Prospect: information for the patient

IMJUDO 20mg/ml concentrate for solution for infusion
tremelimumab

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section4 includes information on how to report these adverse effects.

Read this prospect thoroughly before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor.
• If you experience adverse effects, consult your doctor, even if they are not listed in this prospect. See section4.

1.What is IMJUDO and for what it is used

2.What you need to know before starting to use IMJUDO

3.How to use IMJUDO

4.Possible adverse effects

5.Storage of IMJUDO

6.Contents of the package and additional information

IMJUDO is a cancer medication. It contains the active ingredient tremelimumab, which is a type of medication called anmonoclonal antibody. This medication has been designed to recognize a specific target substance in the body. IMJUDO helps your immune system fight cancer.

IMJUDO in combination with durvalumab is used to treat a type of liver cancer called advanced or unresectable hepatocellular carcinoma (HCC). It is used when your HCC:

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

IMJUDO is used to treat a type of lung cancer called non-microcytic advanced non-small cell lung cancer in adults. It will be used in combination with other cancer medications (durvalumab and chemotherapy).

Since IMJUDO will be administered in combination with other cancer medications, it is essential that you also read the prospectus for these other medications. If you have any questions about these medications, consult your doctor.

You should not receive IMJUDO

• if you are allergic to tremelimumab or any of the other components of this medication (listed in section6). Consult your doctor if you have any doubts.

Warnings and precautions

Consult your doctor before starting to use IMJUDO 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 respiratory or lung problems;
• you have liver problems.

Consult your doctorbefore IMJUDO is administered if you are in any of these situations.

When you receive IMJUDO, you may experience someserious side effects.

Your doctor may administer other medications to prevent more severe complications and help reduce symptoms. Your doctor may delay the next dose of IMJUDO or interrupt your treatment with IMJUDO.Inform your doctor immediatelyif you experience any of the following side effects:

• new or worsening cough; difficulty breathing; chest pain (may be signs ofpulmonary inflammation)
• nausea or vomiting; loss of appetite; right-sided abdominal pain; yellowing of the skin or white of the eyes; drowsiness; dark urine or bleeding or bruising that appears more easily than normal (may be signs ofliver inflammation)
• diarrhea or more frequent bowel movements; black, tar-like, or sticky stools with blood or mucus; severe or sharp abdominal pain (may be signs ofintestinal inflammationor intestinal perforation)
• rapid heart rate; extreme fatigue; weight gain or loss; dizziness or fainting; hair loss; feeling cold; constipation; persistent or unusual headaches (may be signs ofgland inflammation, especially of the thyroid, adrenal glands, pituitary gland, or pancreas)
• increased hunger or thirst; more frequent urination; high blood sugar levels; rapid and deep breathing; confusion; sweet-smelling breath; unusual taste or metallic taste in the mouth or unusual odor of urine or sweat (may be signs ofdiabetes)
• decreased urine output (may be a sign ofkidney inflammation)
• skin rash; itching; blisters on the skin or ulcers in the mouth or on other moist surfaces (may be signs ofskin inflammation)
• chest pain; shortness of breath; irregular heartbeat (may be signs ofheart muscle inflammation)
• muscle pain or weakness or rapid muscle fatigue (may be signs ofinflammationor other muscle problems)
• chills or shivering, itching or rash, flushing, difficulty breathing or wheezing, dizziness or fever (may be signs ofreactions related to perfusion)
• seizures; neck stiffness; headache; fever, chills; vomiting; sensitivity to light; confusion and drowsiness (may be signs ofbrain inflammationor inflammation of the membrane covering the brain and spinal cord)
• spinal cord inflammation(transverse myelitis): symptoms may include pain, numbness, tingling, or weakness in the arms or legs; urinary or intestinal problems, such as frequent urination, incontinence, difficulty urinating, and constipation
• pain; weakness and paralysis in the hands, feet, or arms (may be signs ofnerve inflammation, Guillain-Barré syndrome)
• pain, swelling, and/or stiffness in the joints (may be signs ofjoint inflammation, immunemediated arthritis)
• eye redness, eye pain, light sensitivity, and/or vision changes (may be signs and symptoms ofeye inflammation, uveitis)
• bleeding (from the nose or gums) and/or bruising (may be signs ofdecreased platelets in the blood).

