What is the recommended dosing regimen for Prasugrel (prasugrel)

Prasugrel Dosing Recommendations

The recommended dosing regimen for prasugrel is a 60 mg oral loading dose followed by a 10 mg daily maintenance dose, with dose adjustments required for patients weighing <60 kg or aged ≥75 years. 1

Standard Dosing Protocol

• Initiate prasugrel with a single 60 mg oral loading dose, followed by 10 mg orally once daily 1
• Prasugrel should be administered with aspirin (75-325 mg daily) 1
• Prasugrel may be taken with or without food 1

Timing of Loading Dose

• For patients with UA/NSTEMI, the loading dose should be administered after coronary anatomy is defined 1, 2
• For STEMI patients presenting within 12 hours of symptom onset, the loading dose can be administered at the time of diagnosis 1
• For STEMI patients presenting more than 12 hours after symptom onset, the loading dose should be administered after coronary anatomy is established 1

Special Population Considerations

Low Body Weight Patients (<60 kg)

• Patients weighing <60 kg have increased exposure to the active metabolite and higher bleeding risk 1, 2
• Consider reducing the maintenance dose to 5 mg daily in these patients 1, 2
• The 5 mg maintenance dose has not been prospectively studied in large clinical trials but pharmacokinetic and pharmacodynamic studies suggest it provides similar platelet inhibition as 10 mg in heavier patients 3

Elderly Patients (≥75 years)

• Prasugrel is generally not recommended in patients ≥75 years due to increased risk of fatal and intracranial bleeding 2
• Exception: May be considered in high-risk elderly patients with diabetes or history of prior MI 2, 4
• If used in elderly patients, consider the 5 mg maintenance dose 2, 4

Contraindications

• Prior history of stroke or transient ischemic attack (TIA) 2
• Active pathological bleeding 2
• Patients likely to undergo urgent CABG 2

Duration of Therapy

• For patients receiving drug-eluting stents (DES): at least 12 months and up to 15 months 4
• For patients receiving bare-metal stents (BMS): at least 1 month and ideally up to 12 months 4
• Consider discontinuing prasugrel at least 7 days before any planned surgery to reduce bleeding risk 2, 4

Monitoring and Safety Considerations

• Prasugrel is associated with higher bleeding risk compared to clopidogrel, with TIMI major hemorrhage observed in 2.4% vs 1.8% of patients 4
• Fatal bleeding is significantly higher with prasugrel (0.4%) compared to clopidogrel (0.1%) 4
• Additional risk factors for bleeding include: body weight <60 kg, propensity to bleed, and concomitant use of medications that increase bleeding risk (e.g., warfarin, heparin, fibrinolytic therapy, or NSAIDs) 2
• Consider co-administration of proton pump inhibitors in patients at high risk for gastrointestinal bleeding 5

Common Pitfalls to Avoid

• Administering prasugrel to patients with history of stroke or TIA 2
• Failing to adjust the dose in patients weighing <60 kg 4
• Starting prasugrel in patients likely to undergo urgent CABG 2
• Using prasugrel "upfront" in NSTE-ACS patients before coronary anatomy is defined 2
• Discontinuing prasugrel prematurely (before recommended duration) in patients with stents, which increases risk of stent thrombosis 4