Prasugrel

Usage

Prasugrel, an antiplatelet agent, is prescribed to reduce thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI). This includes patients with unstable angina, non-ST-elevation myocardial infarction (NSTEMI), or ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI. It is administered in conjunction with aspirin.

Alternate Names

• Generic: Prasugrel
• Brand: Effient

How It Works

Pharmacodynamics: Prasugrel is a prodrug rapidly metabolized to its active form, which irreversibly binds to the P2Y12 receptor on platelets. This binding prevents adenosine diphosphate (ADP)-mediated platelet activation and aggregation, inhibiting thrombus formation.

Pharmacokinetics:

• Absorption: Prasugrel is rapidly absorbed and extensively metabolized. Food does not impact absorption.
• Metabolism: Prasugrel undergoes rapid hepatic metabolism via hydrolysis and cytochrome P450 enzymes (mainly CYP3A4 and CYP2B6) to its active metabolite.
• Elimination: The active metabolite and its inactive metabolites are primarily excreted in the urine and feces.

Mode of Action: The active metabolite of Prasugrel selectively and irreversibly binds to the P2Y12 ADP receptor on platelets. This prevents ADP-induced platelet activation and aggregation, effectively reducing the risk of thrombus formation. This is crucial in ACS patients undergoing PCI to prevent stent thrombosis and other cardiovascular events.

Dosage

Standard Dosage

Adults:

• Initial dose: 60 mg loading dose orally once
• Maintenance dose: 10 mg orally once daily in combination with aspirin (75 mg to 325 mg daily).
• Patients <60 kg: Consider 5 mg maintenance dose due to increased bleeding risk.
• Patients ≥75 years: Generally not recommended except for high-risk patients (e.g., diabetes, prior MI) after careful benefit/risk assessment. If used, administer 5 mg daily after the loading dose.

Children: Not recommended.

Special Cases:

• Elderly Patients: Generally not recommended for patients ≥75 years unless benefits outweigh risks in high-risk scenarios. In such cases, a 5 mg maintenance dose should be used. Increased risk of bleeding requires careful monitoring.
• Patients with Renal Impairment: No dosage adjustment is necessary, but monitor for increased bleeding risk, particularly in moderate to severe impairment.
• Patients with Hepatic Dysfunction: No dosage adjustment is necessary for mild to moderate impairment (Child-Pugh Class A or B). Severe hepatic impairment (Child-Pugh C) contraindicates Prasugrel use.
• Patients with Comorbid Conditions: Careful consideration is required for patients with conditions increasing bleeding risk (e.g., recent surgery or trauma, active peptic ulcer disease). Concomitant use of drugs also increasing bleeding risk (e.g., anticoagulants, NSAIDs) warrants close monitoring and potential dose adjustments.

Clinical Use Cases

Prasugrel’s usage is specifically indicated for ACS patients undergoing PCI. It is not indicated for use in settings like:

• Intubation
• Surgical Procedures (except in the context of PCI for ACS)
• Mechanical Ventilation
• Intensive Care Unit (ICU) Use (unless related to ACS and PCI)
• Emergency Situations (outside the scope of ACS managed with PCI).

Dosage Adjustments

Adjustments are necessary for patients <60 kg and those ≥75 years old (as noted above). In other scenarios like renal/hepatic impairment, dose adjustments are not routinely recommended, but careful monitoring for bleeding is crucial. Individualized decisions are required based on bleeding risk and ischemic risk.

Side Effects

Common Side Effects:

• Bleeding (various manifestations, including epistaxis, hematuria, GI bleeding)
• Bruising
• Headache
• Dizziness
• Fatigue

Rare but Serious Side Effects:

• Thrombotic Thrombocytopenic Purpura (TTP)
• Severe, life-threatening bleeding (e.g., intracranial hemorrhage)
• Allergic reactions (including angioedema)

Long-Term Effects: Long-term Prasugrel usage primarily carries the risk of chronic bleeding complications.

Adverse Drug Reactions (ADR): TTP and severe bleeding constitute critical ADRs requiring immediate intervention.

