Dutch Pharmacogenetics Working Group (DPWG) guideline information
for nortriptyline and CYP2D6

last updated 08/10/2011

Summary

The Dutch Pharmacogenetics Working Group Guideline for nortriptyline recommends to reduce the dose for CYP2D6 poor or intermediate metabolizer patients. For CYP2D6 ultrarapid metabolizers, select an alternative drug or increase the dose by 60%. Monitoring of nortriptyline and 10-hydroxynortriptyline plasma concentrations is recommended.

Annotation

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.

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
PM (2 inactive alleles)Reduce dose by 60% and monitor nortriptyline + 10-hydroxynortriptyline plasma concentrations.Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Clinical effect (S): long-standing discomfort (48-168 hr) without permanent injury e.g. failure of therapy with tricyclic antidepressants, atypical antipsychotic drugs; extrapyramidal side effects; parkinsonism; ADE resulting from increased bioavailability of tricyclic antidepressants, metoprolol, propafenone (central effects e.g. dizziness); INR 4.5-6.0; neutropenia 1.0-1.5x109/l; leucopenia 2.0-3.0x109/l; thrombocytopenia 50-75x109/l.
IM (2 decreased activity alleles, or 1 active and 1 inactive allele, or 1 decreased activity and 1 inactive allele)Reduce dose by 40% and monitor nortriptyline + 10-hydroxynortriptyline plasma concentrations.Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Clinical effect (S): long-standing discomfort (48-168 hr) without permanent injury e.g. failure of therapy with tricyclic antidepressants, atypical antipsychotic drugs; extrapyramidal side effects; parkinsonism; ADE resulting from increased bioavailability of tricyclic antidepressants, metoprolol, propafenone (central effects e.g. dizziness); INR 4.5-6.0; neutropenia 1.0-1.5x109/l; leucopenia 2.0-3.0x109/l; thrombocytopenia 50-75x109/l.
UM (gene duplication in absence of inactive or decreased activity alleles)Select alternative drug (e.g., citalopram, sertraline) or increase dose by 60% and monitor nortriptyline + 10-hydroxynortriptyline plasma concentrations.Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Clinical effect (S): long-standing discomfort (48-168 hr) without permanent injury e.g. failure of therapy with tricyclic antidepressants, atypical antipsychotic drugs; extrapyramidal side effects; parkinsonism; ADE resulting from increased bioavailability of tricyclic antidepressants, metoprolol, propafenone (central effects e.g. dizziness); INR 4.5-6.0; neutropenia 1.0-1.5x109/l; leucopenia 2.0-3.0x109/l; thrombocytopenia 50-75x109/l.
Allele TypeAlleles
active*1, *2, *33, *35
decreased activity*9, *10, *17, *29, *36, *41
inactive*3-*8, *11-*16, *19-*21, *38, *40, *42
  • *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

DPWG Guideline publication

Total publications: 1

Reference
1. Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, Nijenhuis M, de Boer A, Grandia L, Maitland-van der Zee A H, Mulder H, Rongen G A P J M, van Schaik R H N, Schalekamp T, Touw D J, van der Weide J, Wilffert B, Deneer V H M, Guchelaar H-J. PubMed

Guideline History