Prasugrel is a potent, third-generation thienopyridine antiplatelet agent specifically indicated to reduce the rate 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 (ADP) receptor on platelets, delivering rapid, consistent, and powerful platelet inhibition. This profile provides a comprehensive overview of its clinical application, pharmacological profile, and essential safety information for healthcare professionals managing high-risk cardiac patients.

Features

• Active Ingredient: Prasugrel hydrochloride.
• Pharmacological Class: P2Y12 ADP receptor antagonist; thienopyridine.
• Mechanism of Action: Irreversible inhibition of the P2Y12 component of ADP receptors on platelet cell membranes, preventing ADP-mediated activation of the glycoprotein GPIIb/IIIa complex and subsequent platelet aggregation.
• Onset of Action: Rapid; significant inhibition observed within 30 minutes of a loading dose.
• 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.
• Excretion: ~68% in urine and ~27% in feces as inactive metabolites.
• Available Formulations: Film-coated tablets (5 mg and 10 mg).

Benefits

• Significantly Reduced Ischemic Events: Demonstrated superior efficacy over clopidogrel in reducing the composite endpoint of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke in ACS patients undergoing PCI.
• Rapid and Potent Antiplatelet Effect: Achieves a higher level of platelet inhibition more consistently and quickly than clopidogrel, which is critical in the acute setting of PCI.
• Lower Incidence of Stent Thrombosis: Associated with a significantly reduced risk of both early and late stent thrombosis, a serious complication of PCI.
• Consistent Pharmacodynamic Response: Exhibits less inter-patient variability in platelet inhibition response compared to clopidogrel, negating the concern for “non-responders” or hyporesponders.
• Fixed-Dosing Regimen: Does not require routine platelet function testing for dose adjustment in the vast majority of patients, simplifying clinical management.

Common use

Prasugrel is indicated for the prophylaxis of atherothrombotic events 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). It is used as part of dual antiplatelet therapy (DAPT), almost always in combination with low-dose aspirin, to prevent stent thrombosis and recurrent ischemic events. Its use is generally reserved for patients at high risk of thrombotic events and low risk of bleeding.

Dosage and direction

• Initiation: Treatment should be initiated with a single 60 mg loading dose.
• Maintenance: Followed by a once-daily 10 mg maintenance dose.
• Duration: In patients with a history of prior stroke or transient ischemic attack (TIA), prasugrel is generally not recommended. For patients weighing less than 60 kg, consider a maintenance dose of 5 mg once daily, though the efficacy and safety of this dose are not fully established.
• Timing: Can be administered with or without food.
• DAPT Duration: The optimal duration of therapy with aspirin and prasugrel is a clinical decision based on the patient’s ischemic versus bleeding risk. Current guidelines generally recommend a minimum of 12 months for ACS patients, but shorter (e.g., 3-6 months) or longer (e.g., >12 months) durations may be considered for specific stents and patient profiles.

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 or stroke.
• Surgical Discontinuation: If possible, discontinue prasugrel at least 7 days prior to any elective surgery to mitigate bleeding risk, as the antiplatelet effect is irreversible for the life of the platelet (~7–10 days).
• Thrombotic Thrombocytopenic Purpura (TTP): TTP, which can be fatal, has been reported rarely with prasugrel and requires prompt treatment, including plasmapheresis.
• Hypersensitivity: Hypersensitivity reactions, including anaphylaxis, have been reported.
• Hepatic Impairment: Avoid use in patients with severe hepatic disease, as these patients may have an increased bleeding risk. No dosage adjustment is necessary in patients with mild to moderate hepatic impairment.
• Renal Impairment: No dosage adjustment is necessary in patients with renal impairment. However, these patients are at greater risk of bleeding and should be monitored closely.

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 and serious adverse reaction is bleeding. Other reported side effects include:

• Very Common (≥1/10): Minor bleeding (e.g., epistaxis, bruising).
• Common (≥1/100 to <1/10): Major bleeding (e.g., gastrointestinal, retroperitoneal), anemia, subcutaneous or dermal bleeding, dyspnea, hypertension, headache, dizziness, nausea, diarrhea, hyperlipidemia, fatigue, non-cardiac chest pain, back pain, hypotension, fever, peripheral edema.
• Uncommon (≥1/1,000 to <1/100): Atrial fibrillation, bradycardia, rash, pruritus, allergic reactions (e.g., angioedema), hypersensitivity, hematoma, eye bleeding, confusion.
• Rare (<1/1,000): Thrombotic Thrombocytopenic Purpura (TTP), severe thrombocytopenia, leukocytopenia, eosinophilia, erythema multiforme, hepatic function abnormalities, anaphylaxis.

Drug interaction

• Other Antithrombotic Agents: Concomitant use with warfarin, other oral anticoagulants, fibrinolytic therapy, or chronic NSAIDs increases the risk of bleeding. Use with extreme caution.
• Opioid Agonists: Concurrent use may delay and reduce the absorption of prasugrel due to reduced gastric motility, potentially diminishing its antiplatelet effect during the acute phase of ACS.
• Proton Pump Inhibitors (PPIs): While some PPIs can reduce the efficacy of clopidogrel, this interaction is not expected with prasugrel due to its different metabolic pathway. PPIs may be co-administered for GI protection.
• Strong CYP3A4 Inducers (e.g., rifampin): May decrease exposure to the active metabolite of prasugrel, potentially reducing efficacy. Avoid concomitant use.

Missed dose

Patients should be instructed to take prasugrel at the same time each day. If a dose is missed, the patient should take one tablet as soon as it is remembered, unless it is almost time for the next scheduled dose. Patients should not take a double dose to make up for a missed one. The consistent antiplatelet effect is maintained by steady-state dosing, and a single missed dose may transiently reduce platelet inhibition.

Overdose

There is no known antidote for prasugrel overdose. Overdose is expected to result in profound platelet inhibition and a significant increase in bleeding risk. Management should be supportive and focus on clinical evidence of bleeding. Platelet transfusion may be considered to reverse the pharmacological effect, though the benefit may be limited due to the irreversible binding of the active metabolite to platelets. Hemodialysis is not expected to enhance elimination, as the active metabolite is highly protein-bound.

Storage

• Store at room temperature between 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 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 and healthcare professionals only. It is a summary and does not include all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. This information is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here.

Reviews

• TRITON-TIMI 38 Trial (New England Journal of Medicine, 2007): “In patients with ACS with scheduled PCI, prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding. Overall mortality did not differ significantly between treatment groups.”
• 2011 ACCF/AHA Focused Update: “Prasugrel should not be administered to patients with a prior history of stroke or TIA. In patients with ACS who are to be managed with PCI, prasugrel should be administered to support PCI as rapidly as possible or immediately after PCI… to decrease thrombotic cardiovascular events (MI, stroke) and stent thrombosis.”
• Real-World Evidence Studies: Numerous observational studies and registries have confirmed the efficacy of prasugrel in reducing ischemic events in real-world ACS/PCI populations, while also highlighting the critical importance of appropriate patient selection to balance ischemic benefit against bleeding risk.