Aspirin + Prasugrel

Usage

Aspirin + Prasugrel is prescribed for the prevention of atherothrombotic events (such as heart attack, stroke, and stent thrombosis) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This includes patients with unstable angina, non-ST-elevation myocardial infarction (NSTEMI), or ST-elevation myocardial infarction (STEMI).

It falls under the pharmacological classification of antiplatelet agents.

The combination acts synergistically to inhibit platelet activation and aggregation, thus preventing blood clot formation in the coronary arteries and improving blood flow.

Alternate Names

While Aspirin + Prasugrel itself doesn’t have alternate names, its components do. Aspirin is also known as acetylsalicylic acid, and Prasugrel is marketed under the brand name Effient. Various generic versions of the combined formulation may also exist.

How It Works

Pharmacodynamics: Aspirin irreversibly inhibits cyclooxygenase-1 (COX-1), reducing thromboxane A2 production and platelet aggregation. Prasugrel, a thienopyridine, irreversibly inhibits the P2Y12 receptor on platelets, further inhibiting platelet activation and aggregation. The combined effect significantly reduces the risk of thrombus formation.

Pharmacokinetics:

• Aspirin: Rapidly absorbed after oral administration. Metabolized in the liver to salicylic acid. Excreted primarily by the kidneys.
• Prasugrel: Rapidly absorbed and metabolized in the liver to its active metabolite. The active metabolite irreversibly binds to the P2Y12 receptor. Excretion is via hepatic and renal pathways.

Mode of Action: Dual antiplatelet therapy inhibits platelet aggregation through different pathways. Aspirin inhibits thromboxane A2 production, a potent platelet activator, while Prasugrel blocks the P2Y12 receptor, preventing ADP-mediated platelet activation.

Receptor Binding/Enzyme Inhibition: Aspirin inhibits COX-1 enzyme. Prasugrel’s active metabolite irreversibly binds to the P2Y12 receptor.

Elimination Pathways: Aspirin is primarily excreted renally as salicylic acid. Prasugrel undergoes hepatic metabolism, and its metabolites are excreted via renal and hepatic routes.

Dosage

Standard Dosage

Adults:

• Loading dose: 60 mg Prasugrel orally once.
• Maintenance dose: 10 mg Prasugrel orally once daily, taken with 75-325 mg of aspirin daily.
• Patients < 60 kg: Consider 5 mg Prasugrel maintenance dose due to increased bleeding risk.
• Patients ≥ 75 years: Generally not recommended except in high-risk situations (e.g., diabetes or prior MI), where a 5 mg maintenance dose may be considered following the 60 mg loading dose.

Children: Not recommended for use in pediatric patients.

Special Cases:

• Elderly Patients: Increased bleeding risk, lower dose recommended (5 mg maintenance).
• Patients with Renal Impairment: No dose adjustment required, but monitor closely for bleeding.
• Patients with Hepatic Dysfunction: Moderate impairment: No dose adjustment needed. Severe impairment: Contraindicated.
• Patients with Comorbid Conditions: Consider individual patient factors, including bleeding risk. Diabetes mellitus increases bleeding risk.

Clinical Use Cases

Dosing follows the standard adult regimen described above in the context of PCI following ACS (unstable angina, NSTEMI, or STEMI). Specific clinical scenarios such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations do not alter the standard dosing regimen, although the potential for increased bleeding risk should be considered. Prasugrel should be discontinued at least 7 days prior to any planned surgical procedures including CABG, if possible.

Dosage Adjustments

Dose reduction to 5 mg daily is recommended for patients weighing less than 60 kg or those aged 75 years and older due to the increased bleeding risk.

Side Effects

Common Side Effects

• Bleeding (e.g., bruising, hematoma, epistaxis)
• Headache
• Dizziness
• Nausea
• Diarrhea

Rare but Serious Side Effects

• Major bleeding (e.g., gastrointestinal bleeding, intracranial hemorrhage)
• Thrombotic thrombocytopenic purpura (TTP)
• Allergic reactions (e.g., rash, angioedema, anaphylaxis)

Long-Term Effects

Chronic bleeding risk with prolonged use.

