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

last updated 08/10/2011

Summary

Reduce the dose of propafenone by 70% for CYP2D6 poor metabolizers, and adjust propafenone dose according to plasma concentrations or use an alternative drug for CYP2D6 intermediate and ultrarapid metabolizers.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for propafenone based on CYP2D6 genotype [Article:21412232]. They suggest a reduced dose for poor metabolizers, and adjusting dose according to plasma concentrations or using an alternative drug for intermediate and ultrarapid metabolizers.

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
PM (2 inactive alleles)Reduce dose by 70%, record ECG, monitor plasma concentrationPublished 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 1.0-1.5x10 9/l; leucopenia 2.0-3.0x10 9/l; thrombocytopenia 50-75x10 9/l
IM (2 decreased activity alleles, or 1 active and 1 inactive allele, or 1 decreased activity and 1 inactive allele)Insufficient data to allow calculation of dose adjustment. Adjust dose in response to plasma concentration and record ECG or select alternative drug (e.g., sotalol, disopyramide, quinidine, amiodarone)Published controlled studies of moderate 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 male, <470 ms female); 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. Adjust dose in response to plasma concentration and record ECG or select alternative drug (e.g., sotalol, disopyramide, quinidine, amiodarone)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 (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x10 9/l; leucopenia 1.0-2.0x10 9/l; thrombocytopenia 25-50x10 9/l; severe diarrhea
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.

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