Renal impairment following the combined use of high-dose methotrexate and procarbazine.

A major side-effect of high-dose methotrexate is renal toxicity, which may develop unexpectedly despite adequate standard precautions such as hydration and alkalinisation of the urine. The pathogenesis is unclear. Recent reports suggest that the combination of high-dose methotrexate with non-chemotherapeutic agents may cause such renal impairment. Three cases of unexpected renal impairment following the combined use of high-dose methotrexate and another cytotoxic agent, procarbazine, are reported. Possible mechanisms of this interaction are discussed, as are recommendations for future combined administration.