Rhabdomyolysis caused by an interaction of simvastatin and fusidic acid

Herring, Roselle; Caldwell, Gordon; Wade, S.

doi:10.1136/bcr.03.2009.1722

Cited by 9 publications

(9 citation statements)

References 11 publications

(9 reference statements)

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“…Furthermore, in countries where FA is available, chronic oral therapy with FA is routinely used in the treatment of Staphylococcus-mediated prosthetic joint infections among the elderly population (Aboltins et al, 2007;Wang et al, 2012). The widespread clinical use of FA in suppressive antibiotic therapy is also associated with several cases of life-threatening rhabdomyolysis (with fatalities) upon coadministration with the 3-hydroxy-3-methylglutaryl CoA reductase inhibitors, atorvastatin and simvastatin (Wenisch et al, 2000;Yuen and McGarity, 2003;Burtenshaw et al, 2008;O'Mahony et al, 2008;Herring et al, 2009;Saeed and Azam, 2009;Collidge et al, 2010;Magee et al, 2010;Teckchandani et al, 2010;Kearney et al, 2012;Gabignon et al, 2013), and more recently, rosuvastatin (Cowan et al, 2013). The package insert for sodium fusidate (Fusidin tablets) was also recently amended with additional warnings to reflect the adverse musculoskeletal findings (https://www.medicines.org.uk/emc/medicine/2448).…”

Section: Introductionmentioning

confidence: 99%

The Antimicrobial Agent Fusidic Acid Inhibits Organic Anion Transporting Polypeptide-Mediated Hepatic Clearance and May Potentiate Statin-Induced Myopathy

Eng

Scialis

Rotter

et al. 2016

Drug Metabolism and Disposition

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Chronic treatment of methicillin-resistant Staphylococcus aureus strains with the bacteriostatic agent fusidic acid (FA) is frequently associated with myopathy including rhabdomyolysis upon coadministration with statins. Because adverse effects with statins are usually the result of drug-drug interactions, we evaluated the inhibitory effects of FA against human CYP3A4 and clinically relevant drug transporters such as organic anion transporting polypeptides OATP1B1 and OATP1B3, multidrug resistant protein 1, and breast cancer resistance protein, which are involved in the oral absorption and/or systemic clearance of statins including atorvastatin, rosuvastatin, and simvastatin. FA was a weak reversible (IC 50 = 295 6 1.0 mM) and time-dependent (K I = 216 6 41 mM and k inact = 0.0179 6 0.001 min 21) inhibitor of CYP3A4-catalyzed midazolam-19-hydroxylase activity in human liver microsomes. FA demonstrated inhibition of multidrug resistant protein 1-mediated digoxin transport with an IC 50 value of 157 6 1.0 mM and was devoid of breast cancer resistance protein inhibition (IC 50 > 500 mM). In contrast, FA showed potent inhibition of OATP1B1-and OATP1B3-specific rosuvastatin transport with IC 50 values of 1.59 mM and 2.47 mM, respectively. Furthermore, coadministration of oral rosuvastatin and FA to rats led to an approximately 19.3-fold and 24.6-fold increase in the rosuvastatin maximum plasma concentration and area under the plasma concentration-time curve, respectively, which could be potentially mediated through inhibitory effects of FA on rat Oatp1a4 (IC 50 = 2.26 mM) and Oatp1b2 (IC 50 = 4.38 mM) transporters, which are responsible for rosuvastatin uptake in rat liver. The potent inhibition of human OATP1B1/OATP1B3 by FA could attenuate hepatic uptake of statins, resulting in increased blood and tissue concentrations, potentially manifesting in musculoskeletal toxicity.

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Section: Introductionmentioning

confidence: 99%

The Antimicrobial Agent Fusidic Acid Inhibits Organic Anion Transporting Polypeptide-Mediated Hepatic Clearance and May Potentiate Statin-Induced Myopathy

Eng

Scialis

Rotter

et al. 2016

Drug Metabolism and Disposition

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“…The coadministration of simvastatin and fusidic acid or colchicine is also associated with increased risk of rhabdomyolysis, especially in patients with kidney impairment [157,[163][164][165][166][167]]. …”

Section: Brief Description Of Drug Interactionsmentioning

confidence: 99%

Safety considerations with fenofibrate/simvastatin combination

Filippatos

Elisaf

2015

Expert Opinion on Drug Safety

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Large randomized clinical trials show that the combined administration of fenofibrate with simvastatin is not associated with significantly increased incidence of serious adverse events compared with simvastatin monotherapy. The incidence of rhabdomyolysis is slightly increased with fibrate/statin combination compared with monotherapy but the actual risk is very low. Although fenofibrate increases creatinine and homocysteine serum levels, the incidence of diabetic nephropathy and thrombotic events was not significantly increased with fenofibrate/simvastatin combination compared with simvastatin monotherapy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial. Furthermore, a decrease in albuminuria was observed with fenofibrate in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and ACCORD Lipid trials. Overall, the combined administration of fenofibrate with simvastatin appears to be safe, unless clinicians give fenofibrate/simvastatin combination to patients with predisposing risk factors for the occurrence of adverse events.

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“…Rhabdomyolysis associated with statin therapy has an incidence of 3.4 per 100 000 patient-years of treatment and is well publicised to be secondary to pharmacological interactions 1 2. It results from the breakdown of striated muscle fibres leading to the release of myoglobin into the blood stream with an associated 10-fold elevation of creatine kinase3 above the normal limit.…”

Section: Introductionmentioning

confidence: 99%

Rhabdomyolysis with simvastatin

Patel

Choudhury²

2011

Case Reports

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As 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ('statins') are being increasingly prescribed for the prevention of cardiovascular disease, this case report describes adverse effects of statin therapy which can sometimes be fatal. It highlights the need for physicians to be aware of individual patient risk factors predisposing to statin induced myopathy. It also highlights the need for further research into cholesterol lowering drugs which do not have such side effects. When prescribing statins for patients, we must also explain potential side effects following initiation of therapy and with dose titrations.

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Rhabdomyolysis caused by an interaction of simvastatin and fusidic acid

Cited by 9 publications

References 11 publications

The Antimicrobial Agent Fusidic Acid Inhibits Organic Anion Transporting Polypeptide-Mediated Hepatic Clearance and May Potentiate Statin-Induced Myopathy

The Antimicrobial Agent Fusidic Acid Inhibits Organic Anion Transporting Polypeptide-Mediated Hepatic Clearance and May Potentiate Statin-Induced Myopathy

Safety considerations with fenofibrate/simvastatin combination

Rhabdomyolysis with simvastatin

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