Drug Interaction Report

MONITOR: Coadministration of allopurinol with cytotoxic agents in patients with neoplastic disease, other than leukemia, may increase the risk of myelosuppressive side effects. Allopurinol therapy alone has been associated with myelosuppressive adverse reactions (e.g., anemia, leukopenia and/or thrombocytopenia). Theoretically, combination with cytotoxic agents may increase this risk, however, data are conflicting. In a well-controlled study of patients on allopurinol who received cyclophosphamide, doxorubicin, bleomycin, procarbazine and/or mechlorethamine (mustine HCl), increases in toxic reactions of the cytotoxic agents were not observed.

MANAGEMENT: Caution as well as closer clinical and laboratory monitoring for the development of myelosuppression are advised when allopurinol is used concomitantly with cytotoxic agents.

ADJUST DOSING INTERVAL: The tolerability of allopurinol may be improved by giving it after a meal. Additionally, when the dose is greater than 300 mg, dividing the total daily dose into smaller doses administered more often may be appropriate to help minimize gastrointestinal irritation.

MONITOR: Concomitant use of allopurinol with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence and sedation.

MANAGEMENT: To improve tolerability, some manufacturers suggest administering allopurinol after a meal. Additionally, if the daily dose is greater than 300 mg, administering allopurinol in divided doses may help reduce gastrointestinal intolerance. Patients should also be counseled to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them.