Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - opdivo

Document Subject

Generated Narrative: MedicinalProductDefinition mpd585d8fe14b9492a241ac7bacfd89f6d

identifier: http://ema.europa.eu/identifier/EU/1/15/1014/001

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: OPDIVO 10 mg/mL concentrate for solution for infusion.

type: Full name

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part: nan

type: Invented name part

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part: nan

type: Scientific name part

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type: Strength part

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type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-d585d8fe14b9492a241ac7bacfd89f6d

identifier: http://ema.europa.eu/identifier/EU/1/15/1014/001

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - opdivo

Attesters

What is in this leaflet

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

OPDIVO is a medicine used to treat:

• advanced melanoma (a type of skin cancer) in adults and adolescents 12 years of age and older
• melanoma after complete resection in adults and adolescents 12 years of age and older (treatment after surgery is called adjuvant therapy)
• advanced non-small cell lung cancer (a type of lung cancer) in adults
• non-small cell lung cancer (a type of lung cancer) prior to resection in adults (treatment prior to surgery is called neoadjuvant therapy)
• malignant pleural mesothelioma (a type of cancer that affects the lining of the lung) in adults
• advanced renal cell carcinoma (advanced kidney cancer) in adults
• classical Hodgkin lymphoma that has come back after or has not responded to previous therapies, including an autologous stem-cell transplant (a transplant of your own blood-producing cells) in adults
• advanced cancer of the head and neck in adults
• advanced urothelial carcinoma (bladder and urinary tract cancer) in adults
• urothelial carcinoma after complete resection in adults
• advanced colorectal cancer (colon or rectal cancer) in adults
• advanced oesophageal cancer (gullet cancer) in adults
• oesophageal (gullet) or gastro-oesophageal junction cancer with residual pathologic disease after chemoradiation followed by surgery in adults
• advanced gastric, gastro-oesophageal junction or oesophageal adenocarcinoma (stomach or gullet cancer) in adults.

It contains the active substance nivolumab, which is a monoclonal antibody, a type of protein designed to recognise and attach to a specific target substance in the body.

Nivolumab attaches to a target protein called programmed death-1 receptor (PD-1) that can switch off the activity of T cells (a type of white blood cell that forms part of the immune system, the body s natural defences). By attaching to PD-1, nivolumab blocks its action and prevents it from switching off your T cells. This helps increase their activity against the melanoma, lung, kidney, lymphoid, head and neck, bladder, colon, rectal, stomach, oesophageal or gastro-oesophageal junction cancer cells.

OPDIVO may be given in combination with other anti-cancer medicines. It is important that you also read the package leaflet for these other medicines. If you have any questions about these medicines, please ask your doctor.

You should not be given OPDIVO

• if you are allergic to nivolumab or any of the other ingredients of this medicine (listed in section 6 "Contents of the pack and other information"). Talk to your doctor if you are not sure.

Warnings and precautions Talk to your doctor before using OPDIVO as it may cause:

• Problems with your heart such as a change in the rhythm or rate of the heartbeat or an abnormal heart rhythm.
• Problems with your lungs such as breathing difficulties or cough. These may be signs of inflammation of the lungs (pneumonitis or interstitial lung disease).
• Diarrhoea (watery, loose or soft stools) or any symptoms of inflammation of the intestines (colitis), such as stomach pain and mucus or blood in stool.
• Inflammation of the liver (hepatitis). Signs and symptoms of hepatitis may include abnormal liver function tests, eye or skin yellowing (jaundice), pain on the right side of your stomach area, or tiredness.
• Inflammation or problems with your kidneys. Signs and symptoms may include abnormal kidney function tests, or decreased volume of urine.
• Problems with your hormone producing glands (including the pituitary, the thyroid, the parathyroid and adrenal glands) that may affect how these glands work. Signs and symptoms that these glands are not working properly may include fatigue (extreme tiredness), weight change or headache, decreased blood levels of calcium and visual disturbances.
• Diabetes including a serious, sometimes life-threatening problem due to acid in the blood produced from diabetes (diabetic ketoacidosis). Symptoms may include feeling more hungry or thirsty than usual, need to urinate more often, weight loss, feeling tired or having difficulty thinking clearly, breath that smells sweet or fruity, a sweet or metallic taste in your mouth, or a different odour to your urine or sweat, feeling sick or being sick, stomach pain, and deep or fast breathing.
• Inflammation of the skin that can lead to severe skin reaction (known as toxic epidermal necrolysis and Stevens-Johnson syndrome). Signs and symptoms of severe skin reaction may include rash, itching, and peeling of the skin (possibly fatal).
• Inflammation of the muscles such as myocarditis (inflammation of the heart muscle), myositis (inflammation of the muscles) and rhabdomyolysis (stiffness in muscles and joints, muscle spasm). Signs and symptoms may include muscle pain, stiffness, weakness, chest pain, or severe fatigue.
• Solid organ transplant rejection.
• Graft-versus-host disease.
• Haemophagocytic lymphohistiocytosis. A rare disease in which our immune system makes too many of otherwise normal infection fighting cells called histiocytes and lymphocytes. Symptoms may include enlarged liver and/or spleen, skin rash, lymph node enlargement, breathing problems, easy bruising, kidney abnormalities, and heart problems.

