Simvastatin, Fenofibrate, and Rhabdomyolysis

Jacob, Sindhu S.; Jacob, Sony; Williams, Craig D.; Deeg, Mark A.

doi:10.2337/diacare.28.5.1258

Cited by 15 publications

(5 citation statements)

References 3 publications

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“…[169] Finally, fibrates serve as markers for relevant genetic defects have been disproportionately found in a population at risk for statin AEs -persons with high triglycerides patients who experience statin myopathy (reviewed in section 5), and impaired fatty acid oxidation (those most likely to receive fibrates) may also be at amplified risk of statin AEs. Fibrates affect the metabolic pathways of statins, leading to a functionally increased gemfibrozil) [227] Fenofibrate [230] dose. Metabolic syndrome factors, particularly hypertension, are linked to an increased 4.…”

Section: Ae Commentmentioning

confidence: 99%

Statin Adverse Effects

Golomb

Evans

2008

American Journal of Cardiovascular Drugs

587

257

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HMG-CoA reductase inhibitors (statins) are a widely used class of drug, and like all medications, have potential for adverse effects (AEs). Here we review the statin AE literature, first focusing on muscle AEs as the most reported problem both in the literature and by patients. Evidence regarding the statin muscle AE mechanism, dose effect, drug interactions, and genetic predisposition is examined. We hypothesize, and provide evidence, that the demonstrated mitochondrial mechanisms for muscle AEs have implications to other nonmuscle AEs in patients treated with statins. In meta-analyses of randomized controlled trials (RCTs), muscle AEs are more frequent with statins than with placebo. A number of manifestations of muscle AEs have been reported, with rhabdomyolysis the most feared. AEs are dose dependent, and risk is amplified by drug interactions that functionally increase statin potency, often through inhibition of the cytochrome P450 3A4 system. An array of additional risk factors for statin AEs are those that amplify (or reflect) mitochondrial or metabolic vulnerability, such as metabolic syndrome factors, thyroid disease, and genetic mutations linked to mitochondrial dysfunction. Converging evidence supports a mitochondrial foundation for muscle AEs associated with statins, and both theoretical and empirical considerations suggest that mitochondrial dysfunction may also underlie many nonmuscle statin AEs. Evidence from RCTs and studies of other designs indicates existence of additional statin-associated AEs, such as cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction. Physician awareness of statin AEs is reportedly low even for the AEs most widely reported by patients. Awareness and vigilance for AEs should be maintained to enable informed treatment decisions, treatment modification if appropriate, improved quality of patient care, and reduced patient morbidity.

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Section: Ae Commentmentioning

confidence: 99%

Statin Adverse Effects

Golomb

Evans

2008

American Journal of Cardiovascular Drugs

587

257

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“…The risk of myopathy does not appear to be significantly different among all the other statins currently available; however, simvastatin at maximal dose of 80 mg was reported to cause more myotoxicity compared to other statins [ 17 ]. The risk for serious muscle toxicity appears to be increased in patients with diabetes, particularly in those with background renal impairment [ 18 , 19 ]. Hypothyroidism increases the risk of statin and/or fibrate-induced rhabdomyolysis [ 20 – 22 ].…”

Section: Discussionmentioning

confidence: 99%

Delayed presentation of severe rhabdomyolysis leading to acute kidney injury following atorvastatin-gemfibrozil combination therapy: a case report

2018

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BackgroundRhabdomyolysis is a rare but serious complication of lipid-lowering therapy. Statin and fibrate combination increases the risk of rhabdomyolysis possibly by pharmacodynamic interactions. Advanced age, diabetes, hypothyroidism, polypharmacy, and renal impairment are known to increase the risk of rhabdomyolysis. Management strategies include fluid resuscitation and urine alkalinization. Renal indications such as refractory hyperkalemia, acidosis, fluid overload, or uremic complications mandate renal replacement therapy in rhabdomyolysis.Case presentationWe report the case of a 62-year-old Sri Lankan Sinhalese man with dyslipidemia, type 2 diabetes mellitus with renal impairment, and hypothyroidism who was on atorvastatin; he was started on gemfibrozil and developed muscle symptoms. Although gemfibrozil was discontinued soon after, he presented with rhabdomyolysis with acute kidney injury 1 month later. He needed hemodialysis due to refractory hyperkalemia, metabolic acidosis, and fluid overload.ConclusionsRhabdomyolysis is a rare but serious complication due to lipid-lowering therapy with statins and fibrates. Treating physicians should be aware and patients should be warned to report about muscle symptoms after starting statins or fibrates. Rhabdomyolysis may occur with mild symptoms and signs and may occur later, even after discontinuation of the drug.

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“…Fifteen of them are summarized in Table 2 [ 1 , 4 – 16 ]. The risk for serious muscle toxicity appears to be increased in elderly patients and in patients with diabetes [ 5 , 11 , 15 ], renal failure [ 4 , 7 , 16 ], or hypothyroidism [ 4 , 5 , 7 , 11 , 13 , 15 , 16 ]. For the patient we present here, tests done 2 months previously found normal results for renal function, thyroid function, and anti-TPO antibody levels.…”

Section: Discussionmentioning

confidence: 99%

Rhabdomyolysis-Induced Acute Renal Failure Following Fenofibrate Therapy: A Case Report and Literature Review

Danış

Akbulut

Özmen

et al. 2010

Case Reports in Medicine

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Fenofibrate, a fibric acid derivative, is used to treat diabetic dyslipidemia, hypertriglyceridemia, and combined hyperlipidemia, administered alone or in combination with statins. Rhabdomyolysis is defined as a pathological condition involving skeletal muscle cell damage leading to the release of toxic intracellular material into circulation. Its major causes include muscle compression or overexertion; trauma; ischemia; toxins; cocaine, alcohol, and drug use; metabolic disorders; infections. However, rhabdomyolysis associated with fenofibrate is extremely rare. Herein we report a 45-year-old female patient who was referred to our department because of generalized muscle pain, fatigue, weakness, and oliguria over the preceding 3 weeks. On the basis of the pathogenesis and clinical and laboratory examinations, a diagnosis of acute renal failure secondary to fenofibrate-induced rhabdomyolysis was made. Weekly followups for patients who are administered fenofibrate are the most important way to prevent possible complications.

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Simvastatin, Fenofibrate, and Rhabdomyolysis

Cited by 15 publications

References 3 publications

Statin Adverse Effects

Statin Adverse Effects

Delayed presentation of severe rhabdomyolysis leading to acute kidney injury following atorvastatin-gemfibrozil combination therapy: a case report

Rhabdomyolysis-Induced Acute Renal Failure Following Fenofibrate Therapy: A Case Report and Literature Review

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