Tecentriq

Patient Information Leaflet

Tecentriq 840 mg concentrate for solution for infusion, 1200 mg concentrate for solution for infusion

atezolizumab
Please read this leaflet carefully before you are given this medicine because it contains important information for you.

• 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 questions, ask your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

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 administered
4. Possible side effects
5. How to store Tecentriq
6. Contents of the pack and other information

1. What Tecentriq is and what it is used for

What Tecentriq is
Tecentriq is an anticancer 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 bind to a specific target in the body.
• This antibody can help the immune system fight cancer.

What Tecentriq is used for
Tecentriq is used in adults to treat:

• a type of bladder cancer called urothelial carcinoma;
• a type of lung cancer called non-small cell lung cancer;
• a type of lung cancer called small cell lung cancer;
• a type of breast cancer called triple-negative breast cancer;
• a type of liver cancer called hepatocellular carcinoma.

Patients may receive Tecentriq when the cancer has spread to other parts of the body or has
reappeared after previous treatment.
Patients may receive Tecentriq when lung cancer has not spread to other parts of the
body, and treatment is given after surgery and chemotherapy. Treatment given 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 of the other anticancer medicines you may be receiving. If you have any questions about these medicines, speak to your doctor.
How Tecentriq works
Tecentriq works by binding to a specific protein in the body called programmed death-ligand 1 (PD-L1). This protein suppresses the body's immune (defence) system, protecting tumour cells and preventing immune cells from attacking them. By binding to PD-L1, Tecentriq helps the immune system fight cancer.

2. What you should know before you are given Tecentriq

You must not be given Tecentriq:

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

If you have any doubts, speak with your doctor or nurse before you are given Tecentriq.
Warnings and precautions
Before you are given Tecentriq, speak with your doctor or nurse:

• if you have an autoimmune disease (a condition in which the body attacks its own cells)
• if you have been told that your cancer has spread to the brain
• if you have previously had inflammation of the lungs (pneumonitis)
• if you currently have or have previously had a chronic viral infection, including hepatitis B or hepatitis C
• if you have human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
• if you have cardiovascular disease (heart-related), a blood disorder, or significant organ damage due to poor blood flow
• if you have previously experienced serious side effects from other therapies with antibodies that help the body’s immune system fight cancer
• if you have been given medicines to stimulate the immune system
• if you have been given medicines to suppress the immune system
• if you have been given a live attenuated vaccine
• if you have been given medicines to treat infections (antibiotics) within the last two weeks.

Tecentriq acts on your immune system. It may cause inflammation in certain parts of the body.
The risk of these side effects may be higher if you already have an autoimmune disease (a condition in which the body attacks its own cells). You may also experience frequent flare-ups of your autoimmune disease, which in most cases will be mild.
If any of these conditions apply to you (or if you have any doubts), discuss them with your doctor or nurse before you are given Tecentriq.
Tecentriq can cause certain side effects that must be immediately reported to your doctor and which may develop weeks or months after the last dose has been administered.
Immediately inform your doctor if you notice any of the following symptoms:

• inflammation of the lungs (pneumonitis), which may include new or worsening cough, shortness of breath, and chest pain;
• inflammation of the liver (hepatitis), which may include yellowing of the skin or eyes, nausea, vomiting, bleeding or bruising, dark urine, and stomach pain;
• inflammation of the intestine (colitis), which may include diarrhoea (loose or watery stools), blood in the stools, and stomach pain;
• inflammation of the thyroid gland, adrenal glands, or pituitary gland (hypothyroidism, hyperthyroidism, adrenal insufficiency, or hypophysitis): symptoms may include fatigue, weight loss, weight gain, mood changes, hair loss, constipation, dizziness, headache, increased thirst, increased urination, and vision changes;
• type 1 diabetes, including a serious, sometimes life-threatening condition caused by acid produced by diabetes in the blood (diabetic ketoacidosis), which may include increased appetite or thirst, increased need to urinate, weight loss, feeling tired or difficulty thinking clearly, breath with a sweet or fruity odour, a sweet or metallic taste in the mouth, or a different odour in urine or sweat, nausea or vomiting, stomach pain, and deep, laboured breathing;
• inflammation of the brain (encephalitis) or inflammation of the membranes covering the brain and spinal cord (meningitis), which may include neck stiffness, headache, fever, chills, vomiting, sensitivity of the eyes to light, confusion, and drowsiness;
• inflammation or problems with nerves (neuropathy), which may include weakness in the muscles of the arms and legs or facial muscles, double vision, difficulty speaking or chewing, numbness and tingling in the hands and feet;
• inflammation of the spinal cord (myelitis): symptoms may include pain, unusual sensations such as numbness, tingling, cold or burning sensations, weakness in the arms or legs, and problems with the bladder and bowel;
• inflammation of the pancreas (pancreatitis), which may include abdominal pain, nausea, and vomiting;
• inflammation of the heart muscle (myocarditis), which may include shortness of breath, reduced ability to tolerate physical activity, feeling tired, chest pain, swelling of the ankles and legs, irregular heartbeat, and fainting;
• inflammation of the kidneys (nephritis), which may include changes in urine production and colour, pelvic pain, and body swelling that may lead to kidney failure;
• inflammation of the muscles (myositis), which may include muscle weakness, fatigue after walking or standing, tripping or falling, and difficulty swallowing or breathing;
• serious infusion-related reactions, including severe allergic reactions (events occurring during or within one day of infusion): these may include fever, chills, shortness of breath, and flushing;
• severe skin reactions ( severe skin reactions , SCAR), which may include rash, itching, blistering of the skin, peeling or ulceration of the skin and/or ulcers in the mucous membranes (lining tissues) of the mouth, nose, throat, or genitals;
• inflammation of the sac around the heart with fluid accumulation in the sac (in some cases) (pericardial diseases): symptoms are similar to those of myocarditis and may include chest pain (usually in the front of the chest, sharp, worsened by deep breathing and improved when sitting and leaning forward in case of pericardial inflammation), cough, irregular heartbeat, swelling of the ankles, legs, or abdomen, shortness of breath, fatigue, and lightheadedness;
• a condition in which the immune system produces many cells that fight infections called histiocytes and lymphocytes, which can cause various symptoms (haemophagocytic lymphohistiocytosis): symptoms may include enlargement of the liver and/or spleen, rash, swollen lymph nodes, breathing problems, bruising, kidney abnormalities, and heart problems;
• inflammation of the middle layer of the eye (uveitis): symptoms may include painful red eyes, changes in vision, or sensitivity to light;
• abnormal destruction of red blood cells (autoimmune haemolytic anaemia): signs and symptoms may include pale skin, fatigue, shortness of breath, dark urine.

