TECENTRIQ 1875 mg INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the Patient

Tecentriq 1875mg solution for injection

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-tumor 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 (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.

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

Do not use Tecentriq:

• if you are allergic to atezolizumab or 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

Ask your doctor or nurse before starting treatment with Tecentriq:

• 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 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 immune deficiency 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 in which the body attacks its own cells). You may also experience frequent exacerbations 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. They 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 may include recent or worsening cough, difficulty breathing, and chest pain
• inflammation of the liver (hepatitis): symptoms may include yellowing of the skin or eyes, nausea, vomiting, bleeding or bruising, dark urine, and stomach pain
• inflammation of the intestine (colitis), symptoms may include diarrhea (watery, loose, or soft stools), blood in the stool, and stomach pain
• inflammation of the thyroid and adrenal glands and pituitary gland (hypothyroidism, hyperthyroidism, or adrenal insufficiency or hypophysitis), symptoms may include fatigue, weight loss, weight gain, mood changes, hair loss, constipation, dizziness, headache, increased thirst, and frequent urination and vision changes.
• type 1 diabetes, including serious problems, sometimes life-threatening, due to the blood becoming acidic produced by diabetes (diabetic ketoacidosis), including symptoms such as feeling hungrier or thirstier than usual, needing to urinate more often, weight loss, feeling tired or having trouble thinking clearly, sweet or fruity breath, 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 may include stiff neck, headache, fever, chills, vomiting, sensitivity to light, confusion, and drowsiness
• inflammation or problems with the nerves (neuropathy), symptoms may 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 may 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 may 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 may include changes in the amount and color of urine, pain in the pelvis, and swelling of the body, and may lead to kidney failure.
• Inflammation of the muscles (myositis); symptoms may include muscle weakness, fatigue after walking or standing, stumbling or falling, and problems swallowing or breathing.
• severe reactions related to the injection (events that occur during or within the first day after the injection), 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.
• 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 may 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 may 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.

Pregnancy and breastfeeding

• If you are pregnant or breastfeeding, 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 being treated with Tecentriq, tell your doctor.

Breastfeeding

It is not known whether Tecentriq passes into breast milk. The risk to the breastfed child cannot be excluded. Ask your doctor whether you should stop breastfeeding 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 1875 mg contains 9 mg of polysorbate 20 in each 15 ml dose, which is equivalent to 0.6 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 caregiver.

3. How to use Tecentriq

You will receive treatment with Tecentriq from a doctor with experience in treating cancer

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 switching your treatment from intravenous Tecentriq to subcutaneous Tecentriq (and vice versa) if they think it is suitable for you.

How much Tecentriq subcutaneous is given

The recommended dose of Tecentriq solution for injection is 1875 mg every three weeks

How Tecentriq subcutaneous is given

Tecentriq is given as an injection under the skin (subcutaneous injection) by a doctor or nurse.

• The injections will be given in the thigh over approximately 7 minutes
• The injection site will be alternated between the left and right thigh
• Your doctor or nurse will make sure that each injection is given in a new place (at least 2.5 cm away from any previous injection site), and where the skin is not red, bruised, tender, or hard
• Different injection sites should be used for other medicines

Duration of treatment

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

If you miss a dose of Tecentriq

If you miss a doctor’s appointment, 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 injections.

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 side effects, although not all people may experience them.

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

Tecentriq Used Alone

The following side 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, lacking 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
• elevation of blood glucose
• 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)
• reaction at the injection site

Uncommon:may affect up to 1 in 100 patients

• inflammation of the pancreas
• 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)
• inflammation of the muscles (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
• increase in creatine phosphokinase in the blood (demonstrated in tests), which can be a sign of muscle or heart inflammation

Rare:may 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 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 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, 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 Anti-Cancer Medicines

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

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 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: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 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 side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that is not listed in this leaflet. You can also report them directly through the national reporting system included in Annex V. By reporting side effects, you can help provide 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 expiry date stated on the packaging and on the label of the vial after EXP. The expiry 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.
• Do not use this medicine if you notice that it is cloudy, discolored, or contains particles

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Tecentriq

• The active substance is atezolizumab. Each ml contains 125 mg of atezolizumab.

