Myopathy and Rhabdomyolysis Associated With Lovastatin-Gemfibrozil Combination Therapy

Pierce, L. Ross; Wysowski, Diane K.; Gross, Thomas P.

doi:10.1001/jama.1990.03450010075034

Cited by 351 publications

(70 citation statements)

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“…Gemfibrozil was reported to increase the risk of rhabdomyolysis with HMG-CoA reductase inhibitors especially in patients with renal dysfunction (13)(14)(15). According to a doctor's letter released in December 1999, cerivastatin and gemfibrozil (another cholesterol-lowering drug) should never be 79 (95%CI; 1.74-4.44).…”

Section: Resultsmentioning

confidence: 99%

Characteristics of Drug-Associated Rhabdomyolysis: Analysis of 8,610 Cases Reported to the U.S. Food and Drug Administration

Ôshima

2011

Intern. Med.

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Objective To describe the characteristics of cases with drug-associated rhabdomyolysis reported to the U.S. Food and Drug Administration (FDA). Methods A retrospective analysis of all drug-associated rhabdomyolysis cases reported to FDA between January 2004 and December 2009 was conducted. The analyses included the number of unique cases, age, gender, body weight and proportion of fatal outcome. Time to onset from beginning of the suspected drugs and frequently reported suspected drugs were also tabulated. Results There were 8,610 cases of drug-associated rhabdomyolysis in the database. Both case numbers and proportion of the fatal outcome appeared stable over the study period. Average age was 43.3 years old. The reported ratio of male to female was approximately 5 to 3. More than half of reported cases developed rhabdomyolysis within a month after beginning the suspected drug. Potential high risk groups for fatal outcome, such as age group younger than 10 years old and body weight group less than 50 kg were suggested. Suspected drugs for younger cases and their probable indication appear to be different from adult cases. There has been long standing controversial concern regarding an increased risk when a fibric acid derivative is added to an HMG-CoA reductase inhibitor. This study suggested that concomitant use of these two kinds of agents may be associated with a lower risk for fatal outcome, whereas renal dysfunction appeared to be associated with a higher risk for fatal outcome among the HMG-CoA reductase inhibitor-associated rhabdomyolysis cases. Conclusion The characteristics of cases of drug-associated rhabdomyolysis were described. Because of the various limitations of a spontaneous reporting-system database, the reported number should be interpreted with caution.

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Section: Resultsmentioning

confidence: 99%

Characteristics of Drug-Associated Rhabdomyolysis: Analysis of 8,610 Cases Reported to the U.S. Food and Drug Administration

Ôshima

2011

Intern. Med.

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“…The concomitant use of gemfibrozil and atorvastatin, lovastatin, pravastatin, or simvastatin has been associated with case reports of rhabdomyolysis. 5,48,49 It is generally believed that the adverse effects of combination therapy with a statin plus a fibrate is based on pharmacodynamic interactions. However, gemfibrozil was shown to increase plasma concentrations of active simvastatin and lovastatin acid forms but minimally the lactone forms, whereas bezafibrate demonstrated no significant effect on the pharmacokinetics of lovastatin.…”

Section: Iii-54 Circulation June 15 2004mentioning

confidence: 99%

Safety of Statins

2004

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Abstract-Statin monotherapy is generally well tolerated, with a low frequency of adverse events. The most important adverse effects associated with statins are myopathy and an asymptomatic increase in hepatic transaminases, both of which occur infrequently. Because statins are prescribed on a long-term basis, however, possible interactions with other drugs deserve particular attention, as many patients will typically receive pharmacological therapy for concomitant conditions during the course of statin treatment.

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“…This regimen has not been widely adopted because of the concern about side effects, mainly myopathy, reported with the lovastatingemfibrozil combination (20). This has not been confirmed by studies using other statin-fibrate combinations (12)(13)(14)(15)(16)(17)(18)(19).…”

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Atorvastatin and Micronized Fenofibrate Alone and in Combination in Type 2 Diabetes With Combined Hyperlipidemia

et al. 2002

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FESC 3OBJECTIVE -This study evaluated the effect of a atorvastatin-fenofibrate combination on lipid profile, in comparison to each drug alone, in patients with type 2 diabetes and combined hyperlipidemia (CHL). RESEARCH DESIGN AND METHODS-A total of 120 consecutive patients, who were free of coronary artery disease (CAD) at entry, were studied for a period of 24 weeks. These patients were randomly assigned to atorvastatin (20 mg/day, n ϭ 40), micronized fenofibrate (200 mg/day, n ϭ 40), or a combination of both (atorvastatin 20 mg/day plus fenofibrate 200 mg/day, n ϭ 40). The effect of treatment on LDL cholesterol, triglycerides (TGs), HDL cholesterol, apolipoprotein A-I and B, lipoprotein(a), and plasma fibrinogen (PF) was recorded. Moreover, the percentage of patients that reached the American Diabetes Association treatment goals and the estimated CAD risk status were calculated.RESULTS -No patient was withdrawn from the study because of side effects. The atorvastatin-fenofibrate combination reduced total cholesterol by 37%, LDL cholesterol by 46%, TGs by 50%, and PF by 20%, whereas it increased HDL cholesterol by 22% (P Ͻ 0.0001 for all). These changes were significantly better than those of both monotherapies. Of the patients on drug combination, 97.5% reached the LDL cholesterol treatment goal of Ͻ100 mg/dl, 100% reached the desirable TG levels of Ͻ200 mg/dl, and 60% reached the optimal HDL cholesterol levels of Ͼ45 mg/dl. These rates were significantly higher than those of both monotherapies. Combined treatment reduced the 10-year probability for myocardial infarction from 21.6 to 4.2%.CONCLUSIONS -The atorvastatin-fenofibrate combination has a highly beneficial effect on all lipid parameters and PF in patients with type 2 diabetes and CHL. It improved patients' CAD risk status significantly more than each drug alone. Diabetes Care 25:1198 -1202, 2002C ombined hyperlipidemia (CHL), a highly atherogenic lipid disorder characterized by increased LDL cholesterol, elevated triglycerides (TGs), and low HDL cholesterol, is not rare in patients with type 2 diabetes (1). Moreover, metabolic abnormalities, such as predominance of small dense LDL particles (2) and increased glycation of LDL (3), raise the atherogenic risk in these patients. Glycemic control appears to improve but not normalize these abnormalities (4). Statins or fibrates can be used in this setting. Statins have been shown to reduce atherosclerosis-related morbidity and mortality in patients with diabetes (5,6). On the other hand, fibrates are drugs that can decrease TG concentrations and elevate HDL cholesterol, thus reducing cardiovascular morbidity and mortality (7,8). Recent studies (9,10) showed that statin or fibrate monotherapies can improve the lipid profile in patients with type 2 diabetes and CHL; however, these affect differe n t a s p e c t s o f l i p o p r o t e i n ( L P ) metabolism. Hence, it is difficult to modify the lipid profile of patients with type 2 diabetes and CHL using monotherapy with either a statin or a fibrate, accordi...

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Myopathy and Rhabdomyolysis Associated With Lovastatin-Gemfibrozil Combination Therapy

Cited by 351 publications

References 34 publications

Characteristics of Drug-Associated Rhabdomyolysis: Analysis of 8,610 Cases Reported to the U.S. Food and Drug Administration

Characteristics of Drug-Associated Rhabdomyolysis: Analysis of 8,610 Cases Reported to the U.S. Food and Drug Administration

Safety of Statins

Atorvastatin and Micronized Fenofibrate Alone and in Combination in Type 2 Diabetes With Combined Hyperlipidemia

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