Simvastatin is one of the most commonly used statins for cholesterol reduction, for instance in the treatment of hypercholesterolemia, hence reducing cardiovascular morbidity and mortality.
Although simvastatin is generally well tolerated, some patients develop muscle-related adverse effects, 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 a muscle enzyme in the blood (creatine kinase, or CK). These adverse drug reactions (ADR) appear to be dose-dependent, especially when the statins are administered at higher doses and in concert with certain other medications.
In order to reduce the risk of muscle injury, the Food and Drug Administration (FDA) recommends against starting simvastatin 80 mg 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 in approximately 60% of the cases is associated with a genetic variant. In fact, some SLCO1B1 gene variants 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. Also, the Clinical Pharmacogenetics Implementation Consortium (CPIC) has established several recommendations on simvastatin dosage based on SLCO1B1 phenotype.
INDICATION FOR SIMVASTATIN PHARMACOGENETIC TESTING
- For individuals with a personal or family history of adverse drug reactions to statins.
- When prescribing statins in a clinical context of cholesterol reduction, namely for hypercholesterolemia or other cardiovascular disease.
WHAT IS EVALUATED IN THE HEARTGENETICS PHARMACOGENETIC TESTING?
SLCO1B1 is the protein product of the SLCO1B1 gene and facilitates the hepatic uptake of statins. SLCO1B1 genetic variants have been associated with lower plasma clearance of simvastatin.
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.
BENEFITS OF GENETIC TESTING
Avoid simvastain side effects by prescribing a tailored dose according to each individual genetic profile.
Based on the prevalent use of simvastatin, a potential benefit of SLCO1B1 genetic testing is a significant reduction in the incidence of simvastatin-induced myopathies and rhabdomyolysis, by identifying those at significant risk and recommending a lower simvastatin dose or an alternative statin as appropriate.
Providing an adequate lipid-lowering therapy is important for the prevention and/or management of cardiovascular diseases. Reducing the ADR by prescribing the most adequate simvastatin dose may promote statin adherence and lower low-density lipoprotein cholesterol levels.
Observations: The results of the genetic testing should be interpreted in the context of the patient’s medical evaluation, family history and racial/ethnic background.
ADDITIONAL INFORMATION FOR HEALTHCARE PROFESSIONALS
FDA recommends that healthcare professionals should:
- Maintain patients on simvastatin 80 mg only if they have been taking this dose for 12 or more months without evidence of muscle toxicity.
- Not start new patients on simvastatin 80 mg.
- Place patients who do not meet their LDL cholesterol (LDL-C) goal on simvastatin 40 mg on alternative LDL-C lowering treatment(s) that provides greater LDL-C
- Follow the recommendations in the simvastatin-containing medicines labels regarding drugs that may increase the risk for muscle injury when used with simvastatin
- Switch patients who need to be initiated on a drug that interacts with simvastatin to an alternative statin with less potential for the drug-drug interaction.
ADDITIONAL INFORMATION FOR PATIENTS
Patients currently taking 80-mg simvastatin-containing medicines should:
- Not stop taking their medicine unless told to by their healthcare professional.
- Review their medical history with their healthcare professional
- Talk to their healthcare professional about any questions or concerns they have about simvastatin-containing medicines.
Adapted from FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for simvastatin to reduce the risk of muscle injury, 6/8/2011
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This article was published on March 19, 2015.