Prescribing Information for the Patient

Tecentriq 840 mg Concentrate for Solution for Infusion

Tecentriq 1 200 mg Concentrate for Solution for Infusion

atezolizumab

Read this Prescribing Information carefully before starting to use this medication, as it contains important information for you.

• Keep this Prescribing Information, as you may need to refer to it again.
• It is essential that you keep the patient information card during your treatment.
• If you have any questions, consult your doctor or nurse.
• If you experience any adverse effects, consult your doctor or nurse, even if they are not listed in this Prescribing Information. See Section 4.

What is Tecentriq

Tecentriq is an antitumor medication that contains the active substance ‘atezolizumab’.

• It is a type of protein that belongs to the group of so-called “monoclonal antibodies”.
• Monoclonal antibodies are a type of protein designed to recognize and bind to a specific target substance in the body.
• This antibody can help your immune system fight cancer.

What is Tecentriq 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 be treated with Tecentriq when their cancers have advanced to other parts of the body or after previous treatment.

Patients may be treated with Tecentriq when their lung cancer has not advanced to other parts of the body, the treatment will be given after surgery and chemotherapy. The treatment after surgery is called adjuvant therapy.

Tecentriq may be given in combination with other cancer medications. It is essential that you also read the prospectus of the other cancer medications you may be receiving. If you have any doubts about these medications, consult your doctor.

How Tecentriq works

Tecentriq acts by binding to a specific protein that exists in your body and is called the ligand of the programmed death receptor 1 (PD-L1). This protein neutralizes the immune system (defenses) of the body, thus protecting cancer cells from the attack of immune cells. By binding to this protein, Tecentriq helps your immune system fight cancer.

No use Tecentriq:

• If you are allergic to atezolizumab or any of the other components of this medication (listed in section 6).

If you are unsure, consult your doctor or nurse before starting to use Tecentriq.

Warnings and precautions

Consult your doctor or nurse before starting to use Tecentriq:

• If you have an autoimmune disease (a condition in which your body attacks its own cells)
• If you have been told that your cancer has spread to your brain
• If you have a history of lung inflammation (called pneumonitis)
• If you have a chronic viral liver infection, including hepatitis B (VHB) or hepatitis C (VHC)
• If you have a human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
• If you have cardiovascular, blood, or significant organ damage due to inadequate blood pressure
• If you have had severe side effects due to antibody therapies administered to treat your cancer
• If you have been given medications to stimulate your immune system
• If you have been given medications to suppress your immune system
• If you have been given a live attenuated vaccine
• If you have received antibiotics to treat infections in the past two weeks

Tecentriq acts on your immune system. This can cause inflammation in different parts of your body. The risk of this occurring may be higher if you already have an autoimmune disease (a condition in which your body attacks its own cells). You may also experience frequent exacerbations of your autoimmune disease, which in most cases will be moderate.

If any of the above occur (or you are unsure), consult your doctor or nurse before using Tecentriq.

Tecentriq may cause some side effects that you should report to your doctor immediately. These may occur weeks or months after the last dose. Report to your doctor immediately if you notice any of the following symptoms:

