Click below to learn more about the use of UGT1A1 genetics in the prescribing of irinotecan.
Irinotecan is a pro-drug, meaning that after being taken orally it must be metabolized to its active form, SN-38, in the liver. SN-38 is then metabolized by a protein, UGT1A1, to its inactive form.
UGT1A1 is the gene that encodes the UGT1A1 liver enzyme. Variation in the UGT1A1 gene results in three metabolizer phenotypes: normal, intermediate, and poor metabolizers. Of these, the poor metabolizer phenotype is associated with decreased UGT1A1 activity and an increased risk of drug toxicity with irinotecan.
Patients who are UGT1A1 poor metabolizers have reduced metabolism of irinotecan’s active metabolite, SN-38, leading to higher drug levels of the active metabolite. This may increase the risk of side effects and toxicity meaning lower doses may be needed. The FDA has provided recommendations to decrease irinotecan doses for UGT1A1 poor metabolizers being prescribed irinotecan.
At UCHealth the use of pharmacogenetics when prescribing irinotecan will occur in patients who meet the following conditions: 1) Provided a blood or saliva sample to the Colorado Biobank, consented for the return of their results, and this sample has undergone genotyping OR the patient is being seen in a clinic which is currently using pharmacogenetic testing as part of standard care (e.g., the UCHealth GI Oncology Clinic). 2) Are prescribed irinotecan.
For patients enrolled in the Biobank, this process takes a minimum of 4-6 weeks but may take several years. Therefore, results will not be available at initial presentation if a patient has not previously enrolled in the Biobank.
If you are a provider AND your patient is a UGT1A1 poor metabolizer, a best practice alert (BPA) will warn you if you attempt to prescribe irinotecan in UCHealth's EHR. This BPA will fire in both the inpatient and ambulatory settings in the UCHealth EHR. The BPA recommends a specific dose reduction when using irinotecan in these patients.
There is patient education text available for UCHealth providers to use in discharge paperwork or the after visit summary (AVS).
Visit our Provider FAQs page here. For immediate questions, secure chat Groups: Pharmacogenomics Service in UCHealth's EHR.