Package Insert: Information for the User

Onureg 200 mg Film-Coated Tablets

Onureg 300 mg Film-Coated Tablets

azacitidine

Read this package insert carefully before you start taking this medicine, because it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

What is Onureg

Onureg is a cancer medication that belongs to a group of medications called antimetabolites. Onureg contains the active ingredient azacitidina.

How is Onureg used

Onureg is used to treat adults with acute myeloid leukemia (AML). It is a type of cancer that affects the bone marrow and can cause problems in the production of normal blood cells.

Onureg is used to maintain the disease under control (remission, when the disease is less severe or not active).

How Onureg works

Onureg acts by preventing the growth of cancer cells. Azacitidina, the active ingredient in Onureg, acts by altering the way cells activate or deactivate genes. It also reduces the production of new genetic material (RNA and DNA). It is believed that these effects block the growth of cancer cells in leukemia.

Consult with your doctor or nurse if you have any questions about how Onureg works or why you have been prescribed this medication.

Do not take Onureg

• if you are allergic to azacitidine or any of the other ingredients in this medicine (listed in section 6);
• if you are breastfeeding.

Warnings and precautions

Blood tests

You will have blood tests before starting treatment with Onureg and during treatment to check that you have enough blood cells and that your liver and kidneys are working properly. Your doctor will decide how often blood tests should be done.

Inform your doctor, pharmacist or nurse immediately if you experience any of the following symptoms during treatment with Onureg:

• bruising or bleeding: this could be due to a low platelet count;
• fever: this could be due to an infection as a result of low white blood cell levels, which can be potentially fatal;
• diarrhea, vomiting or nausea (feeling sick).

Your doctor may need to adjust your dose or temporarily or permanently stop treatment with Onureg. Your doctor may prescribe other medicines to help treat these symptoms.

Children and adolescents

Onureg is not recommended for use in children and adolescents under 18 years old.

Other medicines and Onureg

Inform your doctor if you are taking, have taken recently or may need to take any other medicine. This is because Onureg may affect how other medicines work. Also, other medicines may affect how Onureg works.

Pregnancy, contraception and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medicine. Men should not father a child while receiving treatment with Onureg.

Pregnancy

Onureg should not be used during pregnancy as it may harm the baby. Inform your doctor immediately if you become pregnant during treatment.

Contraception

If you are a woman and can become pregnant, you should use an effective contraceptive method while taking Onureg and for 6 months after stopping treatment with Onureg. Men should use an effective contraceptive method while taking Onureg and for 3 months after stopping treatment with Onureg.

Your doctor will advise you on the most suitable contraceptive method for you.

Breastfeeding

You should not breastfeed while taking Onureg as it may harm your baby.

Fertility

Onureg may affect your ability to have children. Consult your doctor before using this medicine.

Driving and operating machines or tools

You may feel tired or weak or have concentration problems. If this happens or if you experience other side effects, do not drive or operate machines or tools.

Onureg contains lactose

Onureg contains lactose. If your doctor has told you that you have a certain sugar intolerance, consult with them before taking this medicine.

Onureg contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per tablet; this is essentially "sodium-free".

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor.

How much to take

• The recommended dose is 300 mg orally once a day.
• Your doctor may reduce the dose to 200 mg once a day.

Onureg is administered in treatment cycles of 28 days.

• Onureg is taken every day during the first 14 days of each 28-day cycle.
• This is followed by a treatment-free period of 14 days during the rest of the cycle.

Your doctor will indicate the Onureg dose you should take. The doctor may decide:

• to extend treatment beyond the 14 days of each treatment cycle;
• to reduce your dose or temporarily interrupt treatment;
• to reduce treatment to 7 days.

Take Onureg always as indicated by your doctor.

Your doctor will give you a medication that helps reduce nausea and vomiting. You will take this medication 30 minutes before each Onureg tablet, during the first and second treatment cycles. If necessary, your doctor will indicate that you take it for a longer period.

How to take this medication

• Take Onureg once a day - at the same time every day.
• Swallow the tablets whole with a full glass of water.
• To ensure you receive the correct dose, do not break, crush, dissolve, or chew the tablets.
• You can take the medication with food or between meals.

If you vomit after taking a tablet, do not take another dose on the same day. Instead, wait until the next day to take your scheduled dose. Do not take two doses on the same day.

If powder from a broken tablet comes into contact with your skin, wash the skin immediately and thoroughly with water and soap. If the powder enters your eyes, nose, or mouth, rinse the area thoroughly with water.

If you take more Onureg than you should

If you take more tablets than you should, contact your doctor or go to the hospital immediately. If possible, bring the medication packaging and this leaflet.

If you forget to take Onureg

If you forget to take Onureg at your usual time, take your dose as soon as you remember on the same day and take your next dose at your usual time the next day. Do not take a double dose to compensate for a missed or vomited tablet.

If you interrupt treatment with Onureg

Do not stop taking Onureg unless your doctor tells you to.

If you have any other questions about using this medication, ask your doctor.

Like all medications, this medication may produce adverse effects, although not everyone will experience them.

Severe Adverse Effects

Inform your doctor, pharmacist, or nurse immediatelyif you experience any of the following symptoms during treatment with Onureg:

• bruising or bleeding: this could be due to a low count of blood cells called platelets;
• fever: this could be due to an infection as a result of having low white blood cell levels, which is potentially life-threatening;
• diarrhea, vomiting, or nausea (urge to vomit).

Other Adverse Effects Include:

Very Common Adverse Effects(may affect more than 1 in 10 people):

• constipation;
• abdominal pain;
• nasal, sinus, and throat infections;
• lung infection;
• fatigue or weakness;
• loss of appetite
• pain affecting different parts of the body, which may vary from sharp to constant pain;
• joint stiffness;
• back pain.

Common Adverse Effects(may affect up to 1 in 10 people):

• flu;
• urinary tract infection;
• seasonal allergy;
• anxiety;
• weight loss.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through the national notification system included in theAppendix V. By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the blister pack and the box after EXP or CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Onureg

• The active ingredient is azacitidine. Each film-coated tablet contains 200 mg or 300 mg of azacitidine.

• The other components are sodium croscarmellose (E468), magnesium stearate (E572), mannitol (E421), and silicon dioxide (E460, E551) in the form of microcrystalline cellulose.

• The coating of the 200 mg tablet, Opadry II pink, contains: hypromellose (E464), titanium dioxide (E171), lactose monohydrate, polyethylene glycol/macrogol (E1521), triacetin (E1518), and iron oxide red (E172). See section 2 “Onureg contains sodium”.

• The coating of the 300 mg tablet, Opadry II brown, contains: hypromellose (E464), titanium dioxide (E171), lactose monohydrate, polyethylene glycol/macrogol (E1521), triacetin (E1518), iron oxide red (E172), iron oxide yellow (E172), and iron oxide black (E172). See section 2 “Onureg contains sodium”.

Appearance of the product and contents of the packaging

Onureg 200 mg film-coated tablets are pink and oblong with “200” printed on one face and “ONU” on the other face.

Onureg 300 mg film-coated tablets are brown and oblong with “300” printed on one face and “ONU” on the other face.

Film-coated tablets are packaged in aluminum blisters.

Each package contains 7 or 14 film-coated tablets. Some package sizes may only be marketed.

Marketing Authorization Holder

Bristol-Myers Squibb Pharma EEIG

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Responsible Person for Manufacturing

Celgene Distribution B.V.

Orteliuslaan 1000

3528 BD Utrecht

Netherlands

Last revision date of this leaflet:

Other sources of information

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