Tecentriq 1,200 mg concentrate for solution for infusion

• Keep this leaflet. You may need to read it again.
• It is important that you keep the Patient Card with you during treatment.
• 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 Tecentriq is and what it is used for
2. What you need to know before you are given Tecentriq
3. How Tecentriq is given
4. Possible side effects
5. How to store Tecentriq
6. Contents of the pack and other information

Tecentriq is an anti-cancer medicine that contains the active substance atezolizumab.

• It belongs to a group of medicines called monoclonal antibodies.
• A monoclonal antibody is a type of protein designed to recognise and attach to a specific target in the body.
• This antibody can help your immune system fight your cancer.

Tecentriq is used in adults to treat:

• A kind of bladder cancer, called urothelial carcinoma
• A kind of lung cancer, called non-small cell lung cancer
• A kind of lung cancer, called small cell lung cancer
• A kind of breast cancer, called triple negative breast cancer.
• A kind of liver cancer, called hepatocellular carcinoma

Patients may get Tecentriq when their cancer has spread to other parts of the body or has come back after previous treatment.

Patients may get Tecentriq when their lung cancer has not spread to other parts of the body and treatment will be given after surgery and chemotherapy. Treatment after surgery is called adjuvant therapy.

Tecentriq may be given in combination with other anticancer medicines. It is important that you also read the package leaflets for the other anticancer medicines you may be receiving. If you have any questions about these medicines, ask your doctor.

Tecentriq works by attaching to a specific protein in your body called programmed death-ligand 1 (PD-L1). This protein suppresses the body’s immune (defence) system, thereby protecting cancer cells from being attacked by the immune cells. By attaching to the protein, Tecentriq helps your immune system to fight your cancer.

• if you are allergic to atezolizumab 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 you are given Tecentriq.

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

• have an auto-immune disease (a condition where the body attacks its own cells)
• have been told that your cancer has spread to your brain
• have any history of inflammation of your lungs (called pneumonitis)
• have or have had chronic viral infection of the liver, including hepatitis B (HBV) or hepatitis C (HCV)
• have human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS)
• have a significant cardiovascular (heart) disease or blood disorders or organ damage due to inadequate blood flow
• have had serious side effects because of other antibody therapies that help your immune system to fight cancer
• have been given medicines to stimulate your immune system
• have been given medicines to suppress your immune system
• have been given a live, attenuated vaccine
• have been given medicines to treat infections (antibiotics) in the past two weeks

Tecentriq acts on your immune system. It may cause inflammation in parts of your body. Your risk of these side effects may be higher if you already have an autoimmune disease (a condition where the body attacks its own cells). You may also experience frequent flares of your autoimmune disease, which in the majority of cases are mild.

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

Tecentriq may cause some side effects that you must tell your doctor about straight away. They may happen weeks or months after your last dose. Tell your doctor straight away if you notice any of the symptoms below:

