Dacogen

Patient Information Leaflet

Dacogen 50 mg powder for concentrate for solution for infusion

decitabine
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, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, because it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What Dacogen is and what it is used for

What Dacogen is
Dacogen is an antitumour medicine. It contains the active substance 'decitabine'.
What Dacogen is used for
Dacogen is used to treat a type of cancer called 'acute myeloid leukaemia' or 'AML'. This is a type of cancer that affects blood cells. Dacogen will be administered to you only after you have been diagnosed with AML for the first time. This medicine is intended for use in adults.
How Dacogen works
Dacogen works by stopping the growth of cancer cells and causing their death.
If you have any doubts about how Dacogen works or why this medicine has been prescribed for you, consult your doctor or nurse.

2. What you need to know before taking Dacogen

Do not take Dacogen

• if you are allergic to decitabine or to any of the other ingredients of this medicine (listed in section 6);
• if you are breastfeeding.
  If you are unsure about any of the above, consult your doctor, pharmacist, or nurse before using Dacogen.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Dacogen if:

• you have low platelet counts, red blood cells, or white blood cells;
• you have an active infection;
• you have a liver disorder;
• you have severe kidney disease;
• you have a heart condition.

If you are unsure about any of the above, consult your doctor, pharmacist, or nurse before using Dacogen.
Dacogen may cause a serious immune reaction called "differentiation syndrome" (see section 4, "Possible side effects").

Tests and monitoring
Before starting treatment with Dacogen and at the beginning of each treatment cycle, you will need to have blood tests to check that:

• you have sufficient blood cells, and
• your liver and kidneys are functioning properly.
  Consult your doctor to understand the meaning of your blood test results.

Children and adolescents
Dacogen must not be used in children or adolescents under 18 years of age.

Other medicines and Dacogen
Tell your doctor, nurse, or pharmacist if you are taking, have recently taken, or might take any other medicines.
This includes medicines obtained without a prescription and herbal medicines. This is because Dacogen may affect the action of other medicines, and other medicines may affect the action of Dacogen.

Pregnancy and breastfeeding

• If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, ask your doctor for advice before using this medicine.
• You must not take Dacogen during pregnancy as it may harm the unborn baby. If you are of childbearing age, your doctor will ask you to take a pregnancy test before starting treatment with Dacogen.
• If you become pregnant while being treated with Dacogen, inform your doctor immediately.
• Do not breastfeed while taking Dacogen, as it is not known whether it is excreted in breast milk.

Male and female fertility and contraception

• Men must not father a child during treatment with Dacogen.
• Men must use an effective method of contraception during treatment with Dacogen and for 3 months after treatment has ended.
• If you wish to preserve sperm before starting treatment, discuss this with your doctor.
• Women of childbearing age must use an effective method of contraception during treatment and for 6 months after completing treatment.
• If you wish to freeze your eggs before starting treatment, discuss this with your doctor.

Driving and using machines
After taking Dacogen, you may feel tired or weak. If this happens, do not drive or operate machinery or tools.

Potassium and sodium content of Dacogen

• This medicine contains 0.5 mmol of potassium in each vial. After reconstitution, it contains less than 1 mmol (39 mg) of potassium per dose, i.e., essentially "potassium-free".
• This medicine contains 0.29 mmol (6.67 mg) of sodium (the main component of table salt) in each vial. After reconstitution, it contains between 13.8–138 mg of sodium per dose, equivalent to 0.7–7% of the maximum daily sodium intake recommended for an adult. Speak with your doctor if you are on a low-sodium diet.

3. How to use Dacogen

Dacogen will be administered to you by a doctor or a nurse experienced in the administration of this type of medicine.
Recommended dose

• Your doctor will calculate the appropriate dose of Dacogen based on your height and weight (body surface area).
• The dose is 20 mg/m² of body surface area.
• Dacogen will be administered daily for 5 consecutive days, followed by a 3-week treatment break. This constitutes one 'treatment cycle' and is repeated every 4 weeks. Typically, at least 4 treatment cycles are planned.
• Depending on your response to treatment, your doctor may decide to delay dosing and adjust the total number of cycles.

