Drug Interactions between cimetidine and lomustine

MONITOR CLOSELY: Coadministration with cimetidine may potentiate the myelosuppressive effects of carmustine and lomustine. The exact mechanism of interaction is unknown, but may involve additive myelosuppression or inhibition by cimetidine of the hepatic clearance of the nitrosoureas. In one study, marked neutropenia occurred in nine patients with glioblastomas who were administered carmustine, methylprednisolone, and cranial irradiation in combination with cimetidine (1200 mg/day for 1 to 4 weeks). The nadir in neutrophil cell counts in this group averaged 650 +/- 220/microL, compared to 2,160 +/- 240/microL in a group of 31 similarly treated patients who did not receive cimetidine. The neutropenia observed in the cimetidine-treated patients extended through day 42 of the treatment cycle, whereas patients who did not receive cimetidine did not experience significant neutropenia. In another study, leukopenia and thrombocytopenia occurred in 6 of 8 patients treated with carmustine, corticosteroids and cimetidine, compared to 6 out of 40 similarly treated patients who did not receive cimetidine. The interaction has also been reported with lomustine. A 55-year-old patient treated with cimetidine, dexamethasone, phenytoin, and phenobarbital developed severe neutropenia more than 7 weeks after receiving a single 120 mg dose of lomustine. The neutropenia resolved two weeks after discontinuation of cimetidine, and was much less severe with subsequent doses of lomustine given without cimetidine.

MANAGEMENT: Caution is advised if carmustine or lomustine is used in combination with cimetidine. Patients should be closely monitored for the development of delayed myelosuppression that may occur 4 to 6 weeks after administration of the nitrosourea. Blood counts are recommended weekly for at least 6 weeks after a dose. Alternatively, other H2-receptor antagonists such as ranitidine and famotidine may be considered in patients who require treatment with carmustine or lomustine, since they have not been reported to cause the interaction and generally have minimal effects on hepatic metabolism.