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

last updated 08/10/2011

Summary

Select an alternative drug or reduce the initial dose of azathioprine for patients carrying one or two inactive TPMT alleles.

Annotation

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

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
IM (one inactive allele: *2, *3, *4-*18)Select alternative drug or reduce dose by 50%. Increase dose in response of hematologic monitoring and efficacy.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): Failure of lifesaving therapy e.g. anticipated myelosuppression; prevention of breast cancer relapse; arrhythmia; neutropenia < 0.5x109/l; leucopenia < 1.0x109/l; thrombocytopenia < 25x109/l; life-threatening complications from diarrhea.
PM (two inactive alleles: *2, *3, *4-*18)Select alternative drug or reduce dose by 90%. Increase dose in response of hematologic monitoring and efficacy.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): death; arrhythmia; unanticipated myelosuppression.
  • *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