Simvastatin and SLCO1B1

Simvastatin (Zocor® and generic products) is a prodrug, which means that it is converted into its active form after it enters the body. This medication is used to manage and treat high cholesterol levels. Simvastatin also aids in the prevention of coronary events such as heart attacks or strokes.

Once it enters the body, simvastatin is transported into the liver. In the liver cells, simvastatin is converted into its active form, which then inhibits an enzyme that is essential to the formation of cholesterol in the body. Overall, this leads to a decrease in total cholesterol and other forms of cholesterol. This reduces a patient’s risk for experiencing a heart attack because, over time, it reduces blockage in the arteries.

The gene of interest is SLCO1B1, and this gene creates a membrane transporter (OATP1B1). This transporter is responsible for moving compounds, like simvastatin, into the cells of the liver so that it can be converted into its active form.

Variations of the gene, SLCO1B1, have been linked to an increased risk of muscle pain and damage known as myopathy while taking simvastatin. Approximately 11% to 42% of the population possesses a variation of this gene, and this leads to reduced or little presence of the active drug in the liver. The people who have this variation can be referred to as “intermediate” or “poor utilizers” of simvastatin. Approximately 55% to 88% of the population will possess the functional gene, meaning that they are not at an increased risk for myopathy, and they will be exposed to the active drug for an average amount of time. It is recommended that those people that are “intermediate” or “poor utilizers” of simvastatin either start at a lower dose or switch to using an alternative drug which is less likely to increase the risk for a myopathy.

A 45-year old Caucasian male, John, visits his primary care provider for an annual check-up. The patient is obese, a smoker, and diagnosed with type II diabetes. He does not know anything about his SLCO1B1 type. Upon completion of a lipid panel test, John is diagnosed with hyperlipidemia (high cholesterol) and is considered at very high risk for cardiovascular disease. The patient is started on simvastatin for primary prevention. After a week of taking simvastatin, John begins to experience muscle aches and stops taking the medication. One month later, John starts to notice that he gets tired easily and experiences cardiac pain (angina) upon exertion. He rushes to the emergency department. John is diagnosed with chronic stable angina and, upon completion of a blood test, his cholesterol levels are subsequently higher than they previously were. John admits that he had stopped taking the medication after one week because of muscle pain. John consents to genetic testing after this scare and it becomes evident that he is a poor utilizer of simvastatin and should have been prescribed a different drug or a lower dose of simvastatin to reduce his risk of myopathy.

A similar patient, Charles, goes to visit his primary care provider, as well, for an annual check-up around the same time John did. Charles, however, is seeing a physician at a large teaching hospital that is at the forefront of implementing new healthcare technologies. Charles is diagnosed with hyperlipidemia and considered at very high risk for cardiovascular disease. Prior to prescribing any medications, Charles’ physician reviewed his genotype which the hospital offers to all patients prior to starting treatment. The physician notices that Charles is at a drastically increased risk for myopathy if simvastatin is used. The physician knows that this increase in risk is only associated with simvastatin use and prescribes a similar drug to treat Charles’ hyperlipidemia.

The links below provide access to important articles and information relative to simvastatin. The links are to external websites and will be checked regularly for consistency.

• Simvastatin Prescribing Information
• Simvastatin Pharmacogenomic Dosing Guidelines
• Pharmacogenomics Knowledge Base: Simvastatin

Brunham LR, Lansberg PJ, Zhang L, et al. Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin. Pharmacogenomics J. 2012 Jun;12(3):233-37.

DailyMed [Internet]. Bethesda (MD): U.S. National Library of Medicine; c1993-2015. Simvastatin; [cited 2015 Jun 10]; [about 3 screens]. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fdbfe194-b845-42c5-bb87-a48118bc72e7/.

Facts and Comparisons [Internet]. St. Louis (MO): Wolters Kluwer Health, Inc. 2005 March [cited 2013 Dec 9]. Available from: http://online.factsandcomparisons.com/index.aspx/.

PharmGKB [Internet]. Stanford (CA): U.S. Department of Health and Human Services; c2001-2013. SLCO1B1; [cited 2013 Dec 9]; [about 2 screens]. Available from: https://www.pharmgkb.org/gene/PA134865839/.

Ramsey LB, Johnson SG, Caudle KE, et al. The Clinical Pharmacogenetics Implementation cConsortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther. 2014;96(4):423-428.