Drug Interactions

Antineoplastic drugs may participate in several types of drug interactions. Methotrexate, for example, is highly bound to serum albumin and can be displaced by sali-cylates, sulfonamides, phenothiazines, phenytoin, and other organic acids. The induction of hepatic drug-metabolizing enzymes by phenobarbital may alter the metabolism of cyclophosphamide to both active and inactive metabolites. Mercaptopurine metabolism is blocked by allopurinol, an occurrence that may result in lethal toxicity if the dosage of mercaptopurine is not reduced to one-fourth of the usual dosage. Methotrexate is secreted actively by the renal tubules, and its renal clearance may be delayed by salicylates.

Procarbazine exhibits an interesting interaction with ethanol, resulting in headaches, diaphoresis, and facial erythema; patients taking this drug should be forewarned to abstain from alcohol. Procarbazine is also a monoamine oxidase (MAO) inhibitor and may potentiate the effects of drugs that are substrates for this enzyme.

The biliary and renal excretion of some drugs (e.g., anthracyclines, vinca alkaloids, dactinomycin, etopo-side) by the P-glycoprotein multidrug transporter can be inhibited by other drugs that are also transported by P-glycoprotein.

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