Drug Interactions between Tofranil-PM and Yosprala

MONITOR: Preliminary evidence suggests that aspirin may increase the plasma free concentration and pharmacologic effects of imipramine by displacing it from plasma protein binding sites. In 20 patients with endogenous depression given imipramine 150 mg/day for 5 days, administration of aspirin (500 mg every 12 hours for 2 days) decreased the plasma protein binding of imipramine from 84% to 72%. Additionally, the incidence of mild and severe adverse effects associated with imipramine increased nearly 60% and 150%, respectively. Other salicylates are expected to have similar effects due to their high affinity for plasma proteins.

MANAGEMENT: Pharmacologic response to imipramine should be monitored more closely whenever a salicylate is added to or withdrawn from therapy, and the imipramine dosage adjusted as necessary. Patients should be advised to notify their physician if they experience increased adverse effects of imipramine such as dry mouth, constipation, urinary retention, blurred vision, palpitations, and tachycardia.

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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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