Drug Interactions between givosiran and vorasidenib

GENERALLY AVOID: Concomitant use with moderate inhibitors of CYP450 1A2 may increase the plasma concentrations of vorasidenib, which is primarily metabolized by the isoenzyme, and the risk for potential adverse reactions, such as hepatotoxicity. When coadministered with ciprofloxacin, a moderate CYP450 1A2 inhibitor, vorasidenib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.3- and 2.5-fold, respectively.

MANAGEMENT: Concomitant use of vorasidenib with moderate CYP450 1A2 inhibitors should generally be avoided. If concomitant use with moderate CYP450 1A2 inhibitors cannot be avoided, clinical and laboratory monitoring is recommended for the development of increased adverse reactions. Liver function tests should be monitored prior to initiation of treatment and regularly during treatment in accordance with the product labeling. Patients should be advised to seek medical attention if they experience signs and symptoms of hepatotoxicity, such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and/or jaundice. If an interaction is suspected, vorasidenib treatment should be discontinued, interrupted, or the dosage reduced according to the manufacturer's recommendations.