Simvastatin–Amiodarone Interaction Resulting in Rhabdomyolysis, Azotemia, and Possible Hepatotoxicity

Ricaurte, Basma; Guirguis, Amir; Taylor, Harris C.; Zabriskie, Don

doi:10.1345/aph.1g462

Cited by 64 publications

(43 citation statements)

References 25 publications

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“…118 However, lower doses of atorvastatin (10 mg) combined with digoxin did not alter the pharmacokinetics of digoxin. 99 Atorvastatin appears to be the only statin that is reported to have this interaction. The mechanism is not fully understood but may be mediated by an impact of atorvastatin on the intestinal secretion of digoxin medicated by the P-gp efflux transporter, resulting in increased digoxin absorption.…”

Section: Digoxinmentioning

confidence: 99%

“…94 There have been multiple reports of toxicity when amiodarone is prescribed in combination with statins that are CYP3A4 substrates, particularly simvastatin. 92,[95][96][97][98][99][100][101][102] Pharmacokinetic data show an ≈75% increase in simvastatin and the active simvastatin acid AUC and Cmax when amiodarone and simvastatin are coadministered, but no significant pharmacokinetic interaction between amiodarone and pravastatin has been demonstrated. 103 In the SEARCH (Study Evaluating Additional Reduction in Cholesterol and Homocysteine), of 12 064 survivors of myocardial infarction, 8 cases of myopathy and 7 cases of rhabdomyolysis were identified in patients on simvastatin 80 mg in combination with amiodarone versus zero cases in patients allocated to simvastatin 20 mg (relative risk, 8.8; 95% confidence interval, 4.2-18.4).…”

Section: Amiodaronementioning

confidence: 99%

See 1 more Smart Citation

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

233

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: Digoxinmentioning

confidence: 99%

Section: Amiodaronementioning

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

233

194

View full text Add to dashboard Cite

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“…The use of these drugs together can lead to an increase in the risk for myopathy or rhabdomyolysis. In the clinical management, it is recommended to monitor patients for signs and symptoms of rhabdomyolysis or myopathy such as: muscular pain, sensibility or weakness, and dark diuresis (9) . As for the pair of drugs, gentamicin + magnesium sulphate, 31 nurses (60.8%) answered incorrectly about DI and almost all answered incorrectly about its clinical management 50 (98.0%).…”

Section: Discussionmentioning

confidence: 99%

Interação medicamentosa: conhecimento de enfermeiros das unidades de terapia intensiva

Faria

Cassiani

2011

Acta paul. enferm.

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Objective: To evaluate adult intensive care unit (ICU) nurses' knowledge of medication interactions (IM) in three public hospitals in Goias. Methods: A cross-sectional study was conducted using a population of 64 and a sample of 51 nurses. An instrument was constructed to collect data, using information from the database MICROMEDEX ®. Results: Regarding the knowledge of clinical management of IM, there was approximately the same number of right and wrong answers among 50% of the nurses. Nurses had better knowledge about drugs with sedative and analgesic action; nurses demonstrated less knowledge about drugs with anti-infective and anti-hypertensive actions. Conclusion: It is necessary to sensitize the authorities and professionals about the importance of IM in the ICU, and to implement actions for patient safety related to drug therapy. Keywords: Safety management; Safety; Drug interactions; Knowledge RESUMOObjetivo: Avaliar o conhecimento das interações medicamentosas (IM)de enfermeiros que atuam em unidades de terapia intensiva de adultos, de três hospitais públicos de Goiás. Métodos: Estudo descritivo, transversal. População 64 e amostra, 51 enfermeiros. Construiuse um instrumento de coleta de dados, utilizando informações da base de dados MICROMEDEX®. Resultados: Sobre o conhecimento de IM e manejo clínico, houve uma relação de acertos e erros de, aproximadamente, 50% dos enfermeiros. As duplas de medicamentos que os enfermeiros mais acertaram foram relativas a medicamentos com ação sedativa e analgésica e as que apresentaram mais erros, foram as de ação anti-infecciosa e anti-hipertensiva. Conclusão: É necessário sensibilizar autoridades e profissionais sobre a importância das IM na UTI e implementar ações para a segurança dos pacientes na terapêutica medicamentosa. Descritores: Gerenciamento de segurança; Segurança; Interação medicamentosa; Conhecimento RESUMENObjetivo: Evaluar el conocimiento de las interacciones medicamentosas (IM) de enfermeros que actúan en unidades de cuidados intensivos de adultos, de tres hospitales públicos de Goiás. Métodos: Estudio descriptivo, transversal. Población 64 y muestra 51 enfermeros. Se construyó un instrumento de recolección de datos, utilizando informaciones de la base de datos MICROMEDEX®. Resultados: Sobre el conocimiento de IM y manejo clínico, hubo una relación de aciertos y errores de, aproximadamente el 50% de los enfermeros. El par de medicamentos que los enfermeros aciertan más fueron los relativos a medicamentos con acción sedante y analgésica y los que presentaron más errores, fueron los de acción anti-infecciosa y anti-hipertensiva. Conclusión: Es necesario sensibilizar a las autoridades y profesionales sobre la importancia de las IM en la UCI e implementar acciones para la seguridad de los pacientes en la terapéutica medicamentosa. Descriptores: Administración de la seguridad; Seguridad; Interacciones de drogas; Conocimiento

