Drug Interaction Report

MONITOR: Coadministration with drugs that are subject to substantial renal clearance such as trimethoprim/sulfamethoxazole and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in delayed clearance of pralatrexate. The mechanism is competitive inhibition of renal excretion, as approximately 34% of pralatrexate is eliminated unchanged by the kidney.

MANAGEMENT: Caution is advised if pralatrexate is prescribed in combination with trimethoprim/sulfamethoxazole or NSAIDs. Complete blood cell counts as well as renal and hepatic function should be closely monitored. Treatment interruption or dose reduction of pralatrexate may be required if toxicities such as mucositis, myelosuppression, or liver enzyme abnormalities develop. Patients should be advised to contact their physician if they develop oral ulcers, painful swallowing, vomiting, diarrhea, and/or signs and symptoms of myelosuppression such as pallor, dizziness, fatigue, lethargy, fainting, easy bruising or bleeding, or signs of infection such as fever, chills, sore throat, body aches, and other influenza-like symptoms.

MONITOR: Two cases have been reported in which patients on sulfamethoxazole-trimethoprim therapy, after consuming beer, reported flushing, heart palpitations, dyspnea, headache, and nausea (disulfiram - alcohol type reactions). First-generation sulfonylureas have been reported to cause facial flushing when administered with alcohol by inhibiting acetaldehyde dehydrogenase and subsequently causing acetaldehyde accumulation. Since sulfamethoxazole is chemically related to first-generation sulfonylureas, a disulfiram-like reaction with products containing sulfamethoxazole is theoretically possible. However, pharmacokinetic/pharmacodynamic data are lacking and in addition, the two reported cases cannot be clearly attributed to the concomitant use of sulfamethoxazole-trimethoprim and alcohol.

MANAGEMENT: Patients should be alerted to the potential for this interaction and although the risk for this interaction is minimal, caution is recommended while taking sulfamethoxazole-trimethoprim concomitantly with alcohol.