Gazyvaro 1,000 mg concentrate for solution for infusion

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Gazyvaro is and what it is used for
2. What you need to know before you are given Gazyvaro
3. How Gazyvaro is given
4. Possible side effects
5. How to store Gazyvaro
6. Content of the pack and other information

Gazyvaro contains the active substance obinutuzumab, which belongs to a group of medicines called “monoclonal antibodies”. Antibodies work by attaching themselves to specific targets in your body.

Gazyvaro can be used in adults to treat two different types of cancer

• Chronic lymphocytic leukaemia (also called “CLL”)
  • Gazyvaro is used in patients who have not had any treatment for CLL before and who have other illnesses which make it unlikely that they would be able to tolerate a full dose of a different medicine used to treat CLL called fludarabine.
  • Gazyvaro is used together with another medicine for cancer called chlorambucil.
• Follicular lymphoma (also called “FL”)
  • Gazyvaro is used in patients who have not had any treatment for FL
  • Gazyvaro is used in patients who have had at least one treatment with a medicine called rituximab before and whose FL has come back or got worse during or after this treatment.
  • At the start of treatment for FL, Gazyvaro is used together with other medicines for cancer.
  • Gazyvaro can then be used on its own for up to 2 years as a “maintenance treatment”.

• CLL and FL are types of cancer that affect white blood cells called “B-lymphocytes”. The affected “B-lymphocytes” multiply too quickly and live too long. Gazyvaro binds to targets on the surface of the affected “B-lymphocyte” cells and causes them to die.
• When Gazyvaro is given to patients with CLL or FL together with other medicines for cancer - this slows down the time it takes for their disease to get worse.

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

If you are not sure talk to your doctor or nurse before being given Gazyvaro.

Talk to your doctor or nurse before you are given Gazyvaro if:

• you have an infection, or have had an infection in the past which lasted a long time or keeps coming back
• you have ever taken, or been given, medicines which affect your immune system (such as chemotherapy or immunosuppressants)
• you are taking medicines for high blood pressure or medicines used to thin your blood – your doctor might need to alter how you take these
• you have ever had heart problems
• you have ever had brain problems (such as memory problems, difficulty moving or feeling sensations in your body, eyesight problems)
• you have ever had breathing problems or lung problems
• you have ever had “hepatitis B” - a type of liver disease
• you are due to have a vaccine or you know you may need to have one in the near future.

If any of the above apply to you (or you are not sure), talk to your doctor or nurse before you are given Gazyvaro.

Gazyvaro can cause some serious side effects that you need to tell your doctor or nurse about straight away. These include:

Infusion related reactions

• Tell your doctor or nurse straight away if you get any of the infusion related reactions listed at the start of section 4. Infusion related reactions can happen during the infusion or up to 24 hours after the infusion.
• If you get an infusion related reaction, you may require additional treatment, or the infusion may need to be slowed down or stopped. When these symptoms go away, or improve, the infusion can be continued. These reactions are more likely to happen with the first infusion. Your doctor may decide to stop treatment with Gazyvaro if you have a severe infusion related reaction.
• Before each infusion of Gazyvaro, you will be given medicines which help to reduce possible infusion related reactions or “tumour lysis syndrome”. Tumour lysis syndrome is a potentially life-threatening complication, caused by chemical changes in the blood due to the breakdown of dying cancer cells (see section 3).

• PML is a very rare and life-threatening brain infection that has been reported in very few patients having treatment with Gazyvaro.
• Tell your doctor or nurse straight away if you have memory loss, trouble speaking, difficulty walking or problems with your eyesight.
• If you had any of these symptoms before treatment with Gazyvaro, tell your doctor straight away if you notice any changes in them. You may need medical treatment.

• Tell your doctor or nurse straight away if you get any signs of infection after your Gazyvaro treatment (see "Infections" in section 4).

Do not give Gazyvaro to children or young people under 18 years of age. This is because there is no information about its use in these age groups.

Tell your doctor or nurse if you are taking, have recently taken or might start taking any other medicines. This includes medicines obtained without a prescription and herbal medicines.

• Tell your doctor or nurse if you are pregnant, think you might be pregnant or are planning to have a baby. They will help you weigh up the benefit of continuing Gazyvaro against the risk to your baby.
• If you become pregnant during treatment with Gazyvaro, tell your doctor or nurse as soon as possible. This is because treatment with Gazyvaro may affect yours or the baby’s health.

• Do not breast-feed during treatment with Gazyvaro or for 18 months after stopping treatment with Gazyvaro. This is because small amounts of the medicine may pass into your breast milk.

• Use an effective method of contraception while being treated with Gazyvaro.
• Continue to use effective contraception for 18 months after stopping treatment with Gazyvaro.

Gazyvaro is not likely to affect your ability to drive, cycle or use any tools or machines. However, if you get an infusion related reaction, (see section 4), do not drive, cycle or use any tools or machines until the reaction stops.

Chronic lymphocytic leukaemia

• You will be given 6 treatment cycles of Gazyvaro in combination with another medicine for cancer called chlorambucil. Each cycle lasts 28 days.
• On Day 1 of your first cycle, you will be given part of your first Gazyvaro dose of 100 milligrams (mg) very slowly. Your doctor/nurse will monitor you carefully for infusion related reactions.
• If you do not have an infusion related reaction following the small part of your first dose, you may be given the rest of your first dose (900 mg) on the same day.
• If you do have an infusion related reaction following the small part of your first dose, you will be given the rest of your first dose on Day 2.

A typical schedule is shown below.