• inflammation of the lung (pneumonitis): symptoms may include new or worsening cough, shortness of breath, and chest pain
• inflammation of the liver (hepatitis): symptoms may include yellowing of skin or eyes, nausea, vomiting, bleeding or bruising, dark urine, and stomach pain
• inflammation of the intestines (colitis): symptoms may include diarrhoea (watery, loose or soft stools), blood in stools, and stomach pain
• inflammation of the thyroid, adrenal glands and the pituitary gland (hypothyroidism, hyperthyroidism, adrenal insufficiency or hypophysitis): symptoms may include tiredness, weight loss, weight gain, change in mood, hair loss, constipation, dizziness, headaches, increased thirst, increased urination and changes in vision
• type 1 diabetes, including a serious, sometimes life-threatening problem due to acid in the blood produced from diabetes (diabetic ketoacidosis): symptoms may include feeling more hungry or thirsty than usual, need to urinate more often, weight loss, feeling tired or having difficulty thinking clearly, breath that smells sweet or fruity, a sweet or metallic taste in your mouth, or a different odour to your urine or sweat, nausea or vomiting, stomach pain, and deep or fast breathing
• inflammation of the brain (encephalitis) or inflammation of the membrane around the spinal cord and brain (meningitis): symptoms may include neck stiffness, headache, fever, chills, vomiting, eye sensitivity to light, confusion and sleepiness
• inflammation or problems of the nerves (neuropathy): symptoms may include weakness in the arm and leg muscles, or face muscles, double vision, difficulties with speech and chewing, numbness, and tingling in hands and feet
• inflammation of the spinal cord (myelitis): symptoms may include pain, abnormal sensations such as numbness, tingling, coldness or burning, weakness in the arms or legs, and bladder and bowel problems
• inflammation of the pancreas (pancreatitis): symptoms may include abdominal pain, nausea and vomiting
• inflammation of the heart muscle (myocarditis): symptoms may include shortness of breath, decreased exercise tolerance, feeling tired, chest pain, swelling of the ankles or legs, irregular heartbeat, and fainting
• inflammation of the kidneys (nephritis); symptoms may include changes in urine output and colour, pain in pelvis, and swelling of the body and may lead to failure of the kidneys
• inflammation of the muscles (myositis); symptoms may include muscle weakness, fatigue after walking or standing, tripping or falling, and trouble swallowing or breathing
• severe reactions associated with infusion (events occurring during the infusion or within one day of the infusion): may include fever, chills, shortness of breath and flushing
• severe skin reactions (SCARs); which may include rash, itching, skin blistering, peeling or sores, and/or ulcers in the mouth or in lining of the nose, throat or genital area
• inflammation of the heart sac with build-up of fluid in the sac (in some cases) (pericardial disorders): symptoms are similar to those of myocarditis and may include chest pain (usually over the front of the chest, sharp, and worsened by deep breathing and better when you sit up and lean forward in case of inflammation of the heart sac), cough, irregular heartbeat, swelling of the ankles, legs or abdomen, shortness of breath, fatigue, and fainting
• a condition where the immune system makes too many infection-fighting cells called histiocytes and lymphocytes that may cause various symptoms (haemophagocytic lymphohistiocytosis): symptoms may include enlarged liver and/or spleen, skin rash, lymph node enlargement, breathing problems, easy bruising, kidney abnormalities, and heart problems

If you notice any of the symptoms above, tell your doctor straight away.

Do not try to treat yourself with other medicines. Your doctor may:

• Give you other medicines to prevent complications and reduce symptoms.
• Delay giving your next dose of Tecentriq.
• Stop your treatment with Tecentriq.

Before your treatment, your doctor will check your general health. You will also have blood tests during your treatment.

This medicine should not be given to children or adolescents below 18 years of age. This is because the safety and efficacy of Tecentriq have not been established in this age group.

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

• If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.
• You will not be given Tecentriq if you are pregnant unless your doctor considers it necessary. This is because the effect of Tecentriq in pregnant women is not known - it is possible that it could harm your unborn baby.
• If you could become pregnant, you must use effective contraception:
  • while you are being treated with Tecentriq and
  • for 5 months after the last dose.
• If you become pregnant while you are being treated with Tecentriq tell your doctor.

It is not known if Tecentriq gets into breast milk. Ask your doctor if you should stop breast-feeding or if you should stop treatment with Tecentriq.

Tecentriq has minor influence on your ability to drive and use machines. If you feel tired, do not drive or use machines until you feel better.

Tecentriq 840 mg contains 5.6 mg of polysorbate 20 in each 14 ml dose, which is equivalent to 0.4 mg/mL. Tecentriq 1,200 mg contains 8.0 mg of polysorbate 20 in each 20 ml dose, which is equivalent to 0.4 mg/mL. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.

Important information from this package leaflet can be found in the Patient Card you have been given by your doctor. It is important that you keep this Patient Card and show it to your partner or caregivers.

