Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between SLCO1B1 and statins and CYP2C9 and sulfonylureas

Abstract

Aligned with the mission of the Dutch Pharmacogenetics Working Group (DPWG) to promote the implementation of pharmacogenetics (PGx), this guideline is specifically designed to optimize pharmacotherapy of cholesterol lowering medication (statins) and glucose lowering medication (sulfonylureas). The SLCO1B1 c.521 T > C variant reduces the activity of the SLCO1B1 transporter involved in statin transport out of the blood into the liver. High blood concentrations of statins increase the risk of serious myopathy. For simvastatin, the DPWG recommends choosing an alternative in homozygotes for these gene variant and to preferably choose an alternative in heterozygotes. For atorvastatin, the DPWG recommends to preferably choose an alternative in carriers of this gene variant having additional risk factors for myopathy. For rosuvastatin, the DPWG recommends keeping the dose as low as possible in carriers of this gene variant with additional risk factors. No therapy adjustment is required for fluvastatin and pravastatin in carriers of this gene variant. Gene variants can diminish the activity of the enzyme CYP2C9, that converts sulfonylurea to less effective metabolites. Although CYP2C9 gene variants may lead to increased levels of glibenclamide, gliclazide, glimepiride, and tolbutamide, no therapy adjustments are required in patients with these variants. The main reason is that there was either no negative clinical effect or an increase in hypoglycemic, which is of less importance than the increase in effectiveness it signals. The DPWG classifies pre-emptive SLCO1B1 testing as 'essential' for simvastatin 80 mg/day, 'beneficial' for simvastatin up to 40 mg/day, and 'potentially beneficial' for atorvastatin and rosuvastatin.