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Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozil combination therapy

Jennie T Chang1, Judy A Staffa, Mary Parks

  • 1Office of Drug Safety, Food and Drug Administration, Rockville, MD 20857, USA. changJ@cder.fda.gov

Pharmacoepidemiology and Drug Safety
|July 23, 2004
PubMed

Insights

Rhabdomyolysis is a rare but serious side effect of statin and statin-fibrate combination therapy. The cerivastatin reporting rate for rhabdomyolysis was significantly higher than other statins.

Area of Science:

  • Pharmacovigilance
  • Cardiovascular Disease Research
  • Drug Safety

Background:

  • Elevated cholesterol levels, including total cholesterol (total-C) and low-density lipoprotein cholesterol (LDL-C), are significant risk factors for cardiovascular disease (CVD).
  • Statins (HMG-CoA reductase inhibitors) are primary medications for cholesterol reduction, often used in combination with fibric acid derivatives to manage both cholesterol and triglyceride levels.
  • Rhabdomyolysis, a serious adverse event, is a known risk associated with both statin monotherapy and statin-fibrate combination treatments.

Purpose of the Study:

  • To investigate the United States Food and Drug Administration's (FDA's) postmarketing data for rhabdomyolysis cases linked to statin monotherapy and combination therapy.
  • To calculate the reporting rates of rhabdomyolysis for individual statins and statin-fibrate combinations to assess the risk relative to drug usage.

Main Methods:

  • A review of domestic rhabdomyolysis cases associated with statins and statin/gemfibrozil was conducted using the FDA's Adverse Event Reporting System (AERS) database.
  • Rhabdomyolysis was defined by creatine phosphokinase (CPK) levels greater than or equal to 10,000 IU/L, myopathic symptoms, and clinical diagnosis.
  • Reporting rates were calculated by dividing the number of reported cases by the number of prescriptions for each drug, comparing these rates to drug utilization.

Main Results:

  • Out of 866 reported cases, 56% were linked to statin monotherapy and 44% to combination therapy.
  • Over 80% of reported cases for all statins resulted in hospitalization due to renal failure and dialysis, with 80 deaths directly attributed to rhabdomyolysis.
  • Reporting rates for most statins were below 1 per 100,000 prescriptions, while cerivastatin exhibited a significantly higher reporting rate of 4.24 per 100,000 prescriptions.

Conclusions:

  • Rhabdomyolysis is a rare yet severe adverse event associated with statin monotherapy and statin-fibrate combination therapy.
  • Healthcare providers must remain vigilant regarding the potential for muscle toxicity with statin use.
  • Educating patients on the signs and symptoms of muscle toxicity is crucial for optimizing the benefit-risk profile of statin therapy in managing dyslipidemia.
Abstract

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