Duvyzat (Givinostat)
HDAC Inhibitor for Duchenne Muscular Dystrophy
Duvyzat (givinostat) is the first histone deacetylase (HDAC) inhibitor approved for the treatment of Duchenne muscular dystrophy (DMD). It is indicated for patients aged 6 years and older who are still ambulatory and receiving corticosteroid therapy. By inhibiting HDAC enzymes in muscle cells, Duvyzat helps counteract the progressive muscle degradation characteristic of DMD, reducing inflammation, fibrosis, and fatty replacement of muscle tissue.
Quick Facts
Key Takeaways
- Duvyzat is the first HDAC inhibitor approved for Duchenne muscular dystrophy (DMD), targeting inflammation and fibrosis in dystrophic muscles.
- It is taken twice daily as an oral suspension, with dosing based on body weight, and must be used alongside ongoing corticosteroid therapy.
- Regular blood monitoring is essential to check platelet counts and triglyceride levels, as thrombocytopenia and elevated blood fats are common side effects.
- Duvyzat can interact with several medications including carbamazepine, digoxin, and metformin — always inform your doctor about all medicines being taken.
- The oral suspension must be used within 60 days of first opening and should be shaken well (approximately 40 times) before each dose.
What Is Duvyzat and What Is It Used For?
Duvyzat contains the active substance givinostat, a histone deacetylase (HDAC) inhibitor developed specifically for the treatment of Duchenne muscular dystrophy. DMD is a rare, progressive genetic disorder caused by mutations in the dystrophin gene (DMD gene), which encodes the protein dystrophin. Without functional dystrophin, muscle cells become increasingly vulnerable to damage during contraction, leading to chronic inflammation, progressive fibrosis (scarring), fatty infiltration of muscle tissue, and ultimately severe muscle weakness and loss of function.
Givinostat works through a novel mechanism of action that is distinct from gene-based therapies for DMD. By inhibiting the activity of histone deacetylase enzymes within muscle cells, Duvyzat modifies the epigenetic environment surrounding dystrophic muscles. This inhibition has been shown in both preclinical and clinical studies to reduce the pathological remodeling processes that characterize DMD, including inflammation and the replacement of muscle tissue with fibrotic and fatty tissue. The net effect is to help preserve muscle function and slow the progressive decline that patients with DMD experience.
Duchenne muscular dystrophy affects approximately 1 in 3,500 to 5,000 male births worldwide and is one of the most common and severe forms of muscular dystrophy. The condition is X-linked recessive, meaning it predominantly affects boys and young men, though rare cases in females have been documented. Symptoms typically begin between ages 2 and 5, with progressive muscle weakness initially affecting the legs and pelvis before spreading to the arms, neck, and other areas. Most patients lose the ability to walk independently by their early teens without treatment intervention.
Duvyzat has received conditional marketing authorisation from the European Medicines Agency (EMA), meaning it has been approved based on evidence available at the time of approval, with the requirement that the manufacturer provide additional data. The EMA reviews new information about the medicine at least annually and updates the product information as necessary. This conditional approval reflects both the unmet medical need in DMD and the promising clinical evidence supporting givinostat's efficacy in slowing disease progression.
What Should You Know Before Taking Duvyzat?
Contraindications
Do not take Duvyzat if you are allergic to givinostat or any of the other ingredients in the medicine. The inactive ingredients include polysorbate 20, glycerol, tragacanth gum, sodium benzoate, saccharin sodium, liquid sorbitol, tartaric acid, sodium hydroxide, and purified water, along with peach and cream flavoring agents containing propylene glycol. If you have previously experienced an allergic reaction to any of these substances, inform your doctor before starting treatment.
Warnings and Precautions
Several important precautions must be considered before and during treatment with Duvyzat. Your doctor will need to perform regular monitoring throughout the course of therapy to ensure the medicine remains safe and effective.
Thrombocytopenia (low platelet count): Duvyzat can reduce the number of blood cells, particularly platelets, which are essential for proper blood clotting. Your doctor will check your platelet levels before starting treatment and at regular intervals throughout therapy. If your platelet count drops too low, your doctor may reduce your dose or temporarily or permanently discontinue treatment. You should notify your doctor immediately if you experience any unexpected bleeding, unusual bruising, or prolonged bleeding from cuts.
Elevated triglycerides (hypertriglyceridemia): Treatment with Duvyzat can cause an increase in blood fat levels, specifically triglycerides. Blood tests to monitor triglyceride levels will be performed before starting treatment and regularly throughout therapy. If triglyceride levels remain elevated, your doctor may reduce the dose of givinostat. If levels do not improve despite dietary changes and dose reduction, your doctor may decide to discontinue treatment entirely.
