Givinostat

DUVYZAT is a histone deacetylase inhibitor. The precise mechanism by which DUVYZAT exerts its effect in patients with DMD is unknown.

• 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.

• None. None.contraindicated

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 ) 2.1 Recommended Evaluation and Testing Before Initiation of DUVYZAT Obtain and evaluate baseline platelet counts and triglycerides prior to initiation of DUVYZAT [see Warnings and Precautions (5.1 , 5.2) ] . Do not initiate DUVYZAT in patients with a platelet count less than 150 x 10 9 /L. Monitor platelet counts and triglycerides as recommended during treatment to determine if dosage modifications are needed [see Dosage and Administration (2.3) ]. In addition, in patients with underlying cardiac disease or taking concomitant medications that cause QT prolongation, obtain ECGs when initiating treatment with DUVYZAT, during concomitant use, and as clinically indicated [see Dosage and Administration (2.3) , Warnings and Precautions (5.4) , and Drug Interactions (7.2) ] . 2.2 Recommended Dosage The recommended dosage of DUVYZAT is based on body weight and administered orally twice daily with food (see Table 1 ) [see Dosage and Administration (2.4) ] .

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 be considered during treatment with DUVYZAT. Discontinue DUVYZAT if the symptoms persist. ( 2.3 , 5.3 ) QTc Prolongation: Avoid use of DUVYZAT in patients who are at an increased risk for ventricular arrhythmias. ( 2.1 , 5.4 , 7.2 ) 5.1 Hematological Changes DUVYZAT can cause dose-related thrombocytopenia and other signs of myelosuppression, including decreased hemoglobin and neutropenia. In Study 1 [see Clinical Studies (14) ] , thrombocytopenia occurred in 33% of patients treated with DUVYZAT compared to no patients on placebo. The maximum decrease in platelets occurred within the first 2 months of therapy and remained low throughout the course of therapy. In a few patients, thrombocytopenia was associated with bleeding events including epistaxis, hematoma or contusions. Low platelet counts resulted in DUVYZAT dose reduction in 28% of patients. Patients with baseline platelet counts below the lower limit of normal were excluded from the study. Decreased hemoglobin and decreased neutrophils were also observed in patients treated with DUVYZAT compared to placebo.

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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ITF Therapeutics, LLC. at 1-833-582-4312 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In controlled and uncontrolled trials in patients with confirmed DMD, 222 male patients aged 6 years and older were treated with DUVYZAT, including 210 patients treated for ≥ 6 months, 187 patients for ≥ 12 months, and 105 patients for ≥ 24 months. The safety profile of DUVYZAT is based on a double-blind, placebo-controlled, 18-month study in a total of 179 ambulant DMD patients aged 6 years or older on concomitant steroid treatment (Study 1) [see Clinical Studies (14) ] . The dosage in Study 1 was weight-based [see Dosage and Administration (2.2) ] .

Pregnancy: Based on animal data, may cause fetal harm. ( 8.1 ) Hepatic Impairment: Exposure to givinostat is expected to be increased. ( 8.6 ) 8.1 Pregnancy Risk Summary DUVYZAT is indicated for the treatment of DMD, which is a disease of predominantly young male patients. Therefore, there are no adequate data available to assess the use of DUVYZAT in pregnant women. In animal studies, oral administration of givinostat during organogenesis resulted in decreased fetal body weight and increased structural variations; oral administration during pregnancy and lactation resulted in increased embryofetal and offspring mortality and neurobehavioral changes in the offspring. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Oral administration of givinostat (0, 40, 80, or 160 mg/kg/day) to pregnant rats throughout organogenesis resulted in reduced fetal body weight at the highest dose tested and increases in the incidence of skeletal and visceral variations at the mid and high doses. The no-effect dose (40 mg/kg/day) for adverse effects on embryofetal development was associated with maternal plasma exposures (AUC) lower than that in humans at the maximum recommended human dose (MRHD) of 53.2 mg twice daily.

