Capecitabine

Clinical Impact

Concomitant use with allopurinol may decrease concentration of capecitabine’s active metabolites, which may decrease capecitabine efficacy.

Intervention

Avoid the use of allopurinol tablets during treatment with capecitabine

** Chlorpropamide**

Clinical Impact

Allopurinol tablets prolongs the half-life of chlorpropamide as both compete for renal tubular excretion. In patients with renal insufficiency, the risk of hypoglycemia may be increased due to this mechanism.

Intervention

Monitor patients with renal insufficiency for hypoglycemia when administering chlorpropamide and allopurinol tablets concomitantly.

** Cyclosporine**

Clinical Impact

Concomitant use of allopurinol increases cyclosporine concentrations, which may increase the risk of adverse reactions.

Intervention

Increase frequency of monitoring cyclosporine concentrations as reflected in its prescribing information and modify the dosage of cyclosporine as appropriate when used concomitantly with allopurinol tablets.

Cyclophosphamide and Other Cytotoxic Agents

Clinical Impact

Concomitant use of allopurinol with cyclophosphamide and other cytotoxic agents (doxorubicin, bleomycin, procarbazine, mechloroethamine) increases bone marrow suppression among patients with neoplastic disease, except leukemia.

Intervention

Blood count monitoring and regular physician follow-up are recommended.

Dicumarol

Clinical Impact

Allopurinol tablets prolongs the half-life of the anticoagulant, dicumarol. The mechanism of this drug interaction has not been established but should be noted when allopurinol tablet is given to patients already on dicumarol therapy.

Intervention

Monitor prothrombin time. Adjust the dosage of dicumarol accordingly when allopurinol tablet is added to anticoagulant therapy.

Fluorouracil

Clinical Impact

Based on non-clinical data, allopurinol may decrease anti-tumor activity due to suppression of phosphorylation of 5-fluorouracil.

Intervention

Concomitant administration with fluorouracil should be avoided.

Mercaptopurine or Azathioprine

Clinical Impact

Allopurinol inhibits xanthine oxidase mediated metabolism of mercaptopurine and azathioprine. Concomitant use of allopurinol increases the exposure of either mercaptopurine or azathioprine which may increase the risk of their adverse reactions, including myelosuppression [see Warnings and Precautions 5.5].

Intervention

In patients receiving mercaptopurine or azathioprine, the concomitant administration of 300 mg to 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.

Pegloticase

Clinical Impact

Concomitant use of allopurinol tablets and pegloticase may potentially blunt the rise of serum uric acid levels and increase the risk of pegloticase related anaphylaxis in patients whose uric acid level increase to above 6 mg/dL.

Intervention

Discontinue and do not institute allopurinol therapy during treatment with pegloticase.

Theophylline

Clinical Impact

Concomitant use of allopurinol doses greater than or equal to 600 mg/day may decrease the clearance of theophylline

Intervention

Monitor and adjust theophylline doses as reflected in the prescribing information.

Uricosuric Drugs

Clinical Impact

Uricosuric agents increase the excretion of the active allopurinol metabolite oxypurinol. Concomitant use with uricosuric agents decreases oxypurinol exposure which may reduce the inhibition of xanthine oxidase by oxypurinol and increases the urinary excretion of uric acid.
The net effect of such combined therapy may be useful in some patients in achieving minimum serum uric acid levels provided the total urinary uric acid load does not exceed the competence of the patient's kidney function.

Intervention

Monitor uric acid levels due to the increased chance of hypouricemic effects.

Warfarin

Clinical Impact

Allopurinol may inhibit the metabolism of warfarin, possibly enhancing its anticoagulant effect.

Intervention

Monitor patients on concomitant therapy for excessive anticoagulation. Assess INR frequently and adjust warfarin dosage accordingly when allopurinol is added to warfarin therapy.