Gastrointestinal effects: Diarrhea and vomiting are among the most common side effects of Duvyzat. Your doctor may adjust the dose depending on the severity of these symptoms or, if no improvement occurs, may discontinue treatment. Additional medications to manage vomiting, diarrhea, and to prevent excessive fluid loss (dehydration) may be prescribed. Maintaining adequate hydration is particularly important for younger patients.
Cardiac effects: At doses significantly higher than recommended (approximately 5 times the recommended dose), givinostat has been associated with irregular heart rhythms (cardiac arrhythmias). For patients who have an increased risk of heart rhythm disturbances, abnormal electrolyte levels, or who are taking other medications that may affect heart rhythm, the doctor will carefully evaluate whether Duvyzat treatment is appropriate. Cardiac monitoring may be performed when initiating treatment in patients with underlying heart conditions.
Pregnancy and Breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before using Duvyzat. If you become pregnant during treatment, contact your doctor immediately. Although DMD primarily affects males, female caregivers or rare female patients should be aware that Duvyzat should be avoided during pregnancy and breastfeeding due to insufficient safety data in these populations. The potential risk to the developing fetus or nursing infant has not been adequately established.
Driving and Using Machines
Duvyzat may cause dizziness or fatigue. If you experience these symptoms, do not drive or operate machinery until the symptoms resolve. Given that DMD primarily affects pediatric and adolescent patients, this precaution is most relevant for older adolescents and adults who may be driving or using equipment.
Important Information About Ingredients
Sorbitol: Duvyzat contains 400 mg sorbitol per mL. Sorbitol is a source of fructose. If you (or your child) have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic condition that prevents the body from breaking down fructose, consult your doctor before taking this medicine. Patients with fructose intolerance should not take Duvyzat without medical guidance.
Sodium benzoate: The medicine contains 4.4 mg sodium benzoate per mL. Sodium benzoate may increase the risk of jaundice (yellowing of the skin and eyes) in newborns up to 4 weeks of age. This is particularly relevant if Duvyzat is prescribed off-label or in unusual clinical circumstances.
Sodium: Duvyzat contains less than 1 mmol (23 mg) sodium per mL and is therefore essentially sodium-free. This is important for patients on sodium-restricted diets.
How Does Duvyzat Interact with Other Drugs?
Givinostat can affect the way certain other medicines work by increasing their blood levels, which may lead to a higher risk of side effects from those medications. It is essential to inform your doctor or pharmacist about all medications currently being taken, recently taken, or planned to be taken. This includes prescription medicines, over-the-counter drugs, and herbal supplements.
Major Interactions
The following medications require particular caution when used together with Duvyzat, as givinostat may significantly increase their blood levels:
| Medication | Drug Class | Clinical Significance |
|---|---|---|
| Carbamazepine | Anti-epileptic | Increased blood levels; monitor for toxicity signs including dizziness, drowsiness, ataxia |
| Phenytoin | Anti-epileptic | Increased blood levels; therapeutic drug monitoring recommended |
| Digoxin | Cardiac glycoside | Increased blood levels; risk of digoxin toxicity (nausea, visual changes, arrhythmia) |
| Amitriptyline | Tricyclic antidepressant | Increased blood levels; enhanced anticholinergic and sedative effects |
| Metformin | Antidiabetic (biguanide) | Increased blood levels; monitor for gastrointestinal symptoms and lactic acidosis |
Other Interactions
Amiloride (used for high blood pressure) and H2 receptor blockers (used for stomach and intestinal ulcers and heartburn, such as ranitidine, famotidine, and cimetidine) may also have their blood levels increased when used concurrently with Duvyzat. Your doctor may need to adjust the doses of these medications or monitor you more closely for side effects.
QT-prolonging drugs: Caution is recommended when Duvyzat is used together with medications known to cause irregular heart rhythms (QT prolongation). These include certain antibiotics (macrolides, fluoroquinolones), antiarrhythmic drugs, some antipsychotics, and other medications. Your doctor will assess the overall risk of combining these treatments and may perform additional cardiac monitoring, including electrocardiogram (ECG) assessments, if necessary.
What Is the Correct Dosage of Duvyzat?
Always take Duvyzat exactly as your doctor or pharmacist has instructed. The oral suspension should be taken twice daily, with each dose administered with food to reduce the bitter taste of givinostat and to improve gastrointestinal tolerability.