If you notice any of the symptoms listed above, inform your doctor immediately.
Do not try to treat yourself with other medicines. Your doctor may:

• give you other medicines to prevent complications and relieve symptoms;
• delay the next dose of Tecentriq;
• stop treatment with Tecentriq.

Tests and monitoring
Before treatment, your doctor will check your general health status. During treatment, you will also have blood tests.
Children and adolescents
This medicine must not be given to children or adolescents under 18 years of age.
The safety and efficacy of Tecentriq in this age group have not been established.
Other medicines and Tecentriq
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription and herbal medicines.
Pregnancy and contraception

• If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
• If you are pregnant, you will not be given Tecentriq unless your doctor considers it necessary. The effects of Tecentriq in pregnant women are unknown, and the medicine may be harmful to the unborn child.
• If you are of childbearing potential, you must use effective contraception:
  • during treatment with Tecentriq and
  • for 5 months after the last dose.
• Inform your doctor if you become pregnant during treatment with Tecentriq.

Breast-feeding
It is not known whether Tecentriq passes into breast milk. Ask your doctor whether you should stop breast-feeding or stop treatment with Tecentriq.
Driving and using machines
Tecentriq has a minor influence on the ability to drive and use machines. If you feel tired, do not drive or operate machinery until you feel better.
Tecentriq contains polysorbate (E 432)
Tecentriq 840 mg contains 5.6 mg of polysorbate 20 in each 14 ml dose, equivalent to 0.4 mg/mL.
Tecentriq 1 200 mg contains 8.0 mg of polysorbate 20 in each 20 ml dose, equivalent to 0.4 mg/mL.
Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.
Patient Alert Card
Important information from this leaflet can be found on the Patient Alert Card provided by your doctor. It is important that you keep this Patient Alert Card and show it to your partner or caregiver.

3. How Tecentriq is administered

Tecentriq will be administered to you by a doctor experienced in cancer treatment at a hospital or
clinic.
There are two different types (formulations) of Tecentriq:

• one is given by infusion into a vein (intravenous infusion)
• the other is given by injection under the skin (subcutaneous injection).

Your doctor may consider switching your treatment from intravenous Tecentriq to subcutaneous Tecentriq (or vice versa) if they consider it appropriate for you.
How much intravenous Tecentriq is given
The recommended dose is:

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

How intravenous Tecentriq is administered
Tecentriq is given as an infusion (drip) into a vein (intravenously).
The first infusion will be given over 60 minutes.

• Your doctor will monitor you closely during the first infusion.
• If you do not have any reaction to the infusion during the first administration, subsequent infusions may be given over 30 minutes.

How long treatment lasts
Your doctor will continue to give you Tecentriq until you no longer benefit from it. However, treatment may be stopped if side effects become too problematic.
If you miss a dose of Tecentriq
If you miss an appointment, schedule a new one as soon as possible. It is essential to attend your infusions regularly so that treatment remains fully effective.
If you stop treatment with Tecentriq
Do not stop treatment with Tecentriq without first talking to your doctor. Stopping treatment may end the medicine's effect.
If you have any questions about the use of this medicine, speak to your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor immediately if you notice the onset or worsening of any of the side effects listed below, which may develop weeks or months after administration of the last dose. Do not try to treat yourself with other medicines.

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

Very common: may affect more than 1 in 10 people

• fever
• nausea
• vomiting
• extreme tiredness and lack of energy (fatigue)
• lack of energy
• itchy skin
• diarrhoea
• joint pain
• skin 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 that may cause shortness of breath, due to lung inflammation (hypoxia)
• stomach pain
• muscle and bone pain
• liver inflammation
• increased liver enzyme levels (as shown in blood tests) – this may be a sign of liver inflammation
• difficulty swallowing
• blood tests showing low potassium (hypokalaemia) or sodium (hyponatraemia) levels
• low blood pressure (hypotension)
• underactive thyroid (hypothyroidism)
• reactions related to the infusion of the medicine (infusion-related reaction, hypersensitivity, cytokine release syndrome or anaphylaxis)
• flu-like illness
• chills
• inflammation of the intestine
• low platelet count which may lead to increased tendency to bruise or bleed (thrombocytopenia)
• high blood sugar levels
• common cold (rhinopharyngitis)
• mouth and throat pain or dry mouth
• dry skin
• abnormalities in kidney tests (possible kidney damage)
• overactive thyroid (hyperthyroidism)
• inflammation of the sac around the heart with fluid accumulation in the sac (in some cases) (pericardial disease)
• nerve damage causing possible numbness, pain and/or loss of motor function (peripheral neuropathy)
• joint inflammation (arthritis)
• low white blood cell count with or without fever, which may increase the risk of infection (neutropenia)

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 membranes covering the brain and spinal cord
• low adrenal hormone levels
• type 1 diabetes (including diabetic ketoacidosis)
• muscle inflammation (myositis)
• red, dry, scaly patches of thickened skin (psoriasis)
• kidney inflammation
• itching, blistering of the skin, peeling or ulceration of the skin and/or ulcers on mucous membranes (lining tissues) of the mouth, nose, throat or genitals, which may be severe (serious skin reactions)
• inflammation of the pituitary gland, a gland located at the base of the brain
• elevated levels of creatine phosphokinase in the blood (shown in testing), which may be a sign of muscle or heart inflammation
• changes in any skin area and/or genital area associated with dryness, thinning, itching and pain (Lichen)
• eye inflammation (uveitis)
• inflammation around tendons (tenosynovitis)

