YERVOY 5 mg/mL concentrate for infusion solution

Introduction

Package Leaflet: Information for the User

YERVOY5mg/ml concentrate for solution for infusion

ipilimumab

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

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

Contents of the pack

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

1. What is YERVOY and what is it used for

YERVOY contains the active substance ipilimumab, a protein that helps your immune system to 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 from 12 years of age.

Ipilimumab in combination with nivolumab is used to treat

• advanced melanoma (a type of skin cancer) in adults and adolescents from 12 years of age
• 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 (cancer of the colon or rectum) in adults
• advanced oesophageal 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 anti-cancer medicines, it is important that you also read the package leaflet of these other medicines. If you have any questions about these medicines, please ask your doctor.

2. What you need to know before you use YERVOY

You must not receive YERVOY

• if you are allergicto ipilimumab or to any of the other ingredients of this medicine (listed in section 6 "Contents of the pack and other information"). Consult your doctorif you are not sure.

Warnings and precautions

Talk to your doctor before you start using YERVOY, as it can cause:

• Heart problemssuch as an alteration in the rhythm or frequency of the heartbeat or an abnormal heart rhythm.

• Inflammation of the intestine (colitis)that can worsen to cause bleeding or perforation of the intestine. The signs and symptoms of colitis can include diarrhoea (watery, loose or soft stools), an increased number of bowel movements compared to what is normal for you, blood in the stool or darker stools, pain or increased sensitivity in the stomach area.

• Lung problemssuch as difficulty breathing or coughing. These can be signs of inflammation of the lungs (pneumonitis or interstitial lung disease).

• Inflammation of the liver (hepatitis)that can cause liver failure. The signs and symptoms of hepatitis can include yellowing of the eyes or skin (jaundice), pain in the right side of the stomach, tiredness.

• Inflammation of the skinthat can cause a severe skin reaction (known as toxic epidermal necrolysis; Stevens-Johnson syndrome and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)). The signs and symptoms of a severe skin reaction can include skin rash with or without itching, peeling of the skin, dry skin, fever, fatigue, swelling of the face or lymph nodes, increased eosinophils (a type of white blood cell) and effects on the liver, kidneys or lungs. Please note that DRESS can develop weeks or months after your last dose.

• Inflammation of the nervesthat can cause paralysis. The symptoms of nerve problems can include muscle weakness, numbness or tingling in the hands or feet, loss of consciousness or difficulty waking up.

• Inflammation or problems with your kidneys.The signs and symptoms can include abnormal kidney function tests or decreased urine output.

• Inflammation of the hormone-producing glands(especially the pituitary, adrenal and thyroid glands) that could affect the functioning of these glands. The signs and symptoms that your glands are not working properly can include headaches, blurred or double vision, tiredness, decreased sex drive, changes in behaviour.

• Type 1 diabetes, including diabetic ketoacidosis(acid in the blood produced by diabetes).

• Inflammation of the musclessuch as myocarditis (inflammation of the heart muscle), myositis (inflammation of the muscles) and rhabdomyolysis (stiffness in the muscles and joints, muscle spasms). The signs and symptoms can include muscle pain, stiffness, weakness, chest pain or severe fatigue.

• Inflammation of the eyes.The signs and symptoms can include redness of the eyes, eye pain, vision problems, blurred vision or temporary loss of vision.

• Haemophagocytic lymphohistiocytosis.A rare disease in which our immune system produces too many cells that fight infection, called histiocytes and lymphocytes. The symptoms can include enlargement of the liver and/or spleen, skin rash, increased lymph nodes, respiratory problems, easy bruising, kidney problems and heart problems.

• Rejection of transplanted organs.

Tell your doctor immediatelyif you have any of these signs or symptoms or if they get worse. Do not try to treat your symptoms with other medicines.Your doctor may give you other medicines to prevent more serious complications and reduce your symptoms, delay the next dose of YERVOY, or stop your treatment with YERVOY altogether.

Please note that these signs and symptoms can occur lateand can develop weeks or months after your last dose. Before treatment, your doctor will check your general health. You will also have blood testsduring treatment.

Talk to your doctor or nurse before you receive YERVOY

• if you have an autoimmune disease(a problem where the body attacks its own cells);
• if you have or have ever had a chronic viral infection of the liver, including hepatitis B (HBV) or hepatitis C (HCV);
• if you have human immunodeficiency virus(HIV) infection or acquired immune deficiency syndrome (AIDS).

