DUVYZAT

Package leaflet: Information for the patient

Duvyzat 8.86 mg/ml oral suspension

givinostat
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

1. What Duvyzat is and what it is used for
2. What you need to know before taking Duvyzat
3. How to take Duvyzat
4. Possible side effects
5. How to store Duvyzat
6. Contents of the pack and other information

1. What Duvyzat is and what it is used for

Duvyzat contains the active substance givinostat.
It is used to treat Duchenne muscular dystrophy (DMD) in patients aged 6 years and older who are
ambulatory and receiving treatment with corticosteroids.
DMD is caused by mutations in the DMD gene. These genetic changes impair muscle cell function and
lead to progressive muscle degeneration.
By inhibiting the activity of HDAC enzymes in muscle cells, Duvyzat prevents muscle degeneration.

2. What you need to know before taking Duvyzat

Do not take Duvyzat

• if you (or your child) are allergic to givinostat or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor or pharmacist before taking Duvyzat.
Duvyzat reduces the number of blood cells, particularly the number of platelets responsible for blood clotting (a condition called thrombocytopenia).
Your doctor will check your platelet levels in the blood before starting treatment and regularly throughout the entire course of treatment with Duvyzat.
Your doctor may reduce the dose to increase platelet count or discontinue treatment with Duvyzat if thrombocytopenia persists.
Inform your doctor if you notice unexpected bleeding.
Duvyzat may be associated with increased levels of fats (triglycerides) in the blood.
Your doctor will perform blood tests before starting treatment with Duvyzat and regularly during treatment to monitor triglyceride levels.
The dose of givinostat may be reduced if there is a persistent increase in blood fat (triglyceride) levels.
Your doctor may discontinue treatment if fat levels in the blood (triglycerides) do not decrease despite dietary measures and dose reductions.
You may experience diarrhoea and vomiting while taking Duvyzat.
Your doctor may adjust the dose of Duvyzat depending on the severity of diarrhoea or may discontinue treatment if diarrhoea and vomiting do not improve.
Your doctor may consider using medications to treat vomiting and diarrhoea and to prevent excessive fluid loss.
High doses of Duvyzat (5 times higher than the recommended dose) may cause irregular heartbeat. Your doctor will decide whether you can use Duvyzat if there is an increased risk of abnormal heartbeat, abnormal levels of minerals in the body, or if you are taking other medicines concomitantly.
Your doctor may monitor your heart function when starting Duvyzat if you have an underlying heart condition or if you are taking medicines that may cause irregular heartbeat.
Your doctor may consider discontinuing treatment with Duvyzat if an irregular heartbeat is detected.
Inform your doctor, who may discontinue therapy with Duvyzat, if any of the above conditions occur.
Other medicines and Duvyzat
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Duvyzat may increase the risk of adverse effects from other medicines by increasing the levels of these medicines in the blood. Some of these medicines include:

• carbamazepine, phenytoin (medicines used to treat epilepsy),
• amitriptyline (a medicine used to treat low mood and depression),
• digoxin (a medicine used to treat heart failure and abnormal heart rhythm),
• metformin (a medicine used to control type II diabetes),
• amiloride (a medicine used to treat high blood pressure),
• histamine type 2 receptor antagonists (medicines used to treat duodenal and gastric ulcers and common heartburn).

Caution is recommended when Duvyzat is administered with medicines known to cause abnormal heartbeat.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before taking this medicine. If you become pregnant while taking Duvyzat, contact your doctor immediately. The use of Duvyzat should be avoided during pregnancy or breastfeeding.
Driving and using machines
This medicine may cause dizziness or fatigue. If you feel dizzy or tired, do not drive or operate machinery.
Duvyzat contains sorbitol, sodium benzoate, and sodium.
Sorbitol:
This medicine contains 400 mg of sorbitol per ml.
Sorbitol is a source of fructose. If your doctor has informed you that you (or your child) have an intolerance to certain sugars or have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot metabolize fructose, inform your doctor before you (or your child) take or receive this medicine.
Sodium benzoate:
This medicine contains 4.4 mg of sodium benzoate per ml.
Sodium benzoate may increase jaundice (yellowing of the skin and eyes) in newborns (up to 4 weeks of age).
Sodium:
This medicine contains less than 1 mmol (23 mg) of sodium per ml, i.e., essentially ‘sodium-free’.

