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 powerful platelet inhibition. This profile is critical in the high-risk peri-PCI setting, where effective prevention of stent thrombosis and subsequent ischemic events is paramount. Its distinct pharmacokinetic and pharmacodynamic profile offers a significant therapeutic advantage in a carefully selected patient population.

Features

• Active Ingredient: Prasugrel hydrochloride.
• Pharmacological Class: P2Y12 platelet ADP receptor inhibitor; thienopyridine.
• Available Dosage Forms: Film-coated tablets (5 mg and 10 mg).
• Mechanism of Action: Irreversible binding to the P2Y12 receptor on platelets, inhibiting ADP-mediated platelet activation and aggregation.
• Rapid Onset: Achieves >50% inhibition of platelet aggregation (IPA) within 30 minutes and ~80% IPA by 1 hour after a 60 mg loading dose.
• High Level of Inhibition: Provides consistently high levels of platelet inhibition (mean IPA >70%) during maintenance therapy.
• Prodrug Metabolism: Requires conversion to its active metabolite primarily by CYP3A4 and CYP2B6, with minimal contribution from CYP2C9 and CYP2C19, reducing the impact of genetic polymorphisms common with other agents in its class.

Benefits

• Significantly Reduced Ischemic Events: Demonstrated superior efficacy over clopidogrel in reducing the rate of a composite endpoint of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke in the TRITON-TIMI 38 trial.
• Marked Reduction in Stent Thrombosis: Associated with a markedly lower rate of both early and late stent thrombosis, a serious complication of PCI.
• Rapid and Predictable Antiplatelet Effect: The consistent metabolic activation ensures a reliable antiplatelet response, minimizing the concern for high on-treatment platelet reactivity (HPR), which is linked to adverse ischemic outcomes.
• Benefit in High-Risk Patients: Particularly effective in reducing recurrent ischemic events in patients with diabetes mellitus or those presenting with ST-elevation myocardial infarction (STEMI).
• Standardized Dosing: A fixed loading and maintenance dose regimen simplifies administration without the need for routine platelet function testing for most patients.

Common use

Prasugrel is indicated for the prophylaxis of atherothrombotic events in patients with Acute Coronary Syndrome (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, for up to 12 months (or longer based on individual patient risk assessment) to prevent stent thrombosis and recurrent cardiovascular events.

Dosage and direction

• Initiation (Loading Dose): A single 60 mg oral loading dose should be administered promptly at the time of diagnosis of ACS, preferably at the time of PCI.
• Maintenance Therapy: Following the loading dose, a maintenance dose of 10 mg orally once daily is recommended.
• Patients with Low Body Weight: For patients weighing <60 kg, consider a maintenance dose of 5 mg once daily, though the effectiveness of this dose is less established.
• Administration: Can be taken with or without food. Tablets should be swallowed whole; they must not be chewed, broken, or crushed.
• Duration of Therapy: DAPT with aspirin and prasugrel should be continued for at least 12 months after an ACS event unless the risk of bleeding outweighs the benefit of continued therapy.

Precautions

• Bleeding Risk: Prasugrel increases the risk of significant, sometimes fatal, bleeding. It is contraindicated in patients with a history of transient ischemic attack (TIA) or stroke and in those with active pathological bleeding.
• Surgical Procedures: 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 plasmapheresis.
• Hypersensitivity: Hypersensitivity reactions, including anaphylaxis, have been reported.
• Hepatic Impairment: Avoid use in patients with severe hepatic disease, as they may have impaired metabolic function and an increased bleeding risk.

Contraindications

• Active pathological bleeding (e.g., peptic ulcer, intracranial hemorrhage).
• A history of prior 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, which can range from minor to fatal.

• Major Bleeding: Life-threatening or fatal bleeding, requiring transfusion.
• Minor Bleeding: Such as epistaxis, bruising, gingival bleeding.
• Other Common Side Effects: Hypertension, hypercholesterolemia/hyperlipidemia, headache, back pain, dyspnea, nausea, dizziness, cough, fatigue.
• Serious Non-Hemorrhagic Effects: Thrombotic thrombocytopenic purpura (TTP), severe thrombocytopenia, hypersensitivity reactions including anaphylaxis, hepatic enzyme elevations, angioedema, rash.

Drug interaction

• Other Antithrombotic Agents: Concomitant use with warfarin, other anticoagulants, fibrinolytics, or chronic NSAIDs increases the risk of bleeding.
• Opioid Analgesics: May delay and reduce the absorption of prasugrel due to reduced gastric motility. This may diminish its antiplatelet effect, particularly following a loading dose.
• 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. Concomitant use for GI protection is common.
• Strong CYP3A4 Inducers (e.g., rifampin): May decrease exposure to the active metabolite of prasugrel, potentially reducing its efficacy. Avoid concomitant use.

Missed dose

Patients should take the next dose at its scheduled time. They should not take a double dose to make up for a missed dose. Maintaining a consistent daily schedule is important for sustained platelet inhibition.

Overdose

There is no known antidote for prasugrel overdose. Overdose is expected to result in pronounced bleeding complications. Management should consist of prompt cessation of the drug, close monitoring for bleeding, and supportive measures. Platelet transfusion may be partially effective in reversing the antiplatelet effect, as prasugrel irreversibly binds to platelets; transfusion provides new, unaffected platelets. Activated charcoal may be considered if ingestion was recent.

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 for educational and informational purposes only and does not constitute medical advice. It 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 before starting or stopping any 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): The pivotal trial demonstrated that in patients with ACS with scheduled PCI, prasugrel therapy was associated with a significantly reduced risk of the primary efficacy endpoint (a composite of death from cardiovascular causes, nonfatal MI, or nonfatal stroke) compared to clopidogrel (9.9% vs. 12.1%; HR 0.81; P<0.001). This came at the cost of an increased risk of major bleeding, including fatal bleeding.
• Expert Consensus Guidelines (ACC/AHA, ESC): Prasugrel (with a Class of Recommendation I) is a preferred P2Y12 inhibitor in DAPT for ACS patients undergoing PCI who are not at high risk of bleeding and who have no history of stroke or TIA. It is specifically favored in higher-risk subsets such as diabetic patients.
• Real-World Evidence Studies: Numerous registry-based and observational studies have corroborated the efficacy of prasugrel in reducing ischemic events in routine clinical practice, consistently affirming its role as a cornerstone therapy in modern PCI for ACS.