Overview
11 DESCRIPTION DUVYZAT (givinostat) oral suspension contains givinostat hydrochloride monohydrate, a histone deacetylase inhibitor. Givinostat hydrochloride monohydrate is designated chemically as: [6-(diethylaminomethyl)naphthalen-2-yl]methyl[4(hydroxycarbamoyl) phenyl] carbamate hydrochloride monohydrate. The molecular formula is C 24 H 27 N 3 O 4 •HCl•H 2 O and the molecular weight is 475.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action DUVYZAT is a histone deacetylase inhibitor. The precise mechanism by which DUVYZAT exerts its effect in patients with DMD is unknown. 12.2 Pharmacodynamics Muscle Fat Fraction as Assessed by MR Spectroscopy The percentage of fat fraction present in the vastus lateralis muscles (VLM) of the thigh was measured in Study 1 [see Clinical Studies (14) ] using magnetic resonance spectroscopy. At 18 months, for the patients with VLM fat fraction baseline in the range of >5% to ≤30%, a mean increase (absolute difference from baseline levels) of VLM fat fraction was 7.48% in the DUVYZAT-treated patients compared to a 10.89% increase in patients who received placebo. Cardiac Electrophysiology The largest mean increase in QTc interval of 13.
Indications
- 1 INDICATIONS AND USAGE DUVYZAT is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 6 years of age and older. DUVYZAT is a histone deacetylase inhibitor indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 6 years of age and older. ( 1 )
Common Doses
- 22.2 mg
- 2.5 mL
- 31 mg
- 3.5 mL
Dosage
2 DOSAGE AND ADMINISTRATION Obtain and evaluate baseline platelet counts and triglycerides prior to initiation of DUVYZAT. Do not initiate DUVYZAT in patients with a platelet count less than 150 x 10^9/L. ( 2.1 , 5.1 , 5.2 ) The dosage of DUVYZAT is based on patient’s body weight. ( 2.2 ) Administer orally twice daily with food. ( 2.2 ) Dosage modifications may be needed for decreased platelet counts, diarrhea, increased triglycerides, or QTc prolongation. ( 2.3 , 5.1 , 5.2 , 5.3 , 5.4 ) 2.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS 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, hypertriglyceridemia, and pyrexia. ( 6.
Interactions
- 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 of DUVYZAT on Other Drugs CYP3A4 Sensitive Substrates Givinostat is a weak intestinal CYP3A4 inhibitor [see Clinical Pharmacology (12.3) ] .