Drug Interactions between aspirin / omeprazole and Noxafil

GENERALLY AVOID: Coadministration with proton pump inhibitors (PPIs) may decrease the systemic bioavailability of posaconazole from the oral suspension. The proposed mechanism is reduced solubility and absorption of posaconazole due to an increase in gastric pH induced by these agents. When a single 400 mg dose of posaconazole was given to 12 healthy subjects following pretreatment with esomeprazole 40 mg once a day for 3 days, mean posaconazole peak plasma concentration (Cmax) and systemic exposure (AUC) were reduced by 46% and 32%, respectively, compared to posaconazole administered alone under fasting conditions. In the same study, coadministration of posaconazole with 12 ounces of ginger ale, an acidic beverage, increased posaconazole Cmax by 92% and AUC by 70%. When given with both esomeprazole and ginger rale together, posaconazole Cmax and AUC decreased by 33% and 21%, respectively. These data suggest that posaconazole oral bioavailability from non-delayed release formulations is at least partially dependent on gastric pH. Clinical studies in various patient cohorts receiving prophylaxis or treatment for invasive fungal infection have found PPI use to be associated with significantly reduced posaconazole plasma concentrations. The interaction was also suspected in a 58-year-old patient receiving posaconazole for invasive aspergillosis. Posaconazole serum trough level decreased significantly during coadministration with omeprazole for 3 days, but returned to baseline following discontinuation of omeprazole.

MANAGEMENT: Concomitant use of posaconazole oral suspension with proton pump inhibitors should generally be avoided. If possible, prescribers may consider suspending the PPI until completion of posaconazole therapy, or substituting an antifungal agent like fluconazole or voriconazole whose absorption is not affected by stomach pH. Delayed-release tablets of posaconazole may be used with PPIs, as no pharmacokinetic interaction has been demonstrated with esomeprazole.

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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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