Inform your doctor immediatelyif you experience any of the symptoms listed above.

Children and adolescents

IMJUDO should not be used in children or adolescents under 18 years old, as it has not been studied in these patients.

Other medications and IMJUDO

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

Pregnancy and fertility

This medicationis not recommended during pregnancy. Inform your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant. If you can become pregnant, you should use effective birth control while receiving IMJUDO and for at least 3months after receiving the last dose.

Breastfeeding

Inform your doctor if you are breastfeeding. It is unknown whether IMJUDO passes into breast milk. You may be advised not to breastfeed during treatment and for at least 3months after receiving the last dose.

Driving and operating machinery

It is unlikely that IMJUDO will affect your ability to drive and operate machinery. However, if you experience side effects that affect your ability to concentrate and react, you should exercise caution when driving or operating machinery.

IMJUDO has a low sodium content

IMJUDO contains less than 1mmol of sodium (23mg) per dose; this is essentially “sodium-free”.

IMJUDO contains polysorbate

This medication contains 0.3mg of polysorbate 80 in each 1.25ml vial, or 3mg of polysorbate 80 in each 15ml vial, equivalent to 0.2mg/ml. Polysorbates can cause allergic reactions. Inform your doctor if you have any known allergies.

IMJUDO will be administered in a hospital or clinic under the supervision of an experienced doctor. Your doctor will administer IMJUDO through a vein (infusion) over approximately one hour.

It is administered in combination with durvalumab for liver cancer.

Recommended dose:

• If you weigh 40 kg or more, the dose is 300 mg as a single dose.
• If you weigh less than 40 kg, the dose will be 4 mg per kg of body weight.

If you are administered IMJUDO in combination with durvalumab for liver cancer, IMJUDO will be administered first, followed by durvalumab.

It is administered in combination with durvalumab and chemotherapy for lung cancer.

Recommended dose:

• If you weigh 34 kg or more, the dose is 75 mg every 3 weeks.
• If you weigh less than 34 kg, the dose will be 1 mg per kg of body weight every 3 weeks.

You will normally receive a total of 5 doses of IMJUDO. The first 4 doses are administered in weeks 1, 4, 7, and 10. The fifth dose is usually administered 6 weeks later, in week 16. Your doctor will decide exactly how many treatments you need.

If you are administered IMJUDO in combination with durvalumab and chemotherapy, IMJUDO will be administered first, followed by durvalumab and then chemotherapy.

What to do if you miss an appointment for IMJUDO

It is very important not to miss any doses of this medication. If you miss an appointment, call your doctor immediately to schedule a new appointment.

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

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

When you receive IMJUDO, you may experience some serious side effects.You can consult a detailed listin section 22.

Consult your doctor immediatelyif you experience any of the following side effects that have been reported in a clinical trial with patients treated with IMJUDO in combination with durvalumab.

The following side effects have been reported in clinical trials in patients who used IMJUDO in combination with durvalumab:

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

• Subclinical hypothyroidism, which may cause fatigue or weight gain
• Cough
• Diarrhea
• Abdominal pain
• Abnormal liver function tests (elevated aspartate aminotransferase; elevated alanine aminotransferase)
• Skin rash
• Itching
• Fever
• Peripheral edema (swelling of the legs)

Common (may affect up to1 in 10 people)

• Upper respiratory tract infections
• Pneumonia
• Illness similar to the flu
• Oral infections and infections of the soft tissues of the mouth
• Hyperthyroidism, which may cause an accelerated heart rate or weight loss
• Thyroiditis (inflammation of the thyroid gland)
• Decreased levels of hormones produced by the adrenal glands, which may cause fatigue
• Pneumonitis (inflammation of the lungs)
• Abnormal pancreatic function tests
• Colitis (inflammation of the intestine)
• Pancreatitis (inflammation of the pancreas)
• Hepatitis (inflammation of the liver)
• Dermatitis
• Nocturnal sweating
• Muscle pain (myalgia)
• Abnormal renal function tests (elevated creatinine in the blood)
• Urinary pain (dysuria)
• Reaction to the infusion of the drug, which may cause fever or redness

