Prasugrel is a potent, third-generation thienopyridine antiplatelet agent specifically indicated for the reduction of thrombotic cardiovascular events in patients with acute coronary syndromes (ACS) who are to be managed with percutaneous coronary intervention (PCI). It functions as an irreversible antagonist of the P2Y12 adenosine diphosphate receptor on platelets, delivering rapid, consistent, and greater platelet inhibition compared to earlier therapies. This profile provides a comprehensive overview of its clinical pharmacology, appropriate use, and essential safety information for healthcare professionals.

Features

• Active Ingredient: Prasugrel hydrochloride.
• Pharmacological Class: P2Y12 ADP receptor inhibitor; platelet aggregation inhibitor.
• Standard Dosage Form: Film-coated, immediate-release oral tablets.
• Available Strengths: 5 mg and 10 mg tablets.
• Onset of Action: Rapid; significant inhibition of platelet aggregation observed within 30 minutes of a loading dose.
• Peak Plasma Concentration: Approximately 30 minutes post-administration.
• Metabolism: Rapidly hydrolyzed by esterases to an inactive thiolactone, which is then converted to the active metabolite primarily by CYP3A4 and CYP2B6 isoenzymes.
• Elimination Half-life: Approximately 7 hours (range 2–15 hours) for the active metabolite.
• Renal Excretion: ~68% (inactive metabolites); no dosage adjustment required in renal impairment.
• Hepatic Excretion: ~27% (inactive metabolites); not recommended in patients with severe hepatic disease.

Benefits

• Superior Ischemic Event Reduction: Demonstrated significantly greater reduction in the rate of a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke compared to clopidogrel in the TRITON-TIMI 38 trial.
• Reduced Stent Thrombosis: Associated with a significantly lower rate of both early and late stent thrombosis, a critical concern in PCI.
• Rapid and Consistent Antiplatelet Effect: Provides high levels of platelet inhibition with less inter-patient variability, reducing the concern for non-responsiveness (“clopidogrel resistance”).
• Standardized Dosing: A fixed maintenance dose regimen simplifies treatment without the need for routine platelet function testing in the vast majority of patients.
• Proven Efficacy in High-Risk Subgroups: Particularly effective in patients with diabetes mellitus and those presenting with ST-elevation myocardial infarction (STEMI).

Common use

Prasugrel is indicated to reduce the rate of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndromes (unstable angina, non-ST-elevation myocardial infarction [NSTEMI], or ST-elevation myocardial infarction [STEMI]) who are to be managed with percutaneous coronary intervention (PCI). Its use is intended to be part of dual antiplatelet therapy (DAPT), co-administered with aspirin.

Dosage and direction

• Initiation: Treatment should be initiated as a single 60 mg loading dose.
• Maintenance: Followed by a once-daily 10 mg maintenance dose.
• Low-Body-Weight Patients: For patients weighing <60 kg, consider a maintenance dose of 5 mg once daily, though efficacy and safety of the 5 mg dose have not been prospectively studied.
• Timing: Can be administered with or without food.
• Duration: The optimal duration of DAPT (prasugrel plus aspirin) is a clinical decision based on the patient’s ischemic and bleeding risks. Current guidelines generally recommend at least 12 months for ACS patients, unless contraindicated.

Precautions

• Bleeding Risk: Prasugrel increases the risk of significant, sometimes fatal, bleeding. It is contraindicated in patients with active pathological bleeding or a history of transient ischemic attack (TIA) or stroke.
• Surgical Discontinuation: If possible, discontinue prasugrel at least 7 days prior to any elective surgery to mitigate bleeding risk.
• Thrombotic Thrombocytopenic Purpura (TTP): TTP, a potentially fatal condition characterized by thrombocytopenia and microangiopathic hemolytic anemia, has been reported rarely and requires prompt treatment.
• Hypersensitivity: Hypersensitivity reactions including anaphylaxis have been reported.
• Hepatic Impairment: Avoid use in patients with severe hepatic disease, as this may impact bleeding risk.

Contraindications

• Active pathological bleeding (e.g., peptic ulcer, intracranial hemorrhage).
• History of transient ischemic attack (TIA) or stroke.
• Hypersensitivity to prasugrel or any component of the product.

Possible side effect

The most common adverse reaction is bleeding, which can range from minor to severe/life-threatening.

• Very Common (>1/10): Minor bleeding (e.g., epistaxis, bruising).
• Common (1/10 to 1/100): Major bleeding (e.g., gastrointestinal hemorrhage, post-procedural hemorrhage), anemia, subcutaneous hematoma, dyspnea, atrial fibrillation, hypertension, headache, dizziness, nausea, diarrhea, rash, pruritus, back pain.
• Uncommon (1/100 to 1/1000): Severe thrombocytopenia, hypersensitivity reactions (including angioedema), bronchospasm, hypotension, fever.
• Rare (<1/1000): Thrombotic Thrombocytopenic Purpura (TTP), anaphylaxis.

Drug interaction

• Other Antithrombotics: Concomitant use with warfarin, other oral anticoagulants, fibrinolytic therapy, or chronic NSAIDs increases the risk of bleeding. Avoid concomitant use of prasugrel with other potent P2Y12 inhibitors.
• Proton Pump Inhibitors (PPIs): Unlike clopidogrel, no clinically significant interaction has been observed with PPIs like omeprazole, which can be co-administered.
• CYP3A4 Inducers/Inhibitors: Prasugrel’s active metabolite formation may be affected by strong CYP3A4 inducers (e.g., rifampin) or inhibitors (e.g., ketoconazole), but dose adjustments are not recommended.

Missed dose

Patients should take the next scheduled dose at its regular time. They should not take a double dose to make up for a missed dose.

Overdose

There is no known antidote for prasugrel overdose. Overdose is expected to result in pronounced bleeding complications. Management should consist of prompt hemostatic evaluation, including monitoring for signs of bleeding. Platelet transfusion may be considered to reverse the antiplatelet effect, although the irreversible binding of the active metabolite may limit its efficacy. Supportive care is the mainstay of treatment.

Storage

• Store at room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).
• Keep in the original container to protect from moisture and light.
• Keep out of reach of children and pets.

Disclaimer

This information is intended for educational purposes of healthcare professionals and is a summary of the product’s characteristics. It is not exhaustive and does not replace the full Prescribing Information or a healthcare professional’s clinical judgment. The prescriber must review the complete product labeling before initiating therapy. Decisions regarding patient treatment must be based on the independent professional judgment of the clinician, considering the individual patient’s clinical circumstances.

Reviews

• “Based on the robust TRITON-TIMI 38 data, prasugrel remains a cornerstone therapy for our ACS-PCI patients, particularly those at high ischemic risk. The rapid onset and potency are undeniable advantages in the cath lab.” – Interventional Cardiologist, Academic Medical Center
• “While the bleeding risk is a genuine concern and requires careful patient selection, the significant reduction in stent thrombosis makes prasugrel a valuable agent. We use it judiciously, especially in younger patients without stroke risk factors.” – Clinical Pharmacist, Cardiology Group
• “The fixed-dose regimen and lack of interaction with PPIs simplify therapy management from a pharmacy perspective compared to clopidogrel. It’s a predictable and effective drug when used in the correct patient population.” – Pharmacy Director, Hospital Formulary Committee