Drug Interaction Report

MONITOR: Trimethoprim may increase plasma concentrations and decrease clearance of zalcitabine. The mechanism may be inhibition of renal tubular secretion of zalcitabine. The clinical significance is unknown.

MANAGEMENT: Close clinical monitoring for evidence of zalcitabine toxicity (peripheral neuropathy, pancreatitis, lactic acidosis, hepatotoxicity) is recommended when these drugs are used together. In addition, a reduction in zalcitabine dosage may be warranted. Patients should be advised to promptly notify their doctor if they experience numbness, tingling, severe nausea and vomiting, diarrhea, abdominal pain, severe fatigue, or jaundice.

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.

Zalcitabine bioavailability may be decreased by 14% if taken with meals. The mechanism and clinical significance are unknown.