Adverse Drug Reactions (ADR)

• Major bleeding requiring transfusion or surgical intervention
• TTP
• Severe allergic reactions

Contraindications

• Active pathological bleeding (e.g., intracranial hemorrhage, peptic ulcer)
• History of stroke or transient ischemic attack (TIA)
• Severe hepatic impairment
• Hypersensitivity to Prasugrel or any component of the formulation

Drug Interactions

• Anticoagulants (e.g., warfarin, heparin): Increased bleeding risk
• NSAIDs (e.g., ibuprofen, naproxen): Increased bleeding risk
• Other antiplatelet agents (e.g., clopidogrel): Increased bleeding risk
• Opioids: Decreased exposure to Prasugrel. Consider a parenteral antiplatelet agent if concomitant use is required.

Pregnancy and Breastfeeding

Prasugrel’s safety during pregnancy is not well-established. While Prasugrel is not expected to harm the fetus, aspirin use, particularly in the third trimester, poses a bleeding risk to both mother and neonate.

Prasugrel’s presence in breast milk is unknown. Use with caution during breastfeeding, especially in newborns or premature infants.

Drug Profile Summary

• Mechanism of Action: Dual antiplatelet action inhibiting COX-1 and the P2Y12 receptor.
• Side Effects: Bleeding, headache, dizziness.
• Contraindications: Active bleeding, history of stroke/TIA, severe hepatic impairment.
• Drug Interactions: Anticoagulants, NSAIDs, other antiplatelet agents.
• Pregnancy & Breastfeeding: Use with caution. Aspirin is contraindicated in the third trimester.
• Dosage: Loading dose 60 mg, then 10 mg daily (5 mg for patients <60 kg or ≥75 years). Given with 75-325 mg aspirin daily.
• Monitoring Parameters: Signs of bleeding, platelet count, hemoglobin.

Popular Combinations

Aspirin is typically given in combination with Prasugrel.

Precautions

• Assess bleeding risk prior to initiation.
• Monitor for signs of bleeding.
• Avoid concomitant use with other medications that increase bleeding risk.
• Use cautiously in elderly patients and those with renal impairment.
• Discontinue Prasugrel at least 7 days before planned surgeries.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Aspirin + Prasugrel?

A: Loading dose: 60 mg Prasugrel, followed by 10 mg Prasugrel daily (5 mg for patients <60kg or ≥75yrs), along with 75-325 mg aspirin daily.

Q2: What are the contraindications for Aspirin + Prasugrel?

A: Active bleeding, history of stroke/TIA, severe hepatic impairment, hypersensitivity.

Q3: What are the most serious side effects of Aspirin + Prasugrel?

A: Major bleeding, TTP, severe allergic reactions.

Q4: Can Aspirin + Prasugrel be used in pregnancy?

A: Use with caution; aspirin contraindicated in third trimester. Limited safety data available.

Q5: Can Aspirin + Prasugrel be used during breastfeeding?

A: Limited safety data; use with caution.

Q6: How does Aspirin + Prasugrel work?

A: Aspirin inhibits COX-1, while Prasugrel inhibits the P2Y12 receptor, resulting in synergistic inhibition of platelet activation and aggregation.

Q7: What should I monitor in patients on Aspirin + Prasugrel?

A: Monitor for signs of bleeding, platelet count, hemoglobin and hematocrit.

Q8: What are the key drug interactions with Aspirin + Prasugrel?

A: Anticoagulants, NSAIDs, other antiplatelet medications can increase bleeding risk. Opioids can decrease Prasugrel exposure.

Q9: How long should Aspirin + Prasugrel be continued after PCI?

A: At least 6-12 months, but duration is individualized based on ischemic and bleeding risk.