Uncommon (may affect up to 1 in 100people)

• Oral fungal infections
• Low platelet count with signs of excessive bleeding and hematomas (immune thrombocytopenia)
• Low pituitary function; pituitary inflammation
• Type 1 diabetes mellitus
• A disease in which muscles weaken and rapid muscle fatigue occurs (myasthenia gravis)
• Meningitis (inflammation of the membrane covering the spinal cord and brain)
• Myocarditis (inflammation of the heart)
• Hoarseness (dysphonia)
• Pulmonary fibrosis
• Formation of blisters on the skin
• Muscle inflammation (myositis)
• Inflammation of muscles and blood vessels
• Nephritis (inflammation of the kidneys) that may decrease urine output
• Immunemediated arthritis (inflammation of the joints)

Rare (may affect up to 1 in 10,000people)

• Diabetes insipidus
• Uveitis (inflammation of the eye)
• Encephalitis (inflammation of the brain)
• Guillain-Barré syndrome (inflammation of the nerves)
• Intestinal perforation

• Celiac disease (characterized by symptoms such as abdominal pain, diarrhea, and bloating after consuming gluten-containing foods)
• Cystitis (inflammation of the bladder). Symptoms may include frequent and/or painful urination, urgent need to urinate, blood in the urine, abdominal pain or pressure in the lower abdomen.

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

• Transverse myelitis (inflammation of part of the spinal cord)
• Pancreatic exocrine insufficiency (absence or reduction of digestive enzymes produced by the pancreas)

The following side effects have been reported in clinical trials in patients who used IMJUDO in combination with durvalumab and platinum-based chemotherapy:

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

• Upper respiratory tract infections
• Pneumonia
• Low red blood cell count
• Low white blood cell count
• Low platelet count
• Subclinical hypothyroidism, which may cause fatigue or weight gain
• Decreased appetite
• Cough
• Nausea
• Diarrhea
• Vomiting
• Constipation
• Abnormal liver function tests (elevated aspartate aminotransferase; elevated alanine aminotransferase)
• Hair loss
• Skin rash
• Itching
• Joint pain (arthralgia)
• Sensation of fatigue or weakness
• Fever

Common (may affect up to1 in 10 people)

• Illness similar to the flu
• Oral fungal infections
• Low white blood cell count with signs of fever
• Low red blood cell count, white blood cell count, and platelet count (pancytopenia)
• Hyperthyroidism, which may cause an accelerated heart rate or weight loss
• Decreased levels of hormones produced by the adrenal glands, which may cause fatigue
• Low pituitary function; pituitary inflammation
• Thyroiditis (inflammation of the thyroid gland)
• Peripheral neuropathy (inflammation of the nerves that causes numbness, weakness, tingling, or burning pain in the arms and legs)
• Pneumonitis (inflammation of the lungs)
• Hoarseness (dysphonia)
• Oral or lip inflammation
• Abnormal pancreatic function tests
• Abdominal pain
• Colitis (inflammation of the intestine)
• Pancreatitis (inflammation of the pancreas)
• Hepatitis (inflammation of the liver) that may cause nausea or loss of appetite
• Muscle pain (myalgia)
• Abnormal renal function tests (elevated creatinine in the blood)
• Urinary pain (dysuria)
• Peripheral edema (swelling of the legs)
• Reaction to the infusion of the drug, which may cause fever or redness

Uncommon (may affect up to 1 in 100people)

