Brand names: Effient, Efient, Prasita
Indications
Prasugrel, administered in combination with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with acute coronary syndromes (ACS), including:
- Unstable angina (UA)
- Non-ST-elevation myocardial infarction (NSTEMI)
- ST-elevation myocardial infarction (STEMI)
This applies to patients undergoing either primary or delayed percutaneous coronary intervention (PCI).
Contraindications
Prasugrel should not be used in the following situations:
- Hypersensitivity to the active substance or any of the excipients.
- Active pathological bleeding, such as gastrointestinal bleeding or intracranial hemorrhage.
- History of stroke or transient ischemic attack (TIA).
- Severely impaired liver function classified as Child-Pugh Class C.
Dosage
Adults
- Initial dose: A single loading dose of 60 mg.
- Maintenance dose: 10 mg once daily.
- For UA/NSTEMI patients undergoing coronary angiography within 48 hours of hospital admission, the loading dose should be administered at the time of PCI.
- Patients should also take acetylsalicylic acid (ASA) daily (75–325 mg).
Duration of therapy: Premature discontinuation of antiplatelet therapy, including prasugrel, in ACS patients treated with PCI can increase the risk of thrombosis, myocardial infarction, or death. Treatment for up to 12 months is recommended unless clinically indicated to discontinue earlier.
Patients ≥ 75 years
- Use in patients ≥ 75 years is generally not recommended.
- If deemed necessary after careful individual benefit-risk assessment by the prescribing physician:
- Initial dose: 60 mg single loading dose.
- Maintenance dose: 5 mg once daily.
- Rationale: Patients in this age group have higher bleeding risk and increased exposure to the active metabolite of prasugrel.
Patients weighing < 60 kg
- Initial dose: 60 mg single loading dose.
- Maintenance dose: 5 mg once daily.
- A maintenance dose of 10 mg is not recommended due to higher exposure to the active metabolite and increased bleeding risk compared to patients weighing ≥ 60 kg.
Renal impairment
- No dose adjustment is required, including for patients with end-stage renal disease.
- Limited experience exists for patients with impaired renal function.
Hepatic impairment
- No dose adjustment is required for patients with mild to moderate hepatic impairment (Child-Pugh Class A and B).
- Limited experience exists for patients with mild to moderate hepatic impairment.
- Contraindicated in patients with severe hepatic impairment (Child-Pugh Class C).
Pediatric population
- Safety and efficacy in children under 18 years have not been established.
- Limited data are available for children with sickle cell anemia.
Method of Administration
- Route: Oral.
- Prasugrel can be taken with or without food.
- Administering a 60 mg loading dose on an empty stomach may provide the fastest onset of effect.
- Do not crush or split the tablet.
Warnings and Precautions
Bleeding Risk
- In the phase 3 study (TRITON), key exclusion criteria included increased bleeding risk, anemia, thrombocytopenia, and a history of pathological intracranial findings.
- Patients with ACS undergoing PCI treated with prasugrel and ASA exhibited a higher risk of major and minor bleeding, as classified by the TIMI system (Thrombolysis in Myocardial Infarction).
- Prasugrel should only be considered for patients at increased bleeding risk if the benefits of preventing ischemic events outweigh the risk of severe bleeding. Particular caution is required for:
- Patients aged ≥ 75 years.
- Patients with a tendency to bleed (e.g., due to recent trauma, surgery, gastrointestinal bleeding, or active peptic ulcer).
- Patients weighing < 60 kg (maintenance dose of 5 mg recommended instead of 10 mg).
- Patients receiving medications that increase bleeding risk, including oral anticoagulants, clopidogrel, NSAIDs, or fibrinolytics.
- For patients with active bleeding requiring reversal of prasugrel’s pharmacological effect, platelet transfusion may be appropriate.
Patients Aged ≥ 75 Years
- Generally, prasugrel use is not recommended in this group.
- If prescribed after careful benefit-risk assessment, use a lower maintenance dose of 5 mg.
- Clinical studies have shown a higher risk of bleeding, including fatal bleeding, in this age group compared to younger patients.
Renal and Hepatic Impairment
- Limited experience exists for patients with renal impairment (including ESRD) and moderate hepatic impairment. These patients may have an increased bleeding risk and require cautious use.
Bleeding Risk Awareness
- Patients should be informed that bleeding may take longer than usual to stop when using prasugrel (with ASA) and should report any unusual or prolonged bleeding to their healthcare provider.
Timing of Loading Dose in NSTEMI
- In a clinical study (ACCOAST), administering the loading dose 4 hours before coronary angiography increased the risk of bleeding. For UA/NSTEMI patients undergoing coronary angiography within 48 hours of admission, the loading dose should be administered at the time of PCI.
Surgical Procedures
- Patients should inform physicians or dentists about prasugrel use prior to planned surgery or initiating new medications.
- Prasugrel should be discontinued at least 7 days before elective surgery if antiplatelet effects are not desired.
- Patients undergoing coronary artery bypass graft (CABG) surgery within 7 days of stopping prasugrel may experience a threefold increased risk of severe bleeding.
Hypersensitivity Including Angioedema
- Hypersensitivity reactions, including angioedema, have been reported. Patients with a known allergy to thienopyridines should be monitored for signs of hypersensitivity.
Thrombotic Thrombocytopenic Purpura (TTP)
- TTP has been reported with prasugrel use. This serious condition requires immediate treatment.
Interactions with Morphine and Opioids
- Reduced efficacy of prasugrel has been observed in patients receiving prasugrel and morphine concurrently.
Lactose Content
- Prasugrel contains lactose. Patients with rare hereditary conditions such as galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not use this medication.
Sodium Content
- Prasugrel contains less than 1 mmol (23 mg) of sodium per dose, making it essentially sodium-free.