What are the contraindications for Prasugrel (prasugrel hydrochloride)?

Prasugrel Contraindications

Prasugrel is absolutely contraindicated in patients with active pathological bleeding, prior history of transient ischemic attack (TIA) or stroke, and hypersensitivity to prasugrel or its components. 1

Absolute Contraindications

The FDA and ACC/AHA guidelines establish three clear absolute contraindications where prasugrel must not be used:

Active Pathological Bleeding

• Do not use prasugrel in patients with active bleeding such as peptic ulcer disease or intracranial hemorrhage 2, 1
• This contraindication reflects prasugrel's irreversible platelet inhibition and significantly elevated bleeding risk compared to clopidogrel 2

Prior TIA or Stroke

• Prasugrel is contraindicated in any patient with a history of TIA or stroke at any time 2, 1
• In TRITON-TIMI 38, patients with prior TIA/stroke had net harm from prasugrel, with stroke rates of 6.5% (including 2.3% intracranial hemorrhage) versus 1.2% with clopidogrel (HR 1.54; 95% CI 1.02-2.32) 2
• Patients without such history had stroke rates of only 0.9% with prasugrel versus 1.0% with clopidogrel 1
• If a patient develops stroke or TIA while on prasugrel, the drug should generally be discontinued 1

Hypersensitivity

• Prasugrel is contraindicated in patients with documented hypersensitivity reactions (including anaphylaxis) to prasugrel or any component 1

Relative Contraindications and High-Risk Populations

While not absolute contraindications, three patient populations require extreme caution or avoidance:

Age ≥75 Years

• Prasugrel is generally not recommended in patients ≥75 years due to increased fatal and intracranial bleeding risk with uncertain benefit 2
• In TRITON-TIMI 38, patients ≥75 years had no net clinical benefit (HR 0.99; 95% CI 0.81-1.21) 2
• Exception: May consider use in high-risk situations such as patients with diabetes mellitus or prior myocardial infarction, where benefit appears greater 2

Body Weight <60 kg

• Exercise caution in patients weighing <60 kg due to increased exposure to active metabolite and higher bleeding risk 2
• These patients had no net clinical benefit in TRITON-TIMI 38 (HR 1.03; 95% CI 0.69-1.53) 2
• Consider reducing maintenance dose to 5 mg daily in patients <60 kg, though this dose has not been prospectively studied 2, 3

Planned or Likely CABG

• Do not initiate prasugrel in patients likely to undergo urgent coronary artery bypass grafting 2
• Discontinue prasugrel at least 7 days before any planned surgery to allow dissipation of antiplatelet effects 2, 4, 3
• CABG-related TIMI major bleeding was dramatically higher with prasugrel (13.4%) versus clopidogrel (3.2%; HR 4.73; 95% CI 1.90-11.82) 2

Additional Bleeding Risk Factors

Beyond the contraindications above, carefully assess these additional risk factors that increase bleeding with prasugrel:

• Propensity to bleed from any cause 2
• Concomitant medications that increase bleeding risk: warfarin, heparin, fibrinolytic therapy, chronic NSAIDs 2
• Severe hepatic impairment (Child-Pugh Class C) should avoid prasugrel due to lack of safety data 4

Clinical Context for Use

Prasugrel should only be administered after coronary anatomy is defined and a decision to proceed with PCI has been made 2. It is not recommended for routine administration before angiography (such as in the emergency department) or in patients who have not undergone PCI 2. This restriction reflects how prasugrel was studied in TRITON-TIMI 38, where it was given only after the decision to proceed with PCI was established 2.

Bleeding Risk Magnitude

To contextualize the contraindications, prasugrel carries substantial bleeding risks compared to clopidogrel:

• TIMI major hemorrhage: 2.4% versus 1.8% (HR 1.32) 2
• Life-threatening bleeding: 1.4% versus 0.9% (HR 1.52) 2
• Fatal bleeding: 0.4% versus 0.1% 2
• Number needed to harm for major bleeding: 167 patients 2