Simvastatin response

Statins are among the most commonly prescribed drugs in the world to treat hypercholesterolemia and prevent cardiovascular diseases. They effectively lower cholesterol levels by inhibiting the HMG-CoA reductase to reduce cholesterol synthesis. Though well tolerated in general, the most common statin side effect is muscle pain. The symptoms range from mild muscle pain to fatal rhabdomyolysis, especially when statins are administered at higher doses and with certain other medications. A common coding SNP in the SLCO1B1 gene, rs4149056 or SLCO1B1*5, has been significantly associated with a marked increase in systemic exposure to simvastatin and risk of muscle toxicity. The overall effect size and significance of this association are striking for simvastatin compared to other statins. Patients with this specific variant in SLCO1B1 (a transporter of simvastatin) may require a lower simvastatin dose or consider an alternative statin as compared to patients who do not have this variant, and may consider routine creatine kinase (CK) surveillance. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has published a clinical dosing guideline for SLCO1B1 genotype and simvastatin dosing in Clinical Pharmacology & Therapeutics. This guideline is available on the PharmGKB website.

PharmGKB