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

• inflammation of the heart muscle
• myasthenia gravis, a disease that may cause muscle weakness
• haemophagocytic lymphohistiocytosis, a condition in which the immune system produces many cells fighting infections called histiocytes and lymphocytes, which may cause various symptoms
• inflammation of the spinal cord (myelitis)
• weakness of facial nerves and muscles (facial palsy)
• coeliac disease (characterised by symptoms such as stomach pain, diarrhoea and abdominal swelling after consuming foods containing gluten)
• a type of herpes virus infection (cytomegalovirus infection)
• inflammatory disease mainly affecting skin, lungs and eyes (sarcoidosis)
• abnormal destruction of red blood cells (autoimmune haemolytic anaemia)

Other side effects reported with unknown frequency (cannot be estimated from the available data):

• Bladder inflammation. Signs and symptoms may include frequent and/or painful urination (dysuria), urgent need to urinate (pollakiuria), blood in the urine (haematuria), pain or pressure in the lower abdomen.
• Absence or reduction of digestive enzymes produced by the pancreas (pancreatic exocrine insufficiency)

Tecentriq used in combination with other anticancer medicines
The following side effects have been reported in clinical studies with Tecentriq administered in combination with other anticancer medicines:

Very common: may affect more than 1 in 10 people

• low red blood cell count, which may cause tiredness and shortness of breath
• low white blood cell count with or without fever, which may increase the risk of infection (neutropenia, leucopenia)
• low platelet count, which may lead to increased tendency to bruise or bleed (thrombocytopenia)
• constipation
• nerve damage causing possible numbness, pain and/or loss of motor function (peripheral neuropathy)
• underactive thyroid (hypothyroidism)
• loss of appetite
• shortness of breath
• diarrhoea
• nausea
• itchy skin
• skin rash
• joint pain
• feeling very tired (fatigue)
• fever
• headache
• cough
• muscle and bone pain
• vomiting
• back pain
• lack of energy
• lung infection
• common cold (rhinopharyngitis)
• hair loss
• high blood pressure (hypertension)
• swelling of arms or legs

Common: may affect up to 1 in 10 people

• laboratory tests showing low potassium (hypokalaemia) or sodium (hyponatraemia) levels
• inflammation of the mouth or lips
• hoarseness (dysphonia)
• low magnesium levels (hypomagnesaemia), which may cause weakness and muscle cramps, numbness and pain in arms and legs
• presence of protein in urine (proteinuria)
• inflammation of the intestine
• fainting
• increased liver enzyme levels (shown in tests) which may be a sign of liver inflammation
• change in taste sensation (dysgeusia)
• reduced number of lymphocytes (a type of white blood cells) associated with increased risk of infections
• abnormalities in kidney function tests (possible kidney damage)
• overactive thyroid (hyperthyroidism)
• dizziness
• reactions related to the infusion of the medicine (infusion-related reaction, hypersensitivity, cytokine release syndrome or anaphylaxis)
• severe blood infection (sepsis)
• joint inflammation (arthritis)

Uncommon: may affect up to 1 in 100 people

• red, dry, scaly patches of thickened skin (psoriasis)
• itching, blistering of the skin, peeling or ulceration of the skin and/or ulcers on mucous membranes (lining tissues) of the mouth, nose, throat or genitals, which may be severe (serious skin reactions)
• inflammation of the sac around the heart with fluid accumulation in the sac (in some cases) (pericardial disease)
• inflammation of the pituitary gland, a gland located at the base of the brain
• inflammation around tendons (tenosynovitis)

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

• haemophagocytic lymphohistiocytosis, a condition in which the immune system produces many cells fighting infections called histiocytes and lymphocytes, which may cause various symptoms
• weakness of facial nerves and muscles (facial palsy)
• coeliac disease (characterised by symptoms such as stomach pain, diarrhoea and abdominal swelling after consuming foods containing gluten)
• changes in any skin area and/or genital area associated with dryness, thinning, itching and pain (Lichen)
• eye inflammation (uveitis)
• a type of herpes virus infection (cytomegalovirus infection)
• abnormal destruction of red blood cells (autoimmune haemolytic anaemia)

Other side effects reported with unknown frequency (frequency cannot be estimated from the available data):

• Absence or reduction of digestive enzymes produced by the pancreas (pancreatic exocrine insufficiency)

If you notice the onset or worsening of any of the above side effects, inform your doctor immediately.

Reporting of side effects
If you get any side effect, including ones not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Tecentriq

Tecentriq will be stored by healthcare professionals at the hospital or clinic. The storage instructions are as follows.

• Do not use this medicine after the expiry date stated on the carton and on the label of the vial 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 vial in the outer packaging to protect the medicine from light.
• The diluted solution should be stored for no more than 24 hours at 2 °C - 8 °C or 8 hours at room temperature (≤ 25°C), unless the dilution has been carried out under controlled and validated aseptic conditions.
• Do not use the medicine if it is cloudy, shows a change in colour, or contains particles.

Do not dispose of any medicine via wastewater or household waste. Healthcare professionals will dispose of unused medicines. This will help protect the environment.

6. Package contents and other information

What Tecentriq contains

• 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 must be between 3.2 and 16.8 mg/mL.
• The other components are L-histidine, glacial acetic acid, sucrose, polysorbate 20 (E 432) (see section 2 “Tecentriq contains polysorbate”) and water for injections.

Description of the appearance of Tecentriq and contents of the pack
Tecentriq is a concentrate for solution for infusion. It is a clear, colourless to slightly yellowish solution.
Tecentriq is available in packs containing 1 glass vial.

