Effient Drug Interactions

Warfarin: Concomitant administration of Effient with coumarin derivatives other than warfarin has not been studied. Because of the potential for increased risk of bleeding, warfarin (or other coumarin derivatives) and prasugrel should be co-administered with caution (see Precautions).
Non-steroidal anti-inflammatory drugs (NSAIDs): Concomitant administration with chronic NSAIDs has not been studied. Because of the potential for increased risk of bleeding, chronic NSAIDs (including COX-2 inhibitors) and Effient should be co-administered with caution (see Precautions).
Effient can be concomitantly administered with medicinal products metabolised by cytochrome P450 enzymes (including statins), or medicinal products that are inducers or inhibitors of cytochrome P450 enzymes. Effient can also be concomitantly administered with ASA, heparin, digoxin, and medicinal products that elevate gastric pH, including proton pump inhibitors and H₂ blockers. Although not studied in specific interaction studies, Effient has been co-administered in the phase 3 clinical trial with low molecular weight heparin, bivalirudin, and GP IIb/IIIa inhibitors (no information available regarding the type of GP IIb/IIIa inhibitor used) without evidence of clinically significant adverse interactions.
Effects of other medicinal products on Effient: Acetylsalicylic acid: Effient is to be administered concomitantly with acetylsalicylic acid (ASA). Although a pharmacodynamic interaction with ASA leading to an increased risk of bleeding is possible, the demonstration of the efficacy and safety of prasugrel comes from patients concomitantly treated with ASA.
Heparin: A single intravenous bolus dose of unfractionated heparin (100 U/kg) did not significantly alter the prasugrel-mediated inhibition of platelet aggregation. Likewise, prasugrel did not significantly alter the effect of heparin on measures of coagulation. Therefore, both medicinal products can be administered concomitantly. An increased risk of bleeding is possible when Effient is co-administered with heparin.
Statins: Atorvastatin (80 mg daily) did not alter the pharmacokinetics of prasugrel and its inhibition of platelet aggregation. Therefore, statins that are substrates of CYP3A are not anticipated to have an effect on the pharmacokinetics of prasugrel or its inhibition of platelet aggregation.
Medicinal products that elevate gastric pH: Daily co-administration of ranitidine (an H₂-blocker) or lansoprazole (a proton-pump inhibitor) did not change the prasugrel active metabolite's AUC and T_max, but decreased the C_max by 14% and 29%, respectively. In the phase 3 clinical trial, Effient was administered without regard to co-administration of a proton pump inhibitor or H₂ blocker. Administration of the 60 mg prasugrel loading dose without concomitant use of proton-pump inhibitors may provide most rapid onset of action.
Inhibitors of CYP3A: Ketoconazole (400 mg daily), a selective and potent inhibitor of CYP3A4 and CYP3A5, did not affect prasugrel-mediated inhibition of platelet aggregation or the prasugrel active metabolites AUC and T_max, but decreased the C_max by 34% to 46%. Therefore, CYP3A inhibitors such as azole antifungals, HIV protease inhibitors, clarithromycin, telithromycin, verapamil, diltiazem, indinavir, ciprofloxacin, and grapefruit juice are not anticipated to have a significant effect on the pharmacokinetics of the active metabolite.
Inducers of Cytochromes P450: Rifampicin (600 mg daily), a potent inducer of CYP3A and CYP2B6 and an inducer of CYP2C9, CYP2C19, and CYP2C8, did not significantly change the pharmacokinetics of prasugrel. Therefore, known CYP3A inducers eg, rifampicin, carbamazepine and other inducers of cytochromes P-450 are not anticipated to have significant effect on the pharmacokinetics of the active metabolite.
Morphine and other opioids: A delayed and decreased exposure to oral P2Y12 inhibitors, including prasugrel and its active metabolite, has been observed in patients with acute coronary syndrome treated with morphine. This interaction may be related to reduced gastrointestinal motility and apply to other opioids. The clinical relevance is unknown, but data indicate the potential for reduced prasugrel efficacy in patients co-administered prasugrel and morphine. In patients with acute coronary syndrome, in whom morphine cannot be withheld and fast P2Y12 inhibition is deemed crucial, the use of a parenteral P2Y12 inhibitor may be considered.
Effects of Effient on other medicinal products: Digoxin: Prasugrel has no clinically significant effect on the pharmacokinetics of digoxin.
Medicinal products metabolised by CYP2C9: Prasugrel did not inhibit CYP2C9, as it did not affect the pharmacokinetics of S-warfarin. Because of the potential for increased risk of bleeding, warfarin and Effient should be co-administered with caution (see Precautions).
Medicinal Products Metabolized by CYP2B6: Prasugrel is a weak inhibitor of CYP2B6. In healthy subjects, prasugrel decreased exposure to hydroxybupropion, a CYP2B6-mediated metabolite of bupropion, by 23%. This effect is likely to be of clinical concern only when prasugrel is co-administered with medicinal products for which CYP2B6 is the only metabolic pathway and have a narrow therapeutic window (e.g. cyclophosphamide, efavirenz).