TECENTRIQ 1875 MG SOLUTION FOR INJECTION

Patient Information Leaflet

Introduction

Package Leaflet: Information for the Patient

Tecentriq 1875 mg injectable solution

atezolizumab

Read this entire leaflet carefully before you start using this medicine, as it contains important information for you.

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

Leaflet Contents:

1. What Tecentriq is and what it is used for
2. What you need to know before using Tecentriq
3. How to use Tecentriq
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 antitumour medicine that contains the active substance atezolizumab.

• It is a type of protein belonging to a group of medicines known as "monoclonal antibodies".
• Monoclonal antibodies are a type of protein designed to recognise and bind to a specific target substance in the body.
• This antibody can help your immune system fight your 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 be treated with Tecentriq when their cancers have spread to other parts of the body or after prior treatment.

Patients may also be treated with Tecentriq when their lung cancer has not spread to other parts of the body; in this case, treatment will be 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 leaflet of any other anticancer medicines you may be receiving. If you have any questions about these medicines, please consult your doctor.

How Tecentriq works

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

2. What you need to know before 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 unsure, consult your doctor or nurse before starting Tecentriq.

Warnings and precautions

Talk to your doctor or nurse before starting Tecentriq if:

• you have an autoimmune disease (a condition in which the body attacks its own cells)
• you have been told that your cancer has spread to your brain
• you have a history of lung inflammation (called pneumonitis)
• you have or have had chronic viral liver infection, including hepatitis B (HBV) or hepatitis C (HCV)
• you have human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
• you have significant cardiovascular, blood, or organ disorders due to inadequate blood pressure
• you have previously experienced serious adverse reactions to antibody therapies used to treat your cancer
• you have received medicines to stimulate your immune system
• you have received medicines to suppress your immune system
• you have received a live attenuated vaccine
• you have taken medications to treat infections (antibiotics) within the previous two weeks

Tecentriq acts on your immune system. This may cause inflammation in various parts of your body. The risk of this 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 moderate.

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

Tecentriq may cause certain adverse effects that you must report to your doctor immediately. These may occur weeks or months after the last dose. Inform your doctor immediately if you experience any of the following symptoms:

• inflammation of the lung (pneumonitis); symptoms may include new or worsening cough, shortness of breath, and chest pain

• inflammation of the liver (hepatitis); symptoms may include yellowing of 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 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 changes in vision

• type 1 diabetes, including severe, sometimes life-threatening complications due to acidic blood caused by diabetes (diabetic ketoacidosis); symptoms include unusual hunger or thirst, frequent urination, weight loss, feeling tired or difficulty thinking clearly, sweet or fruity breath odor, a sweet or metallic taste in the mouth, unusual odor in 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 neck stiffness, headache, fever, chills, vomiting, sensitivity to light, confusion, and drowsiness

• inflammation or nerve problems (neuropathy); symptoms may include weakness in the muscles of the arms and legs or in the facial muscles, 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 or bowel problems

• inflammation of the pancreas (pancreatitis); symptoms include abdominal pain, nausea, and vomiting

• inflammation of the heart muscle (myocarditis); symptoms may include shortness of breath, reduced 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, pelvic pain, and body swelling, 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 difficulty swallowing or breathing

• serious infusion-related reactions (events occurring during or within the first day after infusion); may include fever, chills, difficulty breathing, and redness

• serious skin reactions (SCARs); which may include rash, itching, blistering, peeling, or ulcers on the skin, and/or ulcers in the mouth or mucosa of the nose, throat, or genital area

• inflammation of the pericardium with fluid accumulation in the sac (in some cases) (pericardial disorders); symptoms are similar to myocarditis and may include chest pain (typically in the front of the chest, sharp, 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, shortness of breath, fatigue, and fainting

• a condition in which the immune system produces too many infection-fighting cells called histiocytes and lymphocytes, which can cause various symptoms (hemophagocytic lymphohistiocytosis); symptoms may include enlargement of the liver and/or spleen, skin rash, swollen lymph nodes, breathing problems, easy bruising, kidney abnormalities, and heart problems.

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

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

• give you other medications to prevent complications and reduce your symptoms
• delay your next Tecentriq dose
• stop your treatment with Tecentriq

Tests and monitoring

Before starting treatment, your doctor will assess your overall health. Blood tests will also be performed during your treatment.

Children and adolescents

This medicine 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 in this age group.

Other medicines and Tecentriq

Tell your doctor or nurse if you are taking, have recently taken, or might need to take any other medicines. This includes over-the-counter medications, including herbal remedies.

