Clopidogrel Induced Hepatic Toxicity

Case Report

Austin J Pharmacol Ther. 2014; 2 (5). 1030

Clopidogrel Induced Hepatic Toxicity

Pegram AH1* and Causey AK2

1Department of Pharmacy Practice, Wingate University School of Pharmacy, USA

2Department of Family Medicine, Cabarrus Family Medicine Residency Program, USA

*Corresponding author: : Pegram AH, Department of Pharmacy Practice, Wingate University School of Pharmacy, 515 N Main Street; Wingate, NC 28174, USA

Received: May 15, 2014; Accepted: July 31, 2014; Published: Aug 05, 2014


A 57 year old female presented to the Emergency Department (ED) with nausea, vomiting and abdominal pain which had worsened since hospital discharge for an non-ST elevation myocardial infarction (NSTEMI) less than 24 hours ago. In the ED, it was noted her liver function tests were extremely elevated (AST=1157 IU/L, ALT=1253 IU/L, and Alkaline Phosphatase=116 IU/L) and further imaging revealed no abnormal hepatic disease or aortic dissection. The patient had been started on clopidogrel, aspirin, promethazine and nitroglycerin 3 days prior to her current ED visit due to the new NSTEMI. She had taken 2 doses each of clopidogrel and aspirin with no difficulties noted during her first hospital stay. The patient was admitted from the ED with hepatic toxicity; subsequently treated with fluid resuscitation over the next 48 hours and possible offending agents were held (atorvastatin and clopidogrel). She was followed with serial liver function tests, which revealed a downward trend and her symptoms of nausea, vomiting and abdominal pain completely resolved over the following 2 days. The medical team agreed that her newly added clopidogrel was the likely cause of her acute liver injury. Clopidogrel induced liver toxicity is reported as a post marketing adverse event in the Plavix® package insert, but only 15 patients worldwide (with 3 US cases) are located in the literature. Although this adverse event appears to be rare, it has been fatal in several cases. Prompt diagnosis of acute hepatic injury with discontinuation of clopidogrel and addition of supportive care may reverse this rapid deterioration of liver function.

Keywords: Clopidogrel; Acute liver injury; Hepatotoxicity


ED: Emergency Department; ALT: Alanine Transaminase; AST: Asparate Aminotransferase; CT: Computed Tomography; NSTEMI: Non-ST-Elevation Myocardial Infarction; mg: Milligrams; IU/L: International Units per Liter; mcg/hr: Micrograms per Hour; ml/hr: Milliliters per Hour; CYP450: Cytochrome P450; ADP: Adenosine Diphosphate; MI: Myocardial Infarction; CABG: Coronary Artery Bypass Graft; ADP: Adenosine Diphosphate; ADR: Adverse Drug Reaction; PCP: Primary Care Physician

Case Presentation

A 57 year old white female with documented normal liver function and no history of alcohol abuse, liver or biliary tract disease presented to the emergency department (ED) with worsening nausea and vomiting over the past 24 hours. She reported associated dizziness, coldness and pain in her back, which subsequently moved to her chest, left shoulder and bilateral legs. Labs were obtained revealing ALT=1253 IU/L, AST=1157 IU/L and Alkaline Phosphatase=116 IU/L. A right upper quadrant ultrasound was obtained which showed no abnormal liver disease. There was a concern for dissection due to patient’s complaint of abdominal pain, so a CT (computed tomography) chest was obtained that revealed no retroperitoneal hemorrhage or abdominal aortic aneurysm. She was admitted to the inpatient family medicine service to investigate the cause of her acute liver injury.

The patient was discharged approximately 24 hours prior to the ED visit after being hospitalized for 2 days with a new onset non-ST-elevation myocardial infarction (NSTEMI). During this previous admission, she underwent a left heart catheterization and was found to have no significant occlusive disease that required stenting. Laboratory results obtained the morning following her heart catheterization revealed normal liver function tests (reported in table 1 as baseline results). Cardiology recommended the addition of clopidogrel 75 mg daily and aspirin 81 mg daily to the patient’s medical regimen. The clopidogrel and aspirin were ordered and the patient received two doses of each medication while hospitalized. The patient was discharged with 4 new medications to her regimen: clopidogrel 75 mg daily, aspirin 81 mg daily, promethazine 12.5 mg every 4 hours as needed for nausea, and nitroglycerin 0.4 mg as needed for chest pain. Before returning to the hospital, she attempted to take promethazine at home, but was not successful in keeping the tablet down to control her nausea. Nitroglycerin was not given prior to her arrival at the ED.

The patient’s past medical history included hypertension, diverticulosis hyperlipidemia, osteoarthritis, spinal enthesopathy, and the new onset NSTEMI 2 days prior to the ED visit. Her current medications included metoprolol tartrate 25 mg twice a day, carisoprodol 350 mg every 8 hours as needed, vitamin D3 2000 IU at bedtime, atorvastatin 20 mg at bedtime, fentanyl 50 mcg/hr patch every 72 hours, lisinopril 10 mg daily, and the recent additions of aspirin, clopidogrel, promethazine and nitroglycerin. Her chronic medications (minus the new additions) were stable and had not been changed or adjusted in over 6 months.

The patient’s newly started clopidogrel and long term atorvastatin were both discontinued upon admission. She was treated with aggressive fluid resuscitation over the next 2 days, receiving normal saline at 250 ml/hr for 13 hours followed by normal saline at 150 ml/hr for approximately 30 hours. During this time, her liver function tests were monitored closely, showing a nice downward trend (see Table 1). A hepatitis panel was also obtained on admission, which resulted in nonreactive results for Hepatitis A, B and C. Her medication list was examined closely for drug-drug interactions, but no interactions (specifically no CYP450 interactions) were found within her current pharmacotherapy regimen. With normalization of liver enzymes using only fluid resuscitation and withdrawal of possible offending agents, clopidogrel was identified as the likely causative agent of the liver injury due to the very recent addition of this medication. The patient’s nausea and vomiting subsided and she was ready for discharge on day 3. She was discharged on her original medication list (including the atorvastatin) minus the clopidogrel, as cardiology recommended no other thienopyridine therapy for at least 2 weeks. At 3 days post hospital follow up with her primary care physician, the liver enzymes had all trended toward normal and patient reported feeling well. At 2 months following this adverse drug event, the liver enzymes had all returned to normal with no complaints from the patient.

Citation: Pegram AH and Causey AK. Clopidogrel Induced Hepatic Toxicity. Austin J Pharmacol Ther. 2014; 2 (5). 1030. ISSN: 2373-6208.