How Dacogen is administered
The solution is given intravenously (by infusion). The administration will last one hour.
If you are given more Dacogen than you should have
The medicine will be administered by a doctor or nurse. In the unlikely event that you receive too much medicine (overdose), your doctor will monitor and manage any adverse effects accordingly.
If you miss an appointment for Dacogen
If you miss an appointment, schedule another one as soon as possible. To ensure this medicine is as effective as possible, it is important to follow the prescribed treatment schedule.
If you have any questions about how to use this medicine, consult your doctor or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them. The following adverse reactions may occur with this medicine.
If you experience any of the following adverse reactions, inform your doctor or nurse immediately

• Fever: may indicate an infection due to low levels of white blood cells (very common);
• Chest pain or difficulty breathing (with or without fever or cough): may indicate a lung infection called "pneumonitis" (very common) or lung inflammation (interstitial lung disease [frequency not known]) or cardiomyopathy (a disease [uncommon] of the heart muscle), which may be accompanied by swelling of the ankles, hands, legs and feet;
• Bleeding: including blood in the stools. This may indicate bleeding in the stomach or intestine (common);
• Difficulty in movement, speech, understanding or vision, sudden severe headache, epileptic seizure, numbness or weakness of one side of the body. These may be signs of intracranial haemorrhage (common);
• Difficulty breathing, swelling of the lips, itching or rash: these may be due to an allergic reaction (hypersensitivity) (common);
• Severe immune reaction (differentiation syndrome) which may cause fever, cough, difficulty breathing, rash, reduced urine output, hypotension (low blood pressure), swelling of arms or legs and rapid weight gain (frequency not known).

If you experience any of the adverse reactions listed above, inform your doctor or nurse immediately.
Other adverse reactions with Dacogen include
Very common (may affect more than 1 in 10 people)

• urinary tract infection
• other infections in any part of the body, caused by bacteria, viruses or fungi
• bleeding or easy bruising: may indicate a decrease in the number of platelets in the blood (thrombocytopenia)
• fatigue or paleness: may indicate a decrease in the number of red blood cells (anaemia)
• high blood sugar levels
• headache
• nosebleed
• diarrhoea
• vomiting
• nausea
• fever
• abnormal liver function

Common (may affect up to 1 in 10 people)

• bacterial blood infection – may indicate low levels of white blood cells
• irritated or runny nose, painful sinusitis
• mouth or tongue ulcers
• elevated levels of "bilirubin" in the blood

Uncommon (may affect up to 1 in 100 people)

• reduction in the number of red blood cells, white blood cells and platelets (pancytopenia)
• heart muscle disease
• red, raised and painful skin lesions, fever and increased white blood cells – may indicate 'acute febrile neutrophilic dermatosis' or 'Sweet's syndrome'

Not known (frequency cannot be estimated from the available data)

• inflammation of the intestine (enterocolitis, colitis and inflammation of the caecum), with symptoms of abdominal pain, bloating or diarrhoea. Enterocolitis may lead to septic complications and may be associated with fatal outcomes.

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

5. How to store Dacogen

• Dacogen will be stored by your doctor, nurse, or pharmacist.
• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and vial label after EXP. The expiry date refers to the last day of that month.
• Do not store above 25°C.
• After reconstitution, the concentrate must be further diluted within 15 minutes with cold infusion fluids. This diluted solution can be stored in the refrigerator at 2°C - 8°C for up to 3 hours, followed by up to 1 hour at room temperature (20°C - 25°C) before administration.
• The doctor, nurse, or pharmacist is responsible for the proper disposal of any unused Dacogen.

6. Package contents and other information

What Dacogen contains

• The active substance is decitabine. Each vial of powder contains 50 mg of decitabine. After reconstitution with 10 ml of water for injections, each ml of concentrate contains 5 mg of decitabine.
• The other components are potassium dihydrogen phosphate (E340), sodium hydroxide (E524), and hydrochloric acid (for pH adjustment). See section 2.