Tell your doctor immediately if you have any of these signs or symptoms or if they get worse. Do not try to treat your symptoms with other medicines on your own. Your doctor may

• give you other medicines in order to prevent complications and reduce your symptoms,
• withhold the next dose of OPDIVO,
• or stop your treatment with OPDIVO altogether. Please note that these signs and symptoms are sometimes delayed, and may develop weeks or months after your last dose. Before treatment, your doctor will check your general health. You will also have blood tests during your treatment. Check with your doctor or nurse before you are given OPDIVO if:
• you have an autoimmune disease (a condition where the body attacks its own cells);
• you have melanoma of the eye;
• you were previously given ipilimumab, another medicine for treating melanoma, and experienced serious side effects because of that medicine;
• you have been told that your cancer has spread to your brain;
• you have any history of inflammation of the lungs;
• you have been taken medicines to suppress your immune system.

Complications of stem cell transplant that uses donor stem cells (allogeneic) after treatment with OPDIVO. These complications can be severe and can lead to death. Your healthcare provider will monitor you for signs of complications if you have an allogeneic stem cell transplant.

Children and adolescents OPDIVO should not be used in children and adolescents below 18 years of age except for adolescents 12 years of age and older with melanoma.

Other medicines and OPDIVO Before you are given OPDIVO, tell your doctor if you are taking any medicines that suppress your immune system, such as corticosteroids, since these medicines may interfere with the effect of OPDIVO. However, once you are treated with OPDIVO, your doctor may give you corticosteroids to reduce any possible side effects that you may have during your treatment and this will not impact the effect of the medicine. Tell your doctor if you are taking or have recently taken any other medicines. Do not take any other medicines during your treatment without talking to your doctor first.

Pregnancy and breast-feeding Tell your doctor if you are pregnant or think you might be, if you are planning to become pregnant, or if you are breast-feeding.

Do not use OPDIVO if you are pregnant unless your doctor specifically tells you to. The effects of OPDIVO in pregnant women are not known, but it is possible that the active substance, nivolumab, could harm an unborn baby.

• You must use effective contraception while you are being treated with OPDIVO and for at least 5 months following the last dose of OPDIVO, if you are a woman who could become pregnant.
• If you become pregnant while using OPDIVO tell your doctor.

It is not known whether OPDIVO gets into breast milk. A risk to the breast-fed infant cannot be excluded. Ask your doctor if you can breast-feed during or after treatment with OPDIVO.

Driving and using machines OPDIVO or OPDIVO in combination with ipilimumab may have a minor influence on the ability to drive and use machines; however, use caution when performing these activities until you are sure that OPDIVO does not adversely affect you.

OPDIVO contains sodium Tell your doctor if you are on a low-sodium (low-salt) diet before you are given OPDIVO. This medicine contains 2.5 mg sodium (main component of cooking/table salt) in each mL of concentrate. OPDIVO contains 10 mg sodium per 4 mL vial, 25 mg sodium per 10 mL vial, 30 mg sodium per 12 mL vial or 60 mg sodium per 24 mL vial, which is equivalent to 0.5%, 1.25%, 1.5% or 3% respectively, of the recommended maximum daily dietary intake of sodium for an adult.

