Imjudo 20 mg/ml concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

IMJUDO 20 mg/ml concentrate for solution for infusion tremelimumab

This medicinal product is subject to additional monitoring, which will allow rapid identification of new safety information. You can help by reporting any side effects you may experience. Information on how to report side effects is included at the end of section 4.

Read the entire leaflet carefully before starting to use this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor.
• If you experience any side effects, consult your doctor, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What IMJUDO is and what it is used for

IMJUDO is an anticancer medicine. It contains the active substance tremelimumab, which is a type of medicine called a monoclonal antibody. This medicine 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 have spread within your liver or to other parts of the body.

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

Since IMJUDO will be administered in combination with other anticancer medicines, it is important that you also read the package leaflet for these other medicines. If you have any questions about these medicines, consult your doctor.

2. What you need to know before using IMJUDO

You should not receive IMJUDO

• if you are allergic to tremelimumab or to any of the other components of this medicine (listed in section 6). Consult your doctor if you have any doubts.

Warnings and precautions

Talk to your doctor before starting IMJUDO if:

• you have an autoimmune disease (a condition 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.

Talk to your doctor before receiving IMJUDO if you are in any of these situations.

When you receive IMJUDO, you may experience some serious side effects.

Your doctor may give you other medicines to prevent more serious complications and help reduce symptoms. Your doctor may delay your next dose of IMJUDO or stop your treatment with IMJUDO. Tell your doctor immediately if you have any of the following side effects:

• new or worsening cough; difficulty breathing; chest pain (these may be signs of lung inflammation)
• nausea or vomiting; loss of appetite; pain on the right side of the stomach; yellowing of the skin or whites of the eyes; drowsiness; dark urine or bleeding or bruising more easily than normal (these may be signs of liver inflammation)
• diarrhoea or more bowel movements than usual; black, tar-like or sticky stools with blood or mucus; severe pain or tenderness in the stomach (these may be signs of intestinal inflammation or a hole in the intestine)
• fast heart rate; extreme tiredness; weight gain or loss; dizziness or fainting; hair loss; feeling cold; constipation; persistent or unusual headaches (these may be signs of inflammation of glands, especially the thyroid, adrenal glands, pituitary gland, or pancreas)
• feeling hungrier or thirstier than usual; more frequent urination; high blood sugar levels; rapid and deep breathing; confusion; sweet-smelling breath; sweet or metallic taste in the mouth, or unusual odour of urine or sweat (these may be signs of diabetes)
• decreased amount of urine passed (this may be a sign of kidney inflammation)
• skin rash; itching; blisters on the skin or ulcers in the mouth or other moist surfaces (these may be signs of skin inflammation)
• chest pain; shortness of breath; irregular heartbeat (these may be signs of inflammation of the heart muscle)
• muscle pain, stiffness, or weakness, or rapid muscle fatigue (these may be signs of inflammation or other problems with muscles)
• chills or shaking, itching or rash, flushing, difficulty breathing or wheezing, dizziness or fever (these may be signs of infusion-related reactions)
• seizures; neck stiffness; headache; fever, chills; vomiting; sensitivity to light; confusion and drowsiness (these may be signs of brain inflammation or of the membrane covering the brain and spinal cord)
• 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, or constipation
• pain, weakness, and paralysis in the hands, feet, or arms (these may be signs of nerve inflammation, Guillain-Barré syndrome)
• joint pain, swelling, and/or stiffness (these may be signs of joint inflammation, immune-mediated arthritis)
• eye redness, eye pain, sensitivity to light, and/or changes in vision (these may be signs and symptoms of eye inflammation, uveitis)
• bleeding (from nose or gums) and/or bruising (these may be signs of low platelet count in the blood).

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

Children and adolescents

IMJUDO must not be used in children or adolescents under 18 years of age as it has not been studied in these patients.

Other medicines and IMJUDO

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

Pregnancy and fertility

This medicine is 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 must use an effective method of contraception while being treated with IMJUDO and for at least 3 months after receiving the last dose.

Breast-feeding

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

Driving and using machines

IMJUDO is unlikely to affect your ability to drive or use machines. However, if you experience side effects that affect your ability to concentrate and react, you should be cautious when driving or using machines.