Standard Dosing by Body Weight
| Body Weight (kg) | Dose per Administration | Givinostat per Dose |
|---|---|---|
| 15 to less than 20 kg | 2.5 mL | 22.15 mg |
| 20 to less than 40 kg | 3.5 mL | 31.01 mg |
| 40 to less than 60 kg | 5.0 mL | 44.30 mg |
| 60 kg or more | 6.0 mL | 53.16 mg |
First Dose Reduction
If certain side effects occur, such as decreased platelet counts, moderate to severe diarrhea (more than 4 bowel movements per day), or elevated triglyceride levels, your doctor may reduce the dose according to the following schedule:
| Body Weight (kg) | Reduced Dose |
|---|---|
| 15 to less than 20 kg | 2.0 mL |
| 20 to less than 40 kg | 2.5 mL |
| 40 to less than 60 kg | 3.5 mL |
| 60 kg or more | 4.5 mL |
Second Dose Reduction
If symptoms do not improve after the first dose reduction, the doctor may further reduce the dose:
| Body Weight (kg) | Further Reduced Dose |
|---|---|
| 15 to less than 20 kg | 1.5 mL |
| 20 to less than 40 kg | 2.0 mL |
| 40 to less than 60 kg | 3.0 mL |
| 60 kg or more | 4.0 mL |
If symptoms persist despite the second dose reduction, or if you experience irregular heartbeats, your doctor may decide to permanently discontinue Duvyzat treatment.
How to Prepare and Take a Dose
Duvyzat oral suspension must be properly prepared before each dose. Follow these steps carefully:
- Shake the bottle: Ensure the bottle is properly sealed, then shake it vigorously by inverting it approximately 40 times over at least 30 seconds until the suspension appears uniform and well-mixed.
- Open the bottle: Press down on the cap and twist it counterclockwise (to the left) to open.
- Prepare the syringe: Use the provided 5 mL graduated oral dosing syringe. For first use, insert the syringe tip into the bottle adapter opening. For subsequent uses, push the plunger all the way in first (to expel air), then firmly insert the tip into the adapter.
- Remove air bubbles: With the bottle inverted, slowly draw a small amount of suspension, then push the plunger all the way in to remove any air bubbles.
- Draw the dose: Slowly pull the plunger until the bottom of the plunger aligns with the marking on the syringe corresponding to your prescribed dose. If the prescribed dose exceeds 5 mL, you will need to use the same syringe more than once.
- Administer the dose: The patient should sit upright. Place the syringe tip against the inside of the cheek and slowly push the plunger until all the medicine has been delivered.
- After use: Replace the bottle cap and tighten clockwise. Wash the syringe with water and allow it to dry. Store the syringe in a clean, dry place.
Missed Dose
If you miss a dose of Duvyzat, take the next dose at the regularly scheduled time. Do not take a double dose to compensate for a missed dose. It is important to maintain a consistent dosing schedule. If you frequently forget doses, speak with your doctor or pharmacist about strategies to help remember.
Overdose
If you or your child takes more than the prescribed dose of Duvyzat, contact your doctor or go to the nearest hospital emergency department immediately. The doctor will determine what treatment is needed, which may include monitoring of heart function (ECG monitoring) given the potential for cardiac effects at supratherapeutic doses. Bring the medicine bottle with you so healthcare providers can see exactly what was taken.
Stopping Treatment
Do not stop taking Duvyzat without first consulting your doctor. The decision to discontinue treatment should be made by your healthcare provider based on a thorough assessment of the benefits and risks. Abrupt discontinuation may not pose an immediate safety risk, but treatment decisions should always be guided by medical expertise.
What Are the Side Effects of Duvyzat?
Like all medicines, Duvyzat can cause side effects, although not everyone experiences them. The frequency and severity of side effects can vary between patients. Your doctor will monitor you regularly for potential adverse effects and may adjust your dose or provide supportive treatment as needed.
The side effects of Duvyzat have been categorized below according to their frequency of occurrence, based on clinical trial data and post-marketing surveillance. Understanding these frequencies can help patients and caregivers know what to watch for and when to contact their healthcare provider.
