Altered methotrexate clearance in the treatment of CNS lymphoma with concurrent use of nitrofurantoin for a urinary tract infection

Abstract

Methotrexate is a widely used chemotherapy agent with a propensity for drug interactions placing the patient at risk for toxicities. There are several modes for altering methotrexate clearance including concomitant drugs leading to toxic effects on the kidneys, medications producing an acidic urine pH, and agents interfering with methotrexate transporters including the organic anion transporter and breast cancer resistance protein efflux pump. We report a case of a patient with central nervous system non-Hodgkin's lymphoma receiving high-dose methotrexate and being concomitantly treated for a urinary tract infection with nitrofurantoin. Subsequently, her initial methotrexate clearance was altered by the introduction of nitrofurantoin and returned to baseline when her nitrofurantoin was discontinued. This is the first case report describing the altered methotrexate clearance from concurrent administration of methotrexate and nitrofurantoin.

A Unique Interaction of Methotrexate and Nitrofurantoin Resulting in Irreversible Pulmonary Fibrosis

“…Because 50-70% of MTX is bound to serum albumin for distribution, it can be displaced by other medications given at the same time. Non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs) may impair MTX clearance in the kidneys, whereas the risk of liver damage and bone marrow suppression is enhanced when using medications with similar adverse drug reactions (ADRs) [ 12 ].…”