Vidaza 25 mg/ml powder for suspension for injection

Vidaza contains the active substance azacitidine. It works by preventing the growth of cancer cells.

Vidaza is used in adults who are not eligible for stem cell transplantation to treat:

• higher-risk myelodysplastic syndromes (MDS) a group of illnesses of the bone marrow resulting in the production of too few blood cells.
• chronic myelomonocytic leukaemia (CMML).
• acute myeloid leukaemia (AML).

Talk to your doctor if you have any questions about how Vidaza works or why this medicine has been prescribed for you.

Do not use Vidaza

• if you are allergic (hypersensitive) to azacitidine or to any of the other ingredients of Vidaza (see section 6).
• if you have advanced liver cancer.
• if you are breastfeeding.

Take special care with Vidaza

Check with your doctor or nurse before using this medicine if you have:

• decreased counts of platelets, red or white blood cells.
• kidney disease.
• liver disease.

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

Vidaza is not recommended for use in children and adolescents below the age of 18.

You will have blood tests before you begin treatment with Vidaza and at the start of each period of treatment (called a ?cycle?). This is to check that you have enough blood cells and that your liver and kidneys are working properly.

For men having Vidaza, please see the section ?Pregnancy and breastfeeding? below.

Taking other medicines

Please tell your doctor or nurse if you are using or have recently used any other medicines including medicines obtained without a prescription and herbal preparations. This is because Vidaza may affect the way some other medicines work. Also, some other medicines may affect the way Vidaza works.

Pregnancy and breastfeeding

You should not use Vidaza during pregnancy as it may be harmful to the baby.
Use an effective method of contraception during and up to 3 months after treatment with Vidaza. Tell your doctor straight away if you become pregnant during treatment with Vidaza.

You must not use Vidaza if you are breastfeeding. It is not known if Vidaza passes into the mother?s milk and therefore you must not breastfeed your baby during treatment.

Men should not father a child while receiving treatment with Vidaza. Use an effective method of contraception during and up to 3 months after treatment with Vidaza.
Talk to your doctor if you wish to conserve your sperm before starting this treatment.

Driving and using machines

No studies of the effects on the ability to drive and use machines have been performed. Some people may feel tired after being given Vidaza. If this happens to you, do not drive or use any tools or machines.

Your doctor will give you another medicine to prevent nausea and vomiting at the start of each treatment cycle, before giving you Vidaza.

The usual dose is 75 mg per m2 body surface area. Your doctor will choose your dose of Vidaza, depending on your general condition, height and weight. Your doctor will check your progress and may change your dose if necessary. Vidaza is given every day for one week, followed by a rest period of 3 weeks. This treatment cycle will be repeated every 4 weeks. You will usually receive at least 6 treatment cycles.

Vidaza will be given to you as an injection under the skin (subcutaneously) by a doctor or nurse. It may be given under the skin on your thigh, tummy or upper arm.

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

Like all medicines, Vidaza can cause side effects, although not everybody gets them.

Tell your doctor straight away if you notice any of the following side effects:

• A fever. This may be due to an infection as a result of having low levels of white blood cells.
• Chest pain or shortness of breath which may be accompanied with a fever. This may be due to an infection of the lung called ?pneumonia?.
• Bleeding. Such as blood in the stools due to bleeding in the stomach or gut.
• Difficulty breathing, swelling of the lips, itching or rash. Thismay be due to an allergic (hypersensitivity) reaction.

Side effects may occur with certain frequencies, which are defined as follows:

very common affects more than 1 user in 10 common affects 1 to 10 users in 100 uncommon affects 1 to 10 users in 1,000 rare affects 1 to 10 users in 10,000 very rare affects less than 1 user in 10,000 not known frequency cannot be estimated from the available data

Very common side effects

• Reduced red blood count (anaemia). You may feel tired and pale.
• Reduced white blood cell count. This may be accompanied by a fever. You are also more likely to get infections.
• A low blood platelet count (thrombocytopenia). You are more prone to bleeding and bruising.
• Constipation, diarrhoea, nausea, vomiting.
• Pneumonia.
• Chest pain, being short of breath.
• Tiredness (fatigue).
• Injection site reaction including redness, pain or a skin reaction.
• Loss of appetite.
• Joint aches.
• Bruising.
• Rash.
• Red or purple spots under your skin.
• Pain in your belly (abdominal pain).
• Itching.
• Fever.
• Sore nose and throat.
• Dizziness.
• Headache.

Common side effects

• Bleeding inside your head.
• An infection of the blood caused by bacteria (sepsis). This may be due to low levels of white cells in your blood.
• Bone marrow failure. This can cause low levels of red and white blood cells and platelets.
• A type of anaemia where your red and white blood cells and platelets are reduced.
• An infection in your urine.
• A viral infection causing cold sores (herpes).
• Bleeding gums, bleeding in the stomach or gut, bleeding from around your back passage due to piles (haemorrhoidal haemorrhage), bleeding in your eye, bleeding under your skin, or into your skin (haematoma).
• Blood in your urine.
• Ulcers of your mouth or tongue.
• Changes to your skin at the injection site. These include swelling, a hard lump, bruising, bleeding into your skin (haematoma), rash, itching and changes in the skin colour.
• Redness of your skin.
• An infection of the nose and throat, or sore throat.
• Sore or runny nose or sinuses (sinusitis).
• Low levels of potassium in your blood.
• High or low blood pressure (hypertension or hypotension).
• Being short of breath when you move.
• Pain in your throat and voicebox.
• Indigestion.
• Weight loss.
• Lethargy.
• Feeling generally unwell.
• Muscle aches.
• Anxiety or having trouble sleeping (insomnia).
• Being confused.
• Hair loss.