IMJUDO has a low sodium content

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

IMJUDO contains polysorbate

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

3. How to use IMJUDO

IMJUDO will be administered to you in a hospital or clinic under the supervision of an experienced doctor. Your doctor will give you IMJUDO as an intravenous infusion (drip into a vein) over approximately one hour.

IMJUDO is given in combination with durvalumab for liver cancer.

Recommended dose:

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

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

IMJUDO is given 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 kilogram of body weight every 3 weeks.

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

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

If you miss an appointment for IMJUDO

It is very important not to miss any doses of this medicine. If you miss an appointment, contact your doctor immediately to reschedule.

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 everybody gets them.

When you receive IMJUDO, you may experience some serious adverse effects. A detailed list is available in section 2.

Contact your doctor immediately if you experience any of the following adverse effects reported in a clinical trial of patients treated with IMJUDO in combination with durvalumab.

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

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

• underactive thyroid gland, which may cause tiredness or weight gain
• cough
• diarrhoea
• stomach pain
• abnormalities in liver function tests (elevated aspartate aminotransferase; elevated alanine aminotransferase)
• skin rash
• itching
• fever
• swelling of legs (peripheral oedema)

Common (may affect up to 1 in 10 people)

• upper respiratory tract infections
• lung infection (pneumonia)
• flu-like illness
• infections of the teeth and soft tissues of the mouth
• overactive thyroid gland, which may cause a rapid heartbeat or weight loss
• inflammation of the thyroid gland (thyroiditis)
• decreased levels of hormones produced by the adrenal glands, which may cause tiredness
• inflammation of the lungs (pneumonitis)
• abnormalities in pancreatic function tests
• inflammation of the intestine (colitis)
• inflammation of the pancreas (pancreatitis)
• inflammation of the liver (hepatitis)
• skin inflammation
• night sweats
• muscle pain (myalgia)
• abnormalities in kidney function tests (elevated blood creatinine)
• pain when urinating (dysuria)
• infusion-related reaction to the medicine which may cause fever or redness

Uncommon (may affect up to 1 in 100 people)

• fungal infection in the mouth
• low platelet count with signs of excessive bleeding and bruising (immune thrombocytopenia)
• underactive pituitary gland; inflammation of the pituitary gland
• type 1 diabetes mellitus
• a condition in which muscles weaken and rapid muscle fatigue occurs (myasthenia gravis)
• inflammation of the membrane covering the spinal cord and brain (meningitis)
• inflammation of the heart (myocarditis)
• hoarseness (dysphonia)
• scarring of lung tissue
• blistering of the skin
• inflammation of the muscles (myositis)
• inflammation of the muscles and blood vessels
• inflammation of the kidneys (nephritis) which may reduce urine output
• inflammation of the joints (immune-mediated arthritis)
• inflammation of the muscles causing pain or stiffness (polymyalgia rheumatica)

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

• diabetes insipidus

• inflammation of the eye (uveitis)

• inflammation of the brain (encephalitis)

• inflammation of the nerves (Guillain-Barré syndrome)

• hole in the intestine (intestinal perforation)

• coeliac disease (characterised by symptoms such as stomach pain, diarrhoea and bloating after eating foods containing gluten)

• inflammation of the bladder (cystitis). 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

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

• inflammation of part of the spinal cord (transverse myelitis)
• absence or reduced production of digestive enzymes by the pancreas (exocrine pancreatic insufficiency)

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

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

• upper respiratory tract infections
• lung infection (pneumonia)
• low red blood cell count
• low white blood cell count
• low platelet count
• underactive thyroid gland, which may cause tiredness or weight gain
• decreased appetite
• cough
• nausea
• diarrhoea
• vomiting
• constipation
• abnormalities in liver function tests (elevated aspartate aminotransferase; elevated alanine aminotransferase)
• hair loss
• skin rash
• itching
• joint pain (arthralgia)
• feeling tired or weak
• fever

Common (may affect up to 1 in 10 people)

