Cyclophosphamide with allopurinol

When chemotherapeutic mercaptopurines (eg, azathioprine) are given concomitantly with allopurinol, their dosage must be reduced by about 75%. Allopurinol may also increase the effect of cyclophosphamide. Allopurinol inhibits the metabolism of probenecid and oral anticoagulants... 

Clinically important, potentially hazardous interactions with allopurinol, chlorambucil, cyclophosphamide, cyclosporine, hemophilus B vaccine, imidapril, mycophenolate, olsalazine, vaccines, warfarin... 

The risk of bone marrow depression by cytostatic drugs is potentiated by allopurinol, which also appears to potentiate the therapeutic effect of purine cytostatic drugs, since it competitively inhibits their metabolic breakdown. Studies in animals suggest that this reaction occurs only with oral mercaptopurine (28), although there is older evidence that the toxicity of cyclophosphamide and other cytostatic drugs can be increased by allopurinol (SED-9, 156). The danger of combining allopurinol with azathioprine has been confirmed by cases of bone marrow suppression, particularly in patients with impaired renal function (SEDA-16,114). 

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. 

This interaction is not established with any certainty. The authors of the randomised study consider that, if necessary, allopurinol can be used safely to prevent hyperuricaemia with the chemotherapy regimens used for lymphomas. However, the other data introduce a note of caution. Be alert for increased cyclophosphamide toxicity if allopurinol is given. 

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