IMFINZI 50 mg/ml concentrate for infusion solution

Introduction

Package Leaflet: Information for the Patient

IMFINZI 50mg/ml concentrate for solution for infusiondurvalumab

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.

• If you have any further questions, ask your doctor.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is IMFINZI and what is it used for

IMFINZI contains the active substance durvalumab, which is a monoclonal antibody, a type of protein designed to recognize a specific target substance in the body. IMFINZI works by helping the immune system fight cancer.

IMFINZI is used in adults to treat a type of lung cancer called non-small cell lung cancer (NSCLC). It is used as monotherapy when NSCLC:

• has spread through the lung, cannot be removed by surgery, and
• has responded or stabilized after initial treatment with chemotherapy and radiotherapy.

It is used in combination with tremelimumab and chemotherapy when NSCLC:

• has spread through both lungs (and/or to other parts of the body), cannot be removed by surgery, and
• has not shown changes (mutations) in the genes called EGFR (epidermal growth factor receptor) or ALK (anaplastic lymphoma kinase).

It is used in combination with platinum-based chemotherapy before surgery (neoadjuvant treatment) and as monotherapy after surgery (adjuvant treatment) when NSCLC:

• has spread through the lung and can be removed by surgery.

IMFINZI is used in adults to treat a type of lung cancer called limited-stage small cell lung cancer (LS-SCLC). It is used when LS-SCLC:

• has not been removed by surgery, and
• has responded or stabilized after initial treatment with chemotherapy and radiotherapy.

IMFINZI in combination with chemotherapy is used in adults to treat a type of lung cancer called extensive-stage small cell lung cancer (ES-SCLC). It is used when ES-SCLC:

• has spread through the lungs (or towards other parts of the body) and
• has not been previously treated.

IMFINZI in combination with chemotherapy is used in adults to treat a type of bile duct cancer and gallbladder cancer, collectively referred to as biliary tract cancers (BTC). It is used when BTC:

• has spread within the bile ducts and gallbladder (or towards other parts of the body).

IMFINZI is used alone or in combination with tremelimumab to treat a type of liver cancer called advanced or unresectable hepatocellular carcinoma (HCC) in adults. It is used when HCC:

• cannot be removed by surgery (unresectable), and
• may have spread within the liver or to other parts of the body.

IMFINZI is used in adult women to treat a type of uterine cancer (endometrial cancer) that has spread beyond the original tumor or has come back (recurrent). It is used in combination with chemotherapy (carboplatin and paclitaxel), followed by:

• IMFINZI as monotherapy when the tumor is MMR deficient, or
• IMFINZI in combination with olaparib when the tumor is MMR proficient.

A test is used to determine the MMR status of the endometrial cancer.

IMFINZI is used to treat a type of bladder cancer called muscle-invasive bladder cancer (MIBC) that occurs when bladder cancer has spread to the muscle layer of the bladder but not to other parts of the body. It is used in combination with chemotherapy (neoadjuvant treatment) before surgical removal of the bladder, followed by IMFINZI as monotherapy after surgery (adjuvant treatment).

If you have any questions about how IMFINZI works or why you have been prescribed this medicine, ask your doctor or pharmacist.

When IMFINZI is given in combination with other cancer medicines, it is also important that you read the package leaflet for these other medicines. If you have any questions about these medicines, ask your doctor.

2. What you need to know before you use IMFINZI

Do not use IMFINZI

• If you are allergic to durvalumab or any of the other ingredients of this medicine (listed in section 6 “Contents of the pack and other information”). If in doubt, consult your doctor.

Warnings and precautions

Talk to your doctor before you start using IMFINZI if:

• you have an autoimmune disease (a disease in which the body's immune system attacks its own cells);
• you have received an organ transplant;
• you have lung or breathing problems;
• you have liver problems.

If you are in any of these situations (or are unsure), talk to your doctor before using IMFINZI.

When you are given IMFINZI, you may experience some serious side effects.

