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Medicina is published by MDPI from Volume 54 Issue 1 (2018). Articles in this Issue were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence. Articles are hosted by MDPI on as a courtesy and upon agreement with Lithuanian Medical Association, Lithuanian University of Health Sciences, and Vilnius University.
Open AccessArticle

Paracetamol and Simvastatin: A Potential Interaction Resulting in Hepatotoxicity

Institute of Physiology and Pharmacology, Medical Academy, Lithuanian University of Health Sciences, Lithuania
Author to whom correspondence should be addressed.
Medicina 2012, 48(7), 56;
Received: 11 January 2012 / Accepted: 30 July 2012 / Published: 4 August 2012
The safety profile of paracetamol and simvastatin is sufficiently well known, although no interactions between these two medicinal products have been described in the scientific literature so far. A 66-year-old female patient who experienced myocardial infarction and underwent coronary artery bypass grafting 9 years ago was taking simvastatin at a daily dose of 10 mg. Liver enzyme tests were carried out regularly, and their results were always normal. Later on, the patient took 6 tablets of fixed combination medicinal product GripexTM (paracetamol, pseudoephedrine, and dextromethorphan) per day due to a fever. The daily dose of paracetamol taken by the patient totaled 1.95 g. The patient developed severe jaundice, nausea, vomiting; blood bilirubin levels increased more than 3 times; alanine transaminase, more than 10 times; and asparagine transaminase, more than 5 times. Paracetamol is metabolized by CYP enzymes (CYP2E1, 1A2, 2A6, 3A4) to a reactive metabolite, N-acetyl-p-benzoquinone-imine (NAPQI). Under conditions of excessive NAPQI formation or reduction in glutathione stores by approximately 70%, NAPQI covalently binds to the cysteinyl sulfhydryl groups of cellular proteins, forming NAPQI-protein adducts. Simvastatin is a substrate of CYP3A4 enzyme. Clinical and pharmacological data, available in the published literature, allow the assumption that simvastatin may induce CYP3A4 and result in increased hepatoxicity of paracetamol.
Keywords: paracetamol; simvastatin; drug interaction; hepatotoxicity paracetamol; simvastatin; drug interaction; hepatotoxicity
MDPI and ACS Style

Gumbrevičius, G.; Sveikata, A.; Sveikatienė, R.; Stankevičius, E. Paracetamol and Simvastatin: A Potential Interaction Resulting in Hepatotoxicity. Medicina 2012, 48, 56.

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