Azaturas 25 mg Suspension

The active substance is azacitidine. AZATURAS 25 mg/mL is an anticancer medicine which belongs to a group of medicines called “anti-metabolites”. AZATURAS 25 mg/mL works by preventing cancer cells from growing. Azacitidine becomes incorporated into the genetic material of cells (ribonucleic acid (RNA) and deoxyribonucleic acid (DNA)). It is thought to work by altering the way the cell turns genes on and off and also by interfering with the production of new RNA and DNA. These actions are thought to correct problems with the maturation and growth of young blood cells in the bone marrow that cause myelodysplastic disorders, and to kill cancerous cells in leukaemia. AZATURAS 25 mg/mL is used in adults 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).
• Refractory anaemia with excess blasts in transformation (RAEB-T), also known as acute myeloid leukaemia (AML).

These are diseases which affect the bone marrow and can cause problems with normal blood cell production.

AZATURAS 25 mg/mL should not be administered to you:

• If you are hypersensitive (allergic) to azacitidine or to any of the other ingredients of this medicine (listed in section 6).
• If you have advanced liver cancer.
• If you are pregnant or breastfeeding (see section 2, “Pregnancy and breastfeeding”).
• You may not receive live vaccines while being treated with AZATURAS 25 mg/mL.
• AZATURAS 25 mg/mL is not recommended for use if you are below the age of 18 years.

Warnings and precautions

Tell your doctor or health care provider before being given the injection:

• If you have decreased counts of platelets, red or white blood cells.
• If you have liver disease.
• If you have kidney disease.
• If you have ever had a heart condition or heart attack, or any history of lung disease.
• If you develop a condition such as necrotising fasciitis (a rare but serious bacterial infection that affects the tissue beneath the skin and surrounding muscles and organs (fascia)); your therapy should be stopped.
• If you are at risk of developing tumour lysis syndrome (a condition that occurs when tumour cells release their contents into the bloodstream).

AZATURAS 25 mg/mL can cause a serious immune reaction called differentiation syndrome, it can be fatal and symptoms and clinical findings include difficulty in breathing, fever, rash, rapid weight gain, low blood pressure and kidney problems.

Blood tests: You will have blood tests before you begin treatment with AZATURAS 25 mg/mL 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.

Children and adolescents

AZATURAS 25 mg/mL is not recommended for use in children and adolescents below the age of 18 years.

Other medicines and AZATURAS 25 mg/mL

Always tell your health care provider if you are taking any other medicine. (This includes all complementary or traditional medicines.) AZATURAS 25 mg/mL may affect the way some other medicines work. Also, some other medicines may affect the way AZATURAS 25 mg/mL works.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, please consult your doctor, pharmacist or other health care provider for advice before receiving AZATURAS 25 mg/mL. You should not use AZATURAS 25 mg/mL during pregnancy as it may be harmful to the baby. Use an effective method of contraception during and up to 3 months after treatment. Tell your doctor straight away if you become pregnant during treatment. You should not breastfeed when using AZATURAS 25 mg/mL. It is not known if this medicine passes into human milk. Men should not father a child while receiving treatment with AZATURAS 25 mg/mL. Use an effective method of contraception during and up to 3 months after treatment with this medicine. 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 AZATURAS 25 mg/mL. If this happens to you, do not drive or use any tools or machines.

Do not share medicines prescribed for you with any other person. You will not be expected to give yourself AZATURAS 25 mg/mL. It will be given to you by a person who is qualified to do so (see section 6). Before giving you AZATURAS 25 mg/mL, your doctor will give you another medicine to prevent nausea and vomiting at the start of each treatment cycle.

• The recommended dose is 75 mg per m2 body surface area. Your doctor will decide your dose of this medicine, depending on your general condition, height and weight. Your doctor will check your progress and may change your dose if necessary.
• AZATURAS 25 mg/mL 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.
• This medicine 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 medicine, ask your doctor, pharmacist or nurse.

If you receive more AZATURAS 25 mg/mL than you should Since a health care provider will administer AZATURAS 25 mg/mL, he/she will control the dosage. However, in the event of overdosage your doctor will manage the overdosage.

If you forget to use AZATURAS 25 mg/mL Since a health care provider will administer AZATURAS 25 mg/mL, it is unlikely that the dose will be missed. If you think you have not been given a dose of AZATURAS 25 mg/mL, tell your doctor or other health care provider immediately.

If you stop using AZATURAS 25 mg/mL It is important to keep receiving AZATURAS 25 mg/mL every day, as long as your doctor prescribes it for you. If you have any further questions on the use of AZATURAS 25 mg/mL, ask your doctor or pharmacist.

AZATURAS 25 mg/mL can have side effects. Not all side effects reported for AZATURAS 25 mg/mL are included in this leaflet. Should your general health worsen or if you experience any untoward effects while receiving AZATURAS 25 mg/mL, please consult your health care provider for advice.

If any of the following happens, stop using AZATURAS 25 mg/mL and tell your doctor immediately or go to the casualty department at your nearest hospital:

• Swelling of your hands, feet, ankles, face, lips and mouth or throat, which may cause difficulty in swallowing or breathing.
• Rash or itching.
• Fainting.