• Lung inflammation (pneumonitis),the symptoms may include recent or worsening cough, difficulty breathing, and chest pain
• Liver inflammation (hepatitis): the symptoms may include yellowing of the skin or eyes, nausea, vomiting, bleeding or bruising, dark urine, and abdominal pain
• Intestinal inflammation (colitis), the symptoms may include diarrhea (watery, loose, or soft stools), blood in the stool, and abdominal pain
• Thyroid and adrenal gland inflammation and pituitary gland inflammation (hypothyroidism, hyperthyroidism, or adrenal insufficiency or hypophysitis), the symptoms may include fatigue, weight loss, weight gain, mood changes, hair loss, constipation, dizziness, headache, increased thirst, increased need to urinate, and changes in vision
• Type 1 diabetes, including severe problems, in some cases life-threatening, due to the blood becoming acidic produced by diabetes (diabetic ketoacidosis), including symptoms such as increased hunger or thirst, increased need to urinate, weight loss, feeling tired or difficulty thinking clearly, breath that smells sweet or fruity, a sweet or metallic taste in the mouth, or a different odor in the urine or sweat, nausea or vomiting, abdominal pain, and deep or rapid breathing
• Brain inflammation (encephalitis) or inflammation of the membrane surrounding the spinal cord and brain (meningitis), the symptoms may include neck stiffness, headache, fever, chills, vomiting, sensitivity to light, confusion, and drowsiness
• Nerve inflammation or problems (neuropathy), the symptoms may include weakness in the muscles of the arms and legs, or in the muscles of the face, double vision, difficulty speaking and swallowing, numbness, and tingling in the hands and feet
• Spinal cord inflammation (myelitis), the symptoms may include pain, abnormal sensations such as numbness, tingling, coldness, or burning, weakness in the arms or legs, and problems with bladder and bowel function
• Pancreas inflammation (pancreatitis), including symptoms such as abdominal pain, nausea, and vomiting
• Heart muscle inflammation (myocarditis), the symptoms may include difficulty breathing, decreased tolerance to exercise, feeling tired, chest pain, swelling of the ankles or legs, irregular heartbeat, and fainting
• Kidney inflammation (nephritis); the symptoms may include changes in the amount and color of urine, pelvic pain, and inflammation of the body, and may lead to kidney failure
• Muscle inflammation (myositis); the symptoms may include muscle weakness, fatigue after walking or standing, stumbling or falling, and difficulty swallowing or breathing
• Severe reactions related to infusion (events that occur during or within the first day after infusion), may include fever, chills, difficulty breathing, and redness
• Severe skin reactions (SCARs); which may include rash, itching, blistering, peeling, or ulcers on the skin, and/or ulcers in the mouth or on the mucous membranes of the nose, throat, or genital area
• Pericardial disorders (inflammation of the sac surrounding the heart with accumulation of fluid in the sac in some cases), the symptoms are similar to those of myocarditis and may include chest pain (usually in the front of the chest, acute and worsens with deep breathing and improves when sitting and leaning forward in case of pericardial inflammation), cough, irregular heartbeat, swelling of the ankles, legs, or abdomen, difficulty breathing, fatigue, and fainting
• A condition in which the immune system produces too many cells that fight infections, called histiocytes and lymphocytes, which may cause various symptoms (hemophagocytic lymphohistiocytosis). These symptoms may include liver and/or spleen enlargement, skin rash, lymph node enlargement, respiratory problems, easy bruising, renal abnormalities, and cardiac problems

Report to your doctor immediatelyif you experience any of the symptoms described above.

Do not try to treat your symptoms with other medications on your own.Your doctor may:

• Administer other medications to prevent complications and reduce your symptoms.
• Wait longer until your next dose of Tecentriq.
• Interrupt your treatment with Tecentriq.

Tests and monitoring

Before your treatment, your doctor will check your overall health status. They will also perform blood tests during your treatment.

Children and adolescents

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

Other medications and Tecentriq

Inform your doctor or nurse if you are taking, have taken recently, or may need to take any other medication. This includes over-the-counter medications, including herbal medications.

Pregnancyand breastfeeding

• If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medication.
• Do not take Tecentriq if you are pregnant unless your doctor has told you to do so. This is because the effect of Tecentriq on pregnant women is unknown - it may cause harm to the baby.
• If you may become pregnant, you must use an effective contraceptive method:

• while you are being treated with Tecentriq and
• for 5 months after the last dose.

• If you become pregnant while being treated with Tecentriq, inform your doctor.

Breastfeeding

The safety of Tecentriq during breastfeeding is unknown. It cannot be ruled out that the baby may be at risk. Ask your doctor if you should stop breastfeeding or if you should stop treatment with Tecentriq.

Driving and operating machinery

Tecentriq may have a minor effect on your ability to drive and operate machinery. If you feel tired, do not drive or operate machinery until you feel better.

Tecentriq contains polysorbate

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 information leaflet

The important information in this leaflet can be found in the Patient Information Leaflet that your doctor has given you. It is essential that you keep this leaflet and show it to your partner or caregiver.

You will receive treatment with Tecentriq from an experienced cancer doctor at a hospital or clinic.

There are two different formulations for Tecentriq:

• one is administered as an intravenous infusion
• the other is administered as a subcutaneous injection.

Your doctor may consider switching your Tecentriq intravenous treatment to Tecentriq subcutaneous (or vice versa) if it is appropriate for you.

How much Tecentriq intravenous is administered

The recommended dose is any of the following:

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

How Tecentriq intravenous is administered

Tecentriq is administered as a drip into a vein (by 'intravenous infusion').

The first infusion will be administered over a period of 60 minutes.

• Your doctor will closely monitor you during the first infusion.
• If you do not have a reaction to the infusion during the first infusion, subsequent infusions will be administered over a period of 30 minutes.

