Drug Interactions between acetazolamide and Yosprala

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.

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Coadministration with proton pump inhibitors may decrease the oral bioavailability of aspirin and other salicylates. The interaction has been studied with omeprazole and aspirin, although data are conflicting. In one study, pretreatment with omeprazole (20 mg/day for 2 days) in 11 healthy volunteers led to a significant and progressively greater reduction in the mean serum salicylate level at 30, 60, and 90 minutes after administration of aspirin (650 mg single dose). The investigators suggest that acid suppression may reduce the lipophilic nature of aspirin, thereby adversely affecting its absorption from the gastrointestinal tract. Another study found no effect of omeprazole pretreatment (20 mg/day for 4 days) on plasma salicylate and aspirin levels, skin bleeding times, or antiplatelet effect of low-dose aspirin (125 mg single dose) in 14 healthy volunteers. However, these results do not exclude the possibility that omeprazole might interfere with the analgesic, antipyretic, or anti-inflammatory effects of aspirin, which has been demonstrated in rats.

Proton pump inhibitors may enhance the release rate of salicylates from enteric-coated formulations due to premature disruption of the coating and intragastric release of the drug secondary to an increase in gastric pH. In eight healthy volunteers, omeprazole pretreatment (20 mg/day for 4 days) did not affect the bioavailability of salicylate from uncoated aspirin tablets but significantly increased the absorption rate of salicylate from enteric-coated sodium salicylate tablets. The clinical significance of this interaction is unknown. Theoretically, it may increase the risk of gastric adverse effects associated with salicylates.

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