Drug Interactions between aspirin / omeprazole and olanzapine

MONITOR: Coadministration with inducers of CYP450 1A2 may decrease the plasma concentrations of olanzapine. Data from available studies indicate that olanzapine is primarily metabolized by CYP450 1A2 and, to a lesser extent, by CYP450 2D6 and uridine diphosphate glucuronosyltransferase (UGT) 1A4. When coadministered with rifampin, a moderate CYP450 1A2 inducer that also induces UGT 1A4, olanzapine peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 11% and 48%, respectively. Coadministration with 200 mg twice daily of carbamazepine, another CYP450 1A2 inducer, caused an approximately 50% increase in the clearance of olanzapine. Higher daily dosages of carbamazepine may cause an even greater increase in olanzapine clearance.

MANAGEMENT: The potential for diminished pharmacologic effects of olanzapine should be considered during coadministration with CYP450 1A2 inducers. Alternative treatments may be required if an interaction is suspected.

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.