Annotation of Dutch Pharmacogenetics Working Group (DPWG) guideline information
for irinotecan and UGT1A1

last updated 08/10/2011

Summary

Reduce the starting dose of irinotecan for UGT1A1*28 homozygous patients receiving more than 250 mg/m2.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for irinotecan based on UGT1A1 genotype [Article:21412232]. They recommend reducing the dose for *28 homozygous patients receiving more than 250 mg/m2.

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
*1/*28None.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): death; arrhythmia; unanticipated myelosuppression.
*28/*28Dose >250mg/m2: reduce initial dose by 30%. Increase dose in response to neutrophil count. Dose <=250mg/m2: no 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): 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.

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