There is some evidence to suggest that incidence of seriousbone marrow depression caused by cyclophosphamide can beincreased by allopurinol, but this was not confirmed in a controlled study. Allopurinol may prolong half-life of cyclophosphamide and increase levels of its cytotoxic metabolites.
A retrospective epidemiological survey of patients in four hospitals who, over a 4-year period, had been treated with cyclophosphamide, found that incidence of serious bone marrow depression was 57.7 % in 26 patients who had also received allopurinol,and 18.8 % in 32 patients who had not (See reference number 1). A pharmacokinetic study in 9 patients with malignant disease and 2 healthy subjects showed that while taking allopurinol 600mg daily concentration of cytotoxic metabolites of cyclophosphamide increased by an average of 37.5 % (range 1.5 to 110%) (See reference number 2). Another pharmacokinetic study reported that half-life of cyclophosphamide was more than twofold longer in 3 children also receiving allopurinol 300 mg/m(See reference number 2), when compared with that in children not given allopurinol (See reference number 3). However, another study found that although allopurinol pre-treatment increased half-life of cyclophosphamide, plasma alkylating activity and urinary metabolite and cyclophosphamide excretion were unchanged (See reference number 4). Moreover, a randomised controlled study,(See reference number 5) designed as a follow-up to survey cited above,(See reference number 1) failed to confirm that allopurinol increased toxicity of cyclophosphamide in 81 patients with Hodgkin’s or non-Hodgkin’s lymphoma. In this study,there was no difference in nadirs for white blood cells and platelets during 3 cycles of cyclophosphamide-containing chemotherapy in 44 patients receiving allopurinol and in 37 patients not receiving allopurinol.
Not understood. Cyclophosphamide itself is inactive, but it is converted by liver into cytotoxic metabolites (See reference number 4). Allopurinol or its metabolite oxypurinol may inhibit their renal excretion,or may alter hepatic metabolism (See reference number 2,3).
This interaction is not established with any certainty. The authors of randomised study consider that, if necessary, allopurinol can be used safely to prevent hyperuricaemia with chemotherapy regimens used for lymphomas (See reference number 5). However, other data introduce a note of caution. Be alert for increased cyclophosphamide toxicity if allopurinol is given.
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