TECENTRIQ 1200 mg Concentrate for Solution for Infusion

Introduction

Package Leaflet: Information for the Patient

Tecentriq 840mg concentrate for solution for infusion

Tecentriq 1 200mg concentrate for solution for infusion

atezolizumab

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

• Keep this leaflet, you may need to read it again.
• It is important that during your treatment you keep the patient information card
• If you have any further questions, ask your doctor or nurse.
• If you experience side effects, ask your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the package leaflet:

1. What is Tecentriq and what is it used for
2. What you need to know before you start using Tecentriq
3. How to use Tecentriq
4. Possible side effects
5. Storage of Tecentriq
6. Contents of the pack and further information

1. What is Tecentriq and what is it used for

What is Tecentriq

Tecentriq is an anti-tumour medicine 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 your 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 can be treated with Tecentriq when their cancers have spread to other parts of the body or after previous treatment.

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

Tecentriq can be given in combination with other anti-cancer medicines. It is important that you also read the package leaflet of the other anti-cancer medicines you may be receiving. If you have any questions about these medicines, ask your doctor.

How Tecentriq works

Tecentriq works by binding to a specific protein that exists in your body and is called programmed death-ligand 1 (PD-L1). This protein neutralizes the immune system (defences) 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.

2. What you need to know before you start using Tecentriq

Do not use Tecentriq:

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

If you are not sure, ask your doctor or nurse before starting treatment with Tecentriq.

Warnings and precautions

Tell your doctor or nurse before starting treatment with Tecentriq:

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

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

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

Tecentriq can cause some side effects that you should tell your doctor about immediately. These can occur weeks or months after the last dose. Tell your doctor immediately if you notice any of the following symptoms:

• inflammation of the lung (pneumonitis), symptoms can include recent or worsening cough, difficulty breathing, and chest pain
• inflammation of the liver (hepatitis): symptoms can include yellowing of the skin or eyes, nausea, vomiting, bleeding or bruising, dark urine, and stomach pain
• inflammation of the intestine (colitis), symptoms can include diarrhoea (watery, loose or soft stools), blood in the stools, and stomach pain
• inflammation of the thyroid and adrenal glands and pituitary gland (hypothyroidism, hyperthyroidism or adrenal insufficiency or hypophysitis), symptoms can include fatigue, weight loss, weight gain, mood changes, hair loss, constipation, dizziness, headache, increased thirst and need to urinate more often and changes in vision.
• type 1 diabetes, including serious and life-threatening complications due to the blood becoming acidic produced by diabetes (diabetic ketoacidosis), including symptoms such as feeling hungry or thirsty, needing to urinate more often, weight loss, feeling tired or having trouble thinking clearly, breath that smells sweet or fruity, a sweet or metallic taste in the mouth, or a different smell in the urine or sweat, nausea or vomiting, stomach pain and deep or rapid breathing
• inflammation of the brain (encephalitis) or inflammation of the membrane surrounding the spinal cord and brain (meningitis), symptoms can include stiff neck, headache, fever, chills, vomiting, sensitivity to light, confusion and drowsiness
• inflammation or problems of the nerves (neuropathy), symptoms can include weakness in the muscles of the arms and legs, or in the muscles of the face, double vision, difficulty speaking and chewing, numbness, and tingling in the hands and feet
• inflammation of the spinal cord (myelitis), symptoms can include pain, abnormal sensations such as numbness, tingling, cold or burning, weakness in the arms or legs and bladder and bowel problems
• inflammation of the pancreas (pancreatitis), including symptoms such as abdominal pain, nausea and vomiting
• inflammation of the heart muscle (myocarditis), symptoms can include difficulty breathing, decreased exercise tolerance, feeling tired, chest pain, swelling of the ankles or legs, irregular heartbeat and fainting
• inflammation of the kidneys (nephritis); symptoms can include changes in the amount and colour of the urine, pain in the pelvis and swelling of the body, and can lead to kidney failure.
• Inflammation of the muscles (myositis); symptoms can include muscle weakness, fatigue after walking or standing, stumbling or falling and problems swallowing or breathing.
• severe infusion-related reactions (events that occur during or within the first day after infusion), can include fever, chills, difficulty breathing and redness.
• severe skin reactions (SCARs); which can 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.
• inflammation of the sac surrounding the heart with fluid accumulation in the sac (in some cases) (pericardial disorders), symptoms are similar to those of myocarditis and can include chest pain (usually in the front of the chest, sharp 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 can cause various symptoms (hemophagocytic lymphohistiocytosis). These symptoms can include enlargement of the liver and/or spleen, skin rash, enlargement of the lymph nodes, respiratory problems, easy bruising, kidney abnormalities and heart problems.

Tell your doctor immediately if you experience any of the above symptoms.

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

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

Tests and checks

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

Children and adolescents

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

Other medicines and Tecentriq

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.

Pregnancyand breast-feeding

• 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.
• Do not take Tecentriq if you are pregnant unless your doctor has told you to. This is because the effect of Tecentriq on pregnant women is not known - it may harm your baby.
• If you could become pregnant, you must use an effective method of 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.