Treatment duration

Your doctor will continue to administer Tecentriq to you as long as you benefit from it. However, treatment will be stopped if adverse effects are not tolerated.

Missing a dose of Tecentriq

If you forget an appointment with your doctor, ask for another one immediately. It is very important to continue administering the infusions for the treatment to be as effective as possible.

Stopping Tecentriq treatment

Do not stop Tecentriq treatment unless you have discussed it with your doctor. Stopping treatment may stop the medication's effect.

If you have any other questions about using this medication, ask your doctor or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

If you experience any of the side effects listed below or they worsen,inform your doctor immediately. They can occur weeks or months after your last dose.Do not administer with other medications on your own.

Tecentriq used alone

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

Very common:can affect more than 1 in 10 patients

• fever
• nausea
• vomiting
• feeling very tired, without energy (fatigue)
• lack of energy
• itching of the skin
• diarrhea
• joint pain
• eruption
• loss of appetite
• difficulty breathing
• urinary tract infection
• back pain
• cough
• headache

Common:can affect up to 1 in 10 patients

• inflammation of the lungs (pneumonitis)
• low oxygen levels that can cause difficulty breathing due to lung inflammation (hypoxia)
• stomach pain
• muscle and bone pain
• inflammation of the liver
• elevation of liver enzymes (shown in tests) that may be a sign of liver inflammation
• difficulty swallowing
• in blood tests, low levels of potassium (hypokalemia) or sodium (hyponatremia) may be found
• low blood pressure (hypotension)
• underactive thyroid gland (hypothyroidism)
• allergic reaction (reaction related to infusion, hypersensitivity, or anaphylaxis)
• flu-like illness
• chills
• inflammation of the intestines
• low platelet count, which may make you more prone to bruising or bleeding
• elevated blood glucose
• common cold (rhinopharyngitis)
• mouth and throat pain or dry mouth
• dry skin
• altered kidney function parameters (possible kidney damage)
• overactive thyroid gland (hyperthyroidism)
• inflammation of the pericardial sac with accumulation of fluid in the sac (in some cases) (pericardial disorders)

Rare:can affect up to 1 in 1,000 patients

• inflammation of the heart muscle
• myasthenia gravis, a disease that can cause muscle weakness
• inflammation of the eyes (uveitis)
• hemophagocytic lymphohistiocytosis, a disorder in which the immune system produces too many cells that fight infections, called histiocytes and lymphocytes, which can cause various symptoms
• inflammation of the spinal cord (myelitis)
• weakness of the facial nerves and muscles (facial paralysis)
• celiac disease (characterized by symptoms such as stomach pain, diarrhea, and bloating after consuming foods containing gluten)

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

• Inflammation of the bladder. Symptoms may include frequent or painful urination, urgent need to urinate, blood in the urine, pain or pressure in the lower abdomen.
• Absence or reduction of pancreatic enzymes produced by the pancreas (exocrine pancreatic insufficiency)

Tecentriq used in combination with cancer medications

The following side effects have been reported in clinical trials when Tecentriq is administered in combination with cancer medications.

Very common:can affect more than 1 in 10 patients

• low red blood cell count, which can cause fatigue and difficulty breathing
• low white blood cell count with or without fever, which can increase the risk of infection (neutropenia, leucopenia)
• low platelet count, which may make you more prone to bruising or bleeding (thrombocytopenia)
• constipation
• nervous system damage, which can cause numbness, pain, or loss of motor function (peripheral neuropathy)
• underactive thyroid gland (hypothyroidism)
• loss of appetite
• difficulty breathing
• diarrhea
• nausea
• itching of the skin
• eruption
• joint pain
• feeling 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 in arms or legs

Common:can affect up to 1 in 10 patients

• blood tests showing low levels of potassium (hypokalemia) or sodium (hyponatremia)
• inflammation of the mouth or lips
• hoarse voice (dysphonia)
• low levels of magnesium (hypomagnesemia), which can cause weakness and muscle cramps, numbness, and pain in arms and legs
• protein in urine (proteinuria)
• syncope
• elevated liver enzymes (detected in tests), which may be a sign of liver inflammation
• change in sense of taste (dysgeusia)
• decrease in lymphocyte count (a type of white blood cell), which is associated with an increased risk of infection
• abnormal kidney function test (possible kidney damage)
• overactive thyroid gland (hyperthyroidism)
• dizziness
• reactions related to infusion
• severe blood infection (sepsis)

