Annotation of DPWG Guideline for metoprolol and CYP2D6
Summary
For CYP2D6 poor and intermediate metabolizer patients, if a GRADUAL REDUCTION in HEART RATE is desired, or in the event of SYMPTOMATIC BRADYCARDIA, use smaller steps in dose titration and/or prescribe no more than 25% or 50% of the standard dose, respectively. For CYP2D6 ultra metabolizers, use the maximum dose for the relevant indication as a target dose, and if the effectiveness is still insufficient: increase the dose based on effectiveness and side effects to 2.5 times the standard dose or select an alternative drug.
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Annotation
Read more about how PharmGKB curates DPWG guidelines using extra information provided by DPWG to enable the interactive genotype tool above.
February 2022 Update
The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has made some minor changes to the text of their recommendations for CYP2D6 intermediate or poor metabolizers taking metoprolol. The table below has been updated to reflect this but the recommendations themselves have not changed. See the DPWG February 2022 guidelines.
November 2018 Update
The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for metoprolol based on CYP2D6 genotype. For CYP2D6 poor and intermediate metabolizer patients, if a GRADUAL REDUCTION in HEART RATE is desired, or in the event of SYMPTOMATIC BRADYCARDIA, increase the dose in smaller steps and/or prescribe no more than 25% or 50% of the standard dose, respectively. For CYP2D6 ultra metabolizers, use the maximum dose for the relevant indication as a target dose, and if the effectiveness is still insufficient: increase the dose based on effectiveness and side effects to 2.5 times the standard dose or select an alternative drug.
Wording in table taken from the Dutch guidelines November 2018 update
Read for more information about this recommendation, Read about gene information from DPWG
Preemptive genotyping
Excerpts from the DPWG risk analysis document for metoprolol and CYP2D6:
The KNMP Pharmacogenetics Working Group considers genotyping before starting metoprolol to be potentially beneficial for the prevention of side effects and drug effectiveness. Genotyping can be considered on an individual patient basis. If, however, the genotype is available, the KNMP Pharmacogenetics Working Group recommends adhering to the gene-drug guideline.
Read more about how DPWG assigns their recommendations for preemptive genotyping.
2011 Guideline
The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for metoprolol based on CYP2D6 genotype [Article:21412232]. They recommend either selecting another drug or dose reduction for poor and intermediate metabolizer patients, with dose titration for ultra metabolizers.