If you experience any of the following, call or see your doctor right away. Your doctor may give you other medicines to prevent more serious complications and to help relieve your symptoms. Your doctor may decide to delay the next dose of IMFINZI or stop your treatment with IMFINZI if you have:

• pneumonitis: symptoms may include new or worsening cough, difficulty breathing, or chest pain;
• hepatitis: symptoms may include nausea or vomiting, loss of appetite, pain in the right side of your stomach, yellowing of your skin or the white part of your eyes, sleepiness, dark urine, or easy bruising or bleeding;

• colitis: symptoms may include diarrhea or more bowel movements than usual, or stools that are black, tarry, sticky, or bloody, severe stomach pain or tenderness, hole in the intestine;

• endocrinopathies(especially thyroid gland, adrenal glands, pituitary gland, and pancreas): symptoms may include increased heart rate, extreme tiredness, weight gain or loss, dizziness or fainting, hair loss, feeling cold, constipation, headaches that do not go away or unusual headaches, stomach pain, nausea, and vomiting;

• type 1 diabetes mellitus: symptoms may include high blood sugar levels, feeling more hungry or thirsty than usual, urinating more often than usual, rapid and deep breathing, confusion, or a sweet smell in your breath, a sweet or metallic taste in your mouth, or a different smell in your urine or sweat;

• inflammation of the kidneys: symptoms may include decreased amount of urine.
• inflammation of the skin: symptoms may include rash, itching, blisters on the skin, or ulcers in the mouth or on other moist surfaces;
• inflammation of the heart muscle: symptoms may include chest pain, difficulty breathing, or irregular heartbeat;
• inflammation or problems of the muscles: symptoms may include pain, stiffness, or weakness in the muscles, or rapid fatigue of the muscles;
• inflammation of the spinal cord(transverse myelitis): symptoms may include pain, numbness, tingling, or weakness in the arms or legs; bladder or bowel problems, such as needing to urinate more often, urinary incontinence, difficulty urinating, and constipation;
• infusion-related reactions: symptoms may include chills or shaking, itching or rash, flushing, difficulty breathing, or wheezing (whistling sound when breathing), dizziness, or fever;
• inflammation of the brain(encephalitis) or inflammation of the membrane surrounding the spinal cord and brain(meningitis): symptoms may include seizures, stiff neck, headache, fever, chills, vomiting, sensitivity of the eyes to light, confusion, and sleepiness;
• inflammation of the nerves: symptoms may include pain, weakness, and paralysis in the limbs (Guillain-Barré syndrome);
• inflammation of the joints: signs and symptoms include pain, swelling, and/or stiffness in the joints (immune-mediated arthritis);
• inflammation of the eye: signs and symptoms include redness of the eyes, eye pain, sensitivity to light, and/or changes in vision (uveitis);
• low platelet count in the blood: symptoms may include bleeding (nosebleeds or bleeding gums) and/or bruising.
• low red blood cell count in blood tests: symptoms may include difficulty breathing, fatigue, pale skin, and/or rapid heartbeat. When IMFINZI is used in combination with another cancer medicine (olaparib), low red blood cell counts may be a sign of "pure red cell aplasia" (PRCA), a condition in which red blood cells are not produced, or "autoimmune hemolytic anemia" (AIHA), excessive destruction of red blood cells.

If you experience any of these symptoms, call or see your doctor right away.

IMFINZI works on your immune system. It can cause inflammation in parts of your body. The risk of you getting these side effects 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 are mild.

Children and adolescents

IMFINZI must not be used in children and adolescents under 18 years because it has not been studied in these patients.

Other medicines and IMFINZI

Tell your doctor if you are taking, have recently taken, or might take any other medicines. This includes herbal medicines and medicines that you buy without a prescription.

Pregnancy

• This medicine is not recommended during pregnancy.
• If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using this medicine.
• If you are a woman who can become pregnant, you must use an effective method of birth control while you are being treated with IMFINZI and for at least 3 months after your last dose.

