Annotation of Dutch Pharmacogenetics Working Group (DPWG) guideline information
for paroxetine and CYP2D6

last updated 08/10/2011

Summary

Select an alternative drug rather than paroxetine for CYP2D6 ultra metabolizer patients.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for paroxetine based on CYP2D6 genotype [Article:21412232]. They suggest using an alternative drug for ultra metabolizers.

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
PM (2 inactive alleles)None.Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Minor clinical effect (S): QTc prolongation (<450 ms men, <470 ms women); INR increase < 4.5. Kinetic effect (S).
IM (2 decreased activity alleles, or 1 active and 1 inactive allele, or 1 decreased activity and 1 inactive allele)None.Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Minor clinical effect (S): QTc prolongation (<450 ms men, <470 ms women); INR increase < 4.5. Kinetic effect (S).
UM (gene duplication in absence of inactive or decreased activity alleles)Insufficient data to allow calculation of dose adjustment. Select alternative drug (e.g., citalopram, sertraline).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.
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 quality."
  • S: statistically significant difference.

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