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

Children and adolescents

YERVOY must not be used in children and adolescents under 18 years of age, except in adolescents from 12 years of age with melanoma.

Other medicines and YERVOY

Before you receive YERVOY, tell your doctor

• if you are taking any other medicine that suppresses your immune system, such as corticosteroids. These medicines may interfere with the effect of YERVOY. However, once you are being treated with YERVOY, your doctor should give you corticosteroids to reduce the side effects you may have with YERVOY.

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

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

Also, tell your doctor if you are taking or have recently taken any other medicines.

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

Pregnancy and breast-feeding

If you are pregnant, might become pregnant or are breast-feeding, consult your doctorbefore using this medicine.

You must not use YERVOY if you are pregnant, unless your doctor specifically recommends it. The effects of YERVOY in pregnant women are not known, but it is possible that the active substance, ipilimumab, could harm the unborn baby.

• You must use effective contraceptive methodswhile you are being treated with YERVOY if you are a woman who can become pregnant.
• If you become pregnant while using YERVOY, tell your doctor.

It is not known if ipilimumab gets into breast milk. However, it is not expected that there will be significant exposure to ipilimumab for the breast-fed baby through breast milk, and no effects on the baby are expected. Ask your doctor if you can continue breast-feeding during or after treatment with YERVOY.

Driving and using machines

Do not drive, ride a bicycle or use machinesafter you have received YERVOY unless you are sure you are well. Feeling tired or weak is a very common side effect of YERVOY. This can affect your ability to drive, ride a bicycle or use machines.

YERVOY contains sodium

Tell your doctorif you are on a low-sodium diet (low-salt diet) before you receive YERVOY.

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

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

3. How to use YERVOY

How YERVOY is given

Treatment with YERVOY will be given to you in a hospital or clinic under the supervision of a doctor with experience.

When YERVOY is given alone for the treatment of skin cancer, YERVOY will be given as an infusion (a drip) into a vein (intravenously) over a period of 30 minutes.

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

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

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

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

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

How much YERVOY is given

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

The amount of YERVOY you receive will be calculated according to your body weight. Depending on the dose, part or all of the contents of the YERVOY vial may be diluted with sodium chloride 9 mg/ml (0.9%) injection solution or glucose 50 mg/ml (5%) injection solution before use. More than one vial may be needed to obtain the required dose.

You will be treated with YERVOY once every 3 weeks, for a total of 4 doses. You may notice the appearance of new lesions or the growth of existing lesions on your skin when you are being treated with YERVOY. Your doctor will continue to give you YERVOY until a total of 4 doses, depending on your tolerance to the treatment.

When YERVOY is given in combination with nivolumab for the treatment of skin cancer in adults and adolescents from 12 years of age, the recommended dose of YERVOY is 3 mg of ipilimumab per kilogram of body weight every 3 weeks for the first 4 doses (combination phase). After that, the recommended dose of nivolumab (single-medicine phase) is 240 mg every 2 weeks or 480 mg every 4 weeks in adults and adolescents from 12 years of age and with a minimum weight of 50 kg or 3 mg of nivolumab per kilogram of body weight every 2 weeks or 6 mg of nivolumab per kilogram of body weight every 4 weeks in adolescents from 12 years of age and with a weight below 50 kg.

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

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

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

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

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 stop treatment with YERVOY

Stopping treatment may stop the effect of the medicine. Do not stop 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 medicine, ask your doctor.

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

Please read the package leaflet of the other anti-cancer medicines to understand the use of these other medicines. If you have any questions about these medicines, please ask your doctor.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. Your doctor will discuss them with you and explain the risks and benefits of your treatment.

Be aware of important symptoms of inflammation

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

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

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

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

• loss of appetite
• diarrhea (watery, loose, or soft stools), vomiting, or feeling sick (nausea), constipation, stomach pain
• skin rash, itching
• pain in muscles, bones, ligaments, tendons, and nerves
• feeling tired or weak, reaction at the injection site, fever, swelling (edema), pain

• Inform your doctor immediatelyif you experience any of these adverse effects.

Do not try to treat your symptoms with other medicines.