You will also find key messages from this package leaflet in the patient alert card you have been given by your doctor. It is important that you keep this patient alert card and show it to your partner or caregivers.

How much OPDIVO is given When OPDIVO is given on its own, the recommended dose is either 240 mg given every 2 weeks or 480 mg given every 4 weeks depending on indication.

When OPDIVO is given on its own, for the treatment of skin cancer in adolescents 12 years of age and older and weighing at least 50 kg, the recommended dose is either 240 mg given every 2 weeks or 480 mg given every 4 weeks. For adolescents 12 years of age and older and weighing less than 50 kg, the recommended dose is either 3 mg of nivolumab per kilogram of your body weight given every 2 weeks or 6 mg of nivolumab per kilogram of your body weight given every 4 weeks.

When OPDIVO is given in combination with ipilimumab for the treatment of skin cancer in adults and adolescents 12 years of age and older, the recommended dose of OPDIVO is 1 mg of nivolumab per kilogram of your body weight for the first 4 doses (combination phase). Thereafter the recommended dose of OPDIVO (single-agent phase) is 240 mg given every 2 weeks or 480 mg given every 4 weeks in adults and adolescents 12 years of age and older and weighing at least 50 kg or 3 mg of nivolumab per kilogram of your body weight given every 2 weeks or 6 mg of nivolumab per kilogram of your body weight given every 4 weeks for adolescents 12 years of age and older and weighing less than 50 kg.

When OPDIVO is given in combination with ipilimumab for the treatment of advanced kidney cancer, the recommended dose of OPDIVO is 3 mg of nivolumab per kilogram of your body weight for the first 4 doses (combination phase). Thereafter, the recommended dose of OPDIVO is 240 mg given every 2 weeks or 480 mg given every 4 weeks (single-agent phase).

When OPDIVO is given in combination with ipilimumab for the treatment of advanced colon or rectal cancer, the recommended dose of OPDIVO is 3 mg of nivolumab per kilogram of your body weight for the first 4 doses (combination phase). Thereafter, the recommended dose of OPDIVO is 240 mg given every 2 weeks (single-agent phase).

When OPDIVO is given in combination with ipilimumab for the treatment of malignant pleural mesothelioma, the recommended dose of OPDIVO is 360 mg every 3 weeks.

When OPDIVO is given in combination with ipilimumab for the treatment of advanced oesophageal cancer, the recommended dose of OPDIVO is 3 mg of nivolumab per kilogram of your body weight every 2 weeks or 360 mg every 3 weeks.

When OPDIVO is given in combination with chemotherapy for the neoadjuvant treatment of non- small cell lung cancer, the recommended dose of OPDIVO is 360 mg every 3 weeks.

When OPDIVO is given in combination with chemotherapy for the treatment of advanced oesophageal cancer, the recommended dose of OPDIVO is 240 mg every 2 weeks or 480 mg every 4 weeks.

When OPDIVO is given in combination with chemotherapy for the treatment of advanced gastric, gastro-oesophageal junction or oesophageal adenocarcinoma, the recommended dose of OPDIVO is 360 mg every 3 weeks or 240 mg every 2 weeks.

When OPDIVO is given in combination with ipilimumab and chemotherapy for the treatment of advanced non-small cell lung cancer, the recommended dose of OPDIVO is 360 mg every 3 weeks. After completion of 2 cycles of chemotherapy, OPDIVO is given in combination with ipilimumab, the recommended dose of OPDIVO is 360 mg every 3 weeks.

When OPDIVO is given in combination with cabozantinib for the treatment of advanced kidney cancer, the recommended dose of OPDIVO is 240 mg given every 2 weeks or 480 mg given every 4 weeks.

Depending on your dose, the appropriate amount of OPDIVO will be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 50 mg/mL (5%) solution for injection before use. More than one vial of OPDIVO may be necessary to obtain the required dose.

How OPDIVO is given You will receive treatment with OPDIVO in a hospital or clinic, under the supervision of an experienced doctor.

OPDIVO will be given to you as an infusion (a drip) into a vein (intravenously) over a period of 30 or 60 minutes, every 2 weeks or 4 weeks, depending on the dose you are receiving. Your doctor will continue giving you OPDIVO for as long as you keep benefitting from it or until you no longer tolerate the treatment.