Breast-feeding

• Tell your doctor if you are breast-feeding.
• Ask your doctor whether you can breast-feed during or after treatment with IMFINZI.
• It is not known whether IMFINZI passes into breast milk.

Driving and using machines

It is unlikely that IMFINZI will affect your ability to drive or use machines.

However, if you have side effects that affect your ability to concentrate and react, you should be careful when driving or using machines.

IMFINZI contains Polysorbate 80

This medicine contains 2 mg of polysorbate 80 in each 10 ml of concentrate, equivalent to 0.2 mg/ml. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.

3. How to use IMFINZI

IMFINZI will be given to you in a hospital or clinic under the supervision of an experienced doctor.

• The recommended dose of IMFINZI is 10 mg per kg of your body weight every 2 weeks, 20 mg per kg of body weight every 4 weeks, 1,120 mg every 3 weeks, or 1,500 mg every 3 or 4 weeks.
• Your doctor will give you IMFINZI through a drip into a vein (intravenous infusion) over about 1 hour.
• Your doctor will decide how many treatments you need.
• Depending on the type of cancer you have, IMFINZI may be given in combination with other cancer medicines.
• When IMFINZI is given in combination with tremelimumab and chemotherapy for your lung cancer, you will first be given tremelimumab followed by IMFINZI and then chemotherapy.
• When IMFINZI is given in combination with chemotherapy for your lung cancer or endometrial cancer, you will first be given IMFINZI followed by chemotherapy.
• When IMFINZI is given in combination with tremelimumab for your liver cancer, you will first be given tremelimumab followed by IMFINZI.
• Read the package leaflet for the other cancer medicines to understand the use of these other medicines. If you have any questions about these medicines, ask your doctor.

If you miss an appointment to receive treatment with IMFINZI

• Call your doctor right away to reschedule your appointment.
• It is very important that you do not miss any dose of this medicine.

If you have any further questions about your treatment, ask your doctor.

4. Possible Adverse Effects

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

When you are administered IMFINZI, you may suffer from some serious adverse effects (see section 2).

Consult your doctor immediately if you experience any of the following adverse effects that have been reported in clinical trials with patients who received IMFINZI as monotherapy:

Very Common (may affect more than 1 in 10 people)

• upper respiratory tract infections
• reduced activity of the thyroid gland, which can cause fatigue or weight gain
• cough
• diarrhea
• stomach pain
• rash or itching of the skin
• joint pain (arthralgia)
• fever

Common (may affect up to 1 in 10 people)

• severe lung infections (pneumonia)
• flu-like illness
• fungal infection in the mouth
• infections of the teeth and soft tissues of the mouth
• excessive activity of the thyroid gland, which can cause increased heart rate or weight loss
• inflammation of the lungs (pneumonitis)
• hoarse voice (dysphonia)
• inflammation of the liver, which can cause nausea or loss of appetite (hepatitis)
• abnormalities in liver function tests (elevated aspartate aminotransferase; elevated alanine aminotransferase)
• night sweats
• muscle pain (myalgia)
• abnormalities in tests that measure kidney function (elevated blood creatinine)
• painful urination (dysuria)
• swelling of the legs (peripheral edema)
• infusion reaction of the medicine, which can cause fever or flushing

Uncommon (may affect up to 1 in 100 people)

• low platelet count in the blood caused by an autoimmune reaction (immune thrombocytopenia)
• inflammation of the thyroid gland (thyroiditis)
• decreased secretion of hormones produced by the adrenal glands, which can cause fatigue
• insufficient activity of the pituitary gland; inflammation of the pituitary gland
• a condition that produces high blood sugar levels (type 1 diabetes mellitus)
• a disorder in which the muscles weaken and rapid muscle fatigue occurs (myasthenia gravis)
• inflammation of the brain (encephalitis)
• inflammation of the heart (myocarditis)
• scarring of lung tissue
• inflammation of the intestine (colitis)
• inflammation of the pancreas (pancreatitis)
• inflammation of the skin (dermatitis)
• thickened, red, dry, scaly, and itchy skin patches (psoriasis)
• blisters on the skin (pemphigoid)
• inflammation of the muscles (myositis)
• inflammation of the joints (immune-mediated arthritis)
• inflammation of the kidneys (nephritis), which can cause a decrease in the amount of urine
• inflammation of the bladder (cystitis). The 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

