Paracetamol and simvastatin: a potential interaction resulting in hepatotoxicity

Medicina (Kaunas). 2012;48(7):379-81.

Abstract

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 Gripex(TM) (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.

Publication types

  • Case Reports

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / adverse effects*
  • Aged
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / adverse effects*
  • Coronary Artery Bypass
  • Cytochrome P-450 CYP3A / metabolism
  • Drug Interactions
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Jaundice / chemically induced
  • Liver / drug effects*
  • Liver / enzymology
  • Myocardial Infarction / prevention & control
  • Myocardial Infarction / surgery
  • Nausea / chemically induced
  • Simvastatin / administration & dosage
  • Simvastatin / adverse effects*
  • Vomiting / chemically induced

Substances

  • Analgesics, Non-Narcotic
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Acetaminophen
  • Simvastatin
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human