Prescribing Information for the User

YERVOY5mg/ml Concentrate for Solution for Infusion

ipilimumab

Read this entire prescribing information carefully before starting to use this medication, as it contains important information for you.

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

YERVOY contains the active ingredient ipilimumab, a protein that helps your immune system attack and destroy cancer cells through your immune cells.

Ipilimumab is only used to treat advanced melanoma (a type of skin cancer) in adults and adolescents aged 12 years or older.

Ipilimumab in combination with nivolumab is used to treat

• advanced melanoma (a type of skin cancer) in adults and adolescents aged 12 years or older
• advanced renal cell carcinoma (advanced kidney cancer) in adults
• malignant pleural mesothelioma (a type of cancer that affects the lining of the lungs) in adults
• advanced colorectal cancer (colon or rectal cancer) in adults
• advanced esophageal cancer (cancer of the tube that connects the mouth to the stomach) in adults.

Ipilimumab in combination with nivolumab and chemotherapy is used to treat advanced non-small cell lung cancer (a type of lung cancer) in adults.

As YERVOY can be given in combination with other anticancer medications, it is essential that you also read the prospectus of these other medications. If you have any doubts about these medications, please consult your doctor.

You should not receive YERVOY

• if you areallergicto ipilimumab or any of the other ingredients in this medicine (listed in section6"Contents of the pack and other information").Consult your doctorif you are unsure.

Warnings and precautions

Consult your doctor before starting to use YERVOY, as it may cause:

Inform your doctor immediatelyif you have any of these signs or symptoms or if they worsen.Do not try to treat your symptoms with other medications.Your doctor may give you other medications to prevent more serious complications and reduce your symptoms, suspend the next dose of YERVOY, or completely stop your treatment with YERVOY.

Please note that these signs and symptomsmay occur lateand may develop weeks or months after the last dose. Before treatment, your doctor will check your overall health status. Blood tests will also be performed during treatment.

Consult your doctor or nurse before receiving YERVOY

• if you have anautoimmune disease(a problem in which the body attacks its own cells);
• if you have or have had achronic viral hepatitisinfection, including hepatitis B (VHB) or hepatitis C (VHC);
• if you havehuman immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)infection.

• if you have had a previous experience of a severe skin reaction after a previous cancer treatment.
• if you have a history of lung inflammation.

Children and adolescents

YERVOY should not be used in children and adolescents under 18years of age, except in adolescents aged 12years or older with melanoma.

Other medications and YERVOY

Before receiving YERVOY, inform your doctor

• if you are taking any other medication that suppresses your immune system, such as corticosteroids. These medications may interfere with the effect of YERVOY. However, once you are in treatment with YERVOY, your doctor should give you corticosteroids to reduce the adverse effects that YERVOY may have.

• if you are taking any medication that prevents blood clotting (anticoagulants). These medications may increase the risk of bleeding in the stomach or intestine, which is a side effect of YERVOY.

• if you have been recently prescribed Zelboraf (vemurafenib, another medication for skin cancer treatment). When YERVOY is administered after vemurafenib, it may increase the risk of skin side effects.

Also, inform your doctor if you are taking or have recently taken other medications.

Do not take other medicationsduring your treatment without consulting your doctor first. According to initial data, the combination of YERVOY (ipilimumab) and vemurafenib is not recommended due to increased liver toxicity.

Pregnancy and breastfeeding

If you are pregnant, if you intend to become pregnant, or if you are breastfeeding,consult your doctorbefore using this medication.

You should not use YERVOY if you are pregnant, unless your doctor specifically recommends it. The active ingredient, ipilimumab, may harm the fetus.

• You must useeffective contraceptive methodswhile taking YERVOY if you are a woman who can become pregnant.
• If you become pregnant while taking YERVOYinform your doctor.

The effect of ipilimumab on breast milk is unknown. However, no significant exposure to ipilimumab is expected for the infant through breast milk, and no effects on the infant are anticipated. Ask your doctor if you can continue breastfeeding during or after treatment with YERVOY.

Driving and operating machinery

Do not drive, ride a bike, or use machinesafter receiving YERVOY unless you are sure you feel well. Feeling tired or weak is a very common side effect of YERVOY. This may affect your ability to drive, ride a bike, or use machines.

