Active Ingredient: KETOCONAZOLE
Ketoconazole directly inhibits the IKr potassium current and alters hERG channel trafficking with an IC50 of 1.92 uM, which is readily exceeded by clinical therapeutic plasma concentrations. In healthy volunteers, ketoconazole induces an average individualized QTc increase of approximately 7 to 7.5 ms. In addition to direct repolarization delay, ketoconazole is an exceptionally potent CYP3A4 inhibitor, causing dramatic exposure increases of co-administered drugs that prolong the QT interval. Multiple fatal cases of Torsades de Pointes have occurred through this pharmacokinetic mechanism. Strict contraindications apply to co-administration with other QT-prolonging CYP3A4 substrates.
https://doi.org/10.1007/s12281-014-0183-0, https://doi.org/10.1111/j.1540-8167.2005.00299.x