Drug Interactions between allopurinol / lesinurad and carboplatin

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.

MONITOR: Coadministration of carboplatin with other nephrotoxic agents may increase the risk of renal impairment due to additive effects on the kidney. Moreover, renal impairment secondary to the use of these agents may reduce the clearance of carboplatin, which is primarily eliminated by renal excretion. This may increase the risk of other adverse effects including severe myelosuppression which is concentration-dependent. Approximately 25% of patients receiving carboplatin exhibit decreases in creatinine clearance, whereas rises in serum creatinine and blood urea nitrogen occur less frequently. Some data suggests hypomagnesemia is the primary indicator of carboplatin-induced nephrotoxicity. Patients receiving multiple courses or single doses exceeding 800 mg/m2 of carboplatin, or those with a history of cisplatin-induced nephrotoxicity, may be at increased risk of renal toxicity.

MANAGEMENT: Renal function and serum magnesium levels should be monitored if carboplatin is used concomitantly with other nephrotoxic agents. The potential for increased toxicity of carboplatin such as peripheral sensory neuropathies and myelosuppression should be considered.