Contraindications

• Absolute: Active pathological bleeding (e.g., intracranial hemorrhage, peptic ulcer), history of stroke or TIA, severe hepatic impairment.
• Relative: Age ≥75 years (generally not recommended, except in high-risk cases), weight <60 kg (consider 5 mg dose), conditions predisposing to bleeding, concomitant use of medications increasing bleeding risk.

Drug Interactions

Prasugrel interacts with several medications, including:

• Anticoagulants (e.g., warfarin): Increased bleeding risk.
• NSAIDs (e.g., ibuprofen, naproxen): Increased bleeding risk.
• Opioid agonists: May delay and reduce Prasugrel absorption.
• CYP3A4 inhibitors/inducers: May affect Prasugrel metabolism.

It’s essential to review a comprehensive drug interaction list before prescribing Prasugrel.

Pregnancy and Breastfeeding

• Pregnancy: Data on Prasugrel use in pregnancy are limited. Consider the potential benefits and risks to the fetus. Animal studies revealed slight decreased fetal body weight at maternally toxic doses.
• Breastfeeding: It is unknown whether Prasugrel is excreted in human milk. Metabolites are present in rat milk. Assess benefits of breastfeeding alongside the mother’s clinical need and any potential risks to the nursing infant. Use with caution.

Drug Profile Summary

• Mechanism of Action: Irreversible P2Y12 receptor inhibitor, preventing platelet activation and aggregation.
• Side Effects: Bleeding (common), TTP and severe hemorrhage (rare but serious).
• Contraindications: Active bleeding, stroke/TIA history, severe hepatic impairment.
• Drug Interactions: Anticoagulants, NSAIDs, opioid agonists, CYP3A4 inhibitors/inducers.
• Pregnancy & Breastfeeding: Limited data; use with caution if benefits outweigh potential risks.
• Dosage: 60 mg loading dose, 10 mg maintenance (5 mg for <60 kg or ≥75 years).
• Monitoring Parameters: Signs of bleeding, hemoglobin, platelet count.

Popular Combinations

Prasugrel is commonly combined with aspirin (75 mg to 325 mg daily) in ACS patients managed with PCI.

Precautions

• Bleeding risk assessment, including medical history, concomitant medications, and lifestyle factors.
• Close monitoring for bleeding signs.
• Caution in elderly, low-weight, and patients with comorbidities increasing bleeding risk.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Prasugrel?

A: 60 mg loading dose, followed by 10 mg daily. For patients <60 kg or ≥75 years old, consider 5 mg daily maintenance dose. Always co-administer with aspirin.

Q2: What is the mechanism of action of Prasugrel?

A: It irreversibly inhibits P2Y12 ADP receptors on platelets, preventing their activation and aggregation.

Q3: What are the major contraindications for Prasugrel?

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

Q4: What are the most common side effects of Prasugrel?

A: Bleeding (various forms) and bruising.

Q5: What should be done if a patient on Prasugrel experiences major bleeding?

A: Discontinue Prasugrel immediately and provide supportive care (e.g., platelet transfusion, if needed).

Q6: How does Prasugrel interact with other antiplatelet medications like clopidogrel?

A: Combining Prasugrel with other antiplatelet medications, especially clopidogrel, can increase the risk of bleeding. Such combinations should be used cautiously and under strict monitoring, and they are generally avoided.

Q7: Can Prasugrel be used in patients with renal impairment?

A: No dose adjustment is necessary in renal impairment, but these patients should be monitored carefully due to higher bleeding risk.

Q8: Is Prasugrel safe during pregnancy?

A: Data on Prasugrel in pregnancy are limited. Use only if potential benefits outweigh the risks to the fetus.

Q9: Can Prasugrel be crushed or chewed?

A: No, Prasugrel tablets should be swallowed whole.

Q10: How long should Prasugrel treatment typically last?

A: Dual antiplatelet therapy (DAPT) with Prasugrel and aspirin is typically recommended for at least 6-12 months after PCI in ACS patients. The duration may vary based on individual factors (ischemic and bleeding risks), and longer durations might be considered for patients with higher ischemic risk and lower bleeding risk. Conversely, shorter durations could be considered in patients with higher bleeding risk and lower ischemic risk. Clinical judgment remains essential.