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.

This medicine is used in adults to treat several different conditions. These include:

• Chronic lymphocytic leukaemia (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 (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.
• Lupus nephritis (LN)
  • Gazyvaro is used in combination with mycophenolate mofetil (MMF) for the treatment of adult patients with active Class III or IV, with or without concomitant Class V, LN (inflammation of the kidney caused by lupus)

• 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.
• LN is a type of kidney disease where the body’s own immune system attacks the kidneys by mistake.
  • Gazyvaro reduces the amount of B-lymphocytes, a kind of immune system cell that is involved in the cause of some of the LN symptoms.
  • Gazyvaro is given to patients with LN together with other medicines. This slows down or stops the immune system from attacking healthy kidney cells.

• 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

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

Also talk to your doctor if you think you may need any vaccinations in the near future, including vaccinations needed to travel to other countries. Some vaccines should not be given at the same time as Gazyvaro or in the months after you receive Gazyvaro. Your doctor will check if you should have any vaccines before you receive 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).

Progressive multifocal leukoencephalopathy (PML)

• 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.

Infections

• 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.

Gazyvaro is given under the supervision of a doctor experienced in such treatment. It is given into a vein as a drip (intravenous infusion) over several hours.

Chronic lymphocytic leukaemia (CLL)

• 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).

Follicular lymphoma (FL)

• 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.

Induction phase

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).

Maintenance phase

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

Lupus nephritis (LN)

You will be given 1,000 mg doses of Gazyvaro as an intravenous infusion as shown in the schedule below:

• Dose 1 (initial infusion): 1,000 mg
• Dose 2 (Week 2, two weeks after Dose 1): 1,000 mg
• Dose 3 (Week 24): 1,000 mg
• Dose 4 (Week 26, two weeks after Dose 3): 1,000 mg
• Dose 5 (six months after Dose 4, and every six months thereafter): 1,000 mg

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.

Serious side effects

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.

Progressive multifocal leukoencephalopathy (PML)

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 notice any of the following side effects:

• 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.

Infections

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 come back 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 get any of these signs after treatment with Gazyvaro, tell your doctor or nurse straight away. If you had infections that keep coming back or long-term infections before the start of Gazyvaro treatment, tell your doctor or nurse about it.

Other side effects

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)
• changes in blood tests: low levels of immunoglobulins (antibodies that help to fight infections)

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

Serious side effects

Infections

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.

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

• sneezing
• runny nose or postnasal drip
• fever
• cough
• chest pain
• fatigue
• rash
• sore throat
• burning pain when passing urine
• flu-like symptoms, feeling weak or generally unwell

If you get any of these signs after treatment with Gazyvaro, tell your doctor or nurse straight away. If you had infections that keep coming back or long-term infections before the start of Gazyvaro treatment, tell your doctor or nurse about it.

Neutropenia

Neutropenia involves having low levels of neutrophils (a type of white blood cell) in your blood. Tell your doctor or nurse straight away if you notice any of the following side effects:

• fever or chills
• cough
• sore throat
• mouth ulcers due to infections
• altered blood tests

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:

• nausea
• fatigue
• dizziness or fainting
• headache
• diarrhoea
• fever, flushing or chills
• vomiting
• shortness of breath or difficulty breathing
• low or high blood pressure
• heart beating very fast
• chest discomfort
• abdominal pain or discomfort
• redness, swelling or discharge
• joint pain, aching muscles

Progressive multifocal leukoencephalopathy (PML)

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

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

• 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.

Other side effects

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

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

• inflammation of the lungs (bronchitis)
• changes in blood tests: low levels of immunoglobulins (antibodies that help to fight infections)

Common (may affect up to 1 in 10 people)

• lung infection (pneumonia)
• herpes simplex viral infection of the mouth (such as cold sores) or the genitals

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 via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• 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.