YERVOY contains sodium

Inform your doctorif you have a low-sodium diet before receiving YERVOY.

This medication contains 23mg of sodium (main component of table salt/for cooking) in each 10ml vial. This is equivalent to 1.15% of the recommended daily maximum sodium intake for an adult.

This medication contains 92mg of sodium (main component of table salt/for cooking) in each 40ml vial. This is equivalent to 4.60% of the recommended daily maximum sodium intake for an adult.

How YERVOY is administered

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

When YERVOY is administered only for the treatment of skin cancer, YERVOY will be administered as an infusion (a drip) into a vein (intravenously) over a period of30minutes.

When YERVOY is administered in combination with nivolumab for the treatment of skin cancer, it will be administered as an infusion over a period of 30minutes every 3weeks during the first 4doses (combination phase). From then on, nivolumab will be administered as an infusion over a period of 30or 60minutes, every 2weeks or 4weeks, depending on the dose you are receiving (single-agent phase).

When YERVOY is administered in combination with nivolumab for the treatment of advanced kidney cancer, it will be administered as an infusion over a period of 30minutes every 3weeks during the first 4doses (combination phase). From then on, nivolumab will be administered as an infusion over a period of 30or 60minutes, every 2weeks or 4weeks, depending on the dose you are receiving (single-agent phase).

When YERVOY is administered in combination with nivolumab for the treatment of advanced colon or rectal cancer in adults, it will be administered as an infusion over a period of 30minutes every 3weeks during the first 4doses (combination phase). From then on, nivolumab will be administered as an infusion over a period of 30minutes, every 2weeks or 4weeks, depending on the dose you are receiving (single-agent phase).

When YERVOY is administered in combination with nivolumab for the treatment of malignant pleural mesothelioma or advanced esophageal cancer, it will be administered as an infusion over a period of 30minutes every 6weeks.

When YERVOY is administered in combination with nivolumab and chemotherapy for the treatment of advanced non-small cell lung cancer, it will be administered as an infusion over a period of 30minutes every 6weeks. After completing 2cycles of chemotherapy, ipilimumab will be administered in combination with nivolumab as an infusion over a period of 30minutes every 6weeks.

How much YERVOY is administered

When YERVOY is administered only for the treatment of skin cancer, the recommended dose is 3mg of ipilimumab per kilogram of body weight.

The amount of YERVOY you will receive will be calculated based on your body weight. Depending on the dose, part or all of the contents of the YERVOY vial may be diluted with 0.9% sodium chloride injection or 5% glucose injection before use. It may be necessary to use more than one vial to obtain the required dose.

You will be treated with YERVOY once every3weeks, a total of4doses. You may notice the appearance of new lesions or the growth of existing lesions on your skin while you are being treated with YERVOY. Your doctor will continue to give you YERVOY until a total of4doses, depending on your tolerance to the treatment.

When YERVOY is administered in combination with nivolumab for the treatment of skin cancer in adults and adolescents 12years of age or older, the recommended dose of YERVOY is 3mg of ipilimumab per kilogram of body weight every 3weeks during the first 4doses (combination phase). From then on, the recommended dose of nivolumab (single-agent phase) is 240mg administered every 2weeks or 480mg administered every 4weeks in adults and adolescents 12years of age or older and with a minimum weight of 50kg or 3mg of nivolumab per kilogram of body weight administered every 2weeks or 6mg of nivolumab per kilogram of body weight administered every 4weeks in adolescents 12years of age or older and with a weight less than 50kg.

When YERVOY is administered in combination with nivolumab for the treatment of advanced kidney cancer, the recommended dose of YERVOY is 1mg of ipilimumab per kilogram of body weight every 3weeks during the first 4doses (combination phase). From then on, the recommended dose of nivolumab is 240mg administered every 2weeks or 480mg administered every 4weeks (single-agent phase).

When YERVOY is administered in combination with nivolumab for the treatment of advanced colon or rectal cancer, the recommended dose of YERVOY is 1mg of ipilimumab per kilogram of body weight every 3weeks during the first 4doses (combination phase). From then on, the recommended dose of nivolumab is 240mg administered every 2weeks or 480mg administered every 4weeks (single-agent phase) depending on the treatment.