Pregnancy and breastfeeding

• If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

• Do not take Tecentriq if you are pregnant unless your doctor has specifically instructed you to do so. This is because the effect of Tecentriq in pregnant women is unknown—there may be a risk of harm to the unborn 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, inform your doctor.

Breastfeeding

It is unknown whether Tecentriq passes into breast milk. A risk to the breastfed infant cannot be excluded. Ask your doctor whether you should discontinue breastfeeding or discontinue treatment with Tecentriq.

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 operate machinery until you feel better.

Tecentriq contains polysorbate

This product 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 Information Card

The important information in this leaflet can be found on the Patient Information Card provided by your doctor. It is important that you keep this card and show it to your partner or caregiver.

3. How to use Tecentriq

You will receive Tecentriq treatment from a doctor experienced in cancer treatment.

There are two different formulations for Tecentriq:

• one is administered as an intravenous infusion (intravenous infusion)
• the other is administered as an injection under the skin (subcutaneous injection).

Your doctor may consider switching your Tecentriq treatment from intravenous to subcutaneous (and vice versa) if deemed appropriate for you.

Dose of subcutaneous Tecentriq

The recommended dose of Tecentriq injectable solution is 1,875 mg every three weeks.

How subcutaneous Tecentriq is administered

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

• 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 ensure that each injection is administered at a new site (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 medications.

Duration of treatment

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

If you miss a dose of Tecentriq

If you miss an appointment with your doctor, reschedule immediately. To ensure the treatment is as effective as possible, it is very important to continue receiving the injections as scheduled.

If you interrupt treatment with Tecentriq

Do not interrupt treatment with Tecentriq unless discussed with your doctor. Interrupting your treatment may stop the medicine's effect.

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

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone experiences them.

If you experience any of the adverse effects listed below, or if they worsen, tell your doctor immediately. These may occur weeks or months after your last dose. Do not take other medicines 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 people

• fever
• nausea
• vomiting
• feeling very tired, lacking energy (fatigue)
• lack of energy
• itchy 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 people

• inflammation of the lungs (pneumonitis)
• low oxygen levels that may cause difficulty breathing as a result of lung inflammation (hypoxia)
• stomach pain
• muscle and bone pain
• liver inflammation
• elevated liver enzymes (shown in tests), which may indicate liver inflammation
• difficulty swallowing
• blood tests may show low levels of potassium (hypokalemia) or sodium (hyponatremia)
• low blood pressure (hypotension)
• underactive thyroid gland (hypothyroidism)
• allergic reaction (infusion-related reaction, hypersensitivity, or anaphylaxis)
• flu-like illness
• chills
• intestinal inflammation
• 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
• abnormal kidney function tests (possible kidney damage)
• overactive thyroid gland (hyperthyroidism)
• inflammation of the sac around the heart with fluid accumulation in the sac (in some cases) (pericardial disorders)
• injection site reaction

Uncommon: may affect up to 1 in 100 people

• pancreas inflammation
• numbness or paralysis – which may be signs of Guillain-Barré syndrome
• inflammation of the membrane surrounding the spinal cord and brain (meningitis)
• low adrenal hormone levels
• type I diabetes (including diabetic ketoacidosis)
• muscle inflammation (myositis)
• dry, scaly, thickened red skin patches (psoriasis)
• kidney inflammation
• itching, blistering, peeling, or ulcers of the skin, and/or ulcers in the mouth or mucosa of the nose, throat, or genital area, which may be severe (serious skin reactions)
• inflammation of the pituitary gland located at the base of the brain
• increased blood creatine phosphokinase (shown in tests), which may indicate muscle or heart inflammation
• changes in any skin and/or genital area associated with dryness, thinning, itching, and pain (lichenoid disorders)

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

• inflammation of the heart muscle (myocarditis)
• myasthenia gravis, a disease that may cause muscle weakness
• eye inflammation (uveitis)
• hemophagocytic lymphohistiocytosis, a disorder in which the immune system produces too many infection-fighting cells called histiocytes and lymphocytes, which may 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 adverse effects reported with unknown frequency (cannot be estimated from available data):

• bladder inflammation. Signs and symptoms may include frequent and/or painful urination, urgent need to urinate, blood in the urine, or 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 medicines