The recommended dose is either:

• 840 milligrams (mg) every two weeks, or
• 1,200 milligrams (mg) every three weeks, or
• 1,680 milligrams (mg) every four weeks.

Tecentriq is given as a drip into a vein (an intravenous infusion).

Your first infusion will be given over 60 minutes.

• Your doctor will monitor you carefully during the first infusion.
• If you do not have an infusion reaction during the first infusion, the next infusions will be given to you over a period of 30 minutes.

Your doctor will keep giving you Tecentriq until you no longer benefit from it. However, it may be stopped if the side effects become too much of a problem.

If you miss an appointment, make another one straight away. For the treatment to be fully effective, it is very important to keep having the infusions.

Do not stop treatment with Tecentriq unless you have discussed this with your doctor. This is because stopping treatment may stop the effect of the medicine.

The following side effects have been reported in clinical trials with Tecentriq used alone:

Very common: may affect more than 1 in 10 people

• fever
• nausea
• vomiting
• feeling very tired with no energy (fatigue)
• lack of energy
• itching of the skin
• diarrhoea
• joint pain
• rash
• loss of appetite
• shortness of breath
• urinary tract infection
• back pain
• cough
• headache

Common: may affect up to 1 in 10 people

• inflammation of the lungs (pneumonitis)
• low oxygen levels, which may cause shortness of breath as a consequence of inflamed lungs (hypoxia)
• stomach pain
• pain in the muscles and bones
• inflammation of the liver
• elevated liver enzymes (shown in tests), which may be a sign of an inflamed liver
• difficulty swallowing
• blood tests showing low levels of potassium (hypokalaemia) or sodium (hyponatremia)
• low blood pressure (hypotension)
• underactive thyroid gland (hypothyroidism)
• allergic reaction (infusion-related reaction, hypersensitivity or anaphylaxis)
• flu-like illness
• chills
• inflammation of the intestines
• low platelet count, which may make you more likely to bruise or bleed (thrombocytopenia)
• high blood sugar
• common cold (nasopharyngitis)
• mouth and throat pain, or dry mouth
• dry skin
• abnormal kidney test (possible kidney damage)
• overactive thyroid gland (hyperthyroidism)
• inflammation of the heart sac with build-up of fluid in the sac (in some cases) (pericardial disorders)
• nerve damage resulting in possible numbness, pain, and/or loss of motor function (peripheral neuropathy)

Uncommon: may affect up to 1 in 100 people

• inflammation of the pancreas
• numbness or paralysis, which may be signs of Guillain-Barré syndrome
• inflammation of the membrane around the spinal cord and brain
• low levels of adrenal hormones
• type 1 diabetes (including diabetic ketoacidosis)
• inflammation of muscles (myositis)
• red, dry, scaly patches of thickened skin (psoriasis)
• inflammation of the kidneys
• itching, skin blistering, peeling or sores, and/or ulcers in the mouth or in lining of nose, throat, or genital area which can be severe (severe skin reactions)
• inflammation of the pituitary gland situated at the base of the brain
• elevated creatine phosphokinase in the blood (shown in test), which may be a sign of muscle or heart inflammation
• changes in any area of the skin and/or genital area that are associated with drying out, thinning, itching and pain (lichen disorders)

Rare: may affect up to 1 in 1,000 people

• inflammation of the heart muscle
• myasthenia gravis, an illness that can cause muscle weakness
• inflammation of the eye (uveitis)
• inflammation of the spinal cord (myelitis)
• weakness of facial nerves and muscles (facial paresis)
• haemophagocytic lymphohistiocytosis, a condition where the immune system makes too many infection-fighting cells called histiocytes and lymphocytes that may cause various symptoms
• coeliac disease (characterised by symptoms such as stomach pain, diarrhoea, and bloating after consuming gluten-containing foods)

Other side effects that have been reported with frequency not known (cannot be estimated from the available data):

