DUVYZAT

Givinostat exhibits linear kinetics with the studied dose range. Systemic exposure to givinostat was dose-proportional across the therapeutic dose range. Steady-state concentrations are achieved within 5 to 7 days after twice daily dosing. An accumulation of less than 2-fold was observed for givinostat after twice daily administration.

AbsorptionAbsolute bioavailability was not determined. The time to maximum plasma concentrations is about 2 to 3 hours after oral administration. Effect of Food ...

The effectiveness of DUVYZAT for the treatment of Duchenne muscular dystrophy (DMD) was evaluated in a randomized, double-blind, placebo-controlled 18-month study (Study 1; NCT02851797). A total of 179 patients were randomized 2:1 to receive either DUVYZAT (n = 118) or placebo (n = 61). A weight-based dose regimen was applied [see Dosage and Administration (2.2) ] . The study included male patients 6 years of age and older with a confirmed diagnosis of DMD who were ambulatory and on a stable dosage of corticosteroids. At baseline, patients had a mean age of 9.8 years, 90% were White, 3% were A...

The following clinically significant adverse reactions are described below and elsewhere in the labeling: Hematological Changes [see Warnings and Precautions (5.1) ] Increased Triglycerides [see Warnings and Precautions (5.2) ] Gastrointestinal Disturbances [see Warnings and Precautions (5.3) ] QTc Prolongation [see Warnings and Precautions (5.4) ] Most common adverse reactions (≥10% in DUVYZAT-treated patients) are diarrhea, abdominal pain, thrombocytopenia, nausea/vomiting, hypertriglyceridemi...

None. None. ( 4 )

Hematological Changes: DUVYZAT can cause dose-related thrombocytopenia and other signs of myelosuppression, including anemia and neutropenia. Monitor platelets; dosage adjustment or discontinuation may be needed. ( 2.3 , 5.1 ) Increased Triglycerides: An increase in triglycerides can occur; dosage modification may be needed. Discontinuation may be needed. ( 2.3 , 5.2 ) Gastrointestinal Disturbances: Adjust dosage if moderate or severe diarrhea occurs. Antiemetics or antidiarrheal medications may...

7 DRUG INTERACTIONS Closely monitor when DUVYZAT is used in combination with an oral CYP3A4 sensitive substrate or a sensitive substrate of the OCT2 transporter, for which a small change in substrate plasma concentration may lead to serious toxicities. ( 7.1 ) Avoid concomitant use with other drugs that prolong the QTc interval; monitor ECG if concomitant use cannot be avoided. ( 7.2 ) 7.1 Effect ...