CPIC Guideline: CYP2D6 Genotyping for Metoprolol Dose Adjustment
This CPIC guideline evaluates pharmacogenomic evidence for six genes and beta-blocker therapy, finding high-level evidence only for CYP2D6 and metoprolol. Poor metabolisers experience significantly greater drug exposure and exaggerated heart rate reduction, warranting dose adjustment or alternative agent selection. For clinical laboratories, the guideline confirms that CYP2D6 testing results are actionable for metoprolol but not yet for other beta-blockers.
The original study
Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy.
- Authors
- Duarte JD, Thomas CD, Lee CR, Huddart R, Agundez JAG, Baye JF, et al.
- Journal
- Clinical pharmacology and therapeutics
- Type
- Journal Article, Practice Guideline, Systematic Review
- PMID
- 38951961
Original abstract
Beta-blockers are widely used medications for a variety of indications, including heart failure, myocardial infarction, cardiac arrhythmias, and hypertension. Genetic variability in pharmacokinetic (e.g., CYP2D6) and pharmacodynamic (e.g., ADRB1, ADRB2, ADRA2C, GRK4, GRK5) genes have been studied in relation to beta-blocker exposure and response. We searched and summarized the strength of the evidence linking beta-blocker exposure and response with the six genes listed above. The level of evidence was high for associations between CYP2D6 genetic variation and both metoprolol exposure and heart rate response. Evidence indicates that CYP2D6 poor metabolizers experience clinically significant greater exposure and lower heart rate in response to metoprolol compared with those who are not poor metabolizers. Therefore, we provide therapeutic recommendations regarding genetically predicted CYP2D6 metabolizer status and metoprolol therapy. However, there was insufficient evidence to make therapeutic recommendations for CYP2D6 and other beta-blockers or for any beta-blocker and the other five genes evaluated (updates at www.cpicpgx.org).