Very Common
- Abdominal pain — stomach pain or discomfort, which may be managed with food intake
- Thrombocytopenia — decreased platelet count, requiring regular blood monitoring
- Diarrhea — frequent or loose stools; maintain adequate hydration
- Hypertriglyceridemia — elevated blood fat (triglyceride) levels detected on blood tests
- Pyrexia — fever or elevated body temperature
- Vomiting — may be reduced by taking the medicine with food
Common
- Anxiety — feelings of worry or nervousness
- Constipation — infrequent or difficult bowel movements
- Decreased appetite — reduced desire to eat
- Dizziness — feeling lightheaded or unsteady
- Erythema — redness of the skin
- Fatigue — unusual tiredness or exhaustion
- Gastroenteritis — diarrhea and vomiting together (stomach flu)
- Bruising — easy bruising, potentially related to low platelet counts
- Elevated TSH — increased thyroid-stimulating hormone in blood tests
- Arthralgia — joint pain
- Myalgia — muscle pain
- Muscle weakness — reduced muscle strength
- Skin rash — visible skin changes or eruptions
When to Contact Your Doctor
While many side effects are manageable and expected, certain symptoms require prompt medical attention. Contact your doctor immediately if you experience signs of serious thrombocytopenia (unexplained bleeding, petechiae — small red or purple spots on the skin, blood in urine or stool), severe or persistent diarrhea or vomiting leading to dehydration, symptoms of heart rhythm disturbances (palpitations, dizziness, fainting), or any other symptoms that concern you or seem unusual.
It is important to report any suspected side effects to your healthcare provider. Reporting adverse reactions helps monitor the ongoing benefit-risk profile of the medicine and contributes to patient safety. In many countries, patients and healthcare professionals can report suspected side effects directly to their national medicines regulatory authority.
How Should You Store Duvyzat?
Proper storage of Duvyzat is important to ensure the medicine remains effective and safe to use throughout its shelf life. The oral suspension should be kept out of the sight and reach of children at all times, stored in a secure location.
Do not use Duvyzat after the expiry date printed on the carton and bottle label (after "EXP"). The expiry date refers to the last day of the stated month. Once the bottle has been opened for the first time, the oral suspension must be used within 60 days. After this period, any remaining suspension should be discarded, even if it appears normal. It can be helpful to write the date of first opening on the bottle label to keep track.
Unused or expired medicines should not be disposed of via household waste or poured down drains. Ask your pharmacist how to properly dispose of medicines that are no longer needed. These measures help protect the environment and prevent accidental exposure.
- Keep out of sight and reach of children
- Check expiry date before each use
- Use within 60 days of first opening
- Note the date of first opening on the bottle
- Clean and dry the oral dosing syringe after each use
- Return unused medicines to a pharmacy for proper disposal
What Does Duvyzat Contain?
The active substance in Duvyzat is givinostat. Each milliliter of oral suspension contains 8.86 mg of givinostat (in the form of givinostat hydrochloride monohydrate). Givinostat is a selective histone deacetylase inhibitor that has been specifically developed for the treatment of Duchenne muscular dystrophy.
Inactive Ingredients (Excipients)
The other ingredients in Duvyzat oral suspension include:
- Polysorbate 20 (E432) — an emulsifier that helps maintain the uniform consistency of the suspension
- Glycerol (E422) — a humectant and sweetener
- Tragacanth gum (E413) — a natural thickening agent derived from plant sap
- Sodium benzoate (E211) — a preservative (4.4 mg per mL)
- Peach flavoring — natural flavoring agents with propylene glycol (E1520)
- Cream flavoring — natural flavoring agents with propylene glycol (E1520)
- Saccharin sodium (E954) — an artificial sweetener
- Liquid sorbitol (E420) — a sweetener and excipient (400 mg per mL)
- Tartaric acid (E334) — for pH adjustment
- Sodium hydroxide (E524) — for pH adjustment
- Purified water — the vehicle for the suspension
Appearance and Packaging
Duvyzat is a white to off-white or slightly pink oral suspension. It is supplied in a single-bottle pack containing 140 mL of suspension. Each pack includes a 5 mL graduated oral dosing syringe, marked in 0.5 mL increments from 1 mL to 5 mL, for accurate dose measurement. If the prescribed dose exceeds 5 mL, the same syringe should be used more than once to deliver the full dose.
Marketing Authorisation Holder and Manufacturer
The marketing authorisation for Duvyzat is held by Italfarmaco S.p.A., based in Milan, Italy. The medicine is manufactured by Italfarmaco S.A. in Alcobendas (Madrid), Spain, or by Italfarmaco S.p.A. in Milan, Italy. For the most current regulatory information, patients may consult the European Medicines Agency (EMA) website or their local medicines regulatory authority.