When YERVOY is administered in combination with nivolumab for the treatment of malignant pleural mesothelioma or advanced esophageal cancer, the recommended dose of YERVOY is 1mg of ipilimumab per kilogram of body weight every 6weeks.

When YERVOY is administered in combination with nivolumab and chemotherapy for the treatment of advanced non-small cell lung cancer, the recommended dose of YERVOY is 1mg of ipilimumab per kilogram of body weight. It will be administered as an infusion over a period of 30minutes every 6weeks.

If you miss a dose of YERVOY

It is very important that you attend all appointments to receive YERVOY. If you miss an appointment, ask your doctor when to schedule your next dose.

If you interrupt treatment with YERVOY

Interrupting treatment may stop the effect of the medication. Do not interrupt treatment with YERVOY unless you have discussed it with your doctor.

If you have any other questions about your treatment or the use of this medication, ask your doctor.

When YERVOY is administered in combination with nivolumab or in combination with nivolumab and chemotherapy, nivolumab will be administered first, followed by YERVOY, and then chemotherapy.

Please refer to the package insert of other anti-cancer medications to understand the use of these other medications. If you have any questions about these medications, please consult your doctor.

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

Be aware of the important symptoms of inflammation

YERVOY acts on the immune system and can causeinflammationin some parts of the body.

Inflammation can cause serious damage to the body and some inflammatory conditions could be potentially fatal.

The following side effects have been reported in patients who received 3mg/kg of ipilimumab alone:

Very common (may affect more than1 in 10patients)

• loss of appetite
• diarrhea (watery, loose or soft stools), vomiting or feeling sick (nausea), constipation, stomach pain
• skin rash, itching
• muscle, bone, ligament, tendon, and nerve pain
• feeling tired or weak, reaction at the injection site, fever, swelling, pain

• Inform your doctor immediatelyif you have any of these side effects.

Do not try to treat your symptoms with other medicines.

Common (may affect up to1 in 10patients)

• severe blood infection (sepsis), urinary tract infection, respiratory tract infection
• tumor pain
• decrease in the number of red blood cells (which carry oxygen), white blood cells (which are important for fighting infections) or platelets (cells that help blood to clot)
• decrease in thyroid function, which can cause fatigue or weight gain, decrease in pituitary function (hypopituitarism) or inflammation (hypophysitis) of the pituitary gland located at the base of the brain
• dehydration
• confusion, depression
• excess fluid accumulation in the brain, nerve damage (which causes pain, weakness, and cramps), dizziness, headache
• blurred vision, eye pain
• irregular or abnormal heart rhythm
• low blood pressure, transient facial and neck flushing, intense heat sensation with sweating and rapid heart rate
• difficulty breathing (dyspnea), cough, hay fever
• gastrointestinal bleeding, intestinal inflammation (colitis), stomach burning, mouth ulcers, and herpes (stomatitis)
• liver function alteration
• inflammation of the internal surface of a particular organ
• inflammation and redness of the skin, skin color changes in patches (vitiligo), urticaria (hives), hair loss or weakening, excessive night sweating, dry skin
• muscle and joint pain (arthralgia), muscle spasms, joint inflammation (arthritis)
• renal failure
• chills, lack of energy
• flu-like illness
• weight loss

• Inform your doctor immediatelyif you have any of these side effects.

Do not try to treat your symptoms with other medicines.

Uncommon (may affect up to1 in 100patients)

• severe blood infection (septic shock), inflammation around the brain or spinal cord, inflammation of the stomach and intestines, inflammation of the intestinal wall (which causes fever, vomiting, and stomach pain), lung infection (pneumonia)
• symptoms due to cancer in the body such as high levels of calcium and cholesterol in the blood, and low levels of sugar in the blood (paraneoplastic syndrome)
• increase in eosinophils (a type of white blood cell)
• allergic reaction
• decrease in the secretion of hormones produced by the adrenal glands (glands located above the kidneys), excessive function of the thyroid gland, which can cause rapid heart rate, sweating, and weight loss, defect of the glands that produce sex hormones
• decrease in the function of the adrenal glands caused by a decrease in the function of the hypothalamus (part of the brain)

• a group of metabolic complications that occur after cancer treatment characterized by high levels of potassium and phosphate in the blood and low levels of calcium in the blood (tumor lysis syndrome)