Marketing Authorisation Holder
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer
Roche Pharma AG
Emil-Barell-Strasse 1
Grenzach-Wyhlen
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Luxembourg/Luxemburg UAB “Roche Lietuva”
N.V. Roche S.A. Tel: +370 5 2546799
België/Belgique/Belgien
Tél/Tel: +32 (0) 2 525 82 11

България Magyarország
Рош България ЕООД Roche (Magyarország) Kft.
Тел: +359 2 818 44 44 Tel.: +36 - 1 279 4500

Česká republika Nederland
Roche s. r. o. Roche Nederland B.V.
Tel: +420 - 2 20382111 Tel: +31 (0) 348 438050

Danmark Norge
Roche Pharmaceuticals A/S Roche Norge AS
Tlf.: +45 - 36 39 99 99 Tlf: +47 - 22 78 90 00

Deutschland Österreich
Roche Pharma AG Roche Austria GmbH
Tel: +49 (0) 7624 140 Tel: +43 (0) 1 27739

Eesti Polska
Roche Eesti OÜ Roche Polska Sp. z o.o.
Tel: +372 - 6 177 380 Tel.: +48 - 22 345 18 88

Ελλάδα, Κύπρος Portugal
Roche (Hellas) A.E. Roche Farmacêutica Química, Lda
Ελλάδα Tel: +351 - 21 425 70 00
Τηλ: +30 210 61 66 100

España România
Roche Farma S.A. Roche România S.R.L.
Tel: +34 - 91 324 81 00 Tel: +40 21 206 47 01

France Slovenija
Roche Roche farmacevtska družba d.o.o.
Tél: +33 (0) 1 47 61 40 00 Tel: +386 - 1 360 26 00

Hrvatska Slovenská republika
Roche d.o.o. Roche Slovensko, s.r.o.
Tel: +385 1 4722 333 Tel: +421 - 2 52638201

Ireland, Malta Suomi/Finland
Roche Products (Ireland) Ltd. Roche Oy
Ireland/L-Irlanda Puh/Tel: +358 (0) 10 554 500
Tel: +353 (0) 1 469 0700

Ísland Sverige
Roche Pharmaceuticals A/S a/s Roche AB
c/o Icepharma hf Tel: +46 (0) 8 726 1200
Sími: +354 540 8000

Italia
Roche S.p.A.
Tel: +39 - 039 2471

Latvija
Roche Latvija SIA
Tel: +371 - 6 7039831

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu

The following information is intended for healthcare professionals only:

Instructions for dilution
For the recommended dose of 840 mg: withdraw 14 mL of concentrated Tecentriq from the vial and
dilute it in an infusion bag made of polyvinyl chloride (PVC), polyolefin (PO), polyethylene (PE), or
polypropylene (PP) containing sodium chloride 9 mg/mL (0.9%) solution for injection.
For the recommended dose of 1 200 mg: withdraw 20 mL of concentrated Tecentriq from the vial and
dilute it in an infusion bag made of polyvinyl chloride (PVC), polyolefin (PO), polyethylene (PE), or
polypropylene (PP) containing sodium chloride 9 mg/mL (0.9%) solution for injection.
For the recommended dose of 1 680 mg: withdraw 28 mL of concentrated Tecentriq from two 840 mg
vials and dilute it in an infusion bag made of polyvinyl chloride (PVC), polyolefin (PO), polyethylene
(PE), or polypropylene (PP) containing sodium chloride 9 mg/mL (0.9%) solution for injection.
After dilution, the final concentration of the diluted solution must be between 3.2 and 16.8 mg/mL. The
infusion bag should be gently inverted to mix the solution, avoiding foam formation. Once prepared, the
infusion should be administered immediately.
Parenteral medicinal products should be inspected visually before administration to ensure there are
no particles and no change in color. If particles or discoloration are observed, the solution must not be
used.
No incompatibilities have been observed between Tecentriq and infusion bags with product-contacting
surfaces made of PVC, PO, PE, or PP. In addition, no incompatibilities have been observed with in-line
filter membranes made of polyethersulfone or polysulfone, or with infusion sets and other infusion
accessories made of PVC, PE, polybutadiene, or polyether urethane.
The use of in-line filter membranes is optional.

Diluted solution
Chemical and physical in-use stability has been demonstrated for up to 24 hours at ≤ 30 °C and for 30
days at a temperature between 2 °C and 8 °C from the time of preparation.
From a microbiological standpoint, the prepared infusion solution should be used immediately.
Otherwise, the in-use storage times and conditions prior to use are the responsibility of the user and
should normally not exceed 24 hours at a temperature between 2 °C and 8 °C or 8 hours at room
temperature (≤ 25 °C), unless dilution occurred under controlled and validated aseptic conditions.

Method of administration
Tecentriq is for intravenous use. Infusions must not be administered as an intravenous bolus (IV push).
The initial dose of Tecentriq should be administered over 60 minutes. If the first infusion is well
tolerated, all subsequent infusions may be administered over 30 minutes.
Do not administer other medicinal products concomitantly through the same infusion line.

Disposal
The release of Tecentriq into the environment should be minimized. Unused medicine and waste
materials derived from this medicine must be disposed of in accordance with local regulations.

Patient information leaflet: information for the patient

Tecentriq 1 875 mg solution for injection

atezolizumab
Please read this leaflet carefully before you are given this medicine because it contains important information for you.

• 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 questions, ask your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

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 administered
4. Possible side effects
5. How to store Tecentriq
6. Contents of the pack and other information

1. What Tecentriq is and what it is used for

What Tecentriq is
Tecentriq is an anticancer 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 bind to a specific target in the body.
• This antibody can help the immune system fight cancer.

What Tecentriq is used for
Tecentriq is used in adults to treat:

• a type of bladder cancer called urothelial carcinoma;
• a type of lung cancer called non-small cell lung cancer;
• a type of lung cancer called small cell lung cancer;
• a type of breast cancer called triple-negative breast cancer;
• a type of liver cancer called hepatocellular carcinoma.

Patients may receive Tecentriq when the cancer has spread to other parts of the body or has
reappeared after previous treatment.
Patients may receive Tecentriq when the lung cancer has not spread to other parts of the body and
treatment is given after surgery and chemotherapy. Treatment given 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 of the other anticancer medicines you may be taking. If you have any
questions about these medicines, please consult your doctor.

