Acute rhabdomyolysis after atorvastatin and fusidic acid therapy

Wenisch, Christoph; Krause, Robert; Fladerer, Petra; Menjawi, Ibrahim El; Pohanka, E

doi:10.1016/s0002-9343(00)00367-3

Cited by 43 publications

(21 citation statements)

References 3 publications

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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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“…We were unaware at the time of his presentation of an interaction between fusidic acid and statins, but subsequently learned that fusidic acid inhibits the CYP3A4 enzyme system and that this particular drug combination is likely to potentiate the toxicities of both drugs. 11,12 We later found seven case reports of rhabdomyolysis due to a fusidic acid-statin interaction, including four of fusidic acid with atorvastatin [13][14][15][16] and three of fusidic acid with simvastatin. [17][18][19] Fusidic acid was the only CYP3A4 inhibitor prescribed in five of these reports.…”

Section: Discussionmentioning

confidence: 99%

Rhabdomyolysis following co-prescription of fusidic acid and atorvastatin

Teckchandani¹,

Robertson²,

Almond³

et al. 2010

JRCPE

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“…The risk of myositis is also increased when statins are coadministered with niacin [67]. Rhabdomyolysis and acute renal failure occurred with a combination of simvastatin and warfarin [68], as well as with simvastatin and clarithromycin [69], atorvastatin and fusidic acid [70], and atorvastatin and cyclosporine [71]. However, the major risk of adverse effects has been shown when statins are used concomitantly with fibrates, so that this combination must be used cautiously, and only after careful risk-benefit analysis [72].…”

Section: Effect Of Combination Therapymentioning

confidence: 99%

Lipid-Lowering Drugs: Are Adverse Effects Predictable and Reversible?

Muscari

Puddu

2002

Cardiology

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Most of the currently available statins and fibric acid derivatives have been implicated in causing complications either in monotherapy or in combination therapy. Adverse events occur more often with the statins that are metabolized via the CYP enzyme system and its 3A4, 2C9 or 2C19 paths. All compounds interfering with the same cytochrome system may either impair or enhance the elimination of statins. Other factors predisposing to adverse effects are age, female sex, renal insufficiency, electrolyte disturbances, infections and trauma. Complications chiefly concern the hepatic function, skeletal muscles and peripheral nerves. The major adverse effect is myopathy, up to rhabdomyolysis with ensuing acute renal insufficiency. Fibrates bind to peroxisome proliferator-activated nuclear receptors α, with subsequent stimulation of fatty acid oxidation and reduction in the rate of hepatic lipid generation. Fibrates are associated with a number of adverse effects, including liver enzyme elevations, gastrointestinal side effects and rhabdomyolysis. The combination of statins with fibrates may cause serious complications and should be avoided when possible. In order to prevent or minimize adverse clinical outcomes, patients should be closely monitored and informed of the most common symptoms.

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Acute rhabdomyolysis after atorvastatin and fusidic acid therapy

Cited by 43 publications

References 3 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

Rhabdomyolysis following co-prescription of fusidic acid and atorvastatin

Lipid-Lowering Drugs: Are Adverse Effects Predictable and Reversible?

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