• mental health changes, decrease in sexual drive
• severe and potentially fatal nerve inflammation (Guillain-Barré syndrome), fainting, nerve inflammation inside the brain, difficulty coordinating movements (ataxia), muscle contractions, difficulty speaking
• eye inflammation (conjunctivitis), bleeding in the eye, inflammation of the colored part of the eye, blurred vision, sensation of a foreign body in the eyes, swollen and watery eyes, eye swelling, eyelid inflammation
• inflammation of blood vessels, vascular disease, restriction of blood supply to the limbs, low blood pressure when standing
• extreme difficulty breathing, fluid accumulation in the lungs, lung inflammation
• intestinal perforation, intestinal inflammation, pancreatitis, stomach ulcer, esophageal inflammation, intestinal obstruction, anal and rectal wall inflammation (characterized by bloody stools and urgent need to defecate)
• liver failure, liver inflammation, liver enlargement, yellow skin or eye discoloration (jaundice)
• severe and potentially fatal skin peeling (toxic epidermal necrolysis)
• muscle inflammation, which causes pain or stiffness in the hip and shoulder

• inflammation of the kidney, or the central nervous system
• multi-organ inflammation
• muscle skeletal inflammation
• muscle weakness

• kidney disease
• absence of menstrual periods
• multi-organ failure, medication infusion-related reaction

• hair color changes
• bladder inflammation, symptoms may include frequent and/or painful urination, urgent need to urinate, blood in the urine, abdominal pain or pressure in the lower abdomen

• Inform your doctor immediatelyif you have any of these side effects.

Do not try to treat your symptoms with other medicines.

Rare (may affect up to1 in 1,000patients)

• inflammatory disease of blood vessels (usually the arteries of the head)
• thyroid gland swelling (thyroiditis)
• skin disease characterized by dry, red patches covered with scales (psoriasis)
• inflammation and redness of the skin (erythema multiforme)
• a severe skin reaction characterized by rash accompanied by one or more of the following: fever, facial or lymph node swelling, eosinophil increase (a type of white blood cell), liver, kidney, or lung effects (reaction called DRESS syndrome)
• a type of inflammatory disorder (probably autoimmune) affecting the eyes, skin, and ear membranes, brain, and spinal cord (Vogt-Koyanagi-Harada syndrome), retinal detachment
• symptoms of type 1 diabetes or diabetic ketoacidosis, including feeling hungrier or thirstier than usual, frequent or painful urination, weight loss, feeling tired, discomfort, stomach pain, rapid breathing, confusion, drowsiness, sweet-smelling breath, metallic or sweet taste in the mouth, or unusual urine or sweat odor
• muscle weakness and fatigue without atrophy (myasthenia gravis)
• pancreatic exocrine insufficiency (absence or reduction of digestive enzymes produced by the pancreas)
• celiac disease (characterized by symptoms such as stomach pain, diarrhea, and bloating after consuming gluten-containing foods)

• Inform your doctor immediatelyif you have any of these side effects.

Do not try to treat your symptoms with other medicines.

Very rare (may affect up to1 in 10,000patients)

• severe allergic reactions, potentially fatal

• Inform your doctor immediatelyif you have any of these side effects.

Do not try to treat your symptoms with other medicines.

In addition, the following side effects have been reported in patients who received other doses of 3mg/kg of YERVOY in clinical trials:

• triple symptoms (meningism): neck stiffness, intolerance to bright light, and headache, flu-like symptoms
• inflammation of the heart muscle, heart muscle weakness, fluid around the heart
• inflammation of the liver, or pancreas, nodules formed by inflammatory cells in various organs of the body

• infection within the abdomen

• painful skin lesions on the arms, legs, and face (erythema nodosum)
• increase in pituitary function

• decrease in parathyroid function

• inflammation of the eye, inflammation of the eye muscle

• decrease in hearing

• poor blood circulation, causing numbness or paleness in the fingers and toes
• damage to the skin and feet tissues, causing redness, swelling, and blisters

• Inform your doctor immediatelyif you have any of these side effects.

Do not try to treat your symptoms with other medicines.