How Tecentriq works
Tecentriq works by binding to a specific protein in the body called programmed death-ligand 1 (PD-L1).
This protein suppresses the body's immune (defence) system, protecting cancer cells and preventing
immune cells from attacking them. By binding to PD-L1, Tecentriq helps the immune system fight cancer.

2. What you should know before you are given Tecentriq

Do not receive Tecentriq:

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

If you have any doubts, speak to your doctor or nurse before you are given Tecentriq.
Warnings and precautions
Before you are given Tecentriq, speak to your doctor or nurse:

• if you have an autoimmune disease (a condition in which the body attacks its own cells)
• if you have been told that your cancer has spread to the brain
• if you have previously had lung inflammation (pneumonitis)
• if you currently have or have previously had a chronic viral infection, including hepatitis B or hepatitis C
• if you have human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
• if you have cardiovascular disease (heart-related), a blood disorder, or significant organ damage due to poor blood flow
• if you have previously experienced serious side effects from other therapies with antibodies that help the body's immune system fight cancer
• if you have been given medicines to stimulate the immune system
• if you have been given medicines to suppress the immune system
• if you have received a live attenuated vaccine
• if you have been given medicines to treat infections (antibiotics) within the last two weeks. Tecentriq acts on your immune system. It may cause inflammation in certain parts of the body. The risk of these side effects may be higher if you already have an autoimmune disease (a condition in which the body attacks its own cells). You may also experience frequent flare-ups of your autoimmune disease, which in most cases will be mild.

If any of these conditions apply to you (or if you have any doubts), discuss them with your doctor or
nurse before you are given Tecentriq.
Tecentriq may cause certain side effects that must be reported immediately to your doctor and that may develop weeks or months after the last dose has been administered.
Contact your doctor immediately if you notice any of the following symptoms:

• inflammation of the lungs (pneumonitis), which may include new or worsening cough, shortness of breath, and chest pain;
• inflammation of the liver (hepatitis), which may include yellowing of the skin or eyes, nausea, vomiting, bleeding or bruising, dark-coloured urine, and stomach pain;
• inflammation of the intestine (colitis), which may include diarrhoea (loose or watery stools), blood in the stools, and stomach pain;
• inflammation of the thyroid gland, adrenal glands, or pituitary gland (hypothyroidism, hyperthyroidism, adrenal insufficiency, or hypophysitis): symptoms may include fatigue, weight loss, weight gain, mood changes, hair loss, constipation, dizziness, headache, increased thirst, increased urination, and vision changes;
• type 1 diabetes, including a serious, sometimes life-threatening condition caused by acid produced by diabetes in the blood (diabetic ketoacidosis), which may include increased appetite or thirst, need to urinate more frequently, weight loss, feeling tired or difficulty thinking clearly, breath with a sweet or fruity odour, a sweet or metallic taste in the mouth, or a different odour in urine or sweat, nausea or vomiting, stomach pain, and deep, laboured breathing;
• inflammation of the brain (encephalitis) or inflammation of the membranes covering the brain and spinal cord (meningitis), which may include neck stiffness, headache, fever, chills, vomiting, sensitivity of the eyes to light, confusion, and drowsiness;
• inflammation or problems with nerves (neuropathy), which may include weakness in the muscles of the arms and legs or facial muscles, double vision, difficulty speaking or chewing, numbness and tingling in the hands and feet;
• inflammation of the spinal cord (myelitis): symptoms may include pain, unusual sensations such as numbness, tingling, cold or burning sensations, weakness in the arms or legs, and problems with the bladder and bowel;
• inflammation of the pancreas (pancreatitis), which may include abdominal pain, nausea, and vomiting;
• inflammation of the heart muscle (myocarditis), which may include shortness of breath, reduced ability to tolerate physical exertion, feeling tired, chest pain, swelling in the ankles and legs, irregular heartbeat, and fainting;
• inflammation of the kidneys (nephritis), which may include changes in urine production and colour, pelvic pain, and body swelling that may lead to kidney failure;
• inflammation of the muscles (myositis), which may include muscle weakness, fatigue after walking or standing, tripping or falling, and difficulty swallowing or breathing;
• serious infusion-related reactions, including severe allergic reactions (events occurring during or within one day after infusion): these may include fever, chills, shortness of breath, and flushing;
• severe skin reactions (severe skin reactions, SCAR), which may include rash, itching, blistering of the skin, peeling or ulceration of the skin, and/or ulcers in the mucous membranes (lining tissues) of the mouth, nose, throat, or genitals;
• inflammation of the sac around the heart with fluid accumulation in the sac (in some cases) (pericardial diseases): symptoms are similar to those of myocarditis and may include chest pain (usually in the front of the chest, sharp, worsened by deep breathing and improved when sitting and leaning 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 in which the immune system produces many cells that fight infections called histiocytes and lymphocytes, which can cause various symptoms (haemophagocytic lymphohistiocytosis): symptoms may include enlargement of the liver and/or spleen, rash, swollen lymph nodes, breathing problems, bruising, kidney abnormalities, and heart problems;
• inflammation of the middle layer of the eye (uveitis): symptoms may include painful red eyes, changes in vision, or sensitivity to light.
• abnormal destruction of red blood cells (autoimmune haemolytic anaemia): signs and symptoms may include pale skin, fatigue, shortness of breath, dark urine.

If you notice any of the symptoms listed above, inform your doctor immediately.
Do not attempt to treat yourself with other medicines. Your doctor may:

• give you other medicines to prevent complications and relieve symptoms;
• delay the administration of your next dose of Tecentriq;
• stop your treatment with Tecentriq.

