Dutch Pharmacogenetics Working Group (DPWG) guideline information
for thioguanine and TPMT

last updated 08/10/2011

Summary

Select an alternative drug rather than thioguanine for intermediate and poor TPMT metabolizers.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for thioguanine based on TPMT genotype [Article:21412232]. They recommend selecting an alternative drug for patients carrying inactive alleles.

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
IM (one inactive allele: *2, *3, *4-*18)Select alternative drug. Insufficient data to allow calculation of dose adjustment.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 0.5-1.0x109/l; leucopenia 1.0-2.0x109/l; thrombocytopenia 25-50x109/l; severe diarrhea.
PM (two inactive alleles: *2, *3, *4-*18)Select alternative drug. Insufficient data to allow calculation of dose adjustment.Published case reports, well documented, and having relevant pharmacokinetic or clinical endpoints. Well documented case series.Clinical effect (S): death; arrhythmia; unanticipated myelosuppression.
  • *See Methods or [Article:18253145] for definition of "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