Allopurinol Interactions

Aluminum Hydroxide
Azathioprine
Chlorpropamide
Cyclosporine
Dicumarol
Fluorouracil, 5-FU
Mercaptopurine, 6-MP
Photosensitizing Agents
Rasburicase
Theophylline, Aminophylline
Thiazide diuretics
Warfarin

Aluminum hydroxide has been reported to interfere with the therapeutic effects of allopurinol. Although this has been reported in only a few patients, it is suggested that aluminum hydroxide may interfere with oral absorption of allopurinol. If these two agents are to be used together, allopurinol should be administered no less than 1 hour before or more than 2 hours after doses of aluminum hydroxide or antacid combinations containing aluminum hydroxide.

Some evidence suggests that allopurinol interferes with the metabolism of warfarin if administered concomitantly, and may lead to increased anticoagulation. However, in one study, allopurinol did not affect the elimination of warfarin. Allopurinol (Zyloprim) has affected the hypoprothrombinemic response to dicumarol, which has resulted in bleeding episodes in some patients. Prothrombin times should be monitored carefully in patients receiving oral anticoagulants when allopurinol therapy is added.

By inhibiting xanthine oxidase, allopurinol inhibits the conversion of mercaptopurine, 6-MP to its inactive metabolites. As a result, the myelosuppressive effects and other side effects of 6-MP will be enhanced. Allopurinol (Zyloprim) should be avoided in patients receiving mercaptopurine. If this is not possible, the dose of 6-MP should be reduced by 75%.

Concomitant use of allopurinol with azathioprine can result in a large increase in azathioprine activity and toxicity (e.g., bone marrow suppression, leukopenia, pancytopenia). The interaction is well-documented (i.e., multiple case reports over the course of decades) and can be potentially life-threatening. The increase in azathioprine activity is due to the ability of allopurinol to inhibit xanthine oxidase-controlled metabolism, thereby decreasing the elimination of azathioprine. When possible, this drug combination should be avoided. If avoidance of cotherapy is not possible, a reduced dosage of azathioprine (e.g., reduce to one-third to one-quarter of the original dose and close hematologic monitoring are required.

Limited evidence suggests that concurrent administration of allopurinol and theophylline can result in a dose-dependent increase in theophylline concentration. Allopurinol (Zyloprim) doses of 600 mg/day appear more likely than 300 mg/day to affect theophylline clearance; however, this interaction should be suspected if theophylline serum concentrations change following initiation or discontinuation of allopurinol.

Limited evidence suggests that concurrent allopurinol can interfere with chlorpropamide elimination. Chlorpropamide half-life was significantly prolonged in several patients who were also receiving Allopurinol (Zyloprim). It is proposed that allopurinol interferes with renal tubular secretion of chlorpropamide. If allopurinol is added to chlorpropamide therapy, patients should be monitored for hypoglycemia.

Preclinical data suggests that allopurinol may decrease the efficacy of photosensitizing agents used in photodynamic therapy.

The occurrence of hypersensitivity reactions may be increased in patients with renal impairment who receive allopurinol and thiazide diuretics in combination. Severe skin reactions including exfoliative dermatitis, toxic epidermal necrolysis and Steven’s Johnson syndrome, which have resulted in death in some cases. It does not appear that the concomitant use of thiazide diuretics and allopurinol leads to increased allopurinol toxicity.

Allopurinol (Zyloprim) may increase concentrations of cyclosporine. Close monitoring of cyclosporine concentrations is required when allopurinol is given concurrently with cyclosporine.

Allopurinol (Zyloprim) can interfere with the activation of fluorouracil, 5-FU. Allopurinol is metabolized to oxypurinol ribonucleotide, which inhibits orotidylate decarboxylase and causes a buildup in the levels of orotic acid. Increased levels of orotic acid block the activation of 5-FU. Theoretically, this may provide protection to host tissues and preserve anti-tumor activity since host tissues, but not all tumors, rely on this activation pathway. However, the reduction of 5-FU toxicity, specifically mucositis, by allopurinol has been inconsistent in clinical trials. In some animal models, allopurinol has decreased the effectiveness of 5-FU.

Caution is recommended for the concomitant use of allopurinol and rasburicase. Rasburicase cannot break down xanthine and hypoxanthine. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and caliculi.

_{[ Last revised: 2/28/2005 1:36:00 PM ]}

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