Irinotecan medicinal products: reduction in the starting dose to reduce the risk of irinotecan induced neutropenia and diarrhea in patients with UGT1A1 *28 and *6 variant.

Summary:

•    Patients with reduced UGT1A1 activity (e.g., homozygous for UGT1A1*28 or *6 variants, such as in Gilbert’s syndrome) are at increased risk for severe neutropenia and diarrhea following irinotecan treatment. This risk increases with the irinotecan dose level. 

•    A reduced irinotecan starting dose should be considered for patients that are UGT1A1 poor metabolisers, although a precise dose reduction in starting dose has not been established, especially patients who are administered doses >180 mg/m² or frail patients. Consideration should be given to applicable clinical guidelines for dose recommendations in this patient population. Subsequent doses may be increased based on individual patient tolerance to treatment. 

•    UGT1A1 genotyping can be used to identify patients at increased risk of severe neutropenia and diarrhea, however the clinical utility of pre-treatment genotyping is uncertain, since UGT1A1 polymorphism does not account for all the toxicity seen from irinotecan therapy.