Drug Interaction Report

MONITOR: Givinostat may increase the systemic exposure and effects of organic cation transporter 2 (OCT2) substrates via inhibition of this renal uptake transporter. During a phase 3 study of givinostat, an average increase in the OCT2 substrate creatinine of 4.76 micromol/L (0.05 mg/dL) from baseline was observed within the first 2 months of treatment. This change in creatinine led the study investigators to conclude that givinostat is a weak inhibitor of OCT2.

MANAGEMENT: Caution and clinical monitoring are advised if givinostat is used in combination with an organic cation transporter 2 (OCT2) substrate, particularly a sensitive substrate for which a small change in the substrate's plasma concentration could result in serious toxicity. The labeling of the substrate should be consulted for specific monitoring, dose adjustment, and discontinuation recommendations should adverse reactions result from this combination.

ADJUST DOSING INTERVAL: Food increases the systemic exposure of givinostat. An open-label, randomized, crossover, single dose food effect study conducted in 12 healthy males used givinostat liquid filled capsules. Subjects received a single oral dose of givinostat (100 mg) in the fasting state or after a high-fat standard meal, with a washout period of at least 1 week in between. The high-fat standard meal resulted in an increase in systemic exposure (AUC) and maximum plasma concentration (Cmax) of about 40% and 23%, respectively, when compared to the fasted state. Additionally, the time to maximum concentration (Tmax) was delayed slightly from 2 to 3 hours.

MANAGEMENT: Givinostat should be administered with food to increase its absorption. In the case of the oral suspension, this can also help mask its bitter taste.