The enzyme that disposes of its active metabolite is the same one behind Gilbert syndrome — a harmless quirk of bilirubin that turns into a dosing problem the moment this drug is prescribed.
Irinotecan is a mainstay of colorectal cancer treatment, and the enzyme that disposes of its active metabolite is the same one behind Gilbert syndrome — a harmless inherited cause of mildly raised bilirubin that perhaps one person in ten carries in the double dose. Those people clear the active metabolite slowly and are at higher risk of severe neutropenia and diarrhoea, which is why the US prescribing information warns about UGT1A1*28 homozygotes and a reduced starting dose is commonly used. This is not a CPIC guideline: CPIC rates the pair level A on the strength of the evidence, but the guidance in use comes from the drug label and from the Dutch pharmacogenetics working group. Testing before the first cycle is routine in some centres and not in others.
US prescribing information for irinotecan (CAMPTOSAR); Dutch Pharmacogenetics Working Group recommendation for UGT1A1 and irinotecan. CPIC lists the pair at level A but has not published a guideline for it.
These are the positions in your own file that carry the genes above. Not every gene in a guideline is one we report — where that is the case the gene appears above without a variant here, and the note says so.
UGT1A1 · rs887829
Read more →UGT1A1 · rs6742078
Read more →UGT1A1 · rs11563251
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