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

Very common: may affect more than 1 in 10 people

• low red blood cell count, which may cause tiredness and difficulty breathing (anemia)
• low white blood cell count with or without fever, which may increase the risk of infection (neutropenia, leukopenia)
• low platelet count, which may make you more prone to bruising or bleeding (thrombocytopenia)
• constipation
• nerve damage causing possible numbness, pain, or loss of motor function (peripheral neuropathy)
• underactive thyroid gland (hypothyroidism)
• loss of appetite
• difficulty breathing
• diarrhea
• nausea
• itchy skin
• rash
• joint pain
• feeling of tiredness (fatigue)
• fever
• headache
• cough
• muscle and bone pain
• vomiting
• back pain
• lack of energy
• lung infection
• common cold (rhinopharyngitis)
• hair loss
• increased blood pressure (hypertension)
• swelling in arms or legs

Common: may affect up to 1 in 10 people

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

Uncommon: may affect up to 1 in 100 people

• dry, scaly, thickened red skin patches (psoriasis)
• itching, blistering, peeling, or ulcers of the skin, and/or ulcers in the mouth or mucosa of the nose, throat, or genital area, 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 located at the base of the brain

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

• hemophagocytic lymphohistiocytosis, a disorder in which the immune system produces too many infection-fighting cells called histiocytes and lymphocytes, which may cause various symptoms
• 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)
• changes in any skin and/or genital area associated with dryness, thinning, itching, and pain (lichenoid disorders)

Other adverse effects reported with unknown frequency (cannot be estimated from available data)

• absence or reduction of digestive 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 effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse 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 pack and on the label of the vial after EXP. The expiry date refers to 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 it appears cloudy, discoloured, or contains particles.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other 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 components are: L-histidine, L-methionine, acetic acid, sucrose, polysorbate 20 (see section 2 “Tecentriq contains polysorbate”), rHuPH20, water for injections.

Nature of the product and contents of the container

Tecentriq is an injectable solution. It is a clear, colourless to pale yellow liquid.

Tecentriq is available in packs containing 1 glass vial.

Marketing Authorization Holder

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

Manufacturer responsible for manufacturing

Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

More information about this medicinal product can be requested by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review 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

This information is intended for healthcare professionals only:

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

Tecentriq injectable solution should be visually inspected for the presence of particles or discoloration prior to administration.

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 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 standpoint, the medicinal product should be used immediately after transfer from the vial to the syringe, as it contains no antimicrobial preservative or bacteriostatic agent.

• Remove the vial from the refrigerator and allow the solution to reach room temperature.
• Withdraw the entire content of the injectable solution from the Tecentriq vial using a sterile syringe and a transfer needle (recommended 18G).
• Remove the transfer needle and attach a transfer set (e.g., winged/butterfly) containing a 23–25G stainless steel needle for injection. Use a subcutaneous infusion set with a residual/retention volume not exceeding 0.5 ml for administration.
• Prime the subcutaneous infusion line with the medicinal product solution to remove air from the line, stopping before the liquid reaches the needle.
• Ensure the syringe contains exactly 15 ml of solution after priming, expelling any excess volume from the syringe.
• Administer immediately to avoid needle blockage. DO NOT store the prepared syringe once it has been connected to the primed subcutaneous infusion set.

If the dose is not administered immediately, refer to “Syringe storage” below.

Syringe storage

• If not used immediately, the storage time prior to use and the storage conditions prior to administration are the responsibility of the user and, in general, should not exceed 24 hours between 2 °C and 8 °C, unless the syringe preparation was carried out under controlled and validated aseptic conditions.
• If the dose is not to be administered immediately, use an aseptic technique to withdraw the entire content of Tecentriq injectable solution from the vial into the syringe, taking into account the dose volume (15 ml) and the priming volume of the subcutaneous infusion device. Replace the transfer needle with a syringe cap. DO NOT attach a subcutaneous infusion set for storage.
• The prepared syringe may be stored for up to 30 days at 2–8 °C and for up to 8 hours at ≤30 °C under diffuse natural light from the time of preparation.
• If the syringe has been refrigerated, allow it to reach room temperature before administration.

Method of administration

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

Prior to administration, remove the Tecentriq subcutaneous solution from the refrigerator and allow it to reach room temperature. For instructions on the use and handling of the Tecentriq injectable formulation prior to administration, refer to section 6.6 of the Summary of Product Characteristics.

Administer 15 ml of Tecentriq subcutaneous injectable solution over approximately 7 minutes into the thigh. Use of a subcutaneous infusion set (e.g., winged/butterfly) is recommended. DO NOT administer to the patient the residual volume remaining in the tubing.

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

Disposal

Any unused medicinal product and waste materials that have come into contact with it should be disposed of in accordance with local requirements.