• inflammation of the bladder; signs and symptoms may include frequent and/or painful urination, urge to pass urine, blood in urine, pain or pressure in lower abdomen.
• lack or reduction of digestive enzymes made by the pancreas (pancreatic exocrine insufficiency)

The following side effects have been reported in clinical trials when Tecentriq is given in combination with anticancer medicines:

Very common: may affect more than 1 in 10 people

• low number of red blood cells, which can cause tiredness and shortness of breath
• low white blood cell count with and without fever, which can increase the risk of infection (neutropenia, leukopenia)
• low platelet count, which may make you more likely to bruise or bleed (thrombocytopenia)
• constipation
• nerve damage resulting in possible numbness, pain, and/or loss of motor function (peripheral neuropathy)
• underactive thyroid gland (hypothyroidism)
• loss of appetite
• shortness of breath
• diarrhoea
• nausea
• itching of the skin
• rash
• joint pain
• feeling very tired (fatigue)
• fever
• headache
• cough
• pain in the muscles and bones
• vomiting
• back pain
• lack of energy
• infection of the lung
• common cold (nasopharyngitis)
• hair loss
• high blood pressure (hypertension)
• swelling in arms or legs

Common: may affect up to 1 in 10 people

• blood tests showing low levels of potassium (hypokalaemia) or sodium (hyponatremia)
• inflammation of the mouth or lips
• hoarse voice (dysphonia)
• low levels of magnesium (hypomagnesaemia), which can cause weakness and muscle cramping, numbness and pain in the arms and legs
• protein in urine (proteinuria)
• inflammation of the intestines
• fainting
• elevated liver enzymes (shown in tests), which may be a sign of an inflamed liver
• changes to sense of taste (dysgeusia)
• decreased number of lymphocyte (a type of white blood cells), which is associated with an increased risk of infection
• abnormal kidney test (possible kidney damage)
• overactive thyroid gland (hyperthyroidism)
• dizziness
• infusion-related reactions
• severe infection in the blood (sepsis)

Uncommon: may affect up to 1 in 100 people

• red, dry, scaly patches of thickened skin (psoriasis)
• itching, skin blistering, peeling or sores, and/or ulcers in the mouth or in lining of nose, throat, or genital area which can be severe (severe skin reactions)
• inflammation of the heart sac with build-up of fluid in the sac (in some cases) (pericardial disorders)
• inflammation of the pituitary gland situated at the base of the brain

Rare: may affect up to 1 in 1,000 people

• weakness of facial nerves and muscles (facial paresis)
• haemophagocytic lymphohistiocytosis, a condition where the immune system makes too many infection-fighting cells called histiocytes and lymphocytes that may cause various symptoms
• coeliac disease (characterised by symptoms such as stomach pain, diarrhoea, and bloating after consuming gluten-containing foods)
• changes in any area of the skin and/or genital area that are associated with drying out, thinning, itching and pain (lichen disorders)

Other side effects that have been reported with frequency not known (cannot be estimated from the available data):

• lack or reduction of digestive enzymes made by the pancreas (pancreatic exocrine insufficiency)

If you notice any of the side effects above or if they get worse, tell your doctor straight away.

If you get any side effects, talk to your doctor, pharmacist 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 atezolizumab. Each mL contains 60 mg of atezolizumab.
  Each 14 mL vial contains 840 mg of atezolizumab.
  Each 20 mL vial contains 1,200 mg of atezolizumab.
• After dilution, the final concentration of the diluted solution should be between 3.2 and 16.8 mg/mL.
• The other ingredients are L-histidine, glacial acetic acid, sucrose, polysorbate 20 (see section 2 “Tecentriq contains Polysorbate”) and water for injections.

Tecentriq is a concentrate for solution for infusion. It is a clear, colourless to slightly yellowish liquid.

Tecentriq is available in a pack containing 1 glass vial.