Rhabdomyolysis in association with simvastatin and dosage increment in clarithromycin

Page, Sean; Yee, KC

doi:10.1111/imj.12464

Cited by 23 publications

(14 citation statements)

References 15 publications

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“…Statin dose and properties are important determinants of myotoxicity, with higher lipophilicity and interaction with drug metabolizing pathways such as CYP increasing risk for adverse muscle . A recent study also showed that individuals with 25‐OH vitamin D3 below 15 mg/mL on statin had a higher incidence of muscle adverse effects compared to those without statin, providing some evidence that vitamin D deficiency also represents another risk condition for muscle adverse effects in patients treated with statins .…”

Section: Risk Factors For Statin‐induced Myopathymentioning

confidence: 99%

The role of mitochondria in statin‐induced myopathy

Apostolopoulou

Corsini

Roden

2015

Eur J Clin Investigation

123

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Section: Risk Factors For Statin‐induced Myopathymentioning

confidence: 99%

The role of mitochondria in statin‐induced myopathy

Apostolopoulou

Corsini

Roden

2015

Eur J Clin Investigation

123

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“…While data concerning this aspect of antimicrobial therapy are limited, certain antibiotics may interfere with the metabolism of statins, which can lead to increased serum levels and thus to an increased risk of adverse effects (84). For instance, certain statins, including simvastatin, lovastatin, and atorvastatin, are metabolized by cytochrome P450 3A4 (CYP3A4) isoenzymes and studies have shown that coprescription with drugs that inhibit CYP3A, such as macrolide antibiotics, can lead to increased adverse effects, including rhabdomyolysis, in elderly patients (85)(86)(87)(88)(89)(90)(91)(92). In light of this, the U.S. FDA has stated that "caution should be exercised when prescribing clarithromycin with statins" and, in particular, that "concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated" (95).…”

Section: Coprescription Of Statins With Antibioticsmentioning

confidence: 99%

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Hennessy

Adams

Reen

et al. 2016

Antimicrob Agents Chemother

108

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bStatins are members of a class of pharmaceutical widely used to reduce high levels of serum cholesterol. In addition, statins have so-called "pleiotropic effects," which include inflammation reduction, immunomodulation, and antimicrobial effects. An increasing number of studies are emerging which detail the attenuation of bacterial growth and in vitro and in vivo virulence by statin treatment. In this review, we describe the current information available concerning the effects of statins on bacterial infections and provide insight regarding the potential use of these compounds as antimicrobial therapeutic agents. O ne of the major undisputed clinical breakthroughs of the 20th century was the discovery of the statin family of drugs. These compounds are renowned for their ability to lower cholesterol levels and are used to treat approximately 40 million individuals with high cholesterol levels worldwide. Since the discovery of mevastatin as a metabolic product of Penicillium citrinum in 1976 (1, 2), a total of nine statins have been characterized, seven of which are approved by the FDA to treat patients with high cholesterol. Structurally, statins are characterized by the presence of a conserved lactone ring (3). This structure is present as a hydrolyzed (active) form in all statins except for mevastatin, lovastatin, and simvastatin; in those statins, the lactone ring is hydrolyzed in the liver (4). Statins can be divided into two broad classes (Fig. 1). Type 1 statins are lipophilic and possess a butyryl side chain-they are said to structurally resemble mevastatin (3). Lovastatin, pravastatin, and simvastatin are type 1 statins. Type 2 statins are classically lipophobic and are distinguished from type 1 by the replacement of the butyryl side chain with a fluorophenol group and typically possess larger side chains than type 1 statins (3). Atorvastatin, cerivastatin, fluvastatin, pitavastatin, and rosuvastatin are type 2 statins.Statins exert their cholesterol-lowering effect by binding to the active site of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR), a rate-limiting enzyme involved in cholesterol biosynthesis (3). HMGR is an integral part of the mevalonate pathway, which not only is essential for cholesterol biosynthesis but also contributes to the production of isoprenoids, lipid compounds that are essential for cell signaling and structure. As well as inhibition of cholesterol, statins have also been found to have a number of cholesterol-independent, socalled "pleiotropic" effects. Statins have been reported to confer anti-inflammatory, immunomodulatory, and anticancer effects on host cells, and these effects are well characterized (5-9). Furthermore, several studies have explored the pleiotropic effects of statins in combating multisystem microbial infections, such as sepsis and pneumonia, and a growing number of studies are demonstrating that statins can directly influence the growth and virulence of bacterial pathogens. With the global increase in antibiotic resistance to existing antib...

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“…However, simvastatin is a substrate of cytochrome P450 3A4 and as a consequence coadministration with potent inhibitors of cytochrome P450 3A4 increases the concentration of HMG-CoA reductase inhibitory activity in plasma and the risk of myopathy and rhabdomyolysis. Hence, the coadministration of simvastatin with ketoconazole, itraconazole, posaconazole, clarithromycin, telithromycin, erythromycin, HIV protease inhibitors (e.g., nelfinavir), danazol and nefazodone is contraindicated [142][143][144][145][146][147][148][149][150][151][152][153][154][155][156][157]. If the administration of a CYP3A4 inhibitor is needed then simvastatin treatment should be at least temporarily stopped.…”

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 in association with simvastatin and dosage increment in clarithromycin

Cited by 23 publications

References 15 publications

The role of mitochondria in statin‐induced myopathy

The role of mitochondria in statin‐induced myopathy

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Safety considerations with fenofibrate/simvastatin combination

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