Frequently Asked Questions About Duvyzat
Duvyzat (givinostat) is used to treat Duchenne muscular dystrophy (DMD) in patients aged 6 years and older who are still able to walk and are being treated with corticosteroids. It is a histone deacetylase (HDAC) inhibitor that works by reducing inflammation and fibrosis in dystrophic muscles, thereby helping to slow the progressive muscle degradation that characterizes DMD. It is the first medicine of its class approved for this indication.
The most common side effects (affecting more than 1 in 10 patients) are abdominal pain, thrombocytopenia (low platelet count), diarrhea, hypertriglyceridemia (elevated blood fats), fever, and vomiting. Common side effects (affecting up to 1 in 10 patients) include anxiety, constipation, decreased appetite, dizziness, skin redness, fatigue, gastroenteritis, bruising, elevated thyroid-stimulating hormone (TSH), joint pain, muscle pain, muscle weakness, and skin rash. Regular blood monitoring is required during treatment.
Duvyzat is taken as an oral suspension twice daily with food. The dose depends on the patient's body weight: 2.5 mL for 15–20 kg, 3.5 mL for 20–40 kg, 5.0 mL for 40–60 kg, and 6.0 mL for 60 kg or more. The bottle must be shaken vigorously (approximately 40 inversions over at least 30 seconds) before each use. The dose is measured using the provided 5 mL graduated oral dosing syringe. The suspension should not be diluted and should be taken immediately after drawing the dose.
Yes, Duvyzat can increase the blood levels of several medications, potentially raising the risk of their side effects. Key interactions include carbamazepine and phenytoin (anti-epileptic drugs), amitriptyline (antidepressant), digoxin (heart medication), metformin (diabetes medication), amiloride (blood pressure medication), and H2 receptor blockers (stomach acid reducers). Additionally, caution is needed with drugs known to cause irregular heart rhythms (QT prolongation). Always tell your doctor about all medications being taken.
Keep Duvyzat out of the sight and reach of children. Do not use after the expiry date on the carton and bottle. Once opened, the suspension must be used within 60 days — it is helpful to write the opening date on the bottle. Clean the oral dosing syringe with water after each use and allow it to dry. Do not dispose of unused medicine via household waste or drains; return it to a pharmacy for safe disposal.
Duvyzat has received a conditional marketing authorisation from the European Medicines Agency (EMA). This means it was approved based on available evidence at the time, with the requirement that the manufacturer (Italfarmaco S.p.A.) provides additional data as it becomes available. The EMA reviews this information at least annually. The conditional approval reflects both the significant unmet medical need in DMD and the positive clinical evidence for givinostat. Regulatory status may vary by country — patients should consult their local medicines agency for the most current information.
References and Sources
This article is based on the following peer-reviewed sources and official regulatory documents. All medical claims are supported by evidence rated according to the GRADE framework.
- European Medicines Agency (EMA). Duvyzat (givinostat) — EPAR Summary for the Public. European Medicines Agency, 2024. Available at: EMA EPAR — Duvyzat.
- Mercuri E, et al. Safety and efficacy of givinostat in boys with Duchenne muscular dystrophy (EPIDYS): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Neurology, 2024. DOI: 10.1016/S1474-4422(23)00421-6.
- Bettica P, et al. Histological effects of givinostat in boys with Duchenne muscular dystrophy. Neuromuscular Disorders, 2016; 26(10):643–649. DOI: 10.1016/j.nmd.2016.07.002.
- World Health Organization (WHO). WHO Model List of Essential Medicines — 23rd Edition. Geneva: WHO, 2023.
- Bushby K, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. The Lancet Neurology, 2010; 9(1):77–93. DOI: 10.1016/S1474-4422(09)70271-6.
- Birnkrant DJ, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. The Lancet Neurology, 2018; 17(4):347–361.
- Consalvi S, et al. Preclinical studies in the mdx mouse model of Duchenne muscular dystrophy with the histone deacetylase inhibitor givinostat. Molecular Medicine, 2013; 19(1):79–87.
Medical Editorial Team
This article has been written and reviewed by qualified medical professionals with expertise in neurology, pharmacology, and pediatric medicine. Our editorial process follows international standards for medical content creation, including the GRADE evidence framework for assessing the quality of evidence.
iMedic Medical Editorial Team — specialists in clinical pharmacology and neuromuscular disorders with extensive experience in evidence-based medicine and medical communication.
iMedic Medical Review Board — independent panel of physicians who verify all medical claims against current international guidelines (EMA, WHO, peer-reviewed literature).
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