Ranolazine-Induced Myopathy in a Patient on Chronic Statin Therapy

Correa, Daniel J.; Landau, Mark E.

doi:10.1097/cnd.0b013e31828525a5

Cited by 10 publications

(4 citation statements)

References 5 publications

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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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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

View full text Add to dashboard Cite

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“…Some cases of rhabdomyolysis were reported after adding ranolazine to atorvastatin therapy through impaired clearance of atorvastatin by sharing CYP450 biotransformation pathway. 19,20 Pravastatin and rosuvastatin are mainly excreted unchanged 21 ; thus, ranolazine is less likely to affect their plasma concentrations. Verapamil inhibits gut P-glycoprotein, which increases ranolazine average plasma concentrations at steady state.…”

Section: Pharmacology Of Ranolazine Pharmacodynamicsmentioning

confidence: 99%

“…Simvastatin has a minor inhibitory effect to CYP3A4 enzyme; thus, it can be safely administered with ranolazine 1000 mg twice daily. Some cases of rhabdomyolysis were reported after adding ranolazine to atorvastatin therapy through impaired clearance of atorvastatin by sharing CYP450 biotransformation pathway . Pravastatin and rosuvastatin are mainly excreted unchanged; thus, ranolazine is less likely to affect their plasma concentrations.…”

Section: Pharmacology Of Ranolazinementioning

confidence: 99%

Ranolazine in Cardiac Arrhythmia

Saad

Mahmoud

Elgendy

et al. 2015

Clinical Cardiology

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Ranolazine utilization in the management of refractory angina has been established by multiple randomized clinical studies. However, there is growing evidence showing an evolving role in the field of cardiac arrhythmias. Multiple experimental and clinical studies have evaluated the role of ranolazine in prevention and management of atrial fibrillation, with ongoing studies on its role in ventricular arrhythmias. In this review, we will discuss the pharmacological, experimental, and clinical evidence behind ranolazine use in the management of various cardiac arrhythmias.

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“…Ranolazine is prescribed for the treatment of chronic cardiac angina. When used in conjunction with concomitant statin therapy, it has been demonstrated to increase serum statin levels, and has been associated with rhabdomyolysis [ 1 - 3 ]. This is the first report of myalgias and elevated creatinine kinase reported without concomitant statin therapy.…”

Section: Introductionmentioning

confidence: 99%

Ranolazine-induced Elevation of Creatinine Kinase in the Absence of Statin Usage

Dein

Manno

Syed

et al. 2018

Cureus

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Ranolazine received Food and Drug Administration (FDA) approval in 2006 for the treatment of chronic angina. Ranolazine has previously been linked to the development of statin-induced myopathy, because it also inhibits CYP3A4, which increases serum statin levels. In the absence of concomitant statin therapy, elevated creatinine kinase (CK) and myalgias on ranolazine monotherapy has never been reported.

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Ranolazine-Induced Myopathy in a Patient on Chronic Statin Therapy

Cited by 10 publications

References 5 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

Ranolazine in Cardiac Arrhythmia

Ranolazine-induced Elevation of Creatinine Kinase in the Absence of Statin Usage

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