Rare:can affect up to 1 in 1,000 patients

• psoriasis
• itching, blistering, peeling, or ulceration of the skin, and/or ulcers in the mouth or on the mucous membranes of the nose, throat, or genital area, which can be severe (severe skin reactions)
• inflammation of the pericardial sac with accumulation of fluid in the sac (in some cases) (pericardial disorders)
• inflammation of the pituitary gland located at the base of the brain

Unknown frequency:cannot be estimated from available data

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

If you notice any of the side effects listed above or if they worsen, inform your doctor immediately.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor, pharmacist, or nurse, even if it is a possible adverse reaction not listed in this prospectus. You can also report them directly through thenational notification system included in theAppendix V.By reporting adverse reactions, you can contribute to providing more information on the safety of this medication.

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

• Do not use this medication after the expiration date that appears on the packaging and on the vial label after EXP. The expiration date is the last day of the month indicated.
• Store in a refrigerator (between 2 °C and 8 °C). Do not freeze.
• Store the vial in the outer packaging to protect it from light.
• The diluted solution should not be stored for more than 24 hours between 2 °C and 8 °C or 8 hours at room temperature (≤ 25 °C), unless the dilution has taken place in validated and controlled aseptic conditions.
• Do not use this medication if you observe that it is cloudy, discolored, or contains particles.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Composition of Tecentriq

• The active ingredient is atezolizumab. Each ml contains 60 mg of atezolizumab.

Each vial of 14 ml contains 840 mg of atezolizumab.

Each vial of 20 ml 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, polisorbate 20 (see section 2 "Tecentriq contains polisorbate") and water for injection.

Appearance of the product and contents of the pack

Tecentriq is a concentrate for solution for infusion. It is a clear, colourless to pale yellow liquid.

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

79639

Grenzach-Wyhlen

Germany

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country:

Last update of the summary of product characteristics

Other sources of information

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

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This information is intended solely for healthcare professionals:

Instructions for dilution

To administer the recommended dose of 840 mg: 14 ml of Tecentriq concentrate should be withdrawn from the vial and diluted in a polyvinyl chloride (PVC), polyolefin (PO), polyethylene (PE) or polypropylene (PP) infusion bag containing 9 mg/ml (0.9%) sodium chloride solution for injection.

To administer the recommended dose of 1,200 mg: 20 ml of Tecentriq concentrate should be withdrawn from the vial and diluted in a polyvinyl chloride (PVC), polyolefin (PO), polyethylene (PE) or polypropylene (PP) infusion bag containing 9 mg/ml (0.9%) sodium chloride solution for injection.

To administer the recommended dose of 1,680 mg: 28 ml of Tecentriq concentrate should be withdrawn from two vials of Tecentriq 840 mg and diluted in a polyvinyl chloride (PVC), polyolefin (PO), polyethylene (PE) or polypropylene (PP) infusion bag containing 9 mg/ml (0.9%) sodium chloride solution for injection.

After dilution, the final concentration of the diluted solution must be between 3.2 and 16.8 mg/ml.

The bag should be gently inverted to mix the solution with the aim of avoiding foam formation. Once the infusion is prepared, it should be administered immediately.

Parenteral medicinal products should be visually inspected for the presence of particles and colour changes before administration. If particles or colour changes are observed, the solution should not be used.

No incompatibilities have been observed between Tecentriq and the PVC, PO, PE or PP infusion bag. Additionally, no incompatibilities have been observed with in-line filters composed of polyethersulfone or polysulfone, or with PVC, PE, polybutadiene or polyurethane infusion sets. The use of in-line filters is optional.

Diluted solution

Chemical and physical stability has been demonstrated for up to 24 hours at ≤ 30 °C and up to 30 days between 2 °C and 8 °C from the time of preparation.

From a microbiological point of view, the infusion solution prepared should be used immediately. If not used immediately, the storage times in use and the conditions prior to use are the responsibility of the user and generally should not be greater than 24 hours between 2 °C and 8 °C or 8 hours at ambient temperature (≤ 25 °C), unless the dilution has taken place in validated and controlled aseptic conditions.

Administration

Tecentriq should be administered by intravenous infusion. Tecentriq infusions should not be administered by rapid infusion or as a bolus intravenous injection.

The initial dose of Tecentriq should be administered over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes.

Do not administer simultaneously with other medicinal products through the same infusion line.

Elimination

The unused medicinal product and all materials that have been in contact with it should be disposed of in accordance with local regulations.