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

last updated 08/10/2011

Summary

Reduce haloperidol dose by 50% or select an alternative drug for CYP2D6 poor metabolizer (PM) genotype patients.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for haloperidol based on CYP2D6 genotype [Article:21412232]. They recommend dose reduction for poor metabolizer patients.

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
PM (2 inactive alleles)Reduce dose by 50% or select alternative drug (e.g., pimozide, flupenthixol, fluphenazine, quetiapine, olanzapine, clozapine).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.
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 women, <470 ms men); 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 adjustent. Be alert to decreased haloperidol plasma concentration and adjust maintenance dose in response to haloperidol plasma concentration or select alternative drug (e.g., pimozide, flupenthixol, fluphenazine, quetiapine, olanzapine, clozapine).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