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Last Updated: 6 months ago

Possible Interaction: Thiamine and Fedratinib

supplement:

Thiamine

Research Papers that Mention the Interaction

In vitro studies indicate that fedratinib potently inhibits the carrier-mediated uptake and transcellular flux of thiamine in Caco-2 cells, suggesting that oral absorption of dietary thiamine is significantly compromised by fedratinib dosing.
Inhibition of thiamine uptake appears unique to fedratinib and is not shared by marketed JAK inhibitors, and this observation is consistent with the known structure-activity relationship for the binding of thiamine to its transporters.
Drug Metabolism and Disposition  •  2014  |  View Paper
Fedratinib inhibited thiamine uptake into Caco-2 cells (IC50 = 0.940 µM) and THTR-2 (IC50 = 1.36 µM) and, to a lesser extent, THTR-1 (IC50 = 7.10 µM) overexpressing cells.
Inhibition of thiamine transporters has been proposed as a putative mechanism for the observation of Wernicke’s encephalopathy and subsequent termination of clinical development of fedratinib , a Janus kinase inhibitor (JAKi).
Drug Metabolism and Disposition  •  2017  |  View Paper
Subsequent analyses have suggested that fedratinib is a potential inhibitor of transporter-dependent thiamine uptake and transcellular flux of thiamine , demonstrated in-vitro in the Caco-2 cell line (Zhang et al, 2014).
British journal of haematology  •  2017  |  View Paper
Suspected cases of Wernicke’s encephalopathy were reported during fedratinib trials in ~1% of patients; thiamine levels should be monitored before and during fedratinib treatment as medically indicated.
Leukemia  •  2020  |  View Paper