Phenytoin + Sulfinpyrazone - Drug Interactions

A review of drug interactions of sulfinpyrazone identified two studies that found interactions with phenytoin (See reference number 1). In first, serum phenytoin levels of 2 out of 5 patients taking phenytoin 250 to 350mg daily were doubled from about 10 to 20 micrograms/mL within 11 days of starting to take sulfinpyrazone 800mg daily. One of remaining patients had a small increase in phenytoin levels, but other two had no changes at all. When sulfinpyrazone was withdrawn, serum phenytoin concentrations fell to their former levels. The second study was a clinical study in epileptic patients that found that sulfinpyrazone 800mg daily for a week increased phenytoin half-life from 10 to 16.5 hrs and reduced metabolic clearance from 59 to 32 mL/minute.

Uncertain. It seems probable that sulfinpyrazone inhibits metabolism of phenytoin by liver, thereby allowing it to accumulate in body and leading to a rise in its serum levels. Displacement of phenytoin from its plasma protein binding sites may also have a small part to play.

Information seems to be limited to these studies,which await confirmation. A similar interaction with phenytoin has been reported with phenylbutazone,which has a very close chemical relationship with sulfinpyrazone (see Phenytoin + Aspirin or NSAIDs interaction). Thus what is known suggests that concurrent use should be monitored and suitable phenytoin dosage reductions made where necessary.

1. Pedersen AK,Jacobsen P, Kampmann JP, Hansen JM. Clinical pharmacokinetics and potentially important drug interactions of sulphinpyrazone. Clin Pharmacokinet (1982) 7, 42–56.