Common (may affect up to 1 in 10 patients)

• severe bacterial infection of the blood (sepsis), urinary tract infection, respiratory tract infection
• tumor pain
• a 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 clot)
• decreased function of the thyroid gland, which can cause fatigue or weight gain, decreased function (hypopituitarism) or inflammation (hypophysitis) of the pituitary gland located at the base of the brain
• dehydration
• confusion, depression
• excessive fluid accumulation in the brain, nerve damage (causing pain, weakness, and cramps), dizziness, headache
• blurred vision, eye pain
• irregular or abnormal heartbeat
• low blood pressure, transient reddening of the face and neck, feeling of intense heat with sweating and rapid heartbeat
• difficulty breathing (dyspnea), cough, hay fever
• bleeding in the stomach or intestine, inflammation of the intestine (colitis), heartburn, ulcers in the mouth and herpes (stomatitis)
• liver function alteration
• inflammation of the inner surface of an organ
• inflammation and reddening of the skin, changes in skin color in patches (vitiligo), hives (itchy, swollen rash), hair loss or weakening, excessive night sweating, dry skin
• pain in muscles and joints (arthralgia), muscle spasms, joint inflammation (arthritis)
• kidney function failure
• chills, lack of energy
• flu-like illness
• weight loss

• Inform your doctor immediatelyif you experience any of these adverse effects.

Do not try to treat your symptoms with other medicines.

Uncommon (may affect up to 1 in 100 patients)

• severe bacterial infection of the blood (septic shock), inflammation around the brain or spinal cord, stomach and intestinal inflammation, intestinal wall inflammation (causing fever, vomiting, and stomach pain), lung infection (pneumonia)
• symptoms due to cancer in the body, such as high calcium and cholesterol levels in the blood, and low blood sugar levels (paraneoplastic syndrome)
• increase in eosinophils (a type of white blood cell)
• allergic reaction
• decrease in hormone secretion produced by the adrenal glands (glands located above the kidneys), excess function of the thyroid gland, which can cause rapid heartbeat, sweating, and weight loss, decreased function (hypopituitarism) or inflammation (hypophysitis) of the pituitary gland
• decrease in adrenal gland function caused by a decrease in hypothalamic function (part of the brain)

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

• changes in mental health, decreased sexual impulse
• severe and potentially fatal nerve inflammation that causes pain, weakness, or paralysis of the limbs (Guillain-Barré syndrome), fainting, inflammation of the nerves within the brain, difficulty coordinating movements (ataxia), agitation, brief involuntary muscle contractions, speech difficulties
• eye inflammation (conjunctivitis), bleeding in the eye, inflammation of the colored part of the eye, reduced vision, feeling of a foreign body in the eyes, swollen and tearful eyes, eye swelling, eyelid inflammation
• inflammation of blood vessels, blood vessel disease, restriction of blood supply to the limbs, low blood pressure when standing up
• extreme difficulty breathing, fluid accumulation in the lungs, lung inflammation
• intestinal perforation, small intestine inflammation, pancreas inflammation (pancreatitis), peptic ulcer, esophagus inflammation, intestinal obstruction, anal and rectal wall inflammation (characterized by bloody stools and urgent need to defecate)
• liver failure, liver inflammation, liver enlargement, yellowing of the skin or eyes (jaundice)
• severe and potentially fatal skin peeling (toxic epidermal necrolysis)
• muscle inflammation, causing pain or stiffness in the hip and shoulder

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

• kidney disease
• absence of menstrual periods
• multi-organ failure, reaction related to drug perfusion

• changes in hair color
• bladder inflammation, 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

• Inform your doctor immediatelyif you experience any of these adverse effects.

Do not try to treat your symptoms with other medicines.

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

• severe allergic reactions, potentially fatal

• Inform your doctor immediatelyif you experience any of these adverse effects.

Do not try to treat your symptoms with other medicines.

In addition, the following uncommon adverse effects (which may affect up to 1 in 100 patients) have been reported in patients who received different doses of YERVOY in clinical trials:

• symptom triad (meningism): neck stiffness, intolerance to bright light, and headache, flu-like illness
• heart muscle inflammation, heart muscle weakness, fluid around the heart
• liver inflammation, or pancreas inflammation, 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)
• increased pituitary gland function

• decreased parathyroid gland function

• eye inflammation, eye muscle inflammation

• hearing loss

• poor blood circulation, causing numbness or paleness in the fingers and toes
• tissue damage in the hands and feet, causing redness, swelling, and blisters

• Inform your doctor immediatelyif you experience any of these adverse effects.

Do not try to treat your symptoms with other medicines.

