Continuing Education Activity

Prasugrel is a medication used in the management and treatment of acute coronary syndrome undergoing percutaneous intervention. Prasugrel is a thienopyridine, which is an irreversible antagonist of the ADP P2Y12 receptor. The antiplatelet effect of prasugrel lasts until the lifespan of platelets. Prasugrel is a prodrug that is converted to an active and inactive metabolite by the hepatic CYP system. This activity covers the indications, dosing, contraindications, mechanism of action, and management of prasugrel in cases where it can provide therapeutic benefit.


  • Describe indications and the mechanism of action of prasugrel.
  • Review adverse effects and contraindications of prasugrel.
  • Summarize pharmacokinetics and pharmacodynamics of prasugrel.
  • Explain the importance of care coordination amongst the interprofessional team to enhance patient safety for anyone that is using prasugrel.


Prasugrel is an antiplatelet agent in the thienopyridine group.[1] Prasugrel is used to decrease the rate of cardiovascular events in patients with acute coronary syndrome (ACS) who are undergoing percutaneous coronary intervention. Prasugrel has approval for medical management of patients with unstable angina or non-ST elevation myocardial infarction (NSTEMI), and patients with ST-elevation myocardial infarction (STEMI) when managed with percutaneous coronary intervention. Prasugrel is an alternative agent to clopidogrel, which has greater platelet aggregation inhibition than clopidogrel.[2] It has shown an increased risk of bleeding in patients receiving prasugrel when compared to clopidogrel, who require urgent or emergent CABG. However, prasugrel was associated with a lower rate of mortality, when compared to clopidogrel.[3]

Mechanism of Action

Prasugrel is a thienopyridine, which is an irreversible antagonist of the ADP P2Y12 receptor.[1] The antiplatelet effect of prasugrel lasts until the lifespan of platelets.

Pharmacokinetics and Pharmacodynamics:

Prasugrel is a prodrug that is converted to an active and inactive metabolite by the hepatic CYP system. The active component (R- 138727) of the metabolites irreversibly blocks P2Y12 at ADP receptors, which prevents GPIIb/IIIa receptor complex activation, and thus reducing platelet aggregation and activation. It is rapidly absorbed and metabolized with its active metabolite peaking approximately after 30 minutes of dosing. The mean elimination half-life of the active metabolite of prasugrel is approximately 3.7 hours.[4] The elimination of 70 percent of the drug occurs through the kidney, with approximately 25 percent in feces.[5] With the onset of action being 30 minutes, it attains steady state within three days.[6] Platelet aggregation returns to baseline status 5 to 9 days following discontinuation of prasugrel, which is reflective of new platelet production.


Prasugrel is only available in tablet formulation; therefore, it can be given only via the oral route. Administration can be without regard to the intake of a meal. When undergoing emergent primary PCI, crushing the tablets is associated with faster absorption, quicker and higher antiplatelet effect that is achievable within 30 minutes of administration.[7] The bioavailability of prasugrel becomes reduced when it is administered via an enteral route bypassing the stomach acidity.

Available dosage forms:

5 mg and 10 mg tablets

Dosing for acute coronary syndromes:

Loading dose: Initial loading dose of 60 mg requires prompt administration as soon as acute coronary syndrome is known. 

Maintenance dose: Maintenance dose for people above the weight of 60 kg is 10 mg daily. As there is an increased risk of bleeding in low weight individuals (weight less than 60 kg) who are taking prasugrel, a lower dose of 5 mg daily can be a consideration. Prasugrel 5 mg in low body weight (< 60 kg) individuals reduced platelet reactivity similarly to 10 mg in higher body weight individuals (> 60 kg).[8] Prasugrel administration should be in combination with aspirin.

Duration of dual antiplatelet treatment after stent placement:

As per ACC/AHA dual antiplatelet therapy guidelines, at least 6 to 12 months of dual antiplatelet therapy (DAPT) treatment is the recommendation in people with ACS receiving either a bare-metal stent or drug-eluting stent. Shorter duration of dual antiplatelet therapy can be considered in patients with low ischemia risk and higher bleeding risk, whereas a longer duration of DAPT treatment may be reasonable in patients with a higher risk of ischemia and lower risk of bleeding. Decisions about the discontinuation of DAPT is individualized and based on clinical judgment.[1]

Use in renal impairment:

No dosage adjustments are required; however, there is an increased risk in bleeding with moderate to severe renal impairment due to decreased excretion of the drug.

