Drug Interaction Report

MONITOR: Coadministration with furosemide may increase the plasma concentrations of oxypurinol, the active metabolite of allopurinol, and the serum urate concentrations. It is unclear if all diuretics have the same effect on oxypurinol. However, other diuretics (e.g., torsemide, bumetanide, ethacrynic acid) are also known to increase serum urate concentrations thus lowering the efficacy of allopurinol. Higher levels of oxypurinol have been associated with an increased risk of allopurinol hypersensitivity reactions, such as skin rash, drug reaction with eosinophilia and systemic symptoms (DRESS) and severe cutaneous adverse reactions (SCAR). Renal impairment has been demonstrated to also be a risk factor for allopurinol hypersensitivity. One proposed mechanism for this interaction is related to the interference of furosemide with the renal clearance of oxypurinol, although the exact details are still unclear.

MANAGEMENT: Caution is recommended when diuretics and allopurinol are coadministered. Patients should be monitored for increased toxicity as well as reduced efficacy, depending on the diuretic agent administered. Particularly when coadministered with furosemide, patients should be advised to stop allopurinol and promptly report any signs of hypersensitivity, including rash, pruritus, fever, or chills.

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.