Metabolism

Givinostat exhibits linear kinetics with the studied dose range. Systemic exposure to givinostat was dose-proportional across the therapeutic dose range.

• Mar 21, 2024NDANDA217865Italfarmaco Spa

1. 1Platelet Count Decreased11023%
2. 2Diarrhoea7115%
3. 3Blood Triglycerides Increased5111%
4. 4Abdominal Discomfort367.5%
5. 5Nausea367.5%
6. 6Vomiting347.1%
7. 7Thrombocytopenia336.9%
8. 8Product Dose Omission Issue285.8%
9. 9Weight Increased265.4%
10. 10Abdominal Pain Upper214.4%
11. 11Pyrexia214.4%
12. 12Off Label Use204.2%
13. 13Gastrointestinal Disorder183.8%
14. 14Abdominal Pain163.3%
15. 15Myalgia153.1%

The 10 most recently updated of 27 ClinicalTrials.gov registrations naming Givinostat as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study Evaluating the Real-World Experience of Givinostat in Patients With Duchenne Muscular Dystrophy
  Recruiting · Observational · 300 enrolled · ITF Therapeutics LLC
  NCT07127978updated 2026-04-15
• Study on Efficacy and Safety of Givinostat Versus Hydroxyurea in Patients With Polycythemia Vera
  Recruiting · Phase 3 · Interventional · 220 enrolled · Italfarmaco
  NCT06093672updated 2026-03-25
• Givinostat in Duchenne's Muscular Dystrophy Long-term Safety and Tolerability Study
  Recruiting · Phase 2 · Phase 3 · Interventional · 206 enrolled · Italfarmaco
  NCT03373968updated 2026-01-21
• Pharmacokinetics, Safety and Tolerability of ITF2357 in Participants With Chronic Hepatic Impairment and With Normal Hepatic Function
  Completed · Phase 1 · Interventional · 24 enrolled · Italfarmaco
  NCT06736223updated 2026-01-12
• Pharmacokinetics and Safety of Givinostat in DMD Patients Ages From at Least 2 Years to Less Then 6 Years Old
  Recruiting · Phase 2 · Interventional · 18 enrolled · Italfarmaco
  NCT06769633updated 2025-07-10
• Efficacy, Safety and Tolerability of Givinostat in Non-ambulant Patients With Duchenne Muscular Dystrophy
  Recruiting · Phase 3 · Interventional · 138 enrolled · Italfarmaco
  NCT05933057updated 2025-05-11
• Long-term Study Evaluating the Effect of Givinostat in Patients With Chronic Myeloproliferative Neoplasms
  Active not recruiting · Phase 2 · Interventional · 90 enrolled · Italfarmaco
  NCT01761968updated 2025-04-30
• DMD Voice: Qualitative Interviews With Patients and Caregivers
  Recruiting · Observational · 68 enrolled · Red Nucleus Enterprise Solutions, LLC
  NCT06925269updated 2025-04-30
• Givinostat and Metabolites Pharmacokinetics in Urine and Plasma (Part 3)
  Completed · Phase 1 · Interventional · 8 enrolled · Italfarmaco
  NCT05860114updated 2025-01-24
• Perpetrator DDI Potential of Givinostat as Inhibitor and Inducer of CYP3A and P-gp Activity
  Completed · Phase 1 · Interventional · 26 enrolled · Italfarmaco
  NCT05492318updated 2025-01-06

Frequently asked questions

How does Givinostat work?

DUVYZAT is a histone deacetylase inhibitor. The precise mechanism by which DUVYZAT exerts its effect in patients with DMD is unknown.

What is Givinostat used for?

According to FDA labeling, Givinostat carries indications including: 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Givinostat?

Givinostat is classified as Other drugs for disorders of the musculo-skeletal system, Histone Deacetylase Inhibitor, Cytochrome P450 3A4 Inhibitors, Histone Deacetylase Inhibitors, Organic Cation Transporter 2 Inhibitors.

What are the brand names for Givinostat?

Givinostat is marketed under brand names including Duvyzat.

What are the contraindications for Givinostat?

Givinostat labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.