When OPDIVO is given in combination with ipilimumab for the treatment of skin, advanced kidney or advanced colon or rectal cancer, you will be given an infusion over a period of 30 minutes, every 3 weeks for the first 4 doses (combination phase). Thereafter it will be given as an infusion over a period of 30 or 60 minutes, every 2 weeks or 4 weeks, depending on the dose you are receiving (single-agent phase).

When OPDIVO is given in combination with ipilimumab for the treatment of malignant pleural mesothelioma, you will be given an infusion over a period of 30 minutes, every 3 weeks.

When OPDIVO is given in combination with ipilimumab for the treatment of advanced oesophageal cancer, you will be given an infusion over a period of 30 minutes, every 2 or 3 weeks, depending on the dose you are receiving.

When OPDIVO is given in combination with chemotherapy for the neoadjuvant treatment of non- small cell lung cancer, you will be given an infusion over a period of 30 minutes, every 3 weeks.

When OPDIVO is given in combination with chemotherapy for the treatment of advanced oesophageal cancer, you will be given an infusion over a period of 30 minutes, every 2 or 4 weeks, depending on the dose you are receiving.

When OPDIVO is given in combination with chemotherapy for the treatment of advanced gastric, gastro-oesophageal junction or oesophageal adenocarcinoma, you will be given an infusion over a period of 30 minutes every 3 weeks or every 2 weeks, depending on the dose you are receiving.

When OPDIVO is given in combination with ipilimumab and chemotherapy for the treatment of advanced non-small cell lung cancer, you will be given an infusion over a period of 30 minutes, every 3 weeks.

When OPDIVO is given in combination with cabozantinib, you will be given an infusion over a period of 30 minutes or 60 minutes, every 2 weeks or 4 weeks, depending on the dose you are receiving.

If you miss a dose of OPDIVO It is very important for you to keep all your appointments to receive OPDIVO. If you miss an appointment, ask your doctor when to schedule your next dose.

If you stop using OPDIVO Stopping your treatment may stop the effect of the medicine. Do not stop treatment with OPDIVO unless you have discussed this with your doctor.

If you have any further questions about your treatment or on the use of this medicine, ask your doctor. When OPDIVO is given in combination with other anti-cancer medicines, you will first be given OPDIVO followed by the other medicine.

Please refer to the package leaflet of these other medicines in order to understand the use of these medicines. If you have questions about them, please ask your doctor.

Like all medicines, this medicine can cause side effects, although not everybody gets them. Your doctor will discuss these with you and will explain the risks and benefits of your treatment.

Be aware of important symptoms of inflammation. OPDIVO acts on your immune system and may cause inflammation in parts of your body. Inflammation may cause serious damage to your body and some inflammatory conditions may be life-threatening and need treatment or withdrawal of OPDIVO.

The following side effects have been reported with OPDIVO alone:

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

• Infections of the upper respiratory tract
• A decreased number of red blood cells (which carry oxygen), white blood cells (which are important in fighting infection) or platelets (cells which help the blood to clot)
• Decreased appetite, high sugar levels in the blood (hyperglycaemia)
• Headache
• Shortness of breath (dyspnoea), cough
• Diarrhoea (watery, loose or soft stools), vomiting, nausea, stomach pain, constipation
• Skin rash sometimes with blisters, itching
• Pain in the muscles, bones (musculoskeletal pain) and joints (arthralgia)
• Feeling tired or weak, fever

Common (may affect up to 1 in 10 people)

• Serious lung infection (pneumonia), bronchitis
• Reactions related to the infusion of the medicine, allergic reaction (including life-threatening allergic reaction)
• Underactive thyroid gland (which can cause tiredness or weight gain), overactive thyroid gland (which can cause rapid heart rate, sweating and weight loss), swelling of the thyroid gland
• Dehydration, decrease in body weight, low sugar levels in the blood (hypoglycaemia)
• Inflammation of the nerves (causing numbness, weakness, tingling or burning pain of the arms and legs), dizziness
• Blurred vision, dry eyes
• Fast heart rate, abnormal heart rhythm
• High blood pressure (hypertension)
• Inflammation of the lungs (pneumonitis, characterised by coughing and difficulty breathing), fluid around the lungs
• Inflammation of the intestines (colitis), mouth ulcers and cold sores (stomatitis), dry mouth
• Skin colour change in patches (vitiligo), dry skin, redness of the skin, unusual hair loss or thinning
• Inflammation of the joints (arthritis)
• Kidney failure (including abrupt loss of kidney function)
• Pain, chest pain, oedema (swelling)