Rare (may affect up to 1 in 1,000 people)

• diabetes insipidus
• inflammation of the eye (uveitis)
• inflammation of the membrane surrounding the spinal cord and brain (meningitis)
• celiac disease (characterized by symptoms such as stomach pain, diarrhea, and bloating after consuming foods that contain gluten)
• inflammation of the muscles that causes pain or stiffness (polymyalgia rheumatica)
• inflammation of the muscles and blood vessels (polymyositis)
• absence or reduction of digestive enzymes produced by the pancreas (exocrine pancreatic insufficiency)

Other Adverse Effects that have been Reported with Unknown Frequency (cannot be estimated from available data)

• inflammation of the nerves (Guillain-Barré syndrome)
• inflammation of part of the spinal cord (transverse myelitis)

The following additional adverse effects have been reported when receiving IMFINZI as monotherapy in clinical trials in patients who received IMFINZI in combination with chemotherapy (the frequency and severity of adverse effects may vary depending on the anticancer drugs received):

Very Common (may affect more than 1 in 10 people)

• low white blood cell count
• low red blood cell count
• low platelet count in the blood
• nausea; vomiting; constipation
• hair loss
• loss of appetite
• feeling of fatigue or weakness
• inflammation of the nerves that causes numbness, weakness, tingling, or burning in the arms and legs (peripheral neuropathy)

Common (may affect up to 1 in 10 people)

• low white blood cell count with signs of fever (febrile neutropenia)
• inflammation of the mouth or lips (stomatitis)

Uncommon (may affect up to 1 in 100 people)

• low red blood cell count, white blood cell count, and platelet count (pancytopenia)

The following additional adverse effects have been reported when receiving IMFINZI as monotherapy in clinical trials in patients who received IMFINZI in combination with tremelimumab and platinum-based chemotherapy (the frequency and severity of adverse effects may vary depending on the anticancer drugs received):

Very Common (may affect more than 1 in 10 people)

• low red blood cell count
• low white blood cell count
• low platelet count in the blood
• loss of appetite
• nausea; vomiting; constipation
• hair loss
• feeling of fatigue or weakness

Common (may affect up to 1 in 10 people)

• low white blood cell count with signs of fever (febrile neutropenia)
• low red blood cell count, white blood cell count, and platelet count (pancytopenia)
• inflammation of the nerves that causes numbness, weakness, tingling, or burning in the arms and legs (peripheral neuropathy)
• inflammation of the mouth or lips (stomatitis)
• abnormalities in pancreatic function tests

Other Adverse Effects that have been Reported with Unknown Frequency (cannot be estimated from available data)

• hole in the intestine (intestinal perforation)

The following additional adverse effects have been reported when receiving IMFINZI as monotherapy in clinical trials in patients who received IMFINZI in combination with tremelimumab:

Common (may affect up to 1 in 10 people)

• abnormalities in pancreatic function tests

Other Adverse Effects that have been Reported with Unknown Frequency (cannot be estimated from available data)

• hole in the intestine (intestinal perforation)

The following additional adverse effects have been reported when receiving IMFINZI as monotherapy in clinical trials in patients who received IMFINZI in combination with platinum-based chemotherapy followed by IMFINZI with olaparib:

Very Common (may affect more than 1 in 10 people)

