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Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozil combination therapy.
Pharmacoepidemiol Drug Saf 2004; 13(7):417-26PD

Abstract

CONTEXT

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.

DESIGN

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.

SETTING

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

PATIENTS

NA.

MAIN OUTCOME MEASURES

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.

Authors+Show Affiliations

Office of Drug Safety, Food and Drug Administration, Rockville, MD 20857, USA. changJ@cder.fda.govNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15269925

Citation

Chang, Jennie T., et al. "Rhabdomyolysis With HMG-CoA Reductase Inhibitors and Gemfibrozil Combination Therapy." Pharmacoepidemiology and Drug Safety, vol. 13, no. 7, 2004, pp. 417-26.
Chang JT, Staffa JA, Parks M, et al. Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozil combination therapy. Pharmacoepidemiol Drug Saf. 2004;13(7):417-26.
Chang, J. T., Staffa, J. A., Parks, M., & Green, L. (2004). Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozil combination therapy. Pharmacoepidemiology and Drug Safety, 13(7), pp. 417-26.
Chang JT, et al. Rhabdomyolysis With HMG-CoA Reductase Inhibitors and Gemfibrozil Combination Therapy. Pharmacoepidemiol Drug Saf. 2004;13(7):417-26. PubMed PMID: 15269925.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozil combination therapy. AU - Chang,Jennie T, AU - Staffa,Judy A, AU - Parks,Mary, AU - Green,Lanh, PY - 2004/7/23/pubmed PY - 2004/9/1/medline PY - 2004/7/23/entrez SP - 417 EP - 26 JF - Pharmacoepidemiology and drug safety JO - Pharmacoepidemiol Drug Saf VL - 13 IS - 7 N2 - CONTEXT: 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. DESIGN: 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. SETTING: Cases were obtained from the FDA adverse event reporting system (AERS) database. PATIENTS: NA. MAIN OUTCOME MEASURES: 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. SN - 1053-8569 UR - https://www.unboundmedicine.com/medline/citation/15269925/Rhabdomyolysis_with_HMG_CoA_reductase_inhibitors_and_gemfibrozil_combination_therapy_ L2 - https://doi.org/10.1002/pds.977 DB - PRIME DP - Unbound Medicine ER -