These are all very serious side effects. If you have them, you may have had a serious reaction to AZATURAS 25 mg/mL. You may need urgent medical attention or hospitalisation.

Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

• Drowsiness, shaking, jaundice, abdominal bloating and easy bruising. These may be symptoms of liver failure and can be life-threatening.
• Swelling of the legs and feet, back pain, reduced passing of water, increased thirst, rapid pulse, dizziness and nausea, vomiting or reduced appetite and feelings of confusion, restlessness or fatigue. These may be symptoms of kidney failure and can be life-threatening.
• A fever. This could be due to an infection as a result of having low levels of white blood cells, which can be life-threatening.
• 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 and can be life-threatening.
• Infection of the deeper layers of skin, which spreads quickly, damaging the skin and tissue, which can be life-threatening (necrotising fasciitis).
• Tumour lysis syndrome - Metabolic complications that can occur during treatment of cancer and sometimes even without treatment. These complications are caused by the product of dying cancer cells and may include the following: changes to blood chemistry; high potassium, phosphorus, uric acid, and low calcium consequently leading to changes in kidney function, heartbeat, seizures, and sometimes death.
• Serious immune reaction (differentiation syndrome) which may cause fever, coughing, difficulty in breathing, rash, decreased urination, low blood pressure (hypotension) and swelling of the arms and legs.

Frequent side effects:

• Nasopharyngitis.
• An infection of the blood caused by bacteria (sepsis). This may be due to low levels of white cells in your blood.
• White coating covering tongue, inner cheeks, and sometimes on the roof of your mouth, gums and tonsils (oral fungal infection).
• Skin infection (cellulitis).
• Sore or runny nose or sinuses (sinusitis).
• A disease affecting the gut which can result in fever, vomiting and stomach pain (diverticulitis).
• An infection in your urinary tract.
• A viral infection causing cold sores (herpes).
• Infection of the skin.
• 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.
• A low blood platelet count (thrombocytopenia). You are more prone to bleeding and bruising.
• 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.
• Loss of appetite.
• Low levels of potassium in your blood.
• Dehydration.
• Having trouble sleeping (insomnia).
• Anxiety.
• Being confused.
• Fainting.
• Bleeding inside your head.
• Dizziness.
• Tiredness.
• Headache.
• Sleepiness, drowsiness (somnolence).
• Bleeding in your eye.
• Collection of fluid around the heart (pericardial effusion).
• High or low blood pressure (hypertension or hypotension).
• A fall in blood pressure when standing (orthostatic hypotension) leading to dizziness when moving to a standing or sitting position.
• Tiny round, brown-purple spots due to bleeding under the skin, may be in a small area due to minor trauma, or widespread due to blood clotting disorder (petechiae).
• Nosebleeds (epistaxis).
• Fluid around the lungs (pleural effusion).
• Shortness of breath (dyspnoea) or difficulty breathing when you move or exercise (dyspnoea on exertion).
• Constipation, diarrhoea, nausea, vomiting.
• Pain in your belly (abdominal pain).
• 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).
• Ulcers of your mouth or tongue.
• Indigestion.
• Itching.
• Rash or increased sweating.
• Bruising.
• Red or purple spots under your skin.
• Hair loss.
• Raised itchy rash on the skin (urticaria).
• Redness of your skin.
• Joint aches.
• Muscle aches or spasms.
• Blood in your urine.
• Painful or difficult urination.
• Tiredness (fatigue).
• Fever.
• Injection site reaction including redness, pain or a skin reaction.
• 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.
• Bleeding due to a catheter line.
• Shivering (chills).
• Feeling generally unwell.

Less frequent side effects:

• Inflammation of the lining around the heart (pericarditis).
• Scarring (fibrosis) of the lungs.
• A collection of pus in the tissue around the anus and rectum.
• Painful skin ulceration (pyoderma gangrenosum).
• A painful skin rash that appears mostly on the arms, face and neck, along with a fever.
• Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to remove acids from the blood into the urine as they should.
• Injection site necrosis (tissue death).

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects

If you get side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects to SAHPRA via the Med Safety App (Medsafety X SAHPRA) and eReporting platform (who-umc-org) found on SAHPRA’s website. By reporting side effects, you can help provide more information on the safety of AZATURAS 25 mg/mL.

• Store all medicines out of reach of children.
• Do not use after the expiry date printed on the carton or vial.
• Your doctor, pharmacist or nurse is responsible for storing AZATURAS 25 mg/mL. They are also responsible for preparing and disposing of any unused AZATURAS 25 mg/mL correctly.

For unopened vials of this medicine: Store at or below 25 °C. When using later on: When stored at 25 °C, the reconstituted product should be administered within 1 hour. If the AZATURAS 25 mg/mL suspension is prepared using water for injections that has not been refrigerated, the suspension must be placed in the refrigerator (2 °C – 8 °C) immediately after it is prepared and kept refrigerated for up to a maximum of 8 hours. After removal from refrigerated conditions, the suspension may be allowed to equilibrate to room temperature (25 °C) for up to 30 minutes prior to administration. If the AZATURAS 25 mg/mL suspension is prepared using water for injections that has been stored in the refrigerator (2 °C – 8 °C), the suspension must be placed in the refrigerator (2 °C – 8 °C) immediately after it is prepared and kept refrigerated for up to a maximum of 22 hours.