Increased dosage of cyclosporine induces myopathy with increased seru creatine kinase in an elderly patient on chronic statin therapy

J Clin Pharm Ther. 2015 Apr;40(2):245-8. doi: 10.1111/jcpt.12240. Epub 2014 Dec 16.

Abstract

What is known and objective: The concomitant administration of atorvastatin and cyclosporine has been shown to increase the serum concentration of 3-hydroxy-3-methylglutaryl coenzyme A, which may be associated with the elevation of creatine kinase and an increased risk of myopathy. Our objective is to report on a case of statin-induced myopathy associated with concomitant use of cyclosporine and other contributing factors.

Case summary: An 88-year-old Chinese male patient with comorbidities received polypharmacy treatment, including atorvastatin and cyclosporine. After the dosage of cyclosporine was increased to 300 mg every day for 8 months, the patient developed body pain and leg weakness, with a serum creatine kinase increase and evidence on magnetic resonance imaging of muscle oedema.

What is new and conclusion: Cyclosporine is a moderate inhibitor of the cytochrome P450 CYP3A4 isoenzyme, which is known to increase the serum level of atorvastatin. We hypothesized that the pharmacological and pharmacokinetic properties of atorvastatin-induced myopathy are the result of its interaction with high dosage of cyclosporine.

Keywords: creatine kinase; cyclosporine; drug-drug interactions; myopathy; statin.

Publication types

  • Case Reports

MeSH terms

  • Aged, 80 and over
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Atorvastatin / adverse effects*
  • Atorvastatin / pharmacokinetics
  • China
  • Cyclosporine / pharmacology*
  • Cytochrome P-450 CYP3A / metabolism
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme Repression
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
  • Immunosuppressive Agents / pharmacology*
  • Male
  • Muscular Diseases / chemically induced*
  • Myoglobin / blood

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Immunosuppressive Agents
  • Myoglobin
  • Cyclosporine
  • Atorvastatin
  • Cytochrome P-450 CYP3A
  • Aspartate Aminotransferases
  • Alanine Transaminase