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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: September 15, 2020.



Prasugrel is an inhibitor of platelet aggregation that is used to decrease the risk of myocardial infarction and stroke in patients with acute coronary syndromes. Prasugrel has been linked to mild and transient serum enzyme elevations during therapy and to rare instances of hypersensitivity reactions accompanied by mild liver injury.


Prasugrel (pra' soo grel) is a thienopyridine inhibitor of adenosine diphosphate (ADP) receptors (P2Y12) on platelets, and is used as an anticoagulant to decrease the risk of recurrent coronary thromboses in patients who undergo interventions during an acute coronary syndrome. Activated platelets release ADP which binds to ADP platelet receptors, causing activation of the intracellular glycoprotein IIb/IIIA complex which triggers platelet adherence and aggregation. The aggregation of platelets plays an important role in the growth of atheromatous plaques, which can lead to coronary, cerebral and peripheral arterial occlusions. Prasugrel is an irreversible inhibitor of the P2Y12 receptor and its effects last for the life time of the platelet (7 to 10 days). In clinical trials, prasugrel therapy during acute coronary events (unstable angina and myocardial infarction) was equivalent or slightly better than clopidogrel in decreasing the frequency of recurrence of myocardial infarction and stent thrombosis. Prasugrel was approved for use in the United States in 2009. Current indications are reduction of recurrent cardiovascular events in patients with acute coronary syndromes who are to be managed with percutaneous coronary intervention. Prasugrel is available in 5 and 10 mg tablets generically and under the commercial name Effient. The usual oral dose is a loading dose of 60 mg followed by 10 mg daily in combination with aspirin. The most common side effect is bleeding (usually epistaxis); other side effects are not common, but can include headache, dizziness, fatigue, gastrointestinal upset, nausea, arthralgias and rash. Rare, but more severe adverse events include major episodes of bleeding and hypersensitivity reactions including anaphylaxis.


Prasugrel is associated with low rates of serum enzyme elevations during therapy, which are similar to those with clopidogrel. In premarketing studies, no instances of clinically apparent liver injury were reported. Since marketing and release, there has been several reports of liver injury attributed to prasugrel often as a part of a hypersensitivity reaction. The onset was within a few weeks of switching from clopidogrel to prasugrel, and was accompanied by mild-to-moderate ALT and GGT elevations that resolved rapidly once prasugrel was replaced by clopidogrel. The liver injury was overshadowed by features of a hypersensitivity syndrome with fever, eosinophilia and diarrhea, which also reversed rapidly with stopping prasugrel. Autoantibodies were not reported. There has also been one report of a case of hepatocellular jaundice that resolved only after stopping prasugrel. There have been no reports of chronic injury or acute liver failure reported with prasugrel, although such instances have been reported with clopidogrel and ticlopidine.

Likelihood score: D (possible rate cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism of prasugrel hepatotoxicity is not known, but is likely to be immunologically mediated and due to hypersensitivity. Prasugrel requires metabolic activation for its antiplatelet effects, which occurs in the liver primarily via the cytochrome P450 system, CYP 3A4 and 2B6. Inhibitors of CYP 3A4 (such as clarithromycin or itraconazole) may result in higher levels of prasugrel and antiplatelet activity, whereas inducers of CYP 3A4 (such as rifampin or phenytoin) may lower levels and result in less of an antiplatelet response.

Outcome and Management

The severity of liver injury associated with prasugrel has been mild and rapidly reversible with stopping therapy. In one instance, switching anticoagulant therapy to clopidogrel was tolerated without recurrence. Rechallenge should be avoided.

Drug Class: Antithrombotic Agents, Antiplatelet Agents

Other Drugs in the Subclass, Antiplatelet Agents: Aspirin, Cangrelor, Clopidogrel, Dipyridamole, Ticagrelor, Ticlopidine, Vorapaxar



Prasugrel – Generic, Effient®


Antithrombotic Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Prasugrel 150322-43-3 C20-H20-F-N-O3-S image 135262112 in the ncbi pubchem database


References updated: 15 September 2020

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    (Textbook of hepatotoxicity published in 1999; ticlopidine, but not clopidogrel or prasugrel is discussed).
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    (Among 1449 patients undergoing coronary angiography treated with prasugrel or ticagrelor, rates of a combined clinical efficacy endpoint were similar in the two groups; no mention of ALT elevations or hepatotoxicity).


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