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“…5 Several factors have been identified that increase the risk for both myopathy and rhabdomyolysis, including advanced age, chronic renal insufficiency, metabolic disorders such as diabetes or hypothyroidism, major surgery, and alcohol abuse. 4,5,7,12,13 In addition, the manufacturer of simvastatin has identified higher simvastatin doses and the use of certain other medications as risk factors.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 The risk of rhabdomyolysis with statin monotherapy is low and dose related. 4,[7][8][9][10] This risk increases in patients taking concomitant drugs that inhibit the cytochrome P450-related statin metabolism such as azole antifungals, cyclosporine, fibrates, macrolides, and non-dihydropyridine calcium channel blockers. 4,7,8 Patients with coronary artery disease are often on a number of medications and therefore the potential for drug interactions is an important consideration.…”

mentioning

confidence: 99%

Severe Rhabdomyolysis and Acute Renal Failure Secondary to Concomitant Use of Simvastatin, Amiodarone, and Atazanavir

Schmidt¹,

Purcell²,

Friedman³

et al. 2007

The Journal of the American Board of Family Medicine

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Objective: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure.Background: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. The ability of statins to reduce the risk of cardiovascular morbidity and mortality in patients with dyslipidemia is well established. [1][2][3] In addition to their unmatched efficacy, the adverse effects associated with statins are usually mild and transient. 4 The most noteworthy adverse effects associated with statins are elevations in liver transaminases, myopathy, and rhabdomyolysis, which is characterized by massive muscle necrosis, myoglobinuria, and acute renal failure. 5,6 The risk of rhabdomyolysis with statin monotherapy is low and dose related. 4,[7][8][9][10] This risk increases in patients taking concomitant drugs that inhibit the cytochrome P450-related statin metabolism such as azole antifungals, cyclosporine, fibrates, macrolides, and non-dihydropyridine calcium channel blockers. 4,7,8 Patients with coronary artery disease are often on a number of medications and therefore the potential for drug interactions is an important consideration. This article describes a case of rhabdomyolysis in a patient taking concomitant simvastatin, amiodarone, and atazanavir. Case ReportA 72-year-old white man (weight, 72 kg; height, 175 cm; body mass index, 23.5 kg/m 2 ) presented to This article was externally peer reviewed.

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Simvastatin–Amiodarone Interaction Resulting in Rhabdomyolysis, Azotemia, and Possible Hepatotoxicity

Abstract: An objective causal assessment suggests that rhabdomyolysis, renal failure, and possibly hepatotoxicity were probably related to an amiodarone-simvastatin interaction.

Cited by 64 publications

References 25 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

Interação medicamentosa: conhecimento de enfermeiros das unidades de terapia intensiva

Severe Rhabdomyolysis and Acute Renal Failure Secondary to Concomitant Use of Simvastatin, Amiodarone, and Atazanavir

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