Tests and monitoring
Before treatment, your doctor will check your general health status. During treatment,
you will also have blood tests.
Children and adolescents
This medicine must not be given to children or adolescents under 18 years of age.
The safety and efficacy of Tecentriq in this age group have not been established.
Other medicines and Tecentriq
Tell your doctor or nurse if you are taking, have recently taken, or might take
any other medicines, including those obtained without a prescription and herbal medicines.
Pregnancy and contraception

• If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
• If you are pregnant, you will not be given Tecentriq unless your doctor considers it necessary. The effects of Tecentriq in pregnant women are unknown, and the medicine may be harmful to the unborn baby.
• If you are of childbearing potential, you must use effective contraception:
  • during treatment with Tecentriq and
  • for 5 months after receiving the last dose.
• Inform your doctor if you become pregnant during treatment with Tecentriq.

Breastfeeding
It is not known whether Tecentriq passes into breast milk. Ask your doctor whether you should stop breastfeeding or discontinue treatment with Tecentriq.
Driving and using machines
Tecentriq has a minor influence on the ability to drive and use machines. If you feel tired, do not drive or operate machinery until you feel better.
Tecentriq contains polysorbate (E 432)
Tecentriq 1,875 mg contains 9 mg of polysorbate 20 in each 15 ml dose, equivalent to 0.6 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.
Patient card
Important information from this leaflet can be found on the Patient Card provided by your doctor. It is important that you keep this Patient Card and show it to your partner or caregiver.

3. How Tecentriq is administered

Tecentriq will be administered to you by a doctor experienced in the treatment of cancer.
There are two different types (formulations) of Tecentriq:

• one is given as an infusion into a vein (intravenous infusion)
• the other is given as an injection under the skin (subcutaneous injection).

Your doctor may consider switching you from intravenous Tecentriq treatment to subcutaneous Tecentriq treatment (and vice versa) if they consider it appropriate for you.
How much subcutaneous Tecentriq is administered
The recommended dose of Tecentriq injectable solution is 1,875 mg every three weeks.
How subcutaneous Tecentriq is administered
Tecentriq is administered by an injection under the skin (subcutaneous injection).

• The injections will be given in the thigh and take approximately 7 minutes.
• The injection site will be alternated between the right and left thigh.
• Your doctor or nurse will ensure that each injection is given at a new site (at least 2.5 cm away from the previous injection site) and in areas where the skin is not red, bruised, tender, or hardened.
• Different injection sites must be used for the administration of other medicines.

How long treatment lasts
Your doctor will continue to administer Tecentriq to you for as long as you continue to benefit from it. However, treatment may be stopped if side effects become too problematic.
If you miss a dose of Tecentriq
If you miss an appointment, schedule a new one immediately. It is essential to attend infusions regularly for the treatment to be fully effective.
If you stop treatment with Tecentriq
Do not stop treatment with Tecentriq without first talking to your doctor. Stopping treatment may end the medicine's effect.
If you have any questions about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately if you notice the onset or worsening of any of the side effects listed
below, which may develop weeks or months after administration of the last dose. Do not attempt to treat
yourself with other medicines.

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

Very common: may affect more than 1 in 10 people

• fever
• nausea
• vomiting
• feeling extremely tired and lacking energy (fatigue)
• lack of energy
• itching of the skin
• diarrhoea
• joint pain
• skin 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 levels of oxygen causing shortness of breath, due to inflammation of the lungs (hypoxia)
• stomach ache
• muscle and bone pain
• liver inflammation
• increased levels of liver enzymes (as shown in blood tests) – which may be a sign of liver inflammation
• difficulty swallowing
• blood tests showing low levels of potassium (hypokalaemia) or sodium (hyponatraemia)
• low blood pressure (hypotension)
• underactive thyroid (hypothyroidism)
• reactions related to the medicine infusion (infusion-related reaction, hypersensitivity, cytokine release syndrome or anaphylaxis)
• flu-like illness
• chills
• inflammation of the intestine
• low platelet count which could lead to increased tendency to bruise or bleed (thrombocytopenia)
• high blood sugar levels
• common cold (rhinopharyngitis)
• mouth and throat pain, or dry mouth
• dry skin
• abnormal kidney function tests (possible kidney damage)
• overactive thyroid (hyperthyroidism)
• inflammation of the sac around the heart with fluid accumulation in the sac (in some cases) (pericardial disorders)
• local reaction at the injection site
• nerve damage causing possible numbness, pain and/or loss of motor function (peripheral neuropathy)
• inflammation of the joints (arthritis)
• low white blood cell count with or without fever, which may increase the risk of infection (neutropenia)

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 membranes covering the brain and spinal cord
• low levels of adrenal hormones
• type 1 diabetes (including diabetic ketoacidosis)
• inflammation of the muscles (myositis)
• red, dry, scaly patches of thickened skin (psoriasis)
• inflammation of the kidneys
• itching, blistering of the skin, peeling or ulceration of the skin and/or ulcers in the mucous membranes (lining tissues) of the mouth, nose, throat or genitals, which may be severe (serious skin reactions)
• inflammation of the pituitary gland, a gland located at the base of the brain
• elevated levels of creatine phosphokinase in the blood (shown in testing), which may be a sign of muscle or heart inflammation
• changes in any area of the skin and/or genital area associated with dryness, thinning, itching and pain (Lichen)
• inflammation of the eyes (uveitis)
• inflammation around the tendons (tenosynovitis)

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

• inflammation of the heart muscle
• myasthenia gravis, a disease that may cause muscle weakness
• haemophagocytic lymphohistiocytosis, a condition in which the immune system produces many cells fighting infections called histiocytes and lymphocytes, which may cause various symptoms
• inflammation of the spinal cord (myelitis)
• weakness of facial nerves and muscles (facial palsy)
• coeliac disease (characterised by symptoms such as stomach pain, diarrhoea and abdominal swelling after consuming foods containing gluten)
• a type of herpes virus infection (cytomegalovirus infection)
• inflammatory disease mainly affecting skin, lungs and eyes (sarcoidosis)
• abnormal destruction of red blood cells (autoimmune haemolytic anaemia)

Other side effects reported with unknown frequency (cannot be estimated from the available data):

• Inflammation of the bladder. Signs and symptoms may include frequent and/or painful urination (dysuria), urgent need to urinate (pollakiuria), presence of blood in the urine (haematuria), pain or pressure in the lower abdomen.
• Absence or reduction of digestive enzymes produced by the pancreas (pancreatic exocrine insufficiency).