Breast-feeding

It is not known whether Tecentriq passes into breast milk. A risk to the breast-fed child cannot be excluded. Ask your doctor if you should stop breast-feeding or stop Tecentriq treatment.

Driving and using machines

Tecentriq may have a 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 contains polysorbate

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.

Patient information card

Important information from this package leaflet can be found on the Patient Information Card that your doctor has given you. It is important that you keep this Card and show it to your partner or carer.

3. How to use Tecentriq

You will receive treatment with Tecentriq from a doctor who is experienced in the treatment of cancer in a hospital or clinic.

There are two different formulations for 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 changing your treatment from intravenous Tecentriq to subcutaneous Tecentriq (and vice versa) if they think it is suitable for you.

How much Tecentriq is given intravenously

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.

How Tecentriq is given intravenously

Tecentriq is given as a drip into a vein (by ‘intravenous infusion’).

The first infusion will be given 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, the following infusions will be given over a period of 30 minutes.

Duration of treatment

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

If you miss a dose of Tecentriq

If you miss an appointment with your doctor, make another one as soon as possible. For the treatment to be as effective as possible, it is very important to continue giving you the infusions.

If you stop treatment with Tecentriq

Do not stop treatment with Tecentriq unless you have discussed it with your doctor. Stopping your treatment may stop the effect of the medicine.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

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

Tecentriq used alone

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

Very common:may 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
• rash
• loss of appetite
• difficulty breathing
• urinary tract infection
• back pain
• cough
• headache

Common:may affect up to 1 in 10 patients

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

Uncommon:may affect up to 1 in 100 patients

• pancreas inflammation
• numbness or paralysis – which can 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)
• muscle inflammation (myositis)
• red, dry, scaly, and thickened skin areas (psoriasis)
• kidney inflammation
• 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, which can be severe (severe skin reactions)
• inflammation of the pituitary gland located at the base of the brain
• increased creatine phosphokinase in the blood (demonstrated in tests), which can be a sign of muscle or cardiac inflammation.

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

• heart muscle inflammation
• myasthenia gravis, a disease that can cause muscle weakness
• eye inflammation (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 in the spinal cord (myelitis)
• Weakness of the nerves and muscles of the face (facial paralysis)
• Celiac disease (characterized by symptoms such as stomach pain, diarrhea, and bloating after consuming foods that contain gluten)

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

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

Tecentriq used in combination with anticancer medications

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

Very common:may 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 can make you more prone to bruising or bleeding (thrombocytopenia)
• constipation
• nerve 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
• rash
• joint pain
• feeling of fatigue (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:may 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)
• fainting
• elevated liver enzymes (detected in tests), which can be a sign of liver inflammation
• change in taste (dysgeusia)
• decrease in the number of lymphocytes (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
• perfusion-related reactions
• severe blood infection (sepsis)

Uncommon:may affect up to 1 in 100 patients

• red, dry, scaly, and thickened skin areas (psoriasis)
• 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, which can be severe (severe skin reactions)
• inflammation of the heart sac with fluid accumulation in the sac (in some cases) (pericardial disorders)
• inflammation of the pituitary gland located at the base of the brain

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

• 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
• Weakness of the nerves and muscles of the face (facial paralysis)
• Celiac disease (characterized by symptoms such as stomach pain, diarrhea, and bloating after consuming foods that contain gluten)

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

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

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

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Tecentriq

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

• Do not use this medicine after the expiration date stated on the packaging and on the label of the vial 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.
• Keep 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 medicine if you observe that it is cloudy, discolored, or contains particles

Medicines should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package contents and additional information

Composition of Tecentriq

• 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 components are L-histidine, glacial acetic acid, sucrose, polysorbate 20 (see section 2 "Tecentriq contains polysorbate"), and water for injectable preparations.

Appearance of the product and package contents

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

Tecentriq is available in packages containing 1 glass vial.

Marketing authorization holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Strasse 1

79639

Grenzach-Wyhlen

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of the last revision of this leaflet

Other sources of information

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

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This information is intended only for healthcare professionals:

Instructions for dilution

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

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

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

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

The bag should be gently inverted to mix the solution in order to avoid foam formation. Once the infusion is prepared, it should be administered immediately.

Parenteral medicines should be inspected visually for particulate matter and color changes before administration. If particles or color changes are observed, the solution should not be used.

No incompatibilities have been observed between Tecentriq and PVC, PO, PE, or PP infusion bags. Additionally, no incompatibilities have been observed with in-line filters with polyethersulfone or polysulfone membranes, nor with infusion sets or other infusion devices made of PVC, PE, polybutadiene, or polyurethane. 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 prepared infusion solution should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user and are generally not 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.

Method of administration

Tecentriq is administered intravenously. Tecentriq infusions should not be administered as rapid infusions or intravenous bolus.

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

Do not administer simultaneously with other medications through the same infusion line

Elimination

The disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.