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

• organ transplant rejection
• a type of blistering skin disease (called pemphigoid)
• a condition in which the immune system produces too many cells that fight infections, called histiocytes and lymphocytes, which can cause various symptoms (called hemophagocytic lymphohistiocytosis). Symptoms may include liver and/or spleen enlargement, skin rash, lymph node enlargement, respiratory problems, easy bruising, kidney abnormalities, and heart problems
• pain, numbness, tingling, or weakness in the arms or legs; bladder or bowel problems, including frequent urination, urinary incontinence, difficulty urinating, and constipation (myelitis)

• Inform your doctor immediatelyif you experience any of these adverse 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 clot)

• abnormal variation in hormone and liver enzyme levels in the blood
• alterations in liver function tests
• abnormal levels of calcium, sodium, phosphate, or potassium in the blood
• presence of blood or protein in the urine
• abnormally high blood and tissue alkalinity
• inability of the kidneys to eliminate acids from the blood normally
• presence of antibodies in the blood against some of your own cells

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

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

• upper respiratory tract infections
• decreased thyroid gland activity (which can cause fatigue or weight gain)
• a 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 clot)
• loss of appetite, high (hyperglycemia) or low (hypoglycemia) blood sugar levels
• 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
• pain in muscles and bones (musculoskeletal pain), joint pain (arthralgia)
• feeling tired or weak, fever, swelling (edema)

• Inform your doctor immediatelyif you experience any of these adverse effects.

Do not try to treat your symptoms with other medicines.

Common (may affect up to 1 in 10 patients)

• lung infection (pneumonia), bronchitis, eye inflammation (conjunctivitis)
• increase in eosinophils (a type of white blood cell)
• allergic reaction, reactions related to drug perfusion
• increased thyroid gland activity (which can cause rapid heartbeat, sweating, and weight loss), decreased hormone secretion produced by the adrenal glands (glands located above the kidneys), decreased function (hypopituitarism) or inflammation (hypophysitis) of the pituitary gland, thyroid gland swelling, diabetes
• dehydration, decreased albumin and phosphate levels in the blood, weight loss
• nerve inflammation (causing numbness, weakness, tingling, or burning in the arms and legs)
• blurred vision, dry eye
• rapid heartbeat, changes in heartbeat rhythm or frequency, irregular or abnormal heartbeat
• high blood pressure (hypertension)
• lung inflammation (pneumonitis, characterized by cough and difficulty breathing), fluid around the lungs
• intestine inflammation (colitis), mouth ulcers and herpes (stomatitis), pancreas inflammation (pancreatitis), dry mouth, stomach inflammation (gastritis)
• liver inflammation
• skin color changes in patches (vitiligo), skin reddening, unusual hair loss or weakening, hives (itchy, swollen rash), dry skin
• joint inflammation (arthritis), muscle spasms, muscle weakness
• kidney failure (including sudden loss of kidney function)
• pain, chest pain, chills

• Inform your doctor immediatelyif you experience any of these adverse effects.

Do not try to treat your symptoms with other medicines.

Uncommon (may affect up to 1 in 100 patients)

• decrease in neutrophils with fever
• diabetic acid in the blood (diabetic ketoacidosis)
• increase in blood acid levels
• brain inflammation; nerve damage causing numbness and weakness (polyneuropathy); foot drop (peroneal nerve paralysis); nerve inflammation caused by the body's attack on itself, causing numbness, weakness, tingling, or burning (autoimmune neuropathy); muscle weakness and fatigue without atrophy (myasthenia gravis)
• eye inflammation, causing redness or pain
• irregular or abnormal heartbeat, heart muscle inflammation, slow heartbeat
• duodenum inflammation
• skin disease with thickened, red, scaly skin (psoriasis), severe skin disease that causes red patches, often with itching, similar to measles, starting on the limbs and sometimes on the face and body (erythema multiforme), severe and potentially fatal skin peeling (Stevens-Johnson syndrome), changes in any skin area and/or genital area associated with dryness, thinning of the skin, itching, and pain (or other lichen disorders)
• pain, tenderness, or weakness in muscles, not caused by exercise (myopathy), muscle inflammation (myositis), muscle inflammation causing pain or stiffness (polymyalgia rheumatica)
• kidney inflammation

• Inform your doctor immediatelyif you experience any of these adverse effects.

Do not try to treat your symptoms with other medicines.

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

• non-infectious, temporary, and reversible 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, most frequently in the lungs (sarcoidosis)
• decreased parathyroid gland function
• temporary nerve inflammation, causing pain, weakness, and paralysis in the limbs (Guillain-Barré syndrome), nerve inflammation
• pain, numbness, tingling, or weakness in the arms or legs

5. Storage of YERVOY

Keep this medication out of 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 the refrigerator (between 2°C and 8°C).

