UGT1A1 genotype testing for irinotecan: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI-PGx).

UK (CERSI-PGx) guideline recommending UGT1A1 genotyping before irinotecan and a 30% dose reduction at Cycle 1 in poor metabolisers

Irinotecan is hydrolysed to its active metabolite SN-38, inactivated mainly by UGT1A1, whose expression is polymorphic. Poor metabolisers (two activity-reducing variants) have an increased risk of toxicity. This UK Centre of Excellence CERSI-PGx guideline recommends UGT1A1 pharmacogenetic testing for any patient about to receive irinotecan for an epithelial malignancy, where testing is available. It advises a 30% dose reduction at the first cycle in poor metabolisers.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A directly actionable recommendation, aligned with the established UGT1A1–irinotecan toxicity link and consistent with international guidelines (CPIC/DPWG). Its value is mainly in anchoring preemptive genotyping practice within a clear regulatory framework for prescribers.

Analysis by Dr Thibaut Benquey