DACOGEN 50 mg powder for concentrate for infusion solution

2. What you need to know before you use Dacogen

Do not use Dacogen

• if you are allergic to decitabine or any of the other ingredients of this medicine (listed in section 6).
• if you are breast-feeding.

If you are not sure if any of the above applies to you, talk to your doctor, pharmacist, or nurse before using Dacogen.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with Dacogen if you:

• have a low number of platelets, red or white blood cells,
• have an infection,
• have liver disease,
• have severe kidney disease,
• have heart disease.

If you are not sure if any of the above applies to you, talk to your doctor, pharmacist, or nurse before using Dacogen.

Tests or checks

You will have blood tests before starting treatment with Dacogen and at the start of each treatment cycle. These tests are to check that:

• you have enough blood cells, and
• your liver and kidneys are working properly.

Ask your doctor about the results of your blood tests.

Children and adolescents

Dacogen must not be used in children and adolescents under 18 years.

Using Dacogen with other medicines

Tell your doctor, nurse, or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription and herbal medicines. Dacogen may affect the way other medicines work. Also, some other medicines may affect the way Dacogen works.

Pregnancy and breast-feeding

• If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.
• Do not use Dacogen if you are pregnant because it may harm your baby. Tell your doctor immediately if you become pregnant during treatment with Dacogen.
• You must not breast-feed if you are using Dacogen, as it is not known whether the medicine passes into breast milk.

Male and female fertility and contraception

• Men must not father a child while using Dacogen.
• Men must use effective contraception during treatment and for 3 months after stopping treatment.
• Ask your doctor if you want to save your sperm before starting treatment.
• Women must use effective contraception during treatment. It is not known when it is safe for women to become pregnant after stopping treatment.
• Ask your doctor if you want to freeze your eggs before starting treatment.

Driving and using machines

You may feel tired or weak after using Dacogen. If this happens, do not drive or use tools or machines.

Dacogen contains potassium and sodium

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

3. How to use Dacogen

Dacogen will be given to you by a doctor or nurse who is trained to administer this type of medicine.

Recommended dose

• Your doctor will calculate your dose of Dacogen, which will depend on your height and weight (body surface area).
• The dose is 20 mg/m2 of body surface area.
• You will receive Dacogen daily for 5 days, followed by 3 weeks without the medicine. This is called a "treatment cycle" and will be repeated every 4 weeks. You will usually receive at least 4 treatment cycles.
• Your doctor may delay your dose and change the total number of cycles, depending on how you respond to treatment.

How Dacogen is given

The solution is given by infusion into a vein over 1 hour.

If you are given more Dacogen than you should

This medicine will be given to you by a doctor or nurse. It is very unlikely that you will be given too much medicine (overdose), but if this happens, your doctor will check you and manage any side effects.

If you miss a dose of Dacogen

If you miss a dose, make another appointment as soon as possible. This is because it is important to follow the treatment schedule for this medicine to be as effective as possible.

If you have any further questions on the use of this product, ask your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects may happen with this medicine.

Tell your doctor or nurse immediately if you get any of the following serious side effects

• Fever: this can be a sign of infection caused by low white blood cell counts (very common).
• Chest pain or difficulty breathing (with or without fever or cough): these can be signs of pneumonia (very common) or inflammation of the lungs (frequency not known) or heart muscle disease (uncommon) which can be accompanied by swelling of the ankles, hands, legs, and feet.
• Bleeding: including blood in your stools. This can be a sign of bleeding in the stomach or intestine (common).
• Difficulty moving, speaking, or understanding, or seeing; severe headache, seizures, numbness, or weakness in any part of your body. These can be symptoms of bleeding in the brain (common).
• Difficulty breathing, swelling of the lips, itching, or skin rash. These can be due to an allergic reaction (common).

Tell your doctor or nurse immediately if you get any of these serious side effects.

Other side effects of Dacogen are

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

• urinary tract infection
• infection in any part of the body, caused by bacteria, viruses, or fungi
• bleeding or bruising more easily - these can be signs of low platelet counts
• feeling tired or pale - these can be signs of low red blood cell counts
• high blood sugar
• headache
• nosebleeds
• diarrhoea
• vomiting
• nausea
• fever
• abnormal liver function

Common(may affect up to 1 in 10 people)

• blood infection caused by bacteria - this can be a sign of low white blood cell counts
• nose or sinus pain, runny nose
• mouth or tongue ulcers
• increased bilirubin levels in the blood

Uncommon(may affect up to 1 in 100 people)

• low numbers of red blood cells, white blood cells, and platelets
• heart muscle disease
• red, raised, and painful plaques on the skin, fever, increased white blood cell count - these can be signs of "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 typhlitis), with symptoms of abdominal pain, bloating, or diarrhoea. Enterocolitis can lead to complications of sepsis and can be associated with a fatal outcome.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Dacogen

• Your doctor, nurse, or pharmacist is responsible for storing Dacogen.
• 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 label after EXP. The expiry date refers to the last day of the month shown.
• Do not store above 25°C.
• After reconstitution, the concentrate must be diluted within 15 minutes using refrigerated infusion fluids. This diluted solution can be stored refrigerated at 2°C - 8°C for a maximum of 3 hours, followed by up to 1 hour at room temperature (20°C - 25°C) before administration.
• Your doctor, nurse, or pharmacist is responsible for the proper disposal of any unused Dacogen.

6. Contents of the pack 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 the concentrate contains 5 mg of decitabine.
• The other ingredients are potassium dihydrogen phosphate (E340), sodium hydroxide (E524), and hydrochloric acid (for pH adjustment). See section 2.

Appearance and pack size

Dacogen is a white or almost white powder for concentrate for solution for infusion. It is available in a 20 ml glass vial containing 50 mg of decitabine. Each pack contains 1 vial.

Marketing authorisation holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Manufacturer

Janssen Pharmaceutica NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

You can ask for more information about this medicine from your local representative of the marketing authorisation holder:

Date of last revision of this leaflet: MM/YYYY

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/.

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This information is intended only for healthcare professionals:

1. RECONSTITUTION

Avoid skin contact with the solution and wear protective gloves. Use the usual procedures for handling cytotoxic drugs.

The powder must be reconstituted under aseptic conditions with 10 ml of water for injections. After reconstitution, each millilitre contains approximately 5 mg of decitabine at a pH of 6.7 to 7.3. Within 15 minutes of reconstitution, the solution must be further diluted with refrigerated infusion fluids (sodium chloride 9 mg/ml (0.9%) or glucose 5% injection) to achieve a final concentration of 0.15 to 1.0 mg/ml.

For the validity period and storage precautions after reconstitution, see section 5 of the leaflet.

1. ADMINISTRATION

Infuse the reconstituted solution intravenously over 1 hour.

1. ELIMINATION

The vials are for single use and any unused solution should be discarded.

Disposal of unused medicine and all materials that have come into contact with it should be done according to local regulations.