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Published on: May 15, 2019
Effects of methimazole on the elimination of irinotecan
Jessica M van der Bol1, Theo J Visser, Walter J Loos
1Department of Medical Oncology, Erasmus MC University Hospital, Daniel den Hoed Cancer Center, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
Purpose:
To study the possible pharmacokinetic and pharmacodynamic interactions between irinotecan and methimazole.
Methods:
A patient treated for colorectal cancer with single agent irinotecan received methimazole co-medication for Graves' disease. Irinotecan pharmacokinetics and side effects were followed during a total of four courses (two courses with and two courses without methimazole).
Results:
Plasma concentrations of the active irinotecan metabolite SN-38 and its inactive metabolite SN-38-Glucuronide were both higher (a mean increase of 14 and 67%, respectively) with methimazole co-medication, compared to irinotecan monotherapy. As a result, the mean SN-38 glucuronidation rate increased with 47% during concurrent treatment. Other possible confounding factors did not change over time. Specific adverse events due to methimazole co-treatment were not seen.
Conclusions:
Additional in vitro experiments suggest that these results can be explained by induction of UGT1A1 by methimazole, leading to higher SN-38G concentrations. The prescribed combination of these drugs may lead to highly toxic intestinal SN-38 levels. We therefore advise physicians to be very careful in combining methimazole with regular irinotecan doses, especially in patients who are prone to irinotecan toxicity.
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