Cycle 1 - this will include three doses of Gazyvaro in the 28 days:

• Day 1 – part of your first dose (100 mg)
• Day 2 or Day 1 (continued) – remainder of first dose 900 mg
• Day 8 – full dose (1,000 mg)
• Day 15 – full dose (1,000 mg)

Cycles 2, 3, 4, 5 and 6 this will be just one dose of Gazyvaro in the 28 days:

• Day 1 – full dose (1,000 mg).

• You will be given 6 or 8 treatment cycles of Gazyvaro in combination with other medicines for cancer - each cycle lasts 28 or 21 days depending on which other cancer medicines are given together with Gazyvaro.
• This induction phase will be followed by a “maintenance phase” - during this time you will be given Gazyvaro every 2 months for up to 2 years as long as your disease does not progress. Based on your disease status after the initial treatment cycles your doctor will decide whether you will receive treatment in the maintenance phase.
• A typical schedule is shown below.

Cycle 1 - this will include three doses of Gazyvaro in the 28 or 21 days depending on which other cancer medicines are given together with Gazyvaro:

• Day 1 - full dose (1,000 mg)
• Day 8 - full dose (1,000 mg)
• Day 15 - full dose (1,000 mg).

Cycles 2-6 or 2-8 - this will be just one dose of Gazyvaro in the 28 or 21 days depending on which other cancer medicines are given together with Gazyvaro:

• Day 1 - full dose (1,000 mg).

• Full dose (1,000 mg) once every 2 months for up to 2 years as long as your disease does not progress.

Before each infusion of Gazyvaro, you will be given medicines to lessen the chance of getting infusion related reactions or tumour lysis syndrome. These may include:

• fluids
• medicines to reduce a fever
• medicines to reduce pain (analgesics)
• medicines to reduce inflammation (corticosteroids)
• medicines to reduce an allergic reaction (anti-histamines)
• medicine to prevent tumour lysis syndrome (such as allopurinol).

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

Infusion related reactions

Tell your doctor or nurse straight away if you get any of the following symptoms during your infusion or up to 24 hours after having your infusion:

Most frequently reported:

• nausea
• fatigue
• dizziness
• headache
• diarrhoea
• fever, flushing or chills
• vomiting
• shortness of breath
• low or high blood pressure
• heart beating very fast
• chest discomfort

Less frequently reported:

• irregular heartbeat
• swelling of the throat or airway
• wheezing, difficulty breathing, tight chest or throat irritation

If you get any of the above, tell your doctor or nurse straight away.

PML is a very rare and life-threatening brain infection that has been reported with Gazyvaro.

Tell your doctor or nurse straight away if you have

• memory loss
• trouble speaking
• difficulty walking
• problems with your eyesight

If you had any of these symptoms before treatment with Gazyvaro, tell your doctor straight away if you notice any changes in them. You may need medical treatment.

You may be more likely to get an infection during and after treatment with Gazyvaro. Often these are colds, but there have been cases of more severe infections. A type of liver disease called “hepatitis B” has also been reported to reoccur in patients who have had hepatitis B in the past.

Tell your doctor or nurse straight away if you get any signs of infection during and after your Gazyvaro treatment. These include:

• fever
• cough
• chest pain
• fatigue
• painful rash
• sore throat
• burning pain when passing urine
• feeling weak or generally unwell

If you had recurring or chronic infections before the start of Gazyvaro treatment, tell your doctor about it.

Tell your doctor or nurse if you notice any of the following side effects:

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

• fever
• lung infection
• headache
• joint pain, back pain
• feeling weak
• feeling tired
• pain in arms and legs
• diarrhoea, constipation
• sleeplessness
• hair loss, itchiness
• urinary tract infection, nose and throat inflammation, shingles
• changes in blood tests:
  • anaemia (low levels of red blood cells)
  • low levels of all types of white blood cell (combined)
  • low levels of neutrophils (a type of white blood cell)
  • low level of platelets (a type of blood cell that helps your blood to clot)
• infection of upper airways (infection of nose, pharynx, larynx and sinuses), cough

Common (may affect up to 1 in 10 people)

• cold sores
• depression, anxiety
• flu (influenza)
• weight increase
• runny or blocked nose
• eczema
• pain in mouth or throat
• muscle and bone pain in your chest
• skin cancer (squamous cell carcinoma, basal cell carcinoma)
• bone pain
• irregular heart beat (atrial fibrillation)
• problems with urinating, urinary incontinence
• high blood pressure
• problems with digestion (e.g. heartburn), haemorrhoids
• changes shown in blood tests:
  • low levels of lymphocytes (a type of white blood cells), fever associated with low levels of neutrophils (a type of white blood cells)
  • increase in potassium, phosphate or uric acid - which can cause kidney problems (part of tumour lysis syndrome)
  • decrease in potassium
• a hole in the stomach or intestines (gastrointestinal perforation, especially in cases where the cancer affects the gastrointestinal tubes)

Uncommon (may affect up to 1 in 100 people)

• abnormal coagulation, including a serious illness where clots form all over the body (disseminated intravascular coagulation)

Tell your doctor or nurse if you notice any of the side effects listed above.

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

United Kingdom

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• The active substance is obinutuzumab: 1,000 mg/40 mL per vial corresponding to a concentration before dilution of 25 mg/mL.
• The other ingredients are histidine, histidine hydrochloride monohydrate, trehalose dihydrate, poloxamer 188 and water for injections.

Gazyvaro is a concentrate for solution for infusion and is a colourless to slightly brown liquid. Gazyvaro is available in a pack containing 1 glass vial.

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder: