Table 2.

Dosing recommendations for simvastatin, when rs4149056 genotype (or phenotype) is available

Genotype at rs4149056	Anticipated phenotype	Implications for simvastatin	Dosing recommendations for simvastatina	Classification of the recommendationb
TT	Normal activity	Normal myopathy risk	FDA recommends against 80 mg (unless already tolerated 12 months). Prescribe desired starting dose and adjust doses of simvastatin based on disease-specific guidelines.	Strong
TC	Intermediate activity	Intermediate myopathy risk	FDA recommends against 80 mg. Consider a lower dose; if suboptimal efficacy, consider an alternative statin.	Strong
CC	Low activity	High myopathy risk	FDA recommends against 80 mg. Prescribe a lower dose or consider an alternative statin; consider routine CK surveillance.	Strong

CK, creatine kinase.

^aIn all cases, the potential for drug–drug interaction should be evaluated prior to initiating a prescription.

^bSee Supplementary Materials (text section entitled “Levels of Evidence”) online for additional details regarding the three-tiered system used to grade the quality of evidence. Further information is available within ref. 41.