Drug Interactions between prasugrel and Yosprala

MONITOR: Concomitant use of prasugrel with other agents that affect hemostasis including aspirin may increase the risk of bleeding. According to the product labeling, the effects of prasugrel on platelet aggregation were not significantly affected by aspirin 150 mg daily. However, bleeding time was increased compared with either drug alone. The safety of prasugrel during coadministration with other salicylates has not been established, but potentiation of gastrointestinal bleeding should be considered.

MANAGEMENT: Although prasugrel may be used with aspirin, caution is advised during coadministration with any salicylate, especially in patients at risk for gastrointestinal ulceration or bleeding. Close clinical and laboratory observation for hemorrhagic complications is recommended. Patients should be advised to contact their physician if they develop potential signs and symptoms of gastrointestinal injury such as abdominal pain, bloating, dizziness, lightheadedness, hematemesis, anorexia, and/or black, tarry stools.

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.

Coadministration with proton pump inhibitors or H2-receptor antagonists may modestly affect the pharmacokinetics of prasugrel, but does not appear to alter its antiplatelet effects. The proposed mechanism is delayed prasugrel dissolution due to increased gastric pH. In 24 healthy subjects, administration of a single 60 mg dose of prasugrel following pretreatment with lansoprazole 30 mg/day for 7 days resulted in a 29% decrease in the peak plasma concentration (Cmax) of the active metabolite of prasugrel and a nonsignificant (12%) decrease in the metabolite's systemic exposure (AUC) compared to administration of prasugrel alone. Lansoprazole had no significant effect on the response to prasugrel as measured by ADP-induced platelet aggregometry. Similarly, daily coadministration of ranitidine reduced the Cmax of the prasugrel active metabolite by 14%, but did not significantly change the AUC or Tmax. No dosage adjustment for prasugrel is necessary when coadministered with drugs that elevate gastric pH, including proton pump inhibitors and H2-receptor antagonists. However, administration of the 60 mg prasugrel loading dose without concomitant use of proton pump inhibitors may provide most rapid onset of action.