Rhabdomyolysis in a patient receiving ranolazine and simvastatin

Hylton, Ann C.; Ezekiel, Tanya O.

doi:10.2146/ajhp090299

Cited by 17 publications

(4 citation statements)

References 7 publications

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“…2,3 Similar to the others, our patient had been taking a statin without complications. However, the temporal association of onset, with improvement after discontinuation is highly suggestive that the addition of ranolazine was the primary etiology.…”

Section: Discussionsupporting

confidence: 81%

Ranolazine-Induced Myopathy in a Patient on Chronic Statin Therapy

Correa

Landau²

2013

Journal of Clinical Neuromuscular Disease

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We present a case demonstrating clinical, electrophysiological, serological, and radiological evidence of a myopathy induced by ranolazine, in a patient otherwise asymptomatic on chronic statin therapy. The patient developed proximal weakness, serum creatine kinase levels of 1875 U/L, electromyography with muscle membrane instability and small short-duration motor unit potentials, and magnetic resonance imaging evidence of muscle edema. The manifestations began within one week of initiation of ranolazine and improved within days after discontinuation. Ranolazine is a weak inhibitor of CYP3A4 known to increase the serum level of simvastatin and its active metabolite 2-fold. We postulate that the addition of ranolazine to a medical regimen that included atorvastatin induced a myoncecrotic myopathy.

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Section: Discussionsupporting

confidence: 81%

Ranolazine-Induced Myopathy in a Patient on Chronic Statin Therapy

Correa

Landau²

2013

Journal of Clinical Neuromuscular Disease

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“…However, there have been at least 3 case reports, some of which are in elderly patients. 81,[121][122][123] Clinically significant DDIs with ranolazine and statins other than simvastatin have not been reported. [124][125][126][127] The FDA-approved product labeling recommends that the maximum dose of simvastatin be limited to 20 mg daily when given in combination with ranolazine.…”

Section: Antianginal Agents Ranolazinementioning

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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“…6,7,10,11 Of note, rhabdomyolysis has also been associated with the use of amlodipine, but only in combination with other drugs, primarily statins. 12,13 Without statin use in this patient, amlodipine is unlikely to be the primary cause of rhabdomyolysis.…”

Section: Discussionmentioning

confidence: 84%