Drug Interaction Report

GENERALLY AVOID: The combination of large doses of salicylates and oral carbonic anhydrase inhibitors (CAI) may rarely result in severe metabolic acidosis and/or salicylate toxicity. The mechanism is unknown but may involve salicylate-induced displacement of CAIs from plasma protein-binding sites and reduced renal clearance, or CAI-induced plasma pH changes resulting in increased amounts of unionised salicylates entering the CNS. Coma and death have been reported. Although this has not been reported with ocular CAIs, the clinician should consider the possibility of an interaction with these agents, also.

MANAGEMENT: In general, concomitant use of antirheumatic doses of salicylates and oral CAIs is not recommended. If coadministration is necessary, careful monitoring of the patient's mental status and acid base balance is strongly recommended. Patients should be advised to promptly notify their physicians if they experience symptoms such as lethargy, tinnitus, confusion, nausea, vomiting, or hyperventilation.

GENERALLY AVOID: Agents that can alkalinize the urine such as thiazide diuretics, carbonic anhydrase inhibitors, and antacids may decrease the antibacterial effectiveness of methenamine by inhibiting its conversion to formaldehyde. Methenamine is most effectively converted in an acidic milieu of pH less than 5.5.

MANAGEMENT: Concomitant use of methenamine-containing preparations with thiazide diuretics, carbonic anhydrase inhibitors, or large doses of antacids should be avoided if possible. Otherwise, frequent urine pH testing may be considered. Some methenamine products may be used with antacids if dosing times are separated by at least one hour. Consult the manufacturer's product labeling for specific recommendations.