How is Prasugrel (prasugrel) dosing adjusted by patient weight?

From the Guidelines

Prasugrel dosing should be adjusted based on patient weight, with patients weighing less than 60 kg receiving a reduced maintenance dose of 5 mg daily (instead of the standard 10 mg daily) following the initial 60 mg loading dose. This weight-based adjustment is necessary because patients under 60 kg have increased exposure to the active metabolite of prasugrel, which increases their risk of bleeding complications 1. The loading dose remains the same (60 mg) regardless of weight. For patients weighing 60 kg or more, the standard maintenance dose of 10 mg daily is appropriate. This weight-based dosing strategy helps optimize the balance between the antiplatelet efficacy of prasugrel and the risk of bleeding events. Some key points to consider when administering prasugrel include:

• Prasugrel should always be administered with aspirin (75-325 mg daily) as part of dual antiplatelet therapy.
• Patients should be informed that prasugrel increases bleeding risk, and they should report any unusual bleeding to their healthcare provider immediately.
• The effectiveness and safety of the 5-mg dose have not been studied prospectively, but it is recommended for patients weighing less than 60 kg due to the increased risk of bleeding.
• Prasugrel is generally not recommended for patients with active pathological bleeding or a history of TIA or stroke, and its use should be carefully considered in patients over 75 years of age due to the increased risk of fatal and intracranial bleeding. It is essential to weigh the benefits and risks of prasugrel therapy in each patient, taking into account their individual characteristics and medical history, to ensure the best possible outcome 1.

From the FDA Drug Label

Dosing in Low Weight Patients Compared to patients weighing ≥60 kg, patients weighing <60 kg have an increased exposure to the active metabolite of prasugrel and an increased risk of bleeding on a 10 mg once daily maintenance dose. Consider lowering the maintenance dose to 5 mg in patients <60 kg. In TRITON-TIMI 38,4.6% of patients treated with prasugrel had body weight <60 kg. Individuals with body weight <60 kg had an increased risk of bleeding and an increased exposure to the active metabolite of prasugrel. Consider lowering the maintenance dose to 5 mg in patients <60 kg.

Prasugrel dosing by weight:

• Patients weighing ≥60 kg: 10 mg once daily
• Patients weighing <60 kg: consider lowering the maintenance dose to 5 mg once daily due to increased exposure to the active metabolite and increased risk of bleeding 2 2 2.

From the Research

Prasugrel Dosing by Weight

• Prasugrel is administered periprocedurally at an oral loading dose of 60 mg followed by daily maintenance doses (MDs) of 10 mg for most patients and 5 mg for patients weighing <60 kg or aged ≥75 years 3.
• The maintenance dose of prasugrel 2.5 mg/day was prescribed for patients with a low body weight (≤50 kg), elderly (≥75 years), or renal insufficiency (eGFR ≤30 mL/min/1.73 m2) in a study of Japanese patients with acute coronary syndrome (ACS) 4.
• Data from a prasugrel phase III study, TRITON-TIMI 38, suggested that a lower MD might be more suitable for patients weighing <60 kg or aged ≥75 years 3.
• Prasugrel therapy should not be used in adults older than 75 years of age, those who have had a recent transient ischemic attack (TIA) or stroke, those who have a low body weight < 60 kg, and those receiving medications or having conditions associated with a bleeding risk unless they are at a high risk for a CV event 5.

Key Considerations

• Patients weighing <60 kg may require a lower maintenance dose of prasugrel, such as 5 mg/day 3.
• Elderly patients (≥75 years) may also require a lower maintenance dose of prasugrel, such as 5 mg/day 3, 5.
• Patients with renal insufficiency (eGFR ≤30 mL/min/1.73 m2) may require a lower maintenance dose of prasugrel, such as 2.5 mg/day 4.