Do not freeze.

Keep in the original packaging to protect from light.

Do not store the 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.

6. Package contents and additional information

YERVOY composition

• The active ingredient is ipilimumab.

Each ml of concentrate contains 5 mg of ipilimumab.

Each 10 ml vial contains 50 mg of ipilimumab.

Each 40 ml vial contains 200 mg of ipilimumab.

• The other components are tris-hydrochloride, sodium chloride (see section 2 "YERVOY contains sodium"), mannitol (E421), pentetic acid, polysorbate 80, sodium hydroxide, hydrochloric acid, and water for injectable preparations.

Appearance of YERVOY and package contents

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

It is available in packages that contain 1 glass vial of 10 ml or 1 glass vial of 40 ml.

Only some package sizes may be marketed.

Marketing authorization holder

Bristol-Myers Squibb Pharma EEIG

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

Date of last revision of this leaflet:

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

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This information is intended only for healthcare professionals:

Preparation must be performed by trained personnel in accordance with good practice standards, especially with regard to asepsis.

Dose calculation:

Ipilimumab as monotherapy or ipilimumab in combination with nivolumab:

The prescribed dosefor the patient is indicated in mg/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 10 ml vial of YERVOY concentrate contains 50 mg of ipilimumab; each 40 ml vial contains 200 mg of ipilimumab.
• Total dose of ipilimumabin mg = patient's weight in kg x prescribed dose in mg/kg.
• Volume of YERVOY concentrateto prepare the dose (ml) = total dose in mg, divided by 5 (YERVOY concentrate concentration is 5 mg/ml).

Infusion preparation:

Ensure aseptic handlingwhen preparing the infusion.

YERVOY can be used for intravenous administration either:

• undiluted, after transfer to an infusion container using a sterile syringe;

or

• after dilutionup to 5 times the original volume of the concentrate (up to 4 parts of diluent per 1 part of concentrate). The final concentration should be in the range of 1 to 4 mg/ml. To dilute the YERVOY concentrate, you can use:
• injectable sodium chloride solution 9 mg/ml (0.9%); or
• injectable glucose solution 50 mg/ml (5%)

STEP1

• Let the appropriate number of YERVOY vials stand at room temperature for approximately 5 minutes.
• Inspect the YERVOY concentrate for particles or color changes. The YERVOY concentrate is a transparent to slightly opalescent, colorless to pale yellow liquid that may contain a few particles. Do not use it if there is an unusual amount of particles and signs of color change.
• Withdraw the necessary volume of YERVOY concentrate using a sterile syringe.

STEP2

• Transfer the concentrate to a sterile evacuated glass bottle or an IV treatment bag (PVC or non-PVC).
• If applicable, dilute with the necessary volume of injectable sodium chloride solution 9 mg/ml (0.9%) or injectable glucose solution 50 mg/ml (5%). To facilitate preparation, the concentrate can also be transferred directly to a preloaded bag containing the appropriate volume of injectable sodium chloride solution 9 mg/ml (0.9%) or injectable glucose solution 50 mg/ml (5%). Gently mix the infusion by manual rotation.

Administration:

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

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

Use a infusion set and a sterile, non-pyrogenic, low-protein-binding in-line filter (pore size 0.2 μm to 1.2 μm).

The YERVOY infusion is compatible with:

• PVC infusion sets
• In-line filters of polyethersulfone (0.2 μm to 1.2 μm) and nylon (0.2 μm)

Flush the line with injectable sodium chloride solution 9 mg/ml (0.9%) or injectable glucose solution 50 mg/ml (5%) at the end of the infusion.

Storage and validity conditions:

Unopened vial

YERVOY should be stored in the refrigerator(between 2°C and 8°C). The vials should be stored in the original packaging to protect them from light. Do not freeze.

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

YERVOY infusion

From a microbiological point of view, once opened, the medication should be infused or diluted and infused immediately.The chemical and physical stability of the undiluted or diluted solution for infusion (between 1 and 4 mg/ml) has been demonstrated for 24 hours at room temperature (between 20°C and 25°C) or refrigerated (between 2°C and 8°C). If not used immediately, the infusion solution (undiluted or diluted) should be used within 24 hours when stored either refrigerated (between 2°C and 8°C) or at room temperature (between 20°C and 25°C). Other storage times and conditions during use are the responsibility of the user.

Disposal:

Do not store the 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.