The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1 and Simvastatin-Induced Myopathy: 2014 Update

Ramsey, Laura B.; Johnson, Samuel G.; Caudle, Kelly E.; Haidar, Cyrine E.; Voora, Deepak; Wilke, Russell A.; Maxwell, Whitney D.; McLeod, Howard L.; Krauss, Ronald M.; Roden, DM; Feng, QiPing; Cooper‐DeHoff, Rhonda M.; Gong, Li; Klein, Teri E.; Wadelius, Mia; Niemi, Mikko

doi:10.1038/clpt.2014.125

Cited by 382 publications

(368 citation statements)

References 37 publications

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“…The risk of myopathy is dose-related and it appears to depend on the levels of the statin in the circulation (as indicated by its association with a SLCO1B1 gene variant that reduces the transport of all statins from the blood into the liver). 78,216,219 Cerivastatin was withdrawn from use because the myopathy rate observed in post-marketing surveillance with approved doses was much higher than with other statins. 220 In the SEARCH randomized trial, simvastatin 80 mg daily produced a more than 10-fold higher rate (at least 1 myopathy case per 1,000 patients treated annually) than 20-40 mg daily (about 1 case per 10,000 annually), 78,221 so the high-dose regimen is no longer recommended routinely.…”

Section: Increases In Rates Of Myopathymentioning

confidence: 99%

Interpretation of the evidence for the efficacy and safety of statin therapy

et al. 2016

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms SummaryThis review is intended to help clinicians, patients and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence that is available from randomized controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment.Large-scale randomized trial evidence shows that statin therapy reduces the risk of heart attacks, ischaemic strokes and coronary revascularization procedures ("major vascular events") by about one quarter for each mmol/L reduction in low density lipoprotein (LDL) cholesterol during each year (after the first) that it continues to be taken. The absolute benefits of statin therapy depend on an individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an effective low-cost statin regimen (e.g. atorvastatin 40 mg daily, costing about £2 per

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Section: Increases In Rates Of Myopathymentioning

confidence: 99%

Interpretation of the evidence for the efficacy and safety of statin therapy

et al. 2016

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“…Similarly to other statins, atorvastatin has been associated with the development of skeletal muscle toxicity (myopathy). The severity of the latter can range from myalgia (muscle pain with no evidence of muscle degradation) to the rare but life-threatening rhabdomyolysis (severe muscle damage potentially accompanied with acute renal failure) [4][5][6][7][8]. It is widely acknowledged that statin-induced myopathy is a concentration-dependent adverse event and that factors such as increased dose and coadministration of compounds altering statin pharmacokinetics substantially increase myopathy risk [9,10].…”

Section: Introductionmentioning

confidence: 99%

Modelling of atorvastatin pharmacokinetics and the identification of the effect of a BCRP polymorphism in the Japanese population

Tsamandouras

Guo

Wendling

et al. 2017

Pharmacogenetics and Genomics

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Aim(s): Ethnicity has a modulating role in atorvastatin pharmacokinetics, with Asian subjects reported to have higher exposure compared to Caucasians. Therefore, it is difficult to safely extrapolate atorvastatin pharmacokinetic data and models across ethnic groups. This work aims to develop a population pharmacokinetic model for atorvastatin and its pharmacologically active metabolites specifically for the Japanese population. Subsequently it is aimed to identify genetic polymorphisms affecting atorvastatin pharmacokinetics in this population. Methods:Atorvastatin acid and o-OH-atorvastatin acid plasma concentrations, clinical/ demographic characteristics and genotypes for 18 genetic polymorphisms (3, 3, 1, 1, 7, 2 and 1 in the ABCB1, ABCG2, CYP3A4, CYP3A5, SLCO1B1, SLCO2B1 and PPARA genes respectively) were collected from 27 Japanese individuals (taking 10mg atorvastatin once daily) and analysed using a population pharmacokinetics modelling approach. Results:The developed population pharmacokinetic model (one-compartment for atorvastatin acid linked through metabolite formation to an additional compartment describing the disposition of o-OH-atorvastatin acid) accurately described the observed data and the associated population variability. Our analysis suggested that subjects carrying one variant allele for the rs2622604 polymorphism (ABCG2) exhibit a 55% (95%CI: 16%-131%) increase in atorvastatin oral bioavailability relatively to the value in individuals without the variant allele. Conclusion:The current work reports the identification in the Japanese population of a BCRP polymorphism, not previously associated with the pharmacokinetics of any statin, that substantially increases atorvastatin acid and o-OH-atorvastatin acid exposure. The developed model may be of clinical importance in order to guide dosing recommendations tailored specifically for the Japanese.

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“…However, clinicians should be aware that in the prevention and/or treatment of diabetes in patients of Asian or African ancestry, they may encounter more cases of 'non-responders' (patients for whom the drug is ineffective, but adverse effects may occur despite this), as well as more frequent adverse effects, such as myalgia, with the use of statins (33).…”

Section: Discussionmentioning

confidence: 99%

“…It may appear that persons of Asian and African ancestry are particularly vulnerable (33). There is a possible relationship between vitamin D deficiency and statin-induced myalgia (34).…”

Section: Lipid-lowering Agentsmentioning

confidence: 99%