Rhabdomyolysis and Renal Failure Associated with Gemfibrozil Monotherapy

Layne, Richard D.; Sehbai, Aasim; Stark, Linda J

doi:10.1345/aph.1d282

Cited by 29 publications

(11 citation statements)

References 19 publications

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“…Both statins and fibrates have been independently associated with a risk of muscle-related toxicity as monotherapy, and statin- fibrate combination therapy increases this risk. [34][35][36][37][38][39] Epidemiological studies have estimated that monotherapy with a fibrate is associated with a 5.5-fold increased risk of muscle-related toxicity compared with statin therapy alone. 40 Muscle-related toxicity has been reported with both available fibrates when used in combination with statins but occurs more frequently with gemfibrozil.…”

Section: Ddis With Nonstatin Lipid-lowering Agents Fibric Acid Derivamentioning

confidence: 99%

Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association

Wiggins¹,

Saseen²,

Page³

et al. 2016

Circulation

249

194

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A drug-drug interaction (DDI) is a pharmacokinetic or pharmacological influence of 1 medication on another that differs from the known or anticipated effects of each agent alone.1 A DDI may result in a change in either drug efficacy or drug toxicity for 1 or both of the interacting medications.2 Pharmacokinetic DDIs result in altered absorption, distribution, metabolism, or excretion of a medication. A pharmacodynamic DDI occurs when 1 medication modifies the pharmacological effect of another in an additive, a synergistic, or an antagonistic fashion.It is estimated that ≈2.8% of hospital admissions occur as a direct result of DDIs. 3 However, the actual incidence of hospitalization secondary to clinically significant DDIs is likely to be highly underestimated because medication-related issues are more commonly reported as adverse drug reactions. Complex underlying disease states also may make recognizing a DDI more challenging, further contributing to a lower reported incidence. The overall clinical impact of a DDI can range from mild to life-threatening. Therefore, not all DDIs require a modification in therapy. The variability in the clinical significance of a DDI depends on both medication-specific and patient-specific factors. Medication-specific factors include the individual pharmacokinetic characteristics of each medication implicated in the DDI (eg, binding affinity, half-life [t 1/2 ]), dose of the medications, serum concentrations, timing and sequence of administration, and duration of therapy. Patient-specific factors include age, sex, lifestyle, genetic polymorphisms causing differences in enzyme expression or activity, and disease impairment affecting drug metabolism (eg, hepatic or renal impairment, cardiac failure) or predisposition to differences in efficacy or safety (eg, statin intolerance in patients with a history of myopathy). Clinically significant DDIs are usually preventable. To optimize patient safety, healthcare providers must have an understanding of the mechanisms, magnitude, and potential consequences of any given DDI. Interpreting this information will assist clinicians in the safe prescribing of medications and permits careful consideration of the benefits and risks of concomitant medications.Statins reduce morbidity and mortality in patients with known atherosclerotic cardiovascular disease (ASCVD) and in many primary prevention patients.4-9 Current guidelines recommend high-intensity statin therapy in all patients with ASCVD age ≤75 years and moderate-to high-intensity statin therapy in patients with ASCVD and age >75 years, diabetes mellitus, and familial hypercholesterolemia and in primary prevention patients with 10-year ASCVD risk ≥7.5%.10 Given the important role of statins in patients with ASCVD and those at high ASCVD risk, combination therapy with statins and other cardiovascular medications is highly likely, and potentially significant DDIs must be considered in patients treated with statins.Another important aspect of prescribing medications in combination is evalu...

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Section: Ddis With Nonstatin Lipid-lowering Agents Fibric Acid Derivamentioning

confidence: 99%

Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association

Wiggins¹,

Saseen²,

Page³

et al. 2016

Circulation

249

194

View full text Add to dashboard Cite

show abstract

“…Although rare with either fibrate, rhabdomyolysis is found much less often with fenofibrate (6 events per million prescriptions) than with gemfibrozil (60 events per million prescriptions) in the US Food and Drug Administration adverse event reporting system database [60]. Risk factors for this complication include decreased renal function, hypothyroidism, and advanced age [61], situations in which gemfibrozil may be especially disadvantageous.…”

Section: Safety and Tolerability Of Fibrate Monotherapymentioning

confidence: 99%

Does the addition of fibrates to statin therapy have a favorable risk to benefit ratio?

Brinton

2008

Curr Atheroscler Rep

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Statins effectively lower low-density lipoprotein cholesterol levels and the risk of cardiovascular disease (CVD) events, and because of this they have become a standard treatment for dyslipidemia and atheroprevention. Unfortunately, statin monotherapy may fail to normalize high triglycerides and low high-density lipoprotein cholesterol, and it prevents only a minority of CVD events. Further treatment of lipid disorders that remain after statin monotherapy should help reduce the residual CVD risk. Fibrate monotherapy lowers high triglyceride levels, raises low high-density lipoprotein cholesterol, and reduces CVD risk; therefore, fibrates are recommended as an adjunct to statins for treatment of residual dyslipidemia and residual CVD risk. This review provides an update on the benefits and risks of fibrate monotherapy and addresses the benefits and risks of adding fibrates to statins.

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“…Rhabdomyolysis was equally rare, occurring in one patient on placebo and three patients on fenofibrate. Individual cases of rhabdomyolysis have been reported in clinical practice with fibrate monotherapy in patients with renal failure and hypothyroidism and in older patients; rhabdomyolysis is less common among individuals with normal creatinine levels at baseline 23–25 …”

Section: Safety and Tolerability Of Fibrate Monotherapymentioning

confidence: 99%

Fibrates in Combination With Statins in the Management of Dyslipidemia

Jacobson

Zimmerman

2006

J of Clinical Hypertension

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While elevated low-density lipoprotein cholesterol is the primary target of hypercholesterolemia treatment, high triglycerides and low high-density lipoprotein cholesterol are also important targets for therapy. Correcting these lipid abnormalities should be an integral part of therapy in hypertensive individuals. Medications such as the fibrates are effective and well tolerated for reducing triglycerides and increasing high-density lipoprotein cholesterol, and their use has resulted in a reduction in cardiovascular events. Fibrates are also recommended as adjunct therapy for patients receiving statins whose low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol is not reduced to goal levels. The combination of a statin and a fibrate may, however, raise the risk of myopathy and rhabdomyolysis. Gemfibrozil, one of the fibrates, but not fenofibrate, interferes with statin glucuronidation, which may increase the risk of myopathy due to elevations in statin serum levels. This may at least partially explain the lower incidence of myopathy with fenofibrate compared with gemfibrozil when combined with statins. Combination therapy with a fibrate and a statin is a potentially useful therapy for patients with atherogenic lipid profiles, for which fenofibrate appears to be a more appropriate choice due to less myopathic potential.

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Rhabdomyolysis and Renal Failure Associated with Gemfibrozil Monotherapy

Abstract: Gemfibrozil monotherapy of hyperlipidemia may predispose to rhabdomyolysis with acute renal failure. Patients using gemfibrozil should be cautioned regarding strenuous exertion, dehydration, and the need for prompt evaluation of myalgias.

Cited by 29 publications

References 19 publications

Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association

Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association

Does the addition of fibrates to statin therapy have a favorable risk to benefit ratio?

Fibrates in Combination With Statins in the Management of Dyslipidemia

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