Annotation of DPWG Guideline for nortriptyline and CYP2D6

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Summary

The Dutch Pharmacogenetics Working Group Guideline for nortriptyline recommends a dose reduction for CYP2D6 poor or intermediate metabolizer patients. For CYP2D6 ultrarapid metabolizers, select an alternative drug or use 1.7 times the standard dose. Monitoring of nortriptyline and 10-hydroxynortriptyline plasma concentrations is recommended.

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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.

November 2018 Update

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for nortriptyline based on CYP2D6 genotype. They recommend a dose increase or use of an alternative antidepressant in CYP2D6 ultrarapid metabolizers (UMs) and a dose reduction in CYP2D6 poor metabolizers (PMs). Monitoring of nortriptyline and Z-10-hydroxynortriptyline plasma concentrations is also recommended.

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 nortriptyline and CYP2D6:

The Dutch Pharmacogenetics Working Group considers genotyping before starting nortriptyline to be potentially beneficial for the prevention of side effects and for drug efficacy. Genotyping can be considered on an individual patient basis. If, however, the genotype is available, the Dutch 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 nortriptyline based on CYP2D6 genotype [Article:21412232]. They recommend reducing the dose for poor and intermediate metabolizer patients and selecting an alternative drug or increasing the dose for ultra metabolizers.

  • *See Methods or [Article:18253145] for definition of "good" and "moderate" quality.
  • S: statistically significant difference.
  • Please see attached PDF for detailed information about the evaluated studies: Nortriptyline CYP2D6

PharmGKB ID

PA166104961