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

• organ transplant rejection
• a condition in which the immune system produces too many cells that fight infections called histiocytes and lymphocytes that can cause various symptoms (lymphohistiocytosis hemophagocytosis). Symptoms may include liver and/or spleen enlargement, skin rash, lymph node swelling, respiratory problems, easy bruising, renal anomalies, and cardiac problems
• muscle, arm, or leg pain; urinary or intestinal problems, including frequent or painful urination, urinary incontinence, difficulty urinating, and constipation (myelitis)

• Inform your doctor immediatelyif you have any of these side effects.

Do not try to treat your symptoms with other medicines.

Changes in laboratory test results

YERVOY may cause changes in laboratory test results performed by your doctor. These include:

• variation in the number of red blood cells (which carry oxygen), white blood cells (which are important for fighting infections) or platelets (cells that help blood to clot)

• abnormal variation in the levels of hormones and liver enzymes in the blood
• abnormal liver function tests
• abnormal levels of calcium, sodium, phosphate, or potassium in the blood
• blood or protein in the urine
• high blood alkalinity and other tissue alkalinity
• renal inability to eliminate blood acids normally
• presence of antibodies in the blood against some of your own cells

The following side effects have been reported with ipilimumab 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 than1 in 10patients)

• upper respiratory tract infections
• decrease in thyroid activity (which can cause fatigue or weight gain)
• decrease in the number of red blood cells (which carry oxygen), white blood cells (which are important for fighting infections) or platelets (cells that help blood to clot)
• loss of appetite, high blood sugar levels (hyperglycemia) or low blood sugar levels (hypoglycemia)
• headache, dizziness
• difficulty breathing (dyspnea), cough
• diarrhea (watery, loose or soft stools), vomiting or feeling sick (nausea), stomach pain, constipation
• skin rash, sometimes with blisters, itching
• muscle and bone pain (musculoskeletal pain), joint pain (arthralgia)
• feeling tired or weak, fever, swelling

• Inform your doctor immediatelyif you have any of these side effects.

Do not try to treat your symptoms with other medicines.

Common (may affect up to1 in 10patients)

• lung infection (pneumonia), bronchitis, eye inflammation (conjunctivitis)
• elevated eosinophils (a type of white blood cell)
• allergic reaction, medication infusion-related reactions
• increase in thyroid activity (which can cause rapid heart rate, sweating, and weight loss), decrease in adrenal gland secretion (glands located above the kidneys), decrease in pituitary function (hypopituitarism) or inflammation (hypophysitis) of the pituitary gland located at the base of the brain, thyroid gland swelling, diabetes
• dehydration, decrease in albumin and phosphate levels in the blood, weight loss
• nerve inflammation (which causes numbness, weakness, tingling, or burning in the arms and legs)
• blurred vision, dry eyes
• rapid heart rate, changes in heart rhythm or frequency, irregular or abnormal heart rhythm
• high blood pressure (hypertension)
• lung inflammation (characterized by cough and difficulty breathing), fluid around the lungs
• intestinal inflammation (colitis), mouth ulcers, and herpes (stomatitis), pancreatitis, dry mouth, stomach inflammation (gastritis)
• liver inflammation
• skin color changes in patches (vitiligo), skin redness, unusual hair loss or weakening, urticaria (hives), dry skin
• joint inflammation (arthritis), muscle spasms, muscle weakness
• renal insufficiency (including sudden loss of renal function)
• pain, chest pain, chills

• Inform your doctor immediatelyif you have any of these side effects.

Do not try to treat your symptoms with other medicines.

Uncommon (may affect up to1 in 100patients)

• decrease in neutrophils with fever
• diabetic ketoacidosis (acid in the blood produced by diabetes)
• increase in blood acid levels
• inflammation of the brain; nerve damage causing numbness and weakness (polyneuropathy); foot drop (peroneal nerve paralysis); autoimmune nerve inflammation causing numbness, weakness, tingling, or burning (neuropathy); muscle weakness and fatigue without atrophy (myasthenia gravis)
• eye inflammation causing redness or pain
• irregular or abnormal heart rhythm, inflammation of the heart muscle, slow heart rate
• inflammation of the duodenum
• chronic skin disease with scaly, red patches (psoriasis), severe skin disease causing red patches, often with itching, similar to measles rash, starting in the extremities and sometimes on the face and rest of the body (erythema multiforme), severe skin peeling (Stevens-Johnson syndrome), changes in any skin area or genital area associated with dryness, thinning of the skin, itching, and pain (lichen sclerosis)
• muscle pain, muscle sensitivity or weakness not caused by exercise (myopathy), muscle inflammation (myositis), muscle inflammation causing pain or stiffness (polymyalgia rheumatica)
• kidney inflammation

• Inform your doctor immediatelyif you have any of these side effects.

