Chemical formula: C₂₀H₂₀FNO₃S Molecular mass: 373.441 g/mol PubChem compound: 6918456
Prasugrel interacts in the following cases:
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 metabolite’s AUC and Tmax, but decreased the Cmax by 34% to 46%. Therefore, CYP3A inhibitors such as azol 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.
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).
Daily co-administration of ranitidine (an H2 blocker) or lansoprazole (a proton pump inhibitor) did not change the prasugrel active metabolite’s AUC and Tmax, but decreased the Cmax by 14% and 29%, respectively. In the phase 3 clinical trial, prasugrel 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.
Concomitant administration of prasugrel 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.
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 prasugrel should be co-administered with caution.
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 coadministered 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.
Patients should be advised to inform physicians and dentists that they are taking prasugrel before any surgery is scheduled and before any new medicinal product is taken. If a patient is to undergo elective surgery, and an antiplatelet effect is not desired, prasugrel should be discontinued at least 7 days prior to surgery. Increased frequency (3-fold) and severity of bleeding may occur in patients undergoing CABG surgery within 7 days of discontinuation of prasugrel. The benefits and risks of prasugrel should be carefully considered in patients in whom the coronary anatomy has not been defined and urgent CABG is a possibility.
Hypersensitivity reactions including angioedema have been reported in patients receiving prasugrel, including in patients with a history of hypersensitivity reaction to clopidogrel. Monitoring for signs of hypersensitivity in patients with a known allergy to thienopyridines is advised.
In the phase 3 clinical trial (TRITON) key exclusion criteria included an increased risk of bleeding; anaemia; thrombocytopaenia; a history of pathological intracranial findings. Patients with acute coronary syndromes undergoing PCI treated with prasugrel and ASA showed an increased risk of major and minor bleeding according to the TIMI classification system. Therefore, the use of prasugrel in patients at increased risk of bleeding should only be considered when the benefits in terms of prevention of ischaemic events are deemed to outweigh the risk of serious bleedings. This concern applies especially to patients:
Thrombotic thrombocytopaenic purpura (TTP) has been reported with the use of prasugrel. TTP is a serious condition and requires prompt treatment.
No clinical study has been conducted in pregnant women.
Animal studies do not indicate direct harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Because animal reproduction studies are not always predictive of a human response, prasugrel should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the foetus.
No clinical study has been conducted breast-feeding women.
It is unknown whether prasugrel is excreted in human breast milk. Animal studies have shown excretion of prasugrel in breast milk. The use of prasugrel during breastfeeding is not recommended.
Prasugrel had no effect on fertility of male and female rats at oral doses up to an exposure 240 times the recommended daily human maintenance dose (based on mg/m²).
Prasugrel is expected to have no or negligible influence on the ability to drive and use machines.
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