Uncommon (may affect up to 1 in 100 people)

• Increase in some white blood cells
• Chronic diseases associated with a build-up of inflammatory cells in various organs and tissues, most commonly the lungs (sarcoidosis)
• Decreased secretion of hormones produced by adrenal glands (glands situated above the kidneys), underactive function (hypopituitarism) or inflammation (hypophysitis) of the pituitary gland situated at the base of the brain, diabetes
• Increased acid levels in the blood (metabolic acidosis)
• Damage to nerves causing numbness and weakness (polyneuropathy), inflammation of the nerves caused by the body attacking itself, causing numbness, weakness, tingling or burning pain (autoimmune neuropathy)
• Inflammation of the eye (which causes pain and redness)
• Inflammation of the heart muscle, inflammation of the covering of the heart and accumulation of fluid around the heart (pericardial disorders), changes in the rhythm or rate of the heartbeat
• Fluid in the lungs
• Inflammation of the pancreas (pancreatitis), inflammation of the stomach (gastritis)
• Inflammation of the liver (hepatitis), blockage of bile ducts (cholestasis)
• Skin disease with thickened patches of red skin, often with silvery scales (psoriasis), skin condition of the face where the nose and cheeks are unusually red (rosacea), severe condition of the skin that causes red, often itchy spots, similar to the rash of measles, which starts on the limbs and sometimes on the face and the rest of the body (erythema multiforme), hives (itchy, bumpy rash)
• Inflammation of the muscles causing pain or stiffness (polymyalgia rheumatica)

Rare (may affect up to 1 in 1000 people)

• A temporary and reversible non-infectious inflammation of the protective membranes surrounding the brain and spinal cord (aseptic meningitis)
• A disease causing the inflammation or enlargement of a lymph node (Kikuchi lymphadenitis)
• Acid in the blood produced from diabetes (diabetic ketoacidosis), decreased function of the parathyroid gland
• A temporary inflammation of the nerves that causes pain, weakness, and paralysis in the extremities (Guillain-Barr syndrome), loss of the protective sheath around nerves (demyelination), a condition in which the muscles become weak and tire easily (myasthenic syndrome), inflammation of the brain
• Inflammatory disease of blood vessels
• Ulcer of the small intestines
• Severe and possibly fatal peeling of the skin (toxic epidermal necrolysis or Stevens-Johnson syndrome)
• Disease in which the immune system attacks the glands that make moisture for the body, such as tears and saliva (Sjogren s syndrome), aching muscles, muscle tenderness or weakness, not caused by exercise (myopathy), inflammation of the muscles (myositis), stiffness in muscles and joints, muscle spasm (rhabdomyolysis)
• Inflammation of the kidney, inflammation of the bladder, signs and symptoms may include frequent and/or painful urination, urge to pass urine, blood in urine, pain or pressure in lower abdomen

Other side effects that have been reported with frequency not known (cannot be estimated from the available data):

• A condition where the immune system makes too many infection-fighting cells called histiocytes and lymphocytes that may cause various symptoms (called haemophagocytic lymphohistiocytosis)
• Solid organ transplant rejection
• A group of metabolic complications occurring after cancer treatment characterised by high blood levels of potassium and phosphate, and low blood levels of calcium (tumour lysis syndrome)
• An inflammatory disorder (most likely of autoimmune origin) affecting the eyes, skin and the membranes of the ears, brain and spinal cord (Vogt-Koyanagi-Harada syndrome)
• Changes in any area of the skin and/or genital area that are associated with drying out, thinning, itching and pain (lichen sclerosus or other lichen disorders)

The following side effects have been reported with OPDIVO in combination with other anti-cancer medicines (the frequency and severity of side effects may vary with the combination of anti-cancer medicines received):