Do not try to treat your symptoms with other medicines.

Rare (may affect up to1 in 1,000patients)

• temporary and reversible non-infectious inflammation of the protective membranes surrounding the brain and spinal cord (aseptic meningitis)
• chronic diseases associated with the accumulation of inflammatory cells in various organs and tissues, more frequently in the lungs (sarcoidosis)
• decrease in parathyroid function
• temporary inflammation of the nerves causing pain, weakness, and paralysis in the limbs (Guillain-Barré syndrome), nerve inflammation
• muscle, arm, or leg pain; urinary or intestinal problems, including frequent or painful urination, urinary incontinence, difficulty urinating, and constipation (myelitis/myelitis transversa)
• intestinal perforation
• severe and potentially fatal skin peeling (toxic epidermal necrolysis), changes in any skin area or genital area associated with dryness, thinning of the skin, itching, and pain (lichen sclerosis)
• chronic joint disease (spondyloarthropathy), disease in which the immune system attacks the glands that produce body hydration, such as tears and saliva (Sjögren's syndrome), muscle stiffness and joint stiffness, muscle spasms (rhabdomyolysis)
• a type of inflammatory disorder (probably autoimmune) affecting the eyes, skin, and ear membranes, brain, and spinal cord (Vogt-Koyanagi-Harada syndrome), retinal detachment
• bladder inflammation, symptoms may include frequent and/or painful urination, urgent need to urinate, blood in the urine, abdominal pain or pressure in the lower abdomen
• pancreatic exocrine insufficiency (absence or reduction of digestive enzymes produced by the pancreas)
• celiac disease (characterized by symptoms such as stomach pain, diarrhea, and bloating after consuming gluten-containing foods)

• Inform your doctor immediatelyif you have any of these side effects.

Do not try to treat your symptoms with other medicines.

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

• organ transplant rejection
• a group of metabolic complications that occur after cancer treatment characterized by high levels of potassium and phosphate in the blood and low levels of calcium in the blood (tumor lysis syndrome)
• inflammation of the heart and fluid accumulation around the heart (pericardial disorders)
• a condition in which the immune system produces too many cells that fight infections called histiocytes and lymphocytes that can cause various symptoms (lymphohistiocytosis hemophagocytosis). Symptoms may include liver and/or spleen enlargement, skin rash, lymph node swelling, respiratory problems, easy bruising, renal anomalies, and cardiac problems

Changes in laboratory test results

YERVOY in combination may cause changes in laboratory test results performed by your doctor. These include:

• abnormal liver function tests (increased levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, or alkaline phosphatase, increased bilirubin levels)
• abnormal renal function tests (increased creatinine levels)
• increased levels of the enzyme that breaks down fats and the enzyme that breaks down carbohydrates
• increased or decreased calcium or potassium levels
• increased or decreased magnesium or sodium levels
• increased levels of thyroid-stimulating hormone

Reporting of side effects

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

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

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

Store in refrigerator (between2°C and8°C).

Do not freeze.

Store in the original packaging to protect it from light.

Do not store unused solution for possible reuse. 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 YERVOY

• The active ingredient is ipilimumab.

Eachml of concentrate contains 5mg of ipilimumab.

Each vial of10ml contains50mg of ipilimumab.

Each vial of40ml contains200mg of ipilimumab.

• The other components are tris‑hydrochloride, sodium chloride (see section2 "YERVOY contains sodium"), mannitol(E421), pentetic acid, polisorbate80, sodium hydroxide, hydrochloric acid, and water for injection.

Appearance of YERVOY and contents of the pack

YERVOY concentrate for solution for infusion is a colourless to pale yellow, transparent to slightly opalescent liquid that may contain a few (isolated) particles.

It is available in packs containing1vial ofglass of 10ml or1vial ofglass of 40ml.

Only some pack sizes may be marketed.

Marketing authorisation holder

Bristol‑MyersSquibbPharmaEEIG

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Manufacturer

CATALENT ANAGNI S.R.L.

