Frågedatum: 2004-12-20
RELIS database 2004; id.nr. 21195, DRUGLINE
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What is known about the interaction between cyclophosphamide and allopurinol?/nA patient with Wegen



Fråga: What is known about the interaction between cyclophosphamide and allopurinol? A patient with Wegener´s granulomatosis is treated with cyclophosphamide (Sendoxan). The patient has pain in his hands that might be due to gout, and allopurinol (Zyloric) treatment is considered.

Sammanfattning: There might be an increased risk of bone marrow depression when allopurinol and cyclophosphamide are used in combination.

Svar: Cyclophosphamide is an alkylating anticancer drug. It is a prodrug that is metabolised to active cytotoxic metabolites (4-hydroxycyclophosphamide and phosphoramide mustard) by different liver enzymes, for example cytochrome P-450 enzymes, and in pheripheral tissues (1). Up to 25% of administered cyclophosphamide is excreted unchanged in the urine (2). Allopurinol is a xanthine oxidase inhibitor used to treat gout and to reduce the risk of hyperurecemia in patients treated with cytostatics. Allopurinol is mainly metabolised to its active metabolite oxipurinol by xanthine oxidase. Oxipurinol is excreted in the urine (1). Allopurinol can cause bone marrow depression, although rarely, and cyclophosphamide causes a dose-related bone marrow depression (3).

When allopurinol (200mgx3) was given to nine patients and two healthy volunteers for 14 days, the concentration of cyclophosphamide metabolites was increased by 37.5%. The plasma half life of unchanged cyclophosphamide was unaltered (4).

In a retrospective study of 58 cancer patients who had received cyclophosphamide, the frequency of bone marrow depression, measured as leukopenia, thrombocytopenia or pancytopenia, was 57.7% in patients (n= 26) cotreated with allopurinol and 18.8% in patients (n=32) not receiving allopurinol (5).

In another study, 143 cancer patients on cytostatics (including cyclophosphamide) were randomised to receive allopurinol during either half of, or all of six cytostatic treatment cycles. No difference in the frequency of bone marrow depression, measured by white blood cell or platelets counts, was observed between the groups (6).

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