• flu-like illness
• fungal infection in the mouth
• low white blood cell count with signs of fever
• low red blood cell count, white blood cell count, and platelets (pancytopenia)
• overactive thyroid gland, which may cause a rapid heartbeat or weight loss
• decreased levels of hormones produced by the adrenal glands, which may cause tiredness
• underactive pituitary gland; inflammation of the pituitary gland
• inflammation of the thyroid gland (thyroiditis)
• inflammation of the nerves causing numbness, weakness, tingling, or burning pain in arms and legs (peripheral neuropathy)
• inflammation of the lungs (pneumonitis)
• hoarseness (dysphonia)
• inflammation of the mouth or lips
• abnormalities in pancreatic function tests
• stomach pain
• inflammation of the intestine (colitis)
• inflammation of the pancreas (pancreatitis)
• inflammation of the liver which may cause nausea or loss of appetite (hepatitis)
• muscle pain (myalgia)
• abnormalities in kidney function tests (elevated blood creatinine)
• pain when urinating (dysuria)
• swelling of legs (peripheral oedema)
• infusion-related reaction to the medicine which may cause fever or redness

Uncommon (may affect up to 1 in 100 people)

• infections of the teeth and soft tissues of the mouth
• low platelet count with signs of excessive bleeding and bruising (immune thrombocytopenia)
• diabetes insipidus
• type 1 diabetes mellitus
• inflammation of the brain (encephalitis)
• inflammation of the heart (myocarditis)
• scarring of lung tissue
• blistering of the skin
• night sweats
• skin inflammation
• inflammation of the muscles (myositis)
• inflammation of the muscles and blood vessels
• inflammation of the kidneys (nephritis) which may reduce urine output
• inflammation of the bladder (cystitis). 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.
• inflammation of the eye (uveitis)
• inflammation of the joints (immune-mediated arthritis)

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

• a condition in which muscles weaken and rapid muscle fatigue occurs (myasthenia gravis)
• inflammation of the nerves (Guillain-Barré syndrome)
• inflammation of the membrane covering the spinal cord and brain (meningitis)
• hole in the intestine (intestinal perforation)
• coeliac disease (characterised by symptoms such as stomach pain, diarrhoea and bloating after eating foods containing gluten)

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

• inflammation of part of the spinal cord (transverse myelitis)
• absence or reduced production of digestive enzymes by the pancreas (exocrine pancreatic insufficiency)
• inflammation of the muscles causing pain or stiffness (polymyalgia rheumatica)

Tell your doctor immediately if you experience any of the adverse effects listed above.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, even if it is an effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of IMJUDO

IMJUDO will be administered in a hospital or clinic, and healthcare professionals will be responsible for its storage.

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

Do not use this medicine after the expiry date stated on the carton 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 in the original packaging to protect from light.

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

Do not store any unused portion of the infusion solution for later use. Any unused medicine and all materials that have been in contact with it must be disposed of in accordance with local regulations.

6. Contents of the container and other information

Composition of IMJUDO

The active substance is tremelimumab.

Each ml 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, monohydrate histidine hydrochloride, trehalose dihydrate, disodium edetate dihydrate (see section 2 “IMJUDO has a low sodium content”), polysorbate 80, water for injections.

Appearance of the medicinal product and contents of the container

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

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

Only certain container sizes may be marketed.

Marketing Authorization Holder

AstraZeneca AB
SE-151 85 Södertälje
Sweden

Manufacturer

AstraZeneca AB
Gärtunavägen
SE-152 57 Södertälje
Sweden

For more information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this summary:

Other sources of information

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

This information is intended for healthcare professionals only:

Preparation and administration of the infusion:

• Parenteral medicines should be inspected visually for particulate matter and discoloration prior to administration. The concentrate is a solution ranging from clear to opalescent, colorless to slightly yellow, free from visible particles. Discard the vial if the solution is cloudy, discolored, or if visible particles are present.
• Do not shake the vial.
• Withdraw the required volume of concentrate from the vial(s) and transfer it to an intravenous bag containing either sodium chloride 9 mg/ml (0.9%) solution for injection or glucose 50 mg/ml (5%) solution for injection to prepare a diluted solution with a final concentration between 0.1 and 10 mg/ml. Mix the diluted solution by gently inverting the bag.
• Use the medicine immediately after dilution. The diluted solution must not be frozen. If not used immediately, the total time from vial puncture to start of administration must not exceed 24 hours between 2 °C and 8 °C or 12 hours at room temperature (up to 25 °C). If refrigerated, intravenous bags must reach room temperature before use. Administer the infusion solution intravenously over 1 hour using a sterile in-line filter with low protein binding, 0.2 or 0.22 microns.
• Do not administer other medicines through the same infusion line.
• IMJUDO is a single-dose product. Discard any unused portion remaining in the vial.

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