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

• Infections of the upper respiratory tract
• A decreased number of red blood cells (which carry oxygen), white blood cells (which are important in fighting infection) or platelets (cells which help the blood to clot)
• Underactive thyroid gland (which can cause tiredness or weight gain), overactive thyroid gland (which can cause rapid heart rate, sweating and weight loss)
• Decreased appetite, decrease in body weight, decreased levels of albumin in the blood, high (hyperglycaemia) or low (hypoglycaemia) sugar levels in the blood
• Inflammation of the nerves (causing numbness, weakness, tingling or burning pain of the arms and legs), headache, dizziness, altered sense of taste
• High blood pressure (hypertension)
• Shortness of breath (dyspnoea), cough, abnormal speaking sound (dysphonia)
• Diarrhoea (watery, loose or soft stools), constipation, vomiting, nausea, stomach pain, mouth ulcers and cold sores (stomatitis), indigestion (dyspepsia)
• Skin rash sometimes with blisters, itching, pain of the hands or soles of the feet: rash or redness of the skin, tingling and tenderness developing to symmetrical redness, swelling and pain primarily on the palm of the hand and sole of the foot (palmar-plantar erythrodysaesthaesia syndrome)
• Pain in the joints (arthralgia), pain in the muscles and bones (musculoskeletal pain), muscle spasm
• Excess protein in urine
• Feeling tired or weak, fever, oedema (swelling)

Common (may affect up to 1 in 10 people)

• Serious lung infection (pneumonia), bronchitis, inflammation of the eye (conjunctivitis)
• Increase in some white blood cells, decrease in neutrophils with fever
• Allergic reaction, reactions related to the infusion of the medicine
• Decreased secretion of hormones produced by adrenal glands (glands situated above the kidneys), underactive function (hypopituitarism) or inflammation (hypophysitis) of the pituitary gland situated at the base of the brain, swelling of the thyroid gland, diabetes
• Dehydration, decreased levels of phosphate in the blood
• Sensations like numbness and tingling (paraesthesia)
• Hearing a persistent sound in your ear when no sound exists (tinnitus)
• Blurred vision, dry eye
• Fast heart rate, abnormal heart rhythm, inflammatory disease of blood vessels
• Formation of a blood clot within a blood vessel (thrombosis)
• Inflammation of the lungs (pneumonitis, characterised by coughing and difficulty breathing), fluid around the lungs, blood clots, nose bleeding
• Inflammation of the intestines (colitis), inflammation of the pancreas (pancreatitis), dry mouth, inflammation of the stomach (gastritis), oral pain, haemorrhoids (piles)
• Inflammation of the liver
• Skin colour change in patches (including vitiligo), redness of the skin, unusual hair loss or thinning, hair colour change, hives (itchy rash), discolouration or abnormal darkening of the skin (skin hyperpigmentation), dry skin
• Inflammation of the joints (arthritis), muscle weakness, aching muscles
• Kidney failure (including abrupt loss of kidney function)
• Pain, chest pain, chills
• Feeling generally unwell (malaise)

Uncommon (may affect up to 1 in 100 people)

• Acid in the blood produced from diabetes (diabetic ketoacidosis)
• Increased acid levels in the blood
• A temporary inflammation of the nerves that causes pain, weakness and paralysis in the extremities (Guillain-Barr syndrome); damage to nerves causing numbness and weakness (polyneuropathy); foot drop (peroneal nerve palsy); inflammation of the nerves caused by the body attacking itself, causing numbness, weakness, tingling or burning pain (autoimmune neuropathy); muscle weakness and tiredness without atrophy (myasthenia gravis or syndrome)
• Inflammation of the brain
• Inflammation of the eye (which causes pain and redness)
• Changes in the rhythm or rate of the heartbeat, slow heart rate, inflammation of the heart muscle
• Intestinal perforation, inflammation of the duodenum, burning or painful sensation in the tongue (glossodynia)
• Severe and possibly fatal peeling of the skin (Stevens-Johnson syndrome), skin disease with thickened patches of red skin, often with silvery scales (psoriasis), severe condition of the skin that causes red, often itchy spots, similar to the rash of measles, which starts on the limbs and sometimes on the face and the rest of the body (erythema multiforme)
• Muscle tenderness or weakness, not caused by exercise (myopathy), inflammation of the muscles (myositis), stiffness in muscles and joints, inflammation of the muscles causing pain or stiffness (polymyalgia rheumatica), bone damage in the jaw, abnormal opening between two body parts, such as an organ or blood vessel and another structure (fistula)
• Inflammation of the kidney, inflammation of the bladder, signs and symptoms may include frequent and/or painful urination, urge to pass urine, blood in urine, pain or pressure in lower abdomen

