concentration of the 10,11 -epoxide metabolite increases. It is recommended that the dose of phenytoin, carbamazepine, and valproic acid be decreased by about 30% when felbamate is added. Felbamate does not appear to interact with either gabapentin or 1am-otrigine. Phenytoin and carbamazepine are enzyme inducers and have been shown to increase the clearance of felbamate. Interactions with warfarin also have been reported. ... 

Disadvantages. The use of felbamate is limited by the association with aplastic anemia and hepatotoxicity, as well as multiple drug interactions. 

Drug Interactions. Phenobarbital is a potent enzyme inducer and may increase the elimination of any drug metabolized by CYP450-or UGT-mediated metabolism. Valproic acid, phenytoin, felbamate, cimetidine, and chloramphenicol inhibit phenobarbital metabolism, necessitating a decrease in dose. Ethanol increases the metabolism of phenobarbital. ... 

Valproate, a substrate for hepatic CYP2C19 and CYP2C9, has an extensive pattern of drug interactions. It increases the plasma concentrations of lamotrigine, CBZ, and phenobarbital and the free fraction of phenytoin by either displacing these drugs from plasma proteins or inhibiting their metabolism. Phenytoin, phenobarbital, and CBZ cause decreased plasma concentrations of valproate, whereas felbamate increases valproate levels. 

Liu H, Delgado MR. Significant drug interaction between valproate and felbamate in epileptic children. Epilepsia (1995) 36 (Suppl 3), S160. 

Dieckhaus, C.M. etal. (2002) Mechanisms of idiosyncratic drug reactions the case of felbamate. Chemico-Biological Interactions, 142 (1-2), 99-117. 

None of the interactions between the benzodiazepines and antiepileptics described here appear to be of major clinical importance, with the possible exception of the interaction between clobazam and felbamate. If both drugs are given be aware that additive sedative or other adverse effects may occur. This may also be possible in some rare cases with chlordiazepoxide or clobazam and phenobarbital clonazepam and lamotrigine or primidone and clorazepate and primidone. 

Dieckhaus CM, Thompson CD, Roller SG, MacDonald TL. Mechanisms of idios5mcratic drug reactions The case of felbamate. Chem Biol Interact 2002 142(1—2) 99—117. 

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