Tecentriq used in combination with other anticancer medicines
The following side effects have been reported in clinical trials with Tecentriq administered in
combination with other anticancer medicines:

Very common: may affect more than 1 in 10 people

• low red blood cell count, which may cause tiredness and shortness of breath
• low white blood cell count with or without fever, which may increase the risk of infection (neutropenia, leucopenia)
• low platelet count, which may lead to increased tendency to bruise or bleed (thrombocytopenia)
• constipation
• nerve damage causing possible numbness, pain and/or loss of motor function (peripheral neuropathy)
• underactive thyroid (hypothyroidism)
• loss of appetite
• shortness of breath
• diarrhoea
• nausea
• itching of the skin
• skin rash
• joint pain
• feeling very tired (fatigue)
• fever
• headache
• cough
• muscle and bone pain
• vomiting
• back pain
• lack of energy
• lung infection
• common cold (rhinopharyngitis)
• hair loss
• high blood pressure (hypertension)
• swelling of the arms or legs

Common: may affect up to 1 in 10 people

• laboratory tests showing low levels of potassium (hypokalaemia) or sodium (hyponatraemia)
• inflammation of the mouth or lips
• hoarseness (dysphonia)
• low levels of magnesium (hypomagnesaemia), which may cause weakness and muscle cramps, numbness and pain in the arms and legs
• presence of protein in the urine (proteinuria)
• inflammation of the intestine
• fainting
• increased levels of liver enzymes (shown in tests) which may be a sign of liver inflammation
• change in taste sensation (dysgeusia)
• reduced number of lymphocytes (a type of white blood cells) associated with increased risk of infections
• abnormal kidney function tests (possible kidney damage)
• overactive thyroid (hyperthyroidism)
• dizziness
• reactions related to the medicine infusion (infusion-related reaction, hypersensitivity, cytokine release syndrome or anaphylaxis)
• severe blood infection (sepsis)
• inflammation of the joints (arthritis)

Uncommon: may affect up to 1 in 100 people

• red, dry, scaly patches of thickened skin (psoriasis)
• itching, blistering of the skin, peeling or ulceration of the skin and/or ulcers in the mucous membranes (lining tissues) of the mouth, nose, throat or genitals, which may be severe (serious skin reactions)
• inflammation of the sac around the heart with fluid accumulation in the sac (in some cases) (pericardial disorders)
• inflammation of the pituitary gland, a gland located at the base of the brain
• inflammation around the tendons (tenosynovitis)

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

• haemophagocytic lymphohistiocytosis, a condition in which the immune system produces many cells fighting infections called histiocytes and lymphocytes, which may cause various symptoms
• weakness of facial nerves and muscles (facial palsy)
• coeliac disease (characterised by symptoms such as stomach pain, diarrhoea and abdominal swelling after consuming foods containing gluten)
• changes in any area of the skin and/or genital area associated with dryness, thinning, itching and pain (Lichen)
• inflammation of the eyes (uveitis)
• a type of herpes virus infection (cytomegalovirus infection)
• abnormal destruction of red blood cells (autoimmune haemolytic anaemia)

Other side effects reported with unknown frequency (cannot be estimated from the available data):

• Absence or reduction of digestive enzymes produced by the pancreas (pancreatic exocrine insufficiency)

If you notice the onset or worsening of any of the above side effects, inform your doctor immediately.

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system listed in Annex V. By reporting
side effects, you can help provide more information on the safety of this medicine.

5. How to store Tecentriq

Tecentriq will be stored by healthcare professionals at the hospital or clinic. The storage instructions are as follows.

• Do not use this medicinal product after the expiry date stated on the carton and on the label of the vial after “Exp./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 vial in the outer packaging to protect the medicinal product from light.
• Do not use the medicinal product if it is cloudy, has changed colour, or contains particles.

Do not dispose of any medicinal product via wastewater or household waste. Healthcare professionals will dispose of unused medicinal products. This will help protect the environment.

6. Package contents and other information

What Tecentriq contains

• The active substance is atezolizumab. Each mL contains 125 mg of atezolizumab. A 15 mL vial of solution contains 1,875 mg of atezolizumab.
• The other components are L-histidine, L-methionine, acetic acid, sucrose, polysorbate 20 (E 432) (see section 2 “Tecentriq contains polysorbate”), recombinant human hyaluronidase (rHuPH20), and water for injections.

Description of the appearance of Tecentriq and contents of the pack
Tecentriq is a clear, colourless to slightly yellowish injectable solution.
Tecentriq is available in packs containing 1 glass vial.

Marketing Authorisation Holder
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer
Roche Pharma AG
Emil-Barell-Strasse 1
Grenzach-Wyhlen
Germany

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Luxembourg/Luxemburg UAB “Roche Lietuva”
N.V. Roche S.A. Tel: +370 5 2546799
België/Belgique/Belgien
Tél/Tel: +32 (0) 2 525 82 11

България Magyarország
Рош България ЕООД Roche (Magyarország) Kft.
Тел: +359 2 818 44 44 Tel.: +36 - 1 279 4500

Česká republika Nederland
Roche s. r. o. Roche Nederland B.V.
Tel: +420 - 2 20382111 Tel: +31 (0) 348 438050

Danmark Norge
Roche Pharmaceuticals A/S Roche Norge AS
Tlf.: +45 - 36 39 99 99 Tlf: +47 - 22 78 90 00

Deutschland Österreich
Roche Pharma AG Roche Austria GmbH
Tel: +49 (0) 7624 140 Tel: +43 (0) 1 27739

Eesti Polska
Roche Eesti OÜ Roche Polska Sp. z o.o.
Tel: +372 - 6 177 380 Tel.: +48 - 22 345 18 88

Ελλάδα, Κύπρος Portugal
Roche (Hellas) A.E. Roche Farmacêutica Química, Lda
Ελλάδα Tel: +351 - 21 425 70 00
Τηλ: +30 210 61 66 100