Rare (may affect up to 1 in 1000 people)

• Temporary and reversible non-infectious inflammation of the protective membranes surrounding the brain and spinal cord (aseptic meningitis)
• Chronic diseases associated with a build-up of inflammatory cells in various organs and tissues, most commonly the lungs (sarcoidosis)
• Decreased function of the parathyroid gland
• A group of metabolic complications occurring after cancer treatment characterised by high blood levels of potassium and phosphate, and low blood levels of calcium (tumour lysis syndrome)
• An inflammatory disorder (most likely of autoimmune origin) affecting the eyes, skin and the membranes of the ears, brain and spinal cord (Vogt-Koyanagi-Harada syndrome)
• Inflammation of the nerves
• Severe and possibly fatal peeling of the skin (toxic epidermal necrolysis), changes in any area of the skin and/or genital area that are associated with drying out, thinning, itching and pain (lichen sclerosus or other lichen disorders)
• Chronic disease of joints (spondyloarthropathy), disease in which the immune system attacks the glands that make moisture for the body, such as tears and saliva (Sjogren s syndrome), muscle spasm (rhabdomyolysis)

Other side effects that have been reported with frequency not known (cannot be estimated from the available data):

• A condition where the immune system makes too many infection-fighting cells called histiocytes and lymphocytes that may cause various symptoms (called haemophagocytic lymphohistiocytosis)
• Solid organ transplant rejection
• Inflammation of the covering of the heart and accumulation of fluid around the heart (pericardial disorders)

Tell your doctor immediately if you get any of the side effects listed above. Do not try to treat your symptoms with other medicines on your own.

Changes in test results OPDIVO alone or in combination may cause changes in the results of tests carried out by your doctor. These include:

• Abnormal liver function tests (increased amounts of the liver enzymes aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, or alkaline phosphatase in your blood, higher blood levels of the waste product bilirubin)
• Abnormal kidney function tests (increased amounts of creatinine in your blood)
• An increased level of the enzyme that breaks down fats and of the enzyme that breaks down starch
• Increased or decreased amount of calcium or potassium
• Increased or decreased blood levels of magnesium or sodium
• Increased amount of thyroid stimulating hormone
• Increase in blood triglyceride levels in the blood
• Increase in cholesterol levels in the blood

Reporting of side effects If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

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

Do not use this medicine after the expiry date which is stated on the carton and the vial label after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2 C to 8 C). Do not freeze. Store in the original package in order to protect from light. The unopened vial can be stored at controlled room temperature up to 25 C with room light for up to 48 hours.

Do not store any unused portion of the infusion solution for reuse. Any unused medicine or waste material should be disposed of in accordance with local requirements.

What OPDIVO contains

• The active substance is nivolumab. Each mL of concentrate for solution for infusion contains 10 mg of nivolumab. Each vial contains either 40 mg (in 4 mL), 100 mg (in 10 mL), 120 mg (in 12 mL) or 240 mg (in 24 mL) of nivolumab.

• The other ingredients are sodium citrate dihydrate, sodium chloride (see section 2 "OPDIVO contains sodium"), mannitol (E421), pentetic acid, polysorbate 80 (E433), sodium hydroxide, hydrochloric acid and water for injections.

What OPDIVO looks like and contents of the pack OPDIVO concentrate for solution for infusion (sterile concentrate) is a clear to opalescent, colourless to pale yellow liquid that may contain few light particles.

It is available in packs containing either 1 vial of 4 mL, 1 vial of 10 mL, 1 vial of 12 mL or 1 vial of 24 mL. Not all pack sizes may be marketed.

Marketing Authorisation Holder Bristol-Myers Squibb Pharma EEIG Plaza Blanchardstown Corporate Park 2 Dublin 15, D15 TIreland

Manufacturer Swords Laboratories Unlimited Company t/a Bristol-Myers Squibb Cruiserath Biologics Cruiserath Road, Mulhuddart Dublin 15, D15 H6EF Ireland

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site: