Cytoskeletal myotoxicity from simvastatin and colchicine

Baker, Steven K.; Goodwin, Susan; Sur, Monalisa; Tarnopolsky, Mark A.

doi:10.1002/mus.20135

Cited by 66 publications

(73 citation statements)

References 24 publications

(28 reference statements)

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“…Fluvastatin and colchicine, however, are cleared through two different CYP450 isoenzymes. The second possible mechanism is synergistic myotoxicity (13). Pathogenesis of colchicine myopathy may be related to the disruption of a cytoskeletal microtubular network that interacts with lysosomes.…”

Section: Discussionmentioning

confidence: 99%

Rhabdomyolysis induced by co-administration of fluvastatin and colchicine

Sarullo

Americo

Pasquale

2015

Monaldi Arch Chest Dis

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A case of fluvastatin-induced rhabdomyolysis after coadministration of colchicine is reported. A 77 year old man with ischemic heart disease, chronic pericardial effusion, diabetes mellitus, dyslipidemia, arterial hypertension, chronic renal failure (stage 2 of classification of chronic kidney disease of National Kidney Foundation) and chronic gout presented with a generalized muscle pain. The patient had been taking 80 mg/day of fluvastatin for 4 years, and, for four weeks before presentation, he had also been taking a dose of colchicine (1.0 mg daily) for an exacerbation of gout. Investigations confirmed the diagnosis of rhabdomyolysis. Discontinuation of fluvastatin and colchicine therapy and adequate fluid administration resulted in the resolution of clinical and biochemical features of rhabdomyolysis. Although neuromuscular adverse effects of fluvastatin and colchicine are well recognized, rhabdomyolysis is rare, making this is only the second case reported of fluvastatin and colchicine co-administration induced rhabdomyolysis in literature.

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Section: Discussionmentioning

confidence: 99%

Rhabdomyolysis induced by co-administration of fluvastatin and colchicine

Sarullo

Americo

Pasquale

2015

Monaldi Arch Chest Dis

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“…Although a recent meta-analysis with approximately 30,000 subjects has shown a low incidence of statininduced adverse effects on muscle, 12 the number of case reports and published letters 6,7,26,27,35 suggest that these adverse events may merit additional study. These case reports and letters are indications that many complaints of muscle pain and fatigue or low-grade myopathy often go undetected in the general clinical population.…”

Section: Discussionmentioning

confidence: 99%

“…These findings resolved several months after discontinuing the statin. 6 Although muscle biopsies and electrophysiological testing of muscle and nerve have been used in isolated incidences to confirm complaints of muscle problems, 26,27 serum CK levels continue to be the most commonly reported mechanism for confirming adverse muscular events.…”

Section: Associated Disease Processes and Symptomsmentioning

confidence: 99%

Potential Adverse Effects of Statins on Muscle

Tomlinson

Mangione

2005

Physical Therapy

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“…However, clinically significant DDIs have been reported with atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin when used in combination with colchicine. [170][171][172][173][174][175][176][177][178][179][180][181][182] The DDI between colchicine and simvastatin is the most frequently reported in the literature, having been the subject of 6 cases. In each case, simvastatin-colchicine combination therapy resulted in myopathy, and 1 case progressed to rhabdomyolysis, multiorgan failure, and death.…”

Section: Miscellaneous Agents Colchicinementioning

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

235

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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Cytoskeletal myotoxicity from simvastatin and colchicine

Cited by 66 publications

References 24 publications

Rhabdomyolysis induced by co-administration of fluvastatin and colchicine

Rhabdomyolysis induced by co-administration of fluvastatin and colchicine

Potential Adverse Effects of Statins on Muscle

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

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