Loc. Fontana del Ceraso snc

Strada Provinciale 12 Casilina, 41

03012 Anagni (FR)

Italy

Swords Laboratories Unlimited Company T/A Bristol‑Myers Squibb Cruiserath Biologics

Cruiserath Road, Mulhuddart

Dublin 15, D15 H6EF

Ireland

Last update of this leaflet:

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

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This information is intended solely for healthcare professionals:

The preparation should be carried out by trained personnel in accordance with good practices, especially with regard to asepsis.

Calculation of the dose:

Ipilimumab in monotherapy or ipilimumab in combination with nivolumab:

Theprescribed dosefor the patient is indicated inmg/kg. According to this prescribed dose, calculate the total dose to be administered. More than one vial of YERVOY concentrate may be needed to give the total dose to the patient.

• Each vial of10ml of YERVOY concentrate contains50mg of ipilimumab; each vial of40ml contains200mg of ipilimumab.
• Total dose of ipilimumabinmg=the patient's weight inkg × the prescribed dose inmg/kg.
• Volume of YERVOY concentrateto prepare the dose (ml)=total dose inmg, divided by5(the concentration of YERVOY concentrate is 5mg/ml).

Preparation of the infusion:

Ensure that you perform aseptic manipulationwhen preparing the infusion.

YERVOY can be used for intravenous administration either:

• without dilution, after transfer to a perfusion container using a sterile syringe;

or

• after dilutionto5times the original volume of the concentrate (to4parts of diluent per1part of concentrate). The final concentration should be in the range of1 to4mg/ml. To dilute the YERVOY concentrate, you can use:
• sodium chloride injection9mg/ml (0.9%); or
• glucose injection,50mg/ml (5%)

STEP1

• Leave the required number of vials of YERVOY at room temperature for approximately5minutes.
• Inspect the YERVOY concentrate for particles or colour changes. The YERVOY concentrate is a colourless to pale yellow, transparent to slightly opalescent liquid that may contain a few (isolated) particles. Do not use it if there is an unusual number of particles and signs of colour change.
• Withdraw the required volume of YERVOY concentrate using a sterile syringe.

STEP2

• Transfer the concentrate to a sterile glass container or to an IV treatment bag (PVC or non-PVC).
• If necessary, dilute with the required volume of sodium chloride injection9mg/ml (0.9%) or glucose injection50mg/ml (5%). To facilitate preparation, the concentrate can also be transferred directly to a pre-loaded bag containing the appropriate volume of sodium chloride injection 9mg/ml (0.9%) or glucose injection 50mg/ml (5%). Mix the infusion gently by manual rotation.

Administration:

The YERVOY infusion should not be administered as an intravenous bolus injection. Administer the YERVOY infusion intravenouslyover a period of30minutes.

The YERVOY infusion should not be administered at the same time by the same intravenous route as other agents. Use a separate intravenous route for the infusion.

Use a sterile, non-pyrogenic, low-protein binding infusion set with a pore size of 0.2μm to 1.2μm.

The YERVOY infusion is compatible with:

• PVC infusion equipment
• In-line filters of polyethersulfone (0.2μm to1.2μm) and nylon (0.2μm)

Flush the line with sodium chloride injection9mg/ml (0.9%) or glucose injection50mg/ml (5%) at the end of the infusion.

Storage conditions and shelf-life:

Unopened vial

YERVOY should bestoredin the refrigerator(between2°C and8°C). The vials should be stored in the original pack to protect them from light. Do not freeze.

Do not use YERVOY after the expiry date shown on the vial label and the pack after CAD. The expiry date is the last day of the month indicated.

YERVOY infusion

From a microbiological point of view, once opened, the medicinal productshould be used or diluted and used immediately.Chemical and physical stability has been demonstrated during the use of the undiluted or diluted infusion solution (between1and4mg/ml) for 24hours at room temperature (between 20°C and25°C) or refrigerated (between2°C and8°C). If not used immediately, the infusion solution (undiluted or diluted) should be used within24hours when stored either refrigerated (between 2°C and8°C) or at room temperature (between20°C and25°C). Other times and conditions of storage during use are the responsibility of the user.

Disposal:

Do not store unused solution for possible reuse. The disposal of unused medicinal product and all materials that have been in contact with it will be carried out in accordance with local regulations.