• low red blood cell count
• low white blood cell count (neutropenia and leucopenia)
• low platelet count in the blood
• loss of appetite
• inflammation of the nerves that causes numbness, weakness, tingling, or burning in the arms and legs (peripheral neuropathy)
• nausea; vomiting; constipation
• dizziness
• headache
• changes in the taste of food (dysgeusia)
• difficulty breathing (dyspnea)
• inflammation of the mouth or lips (stomatitis)
• hair loss
• feeling of fatigue or weakness

Common (may affect up to 1 in 10 people)

• low white blood cell count with fever (febrile neutropenia)
• low levels of lymphocytes, a type of white blood cell
• allergic reactions
• indigestion or heartburn (dyspepsia)
• blood clot in a deep vein, usually in the leg (venous thrombosis), which can cause symptoms such as pain or swelling of the legs
• inability to produce red blood cells (pure red cell aplasia) that can cause symptoms such as difficulty breathing, fatigue, pale skin, or rapid heartbeats

Uncommon (may affect up to 1 in 100 people)

• low red blood cell count, white blood cell count, and platelet count (pancytopenia)

Consult your doctor immediately if you experience any of the above-mentioned adverse effects.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, 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 IMFINZI

IMFINZI will be administered to you in a hospital or clinic, and the healthcare professional will be responsible for its storage. The storage details are as follows:

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date that appears on the carton 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.

Store in the original packaging to protect it from light.

Do not use this medicine if it is cloudy, has changed color, or contains visible particles.

Do not store any unused part of the infusion solution for reuse. The disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.

6. Package Contents and Additional Information

Composition of IMFINZI

The active substance is durvalumab.

Each ml of concentrate for solution for infusion contains 50 mg of durvalumab.

Each vial contains 500 mg of durvalumab in 10 ml of concentrate or 120 mg of durvalumab in 2.4 ml of concentrate.

The other ingredients are: histidine, histidine hydrochloride monohydrate, trehalose dihydrate, polysorbate 80 (E 433), and water for injections.

Appearance of the Product and Package Contents

IMFINZI concentrate for solution for infusion (sterile concentrate) is a clear to opalescent, colorless to slightly yellow solution, without visible particles.

It is presented in packs with 1 glass vial of 2.4 ml concentrate or 1 glass vial of 10 ml concentrate.

Marketing Authorization Holder

AstraZeneca AB

SE-151 85 Södertälje

Sweden

Manufacturer

AstraZeneca AB

Gärtunavägen

SE-152 57 Södertälje

Sweden

You can obtain 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 about this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu

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This information is intended only for healthcare professionals:

Preparation and Administration of the Infusion

• Parenteral medicines should be inspected visually for particles and color change before administration. The concentrate is a sterile, transparent to opalescent, colorless to slightly yellow solution, without visible particles. Discard the vial if the solution is cloudy, has changed color, or contains visible particles.
• Do not shake the vial.
• Withdraw the required volume of concentrate from the vial or vials and transfer it to an intravenous infusion bag containing sodium chloride 9 mg/ml (0.9%) or glucose 50 mg/ml (5%) injection solution, to prepare a diluted solution with a final concentration between 1 mg/ml and 15 mg/ml. To mix the diluted solution, gently invert the bag.
• Once diluted, the medicine should be used immediately. The diluted solution should not be frozen. Chemical and physical stability in use has been demonstrated for up to 30 days between 2°C and 8°C and up to 24 hours at room temperature (up to 25°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 normally not more than 24 hours between 2°C and 8°C or 12 hours at room temperature (up to 25°C), unless the dilution has taken place in controlled and validated aseptic conditions.
• If refrigerated, the intravenous infusion bags should be removed from the refrigerator and allowed to reach room temperature before use. Administer the infusion solution intravenously over 1 hour through a sterile, non-pyrogenic, low-protein-binding in-line filter with a pore size of 0.2 to 0.22 microns.
• Do not administer other medicines through the same infusion line.
• IMFINZI is for single use. Discard any unused portion remaining in the vial.

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