Drug Interaction Report

The renal excretion allopurinol's active metabolite, oxypurinol, may be increased when coadministered with probenecid and/or large doses of salicylates (e.g., aspirin). At the same time, both probenecid and large doses of salicylates may have a hypouricemic effect; allopurinol may also inhibit probenecid metabolism. The clinical significance of this interaction is unknown. Patients should be monitored for altered effects of both allopurinol and probenecid.

ADJUST DOSING INTERVAL: The tolerability of allopurinol may be improved by giving it after a meal. Additionally, when the dose is greater than 300 mg, dividing the total daily dose into smaller doses administered more often may be appropriate to help minimize gastrointestinal irritation.

MONITOR: Concomitant use of allopurinol with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence and sedation.

MANAGEMENT: To improve tolerability, some manufacturers suggest administering allopurinol after a meal. Additionally, if the daily dose is greater than 300 mg, administering allopurinol in divided doses may help reduce gastrointestinal intolerance. Patients should also be counseled to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them.