Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozil combination therapy.
BACKGROUND
Elevated total cholesterol (total-C) and low-density lipoprotein cholesterol (LDL-C) levels are established risk factors for cardiovascular disease (CVD). HMG-CoA reductase inhibitors (statins) are effective cholesterol-lowering drugs that are commonly prescribed to treat this condition. These drugs are often combined with another class of drugs, fibric acid derivatives, to lower both cholesterol and triglyceride levels. Rhabdomyolysis is a known, rare serious side effect of statin monotherapy and of statin-fibrate combination therapy.


OBJECTIVE
To examine Food and Drug Administration's (FDA's) postmarketing database for cases of rhabdomyolysis in relation to monotherapy and combination use and calculate reporting rates for this event.


METHODS
Domestic cases of statin- and statin/gemfibrozil-associated rhabdomyolysis were culled from FDA's database and reviewed. Rhabdomyolysis was defined by CPK > or = 10,000 IU/L, myopathic signs and symptoms and clinical diagnosis of rhabdomyolysis. Reporting rates, consisting of number of reported cases/number of prescriptions for each drug, were then calculated to determine whether the reporting of rhabdomyolysis cases was commensurate with extent of use of each statin in the population.


METHODS
Cases were obtained from the FDA adverse event reporting system (AERS) database.


METHODS
NA.


METHODS
Number of rhabdomyolysis cases were evaluated, along with outcomes, such as renal failure, dialysis and death.


RESULTS
Of 866 total reported cases, 482 (56%) were associated with monotherapy and 384 (44%) related to combination therapy. More than 80% of reported cases for each drug resulted in hospitalization for renal failure and dialysis. 80 patients expired from events related directly to rhabdomyolysis. Reporting rates for all statins, except for cerivastatin, were similar and much lower than 1 per 100,000 prescriptions. The cerivastatin-reporting rate was much higher at 4.24/100,000 prescriptions.


CONCLUSIONS
Rhabdomyolysis is a rare, serious side effect of statin monotherapy and of statin-fibrate combination therapy. Clinicians need to remain cognizant of this potential adverse event and discuss signs and symptoms of muscle toxicity with patients in order improve the benefits-to-risks of treating dyslipidemia with statins.
Office of Drug Safety, Food and Drug Administration, Rockville, MD 20857, USA. changJ@cder.fda.gov
Jennie T
JT
Chang
Judy A
JA
Staffa
Mary
M
Parks
Lanh
L
Green
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D004359:Drug Therapy, Combination; D005260:Female; D015248:Gemfibrozil / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D017891:Pharmacoepidemiology; D012206:Rhabdomyolysis / Q000139:chemically induced* / Q000453:epidemiology / Q000401:mortality; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D015248:Gemfibrozil