What is a Patient Information Leaflet and why is it useful?

The Patient Information Leaflet (PIL) is the leaflet included in the pack with a medicine. It is written for patients and gives information about taking or using a medicine. It is possible that the leaflet in your medicine pack may differ from this version because it may have been updated since your medicine was packaged.

Below is a text only representation of the Patient Information Leaflet, the original can be viewed in PDF format using the link above.

The text only version may be available from RNIB in large print, Braille or audio CD. For further information call RNIB Medicine Leaflet Line on 0800 198 5000. The product code(s) for this leaflet is: EU/1/14/937/001 .

Gazyvaro 1,000 mg concentrate for solution for infusion

Package leaflet: Information for the patient

Gazyvaro 1,000 mg concentrate for solution for infusion

Obinutuzumab

▼This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

  • 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.

What is in this leaflet

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

1. What Gazyvaro is and what it is used for

What Gazyvaro is

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.

What Gazyvaro is used for

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”.

How Gazyvaro works

  • 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.

2. What you need to know before you are given Gazyvaro

You must not be given Gazyvaro if:

  • 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.

Warnings and precautions

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.

Pay attention to the following side effects

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 (also called “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).

Children and adolescents

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.

Other medicines and Gazyvaro

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.

Pregnancy

  • 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.

Breast-feeding

  • 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.

Contraception

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

Driving and using machines

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.

3. How Gazyvaro is given

How Gazyvaro is given

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.

The Gazyvaro treatment

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).

Follicular lymphoma

  • 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.

Medicines given before each infusion

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 a Gazyvaro treatment

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.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects have been reported with this medicine:

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 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.

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 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.

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
  • 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)

  • red eye
  • cold sores
  • depression, anxiety
  • night sweats
  • flu (influenza)
  • weight increase
  • lymph node pain
  • runny or blocked nose
  • eczema
  • nose or throat inflammation
  • pain in mouth or throat
  • muscle and bone pain in your chest
  • skin cancer (squamous cell carcinoma)
  • bone pain, pain in arms and legs
  • irregular heart beat (atrial fibrillation), heart attack
  • problems with urinating, urinary incontinence
  • problems with digestion (e.g. heartburn), inflammation of the intestine, haemorrhoids
  • changes shown in blood tests:
    • low levels of lymphocytes (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.

Uncommon (may affect up to 1 in 100 people)

  • a hole in the stomach or intestines (gastrointestinal perforation, especially in cases where the cancer affects the gastrointestinal tubes).

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

Reporting of side effects

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.

Ireland

HPRA Pharmacovigilance
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website:www.hpra.ie
e-mail:medsafety@hpra.ie

Malta

ADR Reporting
Website:www.medicinesauthority.gov.mt/adrportal

United Kingdom

Yellow Card Scheme
Website:www.mhra.gov.uk/yellowcard

or search for MHRA Yellow Card in the Google Play or Apple App Store

5. How to store Gazyvaro

Gazyvaro will be stored by the healthcare professionals at the hospital or clinic. The storage details are as follows:

  • Keep this medicine out of the sight and reach of children.
  • Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.
  • Store in a refrigerator (2 °C-8 °C). Do not freeze.
  • Keep the container in the outer carton in order to protect from light.

Medicines should not be disposed of via wastewater or household waste. Your healthcare professional will throw away any medicines that are no longer being used. These measures will help protect the environment.

6. Contents of the pack and other information

What Gazyvaro contains

  • 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 L-histidine, L-histidine hydrochloride monohydrate, trehalose dihydrate, poloxamer 188 and water for injections.

What Gazyvaro looks like and contents of the pack

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.

Marketing Authorisation Holder

Roche Registration Limited
6 Falcon Way
Shire Park
Welwyn Garden City
AL7 1TW
United Kingdom

Manufacturer

Roche Pharma AG
Emil-Barell-Strasse 1
D-79639 Grenzach-Wyhlen
Germany

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

United Kingdom
Roche Products Ltd.
Tel: +44 (0) 1707 366000

This leaflet was last revised in October 2017

Other sources of information

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

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