Many examples of therapeutic interactions (drug combinations) are shown in Table 30.2. Non-therapeutic interactions can be serious. A com bination of cytotoxics causing dangerous degree of immunosuppression represents an adverse pharmacodynamic interaction. There is also a general case for alertness with drugs that inhibit the metabolism or renal excretion of other drugs. Cimetidine, an inhibitor of several P450-mediated oxidation reactions, delays the breakdown and increases the toxicity of 5-fluorouracil, and similarly, the xanthine oxidase inhibitor allopurinol increases toxicity of mercaptopurine and cyclophosphamide. The renal tubular excretion of methotrexate is reduced by competition with NSAIDs, leading to methotrexate toxicity.
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