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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 25, 2020.



Ticagrelor is an oral antiplatelet drug that is used with low dose aspirin to decrease the risk of myocardial infarction and stroke in patients with acute coronary syndromes. Ticagrelor has been linked to rare instances of hypersensitivity reactions accompanied by mild liver injury.


Ticagrelor (tye ka' grel or) is a non-thienopyridine, reversible inhibitor of adenosine diphosphate (ADP) receptors (P2Y 12) on platelets and is used 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 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. In clinical trials, ticagrelor therapy during acute coronary events (unstable angina and myocardial infarction) has been shown to decrease the frequency of recurrence of myocardial infarction and stent thrombosis. Ticagrelor was approved for use in the United States in 2011 and has been used in limited numbers of patients for a limited time only. Current indications are reduction of recurrent cardiovascular events in patients with acute coronary syndromes. Ticagrelor is available in 90 mg tablets under the commercial name Brilinta. The usual maintenance dose is 90 mg twice daily in combination with daily low dose aspirin (<100 mg). Side effects are not common, but can include bleeding (12%), dyspnea (14%), headaches, nausea, diarrhea, hypotension and hypersensitivity reactions. Rare but potentially severe adverse reactions include severe bleeding, rhabdomyolysis, complications of drug-drug interactions, angioedema and hypersensitivity reactions.


In several large clinical trials, ticagrelor was not associated with serum enzyme elevations during therapy and no instances of clinically apparent liver injury were reported. While there have been isolated reports of transient and mild serum enzyme elevations during ticagrelor therapy, these have been short lived and asymptomatic. In addition, since marketing and release, there have been no reports of isolated clinically apparent liver injury or jaundice associated with ticagrelor therapy and hepatotoxicity is not mentioned in the product label. On the other hand, there have been several reports of jaundice and liver injury associated with rhabdomyolysis and with thrombotic thrombocytopenic purpura that represented secondary effects of these severe adverse events. Thus, significant liver injury due to ticagrelor occurs but has occurred largely in association with other life-threatening complications.

Likelihood score: D (possible rare cause of liver injury due to complications of severe allergic reactions or drug-drug interactions).

Mechanism of Injury

Ticagrelor, unlike clopidogrel, does not require metabolic activation for its antiplatelet effects. Ticagrelor is metabolized in the liver predominantly via CYP 3A4 and it should be used with caution in patients taking CYP 3A4 inhibitors (such as ketoconazole, clarithromycin, atazanavir and nefazodone), which can increase serum levels, or CYP 3A4 inducers (such as rifampin, dexamethasone and phenytoin) which can decrease drug levels.

Outcome and Management

There is little evidence that ticagrelor can cause liver injury or has any cross sensitivity to other antiplatelet agents, so that switching from clopidogrel or prasugrel after clinically apparent liver injury is probably safe.

Drug Class: Antithrombotic Agents, Antiplatelet Agents

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



Ticagrelor – Brilinta®


Antithrombotic Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Ticagrelor 274693-27-5 C23-H28-F2-N6-O4-S image 135207318 in the ncbi pubchem database


References updated: 25 September 2020

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    (Textbook of hepatotoxicity published in 1999; ticlopidine, but not clopidogrel, prasugrel or ticagrelor is discussed).
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    (Among 990 patients with an acute coronary syndrome treated with one of 2 doses of ticagrelor or clopidogrel for 4-12 weeks, bleeding episodes were similar in the three groups [9.8% and 8.0% vs 8.1%]; no mention of ALT elevations or hepatotoxicity).
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    (Among 18,624 patients with acute coronary syndrome treated with ticagrelor or clopidogrel, deaths from vascular cases within 12 months were less with ticagrelor [9.8% vs 11.7%], while major bleeding rates were similar [11.6% vs 11.2%]; no mention of hepatotoxicity or ALT elevations).
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    (Among 5216 patients with acute coronary syndrome treated with ticagrelor or clopidogrel with a planned noninvasive treatment, cardiovascular death was lower with ticagrelor [12% vs 14.3%], while major bleeding episodes were greater [11.9% vs 10.3%]; no mention of ALT elevations or other adverse events).
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    (Pharmacokinetic study in 20 volunteers, 10 with compensated cirrhosis, found minimally higher exposure after a single dose of ticagrelor in patients with liver disease, but not enough to recommend dose adjustment; no side effects or worsening of liver chemistry results).
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    (74 year old woman developed rhabdomyolysis 2 months after starting ticagrelor having been on atorvastatin for years with complications of septic shock, renal failure and acute hepatic necrosis [bilirubin 3.1 to 9.8 mg/dL, 746 to 1605 U/L, Alk P 260 to 325 U/L, INR 1.8 to 2.0, CPK >90,000 IU/L], with prolonged ICU stay but ultimate resolution of renal and liver abnormalities).
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  • Wang X, Zhang S, Li L, Hua J, Zhu L, Li L, Zhang G. Ticagrelor-induced thrombotic thrombocytopenic purpura: A case report and review of the literature. Medicine (Baltimore). 2018;97:e11206. [PMC free article: PMC6039671] [PubMed: 29952973]
    (87 year old man with a history of acute myocardial infarction developed thrombotic thrombocytopenic purpura 2 months after starting ticagrelor [platelets 3,000, hematocrit 22.3%, bilirubin 16.0 mg/dL, ALT 3947 U/L, Alk P 59 U/L, protime 26.3 sec], with spontaneous improvement but recurrence on restarting ticagrelor leading to multiorgan failure and death).
  • Schüpke S, Neumann FJ, Menichelli M, Mayer K, Bernlochner I, Wöhrle J. Richardt Get al.; ISAR-REACT 5 Trial Investigators. Ticagrelor or prasugrel in patients with acute coronary syndromes. N Engl J Med. 2019;381:1524–34. [PubMed: 31475799]
    (Among 4018 patients with acute coronary syndromes treated with ticagrelor or prasugrel for one year, major cardiovascular events were less with prasugrel [6.9% vs 9.3%], but major bleeding event rates were similar [4.8% vs 5.4%]; no mention of ALT elevations or hepatotoxicity).
  • Navarese EP, Khan SU, Kołodziejczak M, Kubica J, Buccheri S, Cannon CP, Gurbel PA, De Servi S, Budaj A, Bartorelli A, Trabattoni D, Ohman EM, Wallentin L, Roe MT, James S. Comparative efficacy and safety of oral P2Y inhibitors in acute coronary syndrome: network meta-analysis of 52 816 patients from 12 randomized trials. Circulation. 2020;142:150–60. [PMC free article: PMC7489363] [PubMed: 32468837]
    (Metaanalysis of 12 randomized controlled trials in 52,816 patients comparing 3 antiplatelet agents found that prasugrel and ticagrelor had lower rates of cardiovascular mortality and stent thrombosis than clopidogrel, but had higher rates of major bleeding episodes; no mention of ALT elevations or hepatotoxicity).
  • Tarantini G, Mojoli M, Varbella F, Caporale R, Rigattieri S, Andò G, Cirillo P, et al.; DUBIUS Investigators, on behalf of the Italian Society of Interventional Cardiology (SICI-GISE). Timing of oral P2Y inhibitor administration in non-ST elevation acute coronary syndrome. J Am Coll Cardiol 2020: S0735-1097(20)36444-5. Epub ahead of print.
    (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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