Simvastatin (Zocor) – SLCO1B1
Rationale
This drug gene interaction (DGI) pertains to the interaction between the SLCO1B1 gene and simvastatin. Simvastatin works by inhibiting an enzyme called HMG CoA reductase that the liver uses to make cholesterol. Thus, simvastatin reduces blood cholesterol and helps to prevent atherosclerosis (heart disease). Extensive literature indicates patients with a specific alteration in SLCO1B1 will experience increase systemic exposure to simvastatin and risk muscle toxicity.
Information presented on this page is based on evidence provided by the Clinical Pharmacogenomics Implementation Consortium (CPIC®). CPIC provides peer-reviewed, updated, evidence-based, and freely accessible guidelines for implementing pharmacogenomic results into actionable prescribing decisions for providers. CPIC guidelines include standardized terminology and a systematic grading of evidence and clinical recommendations published in a leading journal (Clinical Pharmacology and Therapeutics).
Genetic Variant Information
The SLCO1B1 gene encodes the solute carrier organic anion transporter family member 1b1 (SLCO1B1) enzyme, which is a drug transporter that helps the body get rid of certain medications through the liver. There are different SLCO1B1 gene versions, or variants, and each has a different effect on how well simvastatin is metabolized in the body. Some variants result in normal function while others function only at an intermediate or low level. See chart below for a description of each phenotype and any implications for treatment.
Phenotype |
Prevalence of phenotype (% of patients) |
Variants (genotype) |
Implication for simvastatin |
|---|---|---|---|
| Low function; homozygous variant or mutant | ~0-6% | An individual carrying TWO decreased function alleles | High myopathy risk |
| Intermediate function; heterozygous | ~11-36% | An individual carrying ONE normal function allele and ONE decrease function allele | Intermediate myopathy risk |
| Normal function; homozygous wild type OR normal | ~55-88% | An individual carrying TWO normal function alleles | Normal myopathy risk |
Patient’s genetic information is reported as a diplotype and this corresponds to a phenotype (i.e. risk). To see an interpretation table assigning functional status by genetic variant, click here to visit CPIC and scroll down to click and download “SLCO1B1 diplotype-phenotype table”. A results interpretation by metabolizer status is located below.
Results Interpretation
Simvastatin is a medicine used to manage several different conditions and your genes can affect how well the drug works. CPIC updates guidelines on how to best use these genetic results to support patient care and has published its current recommendations here.
According to the FDA label, the 80 mg dose should be restricted to patients who have been taking the 80 mg dose chronically (e.g. for 12 months or more). Due to the increased risk of myopathy, including rhabdomyolysis, patients unable to achieve their LDL-C goal should with the 40 mg dose should be placed on an alternative LDL-C lowering treatment.
Quality of Results
Genotyping for SCLO1B1 was performed within a certified DNA laboratory at Vanderbilt University Medical Center that is in full compliance with all guidelines established by the government as regulated by the Centers for Medicare & Medicaid Services under the Clinical Laboratory Improvement Act of 1988. This validated clinical laboratory developed test is carried out with strict adherence to protocols outlined by the College of American Pathology. The performance of the assay is closely monitored and the accuracy of the results is determined to be > 99%.
Supporting Evidence
This link will take you to the main page on the CPIC website relating to SCLO1B1 and simvastatin. On the site, you will find links to the main guideline publication and all supplementary information including a table that reports variant frequencies across different races/ethnic groups, a table that defines genetic variants, and a table that provides a phenotype interpretation (i.e. metabolizer status). Additionally, examples of point of care clinical decision support can be found at the bottom of the page.