Drug-Drug

• Disulfiram , acute ingestion of alcohol , amiodarone , ethosuximide , isoniazid , chloramphenicol , sulfonamides , fluoxetine , gabapentin , H2 antagonists , benzodiazepines , omeprazole , ketoconazole , fluconazole , estrogens , succinamides , halothane , methylphenidate , phenothiazines , salicylates , ticlopidine , tolbutamide , topiramate , trazodone , felbamate , and cimetidine may ↑ phenytoin blood levels.

• Barbiturates , carbamazepine , reserpine , and chronic ingestion of alcohol may ↓ phenytoin blood levels.

• Phenytoin may ↓ the effects of amiodarone , benzodiazepines , carbamazepine , chloramphenicol , corticosteroids , disopyramide , warfarin , felbamate , doxycycline , lamotrigine , oral contraceptives , paroxetine , propafenone , rifampin , ritonavir , quinidine , tacrolimus , theophylline , topiramate , tricyclic antidepressants , zonisamide , methadone , cyclosporine , and estrogens .

• IV phenytoin and dopamine may cause additive hypotension.

• Additive CNS depression with other CNS depressants , including alcohol , antihistamines , antidepressants , opioids , and sedative/hypnotics .

• Antacids may ↓ absorption of orally administered phenytoin.

• ↑ systemic clearance of antileukemic drugs teniposide and methotrexate which has been associated with a worse event free survival, phenytoin use is not recommended in children undergoing chemotherapy for acute lymphocytic leukemia.

• Calcium and sucralfate ↓ phenytoin absorption.

• Phenytoin may ↓ absorption of folic acid.

• Concurrent administration of enteral tube feedings may ↓ phenytoin absorption.