Drug Interactions

Allopurinol increases the t122 of probenecid and enhances its uricosuric effect, while probenecid increases the clearance of oxypurinol, thereby increasing dose requirements of allopurinol.

Allopurinol inhibits the enzymatic inactivation of mercaptopurine and its derivative azathio-prine by xanthine oxidase. Thus, when allopurinol is used concomitantly with oral mercaptopurine or azathioprine, dosage of the antineoplastic agent must be reduced by 25-33% (see Chapters 38 and 51). This is of importance when treating gout in the transplant recipient. The risk of bone marrow suppression also is increased when allopurinol is administered with cytotoxic agents that are not metabolized by xanthine oxidase, particularly cyclophosphamide.

Allopurinol may interfere with the hepatic inactivation of warfarin and increased monitoring of prothrombin activity is recommended in patients receiving both medications.

It remains to be established whether the increased incidence of rash in patients receiving concurrent allopurinol and ampicillin should be ascribed to allopurinol or to hyperuricemia. Hyper-sensitivity reactions have been reported in patients with compromised renal function, especially those who are receiving a combination of allopurinol and a thiazide diuretic. The concomitant administration of allopurinol and theophylline leads to increased accumulation of an active metabolite of theophylline, 1-methylxanthine; the concentration of theophylline in plasma also may be increased (see Chapter 27).

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