Description of the appearance of Dacogen and package contents
Dacogen is a white to off-white powder for concentrate for solution for infusion.
It is supplied in a 20 ml glass vial containing 50 mg of decitabine. Each pack contains one vial.
Marketing Authorisation Holder
Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium
Manufacturer
Janssen Pharmaceutica NV
Turnhoutseweg 30
B-2340 Beerse
Belgium
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Janssen-Cilag NV UAB "JOHNSON & JOHNSON"
Tel/Tél: +32 14 64 94 11 Tel: +370 5 278 68 88
България Luxembourg/Luxemburg
„Джонсън & Джонсън България” ЕООД Janssen-Cilag NV
Тел.: +359 2 489 94 00 Tél/Tel: +32 14 64 94 11
Česká republika Magyarország
Janssen-Cilag s.r.o. Janssen-Cilag Kft.
Tel: +420 227 012 227 Tel: +36 1 884 2858
Danmark Malta
Janssen-Cilag A/S AM MANGION LTD.
Tlf: +45 4594 8282 Tel: +356 2397 6000
Deutschland Nederland
Janssen-Cilag GmbH Janssen-Cilag B.V.
Tel: +49 2137 955 955 Tel: + 31 76 711 1111
Eesti Norge
UAB "JOHNSON & JOHNSON" Eesti filiaal Janssen-Cilag AS
Tel: +372 617 7410 Tlf: +47 24 12 65 00
Ελλάδα Österreich
Janssen-Cilag Φαρμακευτική Α.Ε.Β.Ε. Janssen-Cilag Pharma GmbH
Tηλ: +30 210 80 90 000 Tel: +43 1 610 300
España Polska
Janssen-Cilag, S.A. Janssen-Cilag Polska Sp. z o.o.
Tel: +34 91 722 81 00 Tel: +48 22 237 60 00
France Portugal
Janssen-Cilag Janssen-Cilag Farmacêutica, Lda.
Tél: 0 800 25 50 75 / +33 1 55 00 40 03 Tel: +351 214 368 600
Hrvatska România
Johnson & Johnson S.E. d.o.o. Johnson & Johnson România SRL
Tel: +385 1 6610 700 Tel: +40 21 207 1800
Ireland Slovenija
Janssen Sciences Ireland UC Johnson & Johnson d.o.o.
Tel: +353 1 800 709 122 Tel: +386 1 401 18 00
Ísland Slovenská republika
Janssen-Cilag AB Johnson & Johnson s.r.o.
c/o Vistor hf. Tel: +421 232 408 400
Sími: +354 535 7000
Italia Suomi/Finland
Janssen-Cilag SpA Janssen-Cilag Oy
Tel: 800.688.77 / +39 02 2510 1 Puh/Tel: +358 207 531 300
Κύπρος Sverige
Βαρνάβας Χατζηπαναγής Λτδ, Janssen-Cilag AB
Τηλ: +357 22 207 700 Tel: +46 8 626 50 00
Latvija United Kingdom (Northern Ireland)
UAB "JOHNSON & JOHNSON" filiāle Latvijā Janssen Sciences Ireland UC
Tel: +371 678 93561 Tel: +44 1 494 567 444
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/.

The following information is intended for healthcare professionals only:

1. RECONSTITUTION

It is recommended to avoid contact of the solution with the skin and to wear protective gloves. Standard procedures for handling cytotoxic medicinal products must be followed.
The powder must be reconstituted aseptically with 10 ml of water for injections. After reconstitution, each ml contains approximately 5 mg of decitabine, with a pH between 6.7 and 7.3. Within 15 minutes of reconstitution, the solution must be further diluted with cold infusion fluids (2°C - 8°C) (sodium chloride 9 mg/ml [0.9%] or glucose 5% solution for injections) to achieve a final concentration between 0.15 and 1.0 mg/ml. See section 5 of the package leaflet for storage duration and precautions after reconstitution.

2. ADMINISTRATION

Infuse the reconstituted solution intravenously over a period of 1 hour.

3. DISPOSAL

Each vial is for single use only, and any remaining solution must be discarded.
Unused medicine or waste material derived from it must be disposed of appropriately in accordance with local regulations.