Use in hepatic impairment:

No dosage adjustments are necessary for mild to moderate hepatic impairment (Child-Pugh class A and B). Researchers have not studied the use of prasugrel in patients with severe hepatic impairment (Child-Pugh class C); however, it generally correlates with increased bleeding.

Adverse Effects

Bleeding is the most common adverse effect associated with prasugrel. Increased risk of bleeding may occur in patients with weight less than 60 kg, recent trauma, recent surgery, and active bleeding peptic ulcer. Increased risk of bleeding is also seen in renal impairment as it is associated with decreased excretion. There is no antidote available for bleeding caused by prasugrel. If bleeding does occur, theoretically, hemostasis is achievable by a platelet transfusion. However, platelet transfusion within 4 hours of administration of prasugrel may be less effective. If possible, bleeding management should take place without stopping prasugrel, as premature discontinuation of prasugrel is associated with stent thrombosis and increased cardiovascular outcomes.

Thrombotic thrombocytopenic purpura (TTP) is a rare but serious adverse effect associated with thienopyridine use and usually occurs within two weeks of starting treatment.[9] TTP management requires urgent plasmapheresis. 

Indigestion is the most common gastrointestinal side effect associated with prasugrel. Other adverse effects associated with prasugrel use are headache, dizziness, epistaxis, hematoma, and bruising. 

Use of prasugrel with warfarin or NSAIDS, when used chronically, increases the risk of bleeding.


Hypersensitivity to prasugrel or any of the components of the formulation is a contraindication for its use. Other contraindications for starting prasugrel are any pathological bleed or history of transient ischemic attack or stroke. The use of prasugrel is not recommended in patients with age greater than 75 due to the increased risk of bleeding.


Periodic checks for hemoglobin and hematocrit for signs of bleeding. 


Prasugrel causes rapid and irreversible platelet inhibition and can be associated with life-threatening bleeding in case of toxicity. Researchers observed lethality in rats with a dose of 2000 mg/kg. There is no antidote available for use in case of toxicity with prasugrel. The active metabolite of prasugrel is likely not removable via dialysis. 

Enhancing Healthcare Team Outcomes

Prasugrel has extensive use among cardiologists, ED physicians, nurse practitioners, and internists. The choice of an antiplatelet medication depends upon the clinical situation. The addition of thienopyridine to aspirin is the standard of care for patients with acute coronary syndromes and patients undergoing percutaneous coronary intervention. There have been concerns about clopidogrel treatment failure, defined as the inability to achieve adequate antiplatelet effect in an individual taking clopidogrel. An individualized DAPT approach may be potentially guided by genetic or platelet function testing; however, routine screening in percutaneous coronary intervention is not a recommendation. However, platelet function testing merits consideration for DAPT de-escalation.[10]

Nurses are the ones to administer the drugs to the patients when the patients are inpatient and also the first responders when adverse effects occur during an inpatient stay.

The role of a pharmacist is essential to look for any drug-drug interaction with any medication and can recommend discontinuation of any drugs that can alter the effectiveness of prasugrel if they are nonessential. 

As premature discontinuation of dual antiplatelet therapy is associated with stent thrombosis, myocardial infarctions, and increased cardiovascular events, it is crucial to provide education to the patient regarding compliance. Regular follow-ups are essential for the monitoring of bleeding. Discontinuation of DAPT for an elective procedure is an interdisciplinary decision, and DAPT should continue for 6 to 12 months after PCI.

Dual antiplatelet therapy requires interprofessional communication and a team approach, including physicians, nurses, pharmacists, and surgeons, to enhance patient outcomes. [Level V]

Article Details

Article Author

Parth Sampat

Article Editor:

Roopma Wadhwa


11/7/2020 7:51:08 PM

PubMed Link:




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