Uncommon side effects

• Allergic (hypersensitivity) reaction.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or nurse.

Keep out of the reach and sight of children.

Do not use Vidaza after the expiry date which is stated on the vial label and the carton. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.
The reconstituted suspension may be stored at 25°C for 45 minutes or at 2°C to 8°C for 8 hours.

Your doctor or pharmacist are responsible for storing Vidaza. They are also responsible for disposing of any unused Vidaza correctly.

What Vidaza contains

• The active substance is azacitidine. 1 vial contains 100 mg azacitidine. After reconstitution with 4 ml of water for injections, the reconstituted suspension contains 25 mg/ml azacitidine .
• The other ingredient is mannitol (E421).

What Vidaza looks like and contents of the pack

Vidaza is a white powder for suspension for injection and is supplied in a glass vial containing 100 mg of azacitidine.

Marketing Authorisation Holder

Celgene Europe Ltd
Riverside House
Riverside Walk
Windsor
SL4 1NA
United Kingdom

Manufacturer

Baxter Oncology GmbH
Kantstrasse 2
33790 Halle/Westfalen
Germany

OR

Catalent UK Packaging Limited

Sedge CloseGreat Oakley

Headway
Corby

Northamptonshire

NN18 8HS

United Kingdom

This leaflet was last approved in

The following information is intended for medical or healthcare professionals only:

Recommendations for safe handling
Vidaza is a cytotoxic medicinal product and, as with other potentially toxic compounds, caution should be exercised when handling and preparing azacitidine suspensions. Procedures for proper handling and disposal of anticancer medicinal products should be applied.
If reconstituted azacitidine comes into contact with the skin, immediately and thoroughly wash with soap and water. If it comes into contact with mucous membranes, flush thoroughly with water.

Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned below ?Reconstitution Procedure?.

Reconstitution procedure

1. The following supplies should be assembled:

• Vial(s) of azacitidine; vial(s) of water for injections; nonsterile surgical gloves;
• Alcohol wipes; 5 ml injection syringe(s) with needle(s).

2. 4 ml of water for injections should be drawn into the syringe, making sure to purge any air trapped within the syringe.

3. The needle of the syringe containing the 4 ml of water for injections should be inserted through the rubber top of the azacitidine vial followed by injection of the water for injections into the vial.

4. Following removal of the syringe and needle, the vial should be vigorously shaken until a uniform cloudy suspension is achieved. After reconstitution each ml of suspension will contain 25 mg of azacitidine (100 mg/4 ml). The reconstituted product is a homogeneous, cloudy suspension, free of agglomerates. The product should be discarded if it contains large particlesor agglomerates.

5. The rubber top should be cleaned and a new syringe with needle inserted. The vial should then be turned upside down, making sure the needle tip is below the level of the liquid. The plunger should then be pulled back to withdraw the amount of medicinal product required for the proper dose, making sure to purge any air trapped within the syringe. The syringe with needle should then be removed from the vial and the needle disposed of.

6. A fresh subcutaneous needle (recommended 25-gauge) should then be firmly attached to the syringe. The needle should not be purged prior to injection, in order to reduce the incidence of local injection site reactions.

7. If needed (doses over 100 mg) all the above steps for preparation of the suspension should be repeated. For doses greater than 100 mg (4 ml), the dose should be equally divided into 2 syringes (e.g, dose 150 mg = 6 ml, 2 syringes with 3 ml in each syringe).

8. The contents of the dosing syringe must be re-suspended immediately prior to administration. The temperature of the suspension at the time of injection should be approximately 20ºC-25ºC. To re-suspend, vigorously roll the syringe between the palms until a uniform, cloudy suspension is achieved. The product should be discarded if it contains large particles or agglomerates.

The Vidaza suspension should be prepared immediately before use and the reconstituted suspension should be administered within 45 minutes. If elapsed time is greater than 45 minutes, the reconstituted suspension should be discarded appropriately and a new dose prepared. Alternatively, if the product needs to be reconstituted in advance of the administration, it must be placed in a refrigerator (2°C to 8°C) immediately after reconstitution, and kept in the refrigerator for a maximum of 8 hours. If the elapsed time in the refrigerator is greater than 8 hours, the suspension should be discarded appropriately and a new dose prepared. The syringe filled with reconstituted suspension should be allowed up to 30 minutes prior to administration to reach a temperature of approximately 20ºC-25ºC. If the elapsed time is longer than 30 minutes, the suspension should be discarded appropriately and a new dose prepared.

Calculation of an individual dose
The total dose, according to the body surface area (BSA) can be calculated as follows:

Total dose mg Dose mgm2 x BSA m2

The following table is provided only as an example of how to calculate individual azacitidine doses based on an average BSA value of 1.8 m 2.

Total dose based on Number of vials Dose mgm2 of recommended BSA value of 1.8 m2required starting dose Total volume of reconstituted suspension required 75 mgm2 100 135 mg 2 vials 5.4 ml 37.5 mgm 50 267.5 mg 1 vial 2.7 ml 25 mgm2 33 45 mg 1 vial 1.8 ml

Method of administration angle using a Reconstituted Vidaza should be injected subcutaneously insert the needle at a 45-90o25-gauge needle into the upper arm, thigh or abdomen.

Doses greater than 4 ml should be injected into two separate sites.

Injection sites should be rotated. New injections should be given at least 2.5 cm from the previous site and never into areas where the site is tender, bruised, red, or hardened.

Any unused product or waste material should be disposed of in accordance with local requirements.