Genetic Study of Simvastatin Pharmacogenetics
Evaluation of genetic variants that contribute to simvastatin pharmacokinetics and statin-related adverse drug reaction
Why Genetic Study of Simvastatin Pharmacogenetics matter?
According to the FDA, Simvastatin pharmacogenetics is important for determining:
Genetic Study of Simvastatin Pharmacogenetics
An actionable test to prevent adverse side-effects of non-optimal simvastatin drug dosage
The utility of genetic testing is recognized in guidelines related to the management of simvastatin therapeutics.
It is recommended for:
Simvastatin Pharmacogenetics Testing
Evaluation of the genotypes that contribute to statin-related muscle toxicity.
What is evaluated in this test?
Simvastatin genetic test evaluates 3 genetic variants of SLCO1B1 gene related to simvastatin absorption, distribution, metabolism, and excretion (pharmacokinetics).
SLCO1B1 protein, facilitates the hepatic uptake of statins.
SLCO1B1 genetic variants greatly affect the pharmacokinetics of simvastatin and also, to a smaller extent, the pharmacokinetics of other statins, in the following order: pitavastatin, atorvastatin, pravastatin and rosuvastatin.
Table 1. International guidelines for simvastatin dosing recommendations according to each SLCO1B1 diplotype.
Implications for simvastatin
|CPIP Simvastatin dosing recommendations|
|*1a/*1a; *1a/*1b; *1b/*1b||
Normal myopathy risk
|Prescribe desired starting dose and adjust doses based on disease-specific guidelines|
|*1a/*5;*1a/*15; *1a/*17; *1b/*5; *1b/*15; *1b/*17||
Intermediate myopathy risk
|Prescribe a lower dose or consider an alternative statin. Consider routine creatinine kinase surveillance.|
|*5/*5; *5/*15; *5/*17; *15/*15; *15/*17; *17/*17||
High myopathy risk
|Prescribe a lower dose or consider an alternative statin. Consider creatine kinase surveillance.|
Benefits of Genetic Study of Simvastatin Pharmacogenetics
Genetic Study or Simvastatin Pharmacogenetics is a reliable test that evaluates myopathy genetic risk.
A sample of blood or saliva is enough to perform the genetic test.
Defines the genetic risk of simvastatin-induced myopathy
Genetic Study of Simvastatin Pharmacogenetics defines the Simvastatin optimal dose therapy and/or recommends for alternative statin therapy.
Medical doctors can advise therapeutics to define the optimal dose therapy or recommend for an alternative statin.
Up-to-date genetic information.
Although generally well tolerated, simvastatin may cause muscle-related adverse effects in some patients, being skeletal muscle toxicity the most common. Symptoms include pain with or without evidence of muscle degradation (myopathy or myalgia, respectively), and, less frequently, severe muscle damage with acute kidney injury (rhabdomyolysis). Patients with myopathy generally have muscle pain, tenderness or weakness, and an elevation of creatine kinase blood levels. These adverse drug reactions appear to be dose-dependent, especially when statins are administered at higher doses and together with certain other medications [2-4].
Clinical factors, demographic variables and variations in SLCO1B1 gene contribute significantly to the risk of developing statin-induced muscle toxicity [2,4,5].
Some SLCO1B1 gene haplotypes are associated with increased risk of composite adverse events in patients with hypercholesterolemia when treated with statins (atorvastatin, pravastatin or simvastatin). The incidence of statin-induced myopathy has been reported to be between 27% and 50% in carriers of this genetic variant, dropping to 19% in non-carriers [3,4].
The pharmacogenetic test in patients taking statins could improve treatment adherence and efficacy. Every patient could receive his/her own genetic profile associated with individual pharmacokinetics of statins and the corresponding genetic risk for toxicities.
Key protein and gene:
SLCO1B1– Solute Carrier Organic Anion Transporter Family, member 1B1
Encodes the SLCO1B1 protein, a liver specific transporter that mediates the transport of statins such as simvastatin or atorvastatin, and other exogenous and/or endogenous substances into hepatocytes.
Practice-based data suggests the association between rs4149056 and muscle toxicity is stronger for simvastatin than for other drugs within the class.
Simvastatin genetic painel
The Simvastatin genetic test developed by HeartGenetics includes the evaluation of 3 genetic variants in SLCO1B1 gene associated with myopathy risk
How Genetic variants are selected:
Our research is supported by peer review papers that have been published in the reference journals in the field.
All genetic variants have been validated in reference databases (HGMDP, NCBI-OMIM, NCBI- ClinVar, NCBI-Variation Reporter and Ensembl).
The knowledge in our databases was approved by internationally recognized medical geneticists and cardiologists.
Genetic testing is recommended by several renowned international organizations, such as the Food and Drug Administration (FDA) and the Clinical Pharmacogenetics Implementation Consortium (CPIC)
According to the Food and Drug Administration:
In order to reduce the risk of muscle injury, the FDA recommends against 80 daily simvastatin dosage in new patients and also in those already taking lower doses of the drug. According to the FDA, the risk of myopathy is higher during the first year of treatment and approximately 60% of the cases are associated with SLCO1B1 genetic variants. These are strongly associated with an increased risk of statin-induced myopathy. Genotyping these variants may help to achieve the benefits of statin therapy more safely and effectively.
The Clinical Pharmacogenetics Implementation Consortium (CPIC) that develops peer-reviewed gene-drug guidelines based on new developments in the field, has established several recommendations on simvastatin dosage based on SLCO1B1 genotype.
HeartGenetics’ Simvastatin Pharmacogenetics reports?
The simvastatin pharmacogenetics panel includes high-risk genetic variants associated to myophaty
The methodology is targeted to the presence / absence of a specific genetic variant associated to myophaty.
The used technology has a 99% of accuracy.
All evidences are supported by updated scientific knowledge and validated by medical doctors.
All results include supporting information for each genetic variant including scientific references to guide the interpretation of test results.
HeartGenetics reports follow the recommendations from the European Society of Human Genetics
Contact us here for a report example.
Food and Drug Administration webpage: http://www.fda.gov/
Nat Rev Drug Discov. 2007. 6(11):904-16. Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges.
Clin Pharmacol Ther. 2013. 94(6):695-701. SLCO1B1 genetic variant associated with statin-induced myopathy: a proof-of-concept study using the clinical practice research datalink.
J Am Coll Cardiol. 2009. 54(17):1609-16. The SLCO1B1*5 genetic variant is associated with statin-induced side effects.
Clin Pharmacol Ther. 2014. 96(4):423-8. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update.
FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury 6/8/2011: http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm
Clin Pharmacol Ther. 2011. 89(2):210-6. Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: a go-DARTS study.
N Engl J Med. 2008. 359(8):789-99. SLCO1B1 variants and statin-induced myopathy–a genomewide study.