Each 15 ml vial contains 1,875 mg of atezolizumab.

The other ingredients are: L-histidine, L-methionine, acetic acid, sucrose, polysorbate 20 (see section 2 "Tecentriq contains polysorbate"), rHuPH20, water for injection

Appearance of the Product and Package Contents

Tecentriq is an injectable solution. 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 Last Revision of this Leaflet:

Other Sources of Information

Detailed information on 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:

To prevent errors, it is essential to review the labels of the vials to ensure the correct use of the formulation (intravenous or subcutaneous) as prescribed for the patient.

Tecentriq injectable solution must be visually inspected to ensure that it does not contain particles or discoloration before administration.

Tecentriq injectable solution is a ready-to-use solution that MUST NOT be diluted or mixed with other medicines.

Tecentriq injectable solution is for single use only and should only be prepared by a healthcare professional.

No incompatibilities have been observed between Tecentriq and polypropylene (PP), polycarbonate, stainless steel (SS), polyvinyl chloride (PVC), and polyurethane (PU).

Preparation of the Syringe

From a microbiological point of view, the medicine should be used immediately, since it is transferred from the vial to the syringe, as it does not contain any antimicrobial preservative or bacteriostatic agent

• Remove the vial from the refrigerator and let the solution reach room temperature.
• Withdraw the entire contents of the Tecentriq injectable solution from the vial with a sterile syringe and a transfer needle (recommended 18G).
• Remove the transfer needle and attach to a transfer set (e.g., winged/butterfly) that contains a stainless steel needle 23-25G for injection. Use a subcutaneous infusion set with a residual volume/retention not exceeding 0.5 ml for administration.
• Prime the subcutaneous infusion line with the medicinal product solution to eliminate air from the infusion line and stop before the liquid reaches the needle.
• Ensure that the syringe contains exactly 15 ml of the solution after priming and expel any excess volume from the syringe.
• Administer immediately to avoid needle clogging. DO NOT store the prepared syringe that has been attached to the subcutaneous infusion set and primed.

If the dose is not administered immediately, see "Storage of the Syringe" below.

Storage of the Syringe

• If not used immediately, the storage time until use and the storage conditions are the responsibility of the user and should not exceed 24 hours between 2 °C and 8 °C, unless the syringe preparation has been performed under controlled and validated aseptic conditions.
• If the dose is not to be administered immediately, use an aseptic technique to withdraw the entire contents of Tecentriq injectable solution from the vial to the syringe, taking into account the dose volume (15 ml) and the priming volume of the subcutaneous infusion set. The transfer needle should be replaced with a syringe closure cap. DO NOT attach a subcutaneous infusion set for storage.
• The prepared syringe can be stored for a maximum of 30 days at 2 to 8 °C and for a maximum of 8 hours at ≤30 °C with diffuse natural light from the time of preparation.
• If the syringe has been stored in a refrigerator, it should be allowed to reach room temperature before administration.

Method of Administration

The Tecentriq SC formulation cannot be used for intravenous administration and should only be used as a subcutaneous injection.

Before administration, remove the Tecentriq subcutaneous solution from the refrigerator and let it reach room temperature. For instructions on the use and handling of the Tecentriq injectable formulation before administration, see section 6.6 of the summary of product characteristics.

Administer 15 ml of Tecentriq injectable solution subcutaneously in the thigh over approximately 7 minutes. The use of a subcutaneous infusion set (e.g., winged/butterfly) is recommended. DO NOT administer the residual volume that remains in the tube to the patient.

The injection site should be alternated between the right and left thigh. New injections should be administered at least 2.5 cm from the previous site and never in areas where the skin is red, bruised, sensitive, or hard. During treatment with the Tecentriq subcutaneous formulation, it is preferable that other subcutaneously administered products be administered in different areas.

Disposal

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