• Oral infections and infections of the soft tissues of the mouth
• Low platelet count with signs of excessive bleeding and hematomas (immune thrombocytopenia)
• Diabetes insipidus
• Type 1 diabetes mellitus
• Encephalitis (inflammation of the brain)
• Myocarditis (inflammation of the heart)
• Pulmonary fibrosis
• Formation of blisters on the skin
• Nocturnal sweating
• Dermatitis
• Muscle inflammation (myositis)
• Inflammation of muscles and blood vessels
• Nephritis (inflammation of the kidneys) that may decrease urine output
• Cystitis (inflammation of the bladder). Symptoms may include frequent and/or painful urination, urgent need to urinate, blood in the urine, abdominal pain or pressure in the lower abdomen.
• Uveitis (inflammation of the eye)
• Immunemediated arthritis (inflammation of the joints)

Rare (may affect up to 1 in 10,000people)

• A disease in which muscles weaken and rapid muscle fatigue occurs (myasthenia gravis)
• Guillain-Barré syndrome (inflammation of the nerves)
• Meningitis (inflammation of the membrane covering the spinal cord and brain)
• Intestinal perforation
• Celiac disease (characterized by symptoms such as abdominal pain, diarrhea, and bloating after consuming gluten-containing foods)

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

• Transverse myelitis (inflammation of part of the spinal cord)
• Pancreatic exocrine insufficiency (absence or reduction of digestive enzymes produced by the pancreas)

Inform your doctor immediatelyif you experience any of the side effects mentioned above.

Reporting of side effects

If you experience any type of side effect,consult your doctor, even if it is a side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

IMJUDO will be administered in a hospital or clinic and the healthcare professional will be responsible for its conservation.

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

Do not use this medication after the expiration date that appears on the box and on the vial label after CAD. The expiration date is the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C).

Do not freeze.

Store in the original packaging to protect it from light.

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

Do not conserve the unused portion of the infusion solution for re-use. The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

Composition of IMJUDO

The active principle is tremelimumab.

Each milliliter of concentrate for solution for infusion contains 20 mg of tremelimumab.

Each vial contains 300 mg of tremelimumab in 15 ml of concentrate or 25 mg of tremelimumab in 1.25 ml of concentrate.

The other components are: histidine, hydrochloride monohydrate of histidine, trehalose dihydrate, disodium edetate dihydrate (see section 2 “IMJUDO has a low sodium content”), polysorbate 80, water for injection.

Appearance of the product and contents of the pack

IMJUDO concentrate for solution for infusion (sterile concentrate) is a sterile, preservative-free solution, transparent to slightly opalescent, colorless to slightly yellow, free of visible particles.

It is presented in containers containing 1 vial of 1.25 ml of concentrate or 1 vial of 15 ml of concentrate.

Only some pack sizes may be marketed.

Marketing Authorization Holder

AstraZeneca AB

SE-151 85 Södertälje

Sweden

Responsible for manufacturing

AstraZeneca AB

Gärtunavägen

SE-152 57 Södertälje

Sweden

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

Last update of this leaflet:

Other sources of information

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

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This information is intended for healthcare professionals only:

Preparation and administration of the infusion:

• Parenteral medicines should be visually inspected for the presence of particles and colour changes before administration. The concentrate is a transparent to slightly opalescent, colourless to slightly yellow, free of visible particles solution. Discard the vial if the solution is turbid, has colour changes or visible particles are observed.
• Do not agitate the vial.
• Extract the required volume of concentrate from the vial or vials and transfer it to an intravenous bag containing sodium chloride 9 mg/ml (0.9%) or glucose 50 mg/ml (5%) solution for injection to prepare a diluted solution with a final concentration ranging from 0.1 to 10 mg/ml. Mix the diluted solution gently by inverting the bag.
• Use the medicinal product immediately after dilution. The diluted solution should not be frozen. If not used immediately, the total time from piercing the vial to the start of administration should not exceed 24 hours between 2°C and 8°C or 12 hours at room temperature (up to 25°C). If refrigerated, intravenous bags should reach room temperature before use. Administer the infusion solution intravenously over 1 hour using a sterile in-line filter with a pore size of 0.2 or 0.22 microns with low protein binding.
• Do not administer other medicinal products through the same infusion line.
• IMJUDO is a single dose. Discard any unused portion remaining in the vial.

Elimination of unused medicinal product and all materials that have been in contact with it will be carried out in accordance with local regulations.