España România
Roche Farma S.A. Roche România S.R.L.
Tel: +34 - 91 324 81 00 Tel: +40 21 206 47 01

France Slovenija
Roche Roche farmacevtska družba d.o.o.
Tél: +33 (0) 1 47 61 40 00 Tel: +386 - 1 360 26 00

Hrvatska Slovenská republika
Roche d.o.o. Roche Slovensko, s.r.o.
Tel: +385 1 4722 333 Tel: +421 - 2 52638201

Ireland, Malta Suomi/Finland
Roche Products (Ireland) Ltd. Roche Oy
Ireland/L-Irlanda Puh/Tel: +358 (0) 10 554 500
Tel: +353 (0) 1 469 0700

Ísland Sverige
Roche Pharmaceuticals A/S a/s Roche AB
c/o Icepharma hf Tel: +46 (0) 8 726 1200
Sími: +354 540 8000

Italia
Roche S.p.A.
Tel: +39 - 039 2471

Latvija
Roche Latvija SIA
Tel: +371 - 6 7039831

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu

The following information is intended exclusively for healthcare professionals:

To avoid therapeutic errors, it is important to check the vial label to ensure that the correct formulation (intravenous or subcutaneous) is administered to the patient as prescribed.
Tecentriq injectable solution must be inspected visually before administration to confirm the absence of particulate matter or discoloration.
Tecentriq injectable solution is a ready-to-use solution that MUST NOT be diluted or mixed with other medicinal products.
Tecentriq injectable solution is for single use only and must be prepared by a healthcare professional.
No incompatibilities have been observed between Tecentriq injectable solution and polypropylene (PP), polycarbonate (PC), stainless steel (SS), polyvinyl chloride (PVC), or polyurethane (PU).

Syringe preparation
From a microbiological standpoint, Tecentriq injectable solution should be used immediately after transfer from the vial to the syringe, as the medicinal product does not contain antimicrobial preservatives or bacteriostatic agents.

• Remove the vial from the refrigerator and allow the solution to reach room temperature.
• Withdraw the entire contents of Tecentriq injectable solution from the vial using a sterile syringe and a transfer needle (preferably 18 G gauge).
• Remove the transfer needle and attach a subcutaneous infusion set (e.g., butterfly system) containing a stainless steel injection needle with a gauge of 23–25 G. For administration, use a subcutaneous infusion set with a residual dead volume NOT exceeding 0.5 mL.
• Prime the subcutaneous infusion line with the medicinal solution to expel air, stopping before the liquid reaches the needle.
• Ensure that exactly 15 mL of solution remain in the syringe after priming and after expelling any excess volume.
• Administer immediately to avoid needle blockage. DO NOT store the prepared syringe once it has been connected to a pre-primed subcutaneous infusion set.

If not administered immediately, refer to the section “Storage of the prepared syringe” below.

Storage of the prepared syringe

• If the prepared syringe is not used immediately, the responsibility for storage times and conditions prior to use lies with the user and should normally not exceed 24 hours at a temperature of 2 °C to 8 °C, unless preparation occurred under controlled, validated aseptic conditions.
• If the dose is not to be administered immediately, withdraw aseptically the full volume of Tecentriq injectable solution from the vial into the syringe, accounting for both the dose volume (15 mL) and the priming volume of the subcutaneous infusion set. Replace the transfer needle with a syringe cap. DO NOT attach a subcutaneous infusion set during storage.
• The prepared syringe may be stored for a maximum of 30 days at 2°C to 8°C and for up to 8 hours at a temperature not exceeding 30°C under diffused daylight conditions, starting from the time of preparation.
• If the syringe has been refrigerated, allow it to reach room temperature before administration.

Method of administration
Tecentriq injectable solution is NOT intended for intravenous administration and must be administered exclusively via subcutaneous injection.
Prior to administration, remove Tecentriq injectable solution from the refrigerator and allow the solution to reach room temperature. For instructions on the use and handling of Tecentriq injectable solution before administration, refer to section 6.6 of the Summary of Product Characteristics (SmPC).
Administer 15 mL of Tecentriq injectable solution via subcutaneous injection into the thigh over approximately 7 minutes. Use of a subcutaneous infusion set (e.g., butterfly system) is recommended.
DO NOT administer the residual dead volume remaining in the tubing to the patient.
The injection site should be alternated only between the right and left thigh. New injections should be administered at least 2.5 cm away from the previous injection site and never into areas where the skin appears red, bruised, tender, or hardened. During treatment with the subcutaneous formulation of Tecentriq, subcutaneous administration of other drugs should preferably be given at different injection sites.

Disposal
The release of Tecentriq into the environment should be minimized. Unused medicinal product and waste materials derived from its use must be disposed of in accordance with local regulations.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND REASONS FOR THE VARIATION OF THE TERMS OF THE MARKETING AUTHORISATIONS

Scientific conclusions
Taking into account the evaluation by the Pharmacovigilance and Risk Assessment Committee (PRAC) of the Periodic Safety Update Report (PSUR) for atezolizumab, the PRAC's scientific conclusions are as follows:

Considering the available data on autoimmune hemolytic anemia from spontaneous reports and a plausible mechanism of action, the PRAC considers that a causal relationship between atezolizumab and autoimmune hemolytic anemia is at least a reasonable possibility, given the potential class effect. The PRAC concluded that the product information for medicinal products containing atezolizumab should be amended accordingly.

Considering the available data on neutropenia from clinical studies, post-marketing experience, and the literature, the PRAC considers that a causal relationship between atezolizumab (as monotherapy) and neutropenia is at least a reasonable possibility. The PRAC concluded that the product information for medicinal products containing atezolizumab should be amended accordingly.

Having reviewed the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the overall conclusions and the rationale of the recommendation.

Reasons for the variation of the terms of the marketing authorisations
Based on the scientific conclusions on atezolizumab, the CHMP considers that the benefit-risk balance of medicinal products containing atezolizumab remains unchanged, subject to the proposed amendments to the product information.
The CHMP recommends a variation to the terms of the marketing authorisations.