Risk factors for toxicity
Phenytoin has saturable metabolism that can prolong half-life in toxicity.
Phenytoin is also a substrate for the cytochrome P450 drug metabolising system enzymes, CYP2C9 and CYP 2C19. People taking drugs that inhibit these enzymes are more susceptible to toxic effects of phenytoin because enzyme inhibition can raise serum phenytoin concentration and prolong half-life1.
The combination of these factors can cause very prolonged toxicity.
1 Drugs that inhibit the cytochrome P450 enzymes, CYP2C9 and CYP2C19, can raise serum phenytoin concentration and prolong half-life. They include amiodarone, cimetidine, clarithromycin, trimethoprim plus sulfamethoxazole, disulfiram, efavirnez, etravirine, esomeprazole, fluconazole, fluoxetine, fluvoxamine, isoniazid, ketoconazole, metronidazole, miconazole, omeprazole, oxcarbazepine, ritonavir, sulfonamides, topiramate, voriconazole and 5-fluorouracil. This list is not exhaustive.Return