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

last updated 08/10/2011

Summary

For CYP2D6 poor metabolizers (PM), select an alternative to tramadol (not oxycodone or codeine) and be alert for symptoms of insufficient pain relief. For CYP2D6 intermediate metabolizers (IM), be alert for symptoms of insufficient pain relief, and consider dose increase or select an alternative to tramadol (not oxycodone or codeine). For CYP2D6 ultrarapid metabolizers, use a 30% decreased dose and be alert for ADEs, or use an alternative to tramadol (not oxycodone or codeine).

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for tramadol based on CYP2D6 genotypes [Article:21412232]. For PM and IM genotypes, they recommend selecting an alternative drug (not oxycodone or codeine) and/or being extra alert to symptoms of insufficient pain relief. For UM genotypes, they recommend using a 30% decreased dose and being alert for ADEs, or using an alternative drug (not oxycodone or codeine).

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
PM (two inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) alleles)Select alternative drug-not oxycodone or codeine- or be alert to symptoms of insufficient pain relief.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): short-lived discomfort (< 48 hr) without permanent injury: e.g. reduced decrease in resting heart rate; reduction in exercise tachycardia; decreased pain relief from oxycodone; ADE resulting from increased bioavailability of atomoxetine (decreased appetite, insomnia, sleep disturbance etc.); neutropenia > 1.5x109/l; leucopenia > 3.0x109/l; thrombocytopenia > 75x109/l; moderate diarrhea not affecting daily activities; reduced glucose increase following oral glucose tolerance test.
IM (two decreased-activity (*9, *10, *17, *29, *36, *41) alleles or carrying one active (*1, *2, *33, *35) and one inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) allele, or carrying one decreased-activity (*9, *10, *17, *29, *36, *41) allele and one inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) allele)Be alert to decreased efficacy. Consider dose increase. If response is still inadequate, select alternative drug- not oxycodone or codeine-or be alert to symptoms of insufficient pain relief.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): short-lived discomfort (< 48 hr) without permanent injury: e.g. reduced decrease in resting heart rate; reduction in exercise tachycardia; decreased pain relief from oxycodone; ADE resulting from increased bioavailability of atomoxetine (decreased appetite, insomnia, sleep disturbance etc); neutropenia > 1.5x109/l; leucopenia > 3.0x109/l; thrombocytopenia > 75x109/l; moderate diarrhea not affecting daily activities; reduced glucose increase following oral glucose tolerance test.
UM (a gene duplication in absence of inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) or decreased-activity (*9, *10, *17, *29, *36, *41) alleles)Reduce dose by 30% and be alert to ADEs (e.g., nausea, vomiting, constipation, respiratory depression, confusion, urinary retention) or select alternative drug (e.g., acetaminophen, NSAID, morphine-not oxycodone or codeine).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.
  • *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