3. How to take Duvyzat

Take this medicine exactly as instructed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Duvyzat must be taken orally, using a syringe. It must be taken twice daily. The recommended dose of Duvyzat depends on body weight, as shown in Table 1.
Table 1 - Recommended dose

If your prescribed dose is more than 5 ml per dose, you may use the same oral syringe more than once.
Your dose may need to be reduced (see Table 2) by your doctor if certain symptoms occur (see Warnings and precautions):
decrease in platelet count;
moderate or severe diarrhoea (more than 4 bowel movements per day);
increase in blood fat levels.
Table 2 - First dose reduction

If the above abnormalities do not improve, the doctor may further reduce the dose (see Table 3).
Table 3 - Second dose reduction

If these abnormalities continue to persist or if an irregular heartbeat occurs, your doctor may consider discontinuing treatment with Duvyzat.
Method of administration
Duvyzat is for oral use.
The oral suspension must be shaken manually approximately 40 times for at least 30 seconds by continuously inverting the bottle up and down until the oral suspension is well mixed and appears homogeneous.
The suspension is dosed using the graduated oral syringe provided.
Important information on Duvyzat dosing:
Ask your doctor or pharmacist to show you how to measure the prescribed dose.

• Take Duvyzat as prescribed by your doctor (see Tables 1, 2, 3);
• The recommended dose of Duvyzat should be taken orally twice daily;
• Take Duvyzat as is (it must not be diluted with water or other liquids);
• Take Duvyzat with food to reduce the bitter taste of givinostat;
• Always use the oral syringe (5 ml) provided with the medicine to take Duvyzat.

For first use of the bottle only: remove the Duvyzat bottle and the 5 ml oral syringe from the box (see Figure A).	Figure A
Step 1. Ensure the bottle is properly closed and shake it vigorously approximately 40 times for at least 30 seconds by continuously turning it upside down and right side up (see Figure B). Stop when the Duvyzat oral suspension is well mixed and appears homogeneous.	Figure B
Step 2. Open the bottle by pressing down on the cap and turning it to the left (counterclockwise) (see Figure C). Do not discard the bottle cap.	Figure C
Step 3. For first use only: take the provided oral syringe and firmly insert its tip into the opening of the bottle adapter (see Figure D). For all subsequent uses: take the provided oral syringe, push the plunger fully in (to remove air), and firmly insert the syringe tip into the opening of the bottle adapter (see Figure D).	Figure D
Step 4. While holding the oral syringe securely in place, turn the bottle upside down. Slowly pull the plunger outward to draw a small amount of suspension into the syringe. Then push the plunger fully forward to remove any air bubbles (see Figure E).	Figure E
Step 5. Slowly pull the plunger outward until the bottom edge of the plunger aligns with the measurement marking on the oral syringe corresponding to the prescribed dose of Duvyzat (see Figure F). If your prescribed dose is greater than 5 ml, you will need to repeat the process using the same oral syringe more than once.	Figure F
Step 6. While keeping the plunger in position, turn the bottle upright and gently place it on a flat surface. Remove the oral syringe by gently rotating and pulling it out from the bottle adapter opening. Do not hold the oral syringe by the plunger, as it may slip out (see Figure G). Take or administer Duvyzat immediately after drawing it into the oral syringe. Do not store the filled oral syringe.	Figure G
Step 7. Check that the prescribed volume (ml) of Duvyzat has been drawn into the oral syringe (see Figure H). Figure H shows an example of a 5 ml dose. Your dose may be a different volume.	Figure H
Step 8. The child or adult should sit in an upright position when taking a dose of Duvyzat. Place the tip of the oral syringe inside the cheek. Slowly press the plunger fully until no medication remains in the oral syringe. If the prescribed dose is greater than 5 ml, repeat from Step 3 to Step 8 to administer the remaining portion of the dose.
Step 9. After use, replace the cap on the bottle and turn it to the right (clockwise) to close the bottle securely (see Figure I).	Figure I
Step 10. Wash the oral syringe with water and allow it to air dry. Store the oral syringe in a clean, dry place.

