Allopurinol drug interactions

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

List of drug interactions

Mercaptopurine/azathioprine

Dicumarol

Uricosuric agents

Thiazide diuretics

Ampicillin/amoxicillin

Cyclophosphamide/other cytotoxic agents

Tolbutamide

Chlorpropamide

Cyclosporine

Drug/laboratory test interactions

Mercaptopurine/azathioprine

In patients receiving mercaptopurine or azathioprine, the concomitant administration of 300-600 mg of Allopurinol per day will require a reduction in dose to approximately one-third to one-fourth of the usual dose of mercaptopurine or azathioprine. Subsequent adjustment of doses of mercaptopurine or azathioprine should be made on the basis of therapeutic response and the appearance of toxic effects. Return to top

Dicumarol

It has been reported that Allopurinol prolongs the half-life of the anticoagulant, dicumarol. The clinical basis of this drug interaction has not been established but should be noted when Allopurinol is given to patients already on dicumarol therapy. Return to top

Uricosuric agents

Since the excretion of oxipurinol is similar to that of urate, uricosuric agents, which increase the excretion of urate, are also likely to increase the excretion of oxipurinol and thus lower the degree of inhibition of xanthine oxidase. The concomitant administration of uricosuric agents and Allopurinol has been associated with a decrease in the excretion of oxypurines (hypoxanthine and xanthine) and an increase in urinary uric acid excretion compared with that observed with Allopurinol alone. Although clinical evidence to date has not demonstrated renal precipitation of oxypurines in patients either on Allopurinol alone or in combination with uricosuric agents, the possibility should be kept in mind. Return to top

Thiazide diuretics

The reports that the concomitant use of Allopurinol and thiazide diuretics may contribute to the enhancement of Allopurinol toxicity in some patients have been reviewed in an attempt to establish a cause-and-effect relationship and a mechanism of causation. Review of these case reports indicates that the patients were mainly receiving thiazide diuretics for hypertension and that tests to rule out decreased renal function secondary to hypertensive nephropathy were not often performed. In those patients in whom renal insufficiency was documented, however, the recommendation to lower the dose of Allopurinol was not followed. Although a causal mechanism and a cause-and-effect relationship have not been established, current evidence suggests that renal function should be monitored in patients on thiazide diuretics and Allopurinol even in the absence of renal failure, and dosage levels should be even more conservatively adjusted in those patients on such combined therapy if diminished renal function is detected. Return to top

Ampicillin/amoxicillin

An increase in the frequency of skin rash has been reported among patients receiving ampicillin or amoxicillin concurrently with Allopurinol compared to patients who are not receiving both drugs. The cause of the reported association has not been established. Return to top

Cyclophosphamide/other cytotoxic agents

Enhanced bone marrow suppression by cyclophosphamide and other cytotoxic agents has been reported among patients with neoplastic disease, except leukemia, in the presence of Allopurinol. However, in a well-controlled study of patients with lymphoma on combination therapy, Allopurinol did not increase the marrow toxicity of patients treated with cyclophosphamide, doxorubicin, bleomycin, procarbazine and/or mechlorethamine. Return to top

Tolbutamide

Tolbutamide’s conversion to inactive metabolites has been shown to be catalyzed by xanthine oxidase from rat liver. The clinical significance, if any, of this observation is unknown. Return to top

Chlorpropamide

Chlorpropamide’s plasma half-life may be prolonged by Allopurinol, since Allopurinol and chlorpropamide may compete for excretion in the renal tubule. The risk of hypoglycemia secondary to this mechanism may be increased if Allopurinol and chlorpropamide are given concomitantly in the presence of renal insufficiency. Return to top

Cyclosporine

Rare reports indicate that cyclosporine levels may be increased during concomitant treatment with Allopurinol. Monitoring of cyclosporine levels and possible adjustment of cyclosporine dosage should be considered when these drugs are co-administered. Return to top

Drug/laboratory test interactions

Allopurinol is not known to alter the accuracy of laboratory tests. Return to top

Complete List of Allopurinol Drug Interactions

Major Interactions

Moderate Interactions

Minor Interactions

Adapted from the FDA Package Insert.