If you take more Duvyzat than you should
Contact your doctor or a hospital if you take more Duvyzat than prescribed.
Your doctor will decide what treatment you need. This may include monitoring of your cardiac function.

If you forget to take Duvyzat
It is important to take the correct dose.
If you forget a dose, take the next dose at the scheduled time.
Do not take a double dose to make up for the missed dose.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

If you stop treatment with Duvyzat
Do not stop treatment with Duvyzat without first talking to your doctor.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
After taking Duvyzat, you may experience one or more of the following side effects:

Very common side effects (may affect more than 1 in 10 people):

• stomach ache (abdominal pain)
• decreased platelet count in the blood (thrombocytopenia)
• diarrhoea
• high levels of fats in the blood (hypertriglyceridemia)
• fever (pyrexia)
• vomiting

Common side effects (may affect up to 1 in 10 people):

• anxiety
• constipation
• decreased appetite
• dizziness
• skin redness (erythema)
• tiredness (fatigue)
• diarrhoea and vomiting (gastroenteritis)
• collection of blood under the skin (haematoma)
• increased levels of thyroid stimulating hormone (TSH) in the blood
• joint pain (arthralgia)
• muscle pain (myalgia)
• muscle weakness
• rash

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse.
You can also report side effects directly via the national reporting system detailed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Duvyzat

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and vial after
Exp. The expiry date refers to the last day of that month.
After opening, use within 60 days.
Discard any unused oral suspension of Duvyzat remaining after 60 days from first opening of the container.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Duvyzat contains
The active substance is givinostat.
Each ml of oral suspension contains 8.86 mg of givinostat (as monohydrochloride monohydrate).
The other ingredients are: polysorbate 20 (E432), glycerol (E422), tragacanth gum (E413), sodium benzoate (E211), peach flavour (natural flavours, flavouring substances, propylene glycol E1520), cream flavour (natural flavours, flavouring substances, propylene glycol E1520), sodium saccharin (E954), liquid sorbitol (E420), tartaric acid (E334), sodium hydroxide (E524), purified water.

Description of the appearance of Duvyzat and contents of the pack
Duvyzat is an oral suspension that is white to off-white or slightly pink in colour.
Pack size: one 140 ml bottle.
The bottle is supplied with a 5 ml graduated oral syringe. The oral syringe is graduated from 1 to 5 ml in 0.5 ml increments.

Marketing Authorisation Holder
Italfarmaco S.p.A.
Viale F. Testi, 330
20126 Milan
Italy

Manufacturer
Italfarmaco S.A.
San Rafael, 3
28108 Alcobendas (Madrid)
Spain

Scan the code with a mobile device to access the package leaflet in different languages.

Or visit the URL https://www.duvyzat.eu

This medicinal product has been granted a conditional marketing authorisation. This means that additional data on this medicinal product are required.
The European Medicines Agency will review new information on this medicinal product at least annually, and this package leaflet will be updated as necessary.
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu

ANNEX IV
CONCLUSIONS ON THE GRANTING OF THE CONDITIONAL MARKETING AUTHORISATION AND THE PRESENTATIONS
SUBMITTED BY THE EUROPEAN MEDICINES AGENCY

Conclusions presented by the European Medicines Agency on:

• Granting of a conditional marketing authorisation
  Following assessment of the application for marketing authorisation, the Committee for Medicinal Products for Human Use (CHMP) concluded that the benefit-risk balance is favourable and recommended granting a conditional marketing authorisation, as further described in the European Public Assessment Report (EPAR).

• Similarity
  The Committee for Medicinal Products for Human Use (CHMP) considers that Duvyzat is similar to authorised orphan medicinal products under Article 3 of Regulation (EC) No 847/2000, as further described in the European Public Assessment Report (EPAR).