Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - opdualag

Document Subject

Generated Narrative: MedicinalProductDefinition mpf005fd757731f79c852474cccf35506b

identifier: http://ema.europa.eu/identifier/EU/1/22/1679/001

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: Opdualag 240 mg/80 mg 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-f005fd757731f79c852474cccf35506b

identifier: http://ema.europa.eu/identifier/EU/1/22/1679/001

status: Final

type: Package Leaflet

category: Raw

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

author: Organization ACME industry

title: TEST PURPOSES ONLY - opdualag

Attesters

What is in this leaflet

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

Opdualag is a cancer medicine used to treat advanced melanoma (a type of skin cancer that can spread elsewhere in the body). It can be used in adults and in adolescents 12 years of age and older.

Opdualag contains two active substances: nivolumab and relatlimab. Both active substances are monoclonal antibodies, proteins designed to recognise and attach to a specific target substance in the body. Nivolumab attaches to a target protein called PD 1. Relatlimab attaches to a target protein called LAG-3. PD 1 and LAG-3 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 the two proteins, nivolumab and relatlimab block their actions and prevent them from switching off your T cells. This helps increase the T cell activity against the melanoma cancer cells.

You should not be given Opdualag

• if you are allergic to nivolumab, relatlimab or any of the other ingredients of this medicine (listed in section 6). Talk to your doctor if you are not sure.

Warnings and precautions

Talk to your doctor before you get Opdualag as it may cause:

• 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 inflammation of the intestines (colitis) with symptoms 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 in the right side of your stomach area, or tiredness.
• Inflammation of or problems with your kidneys. Signs and symptoms may include abnormal kidney function tests, or decrease in amount of urine.
• Problems with your hormone producing glands (including the pituitary, thyroid and adrenal glands), which 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 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 heart muscle (myocarditis). Signs and symptoms may include chest pain, irregular and/or rapid heartbeat, fatigue, swelling in the ankles or shortness of breath.
• Haemophagocytic lymphohistiocytosis. A rare disease in which your immune system makes too many otherwise normal infection-fighting cells called histiocytes and lymphocytes. Symptoms may include enlarged liver and/or spleen, skin rash, swollen lymph glands, breathing problems, easy bruising, kidney abnormalities, and heart problems.
• Solid organ transplant rejection.
• Graft-versus-host disease after stem cell transplantation (where the transplanted cells from a donor attack your own cells). If you have received one of these transplants, your doctor will consider whether you should receive treatment with Opdualag. Graft-versus-host disease can be severe and can lead to death.
• Infusion reactions, which may include shortness of breath, itching or rash, dizziness or fever.

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 to prevent complications and reduce your symptoms,
• skip your next dose of Opdualag,
• or stop your treatment with Opdualag 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 Opdualag if:

• you have an active autoimmune disease (a condition where the body attacks its own cells);
• you have melanoma of the eye;
• you have been told that your cancer has spread to your brain;
• you have been taking medicines to suppress your immune system.

Children and adolescents Opdualag should not be used in children below 12 years of age.

Other medicines and Opdualag Before you are given Opdualag, 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 Opdualag. However, once you are treated with Opdualag, your doctor may give you corticosteroids to reduce any possible side effects that you may have during your treatment. Tell your doctor if you are taking, have recently taken or are planning to take any other medicines. Do not take any other medicines during your treatment without talking to your doctor first.

Pregnancy and breast-feeding If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

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

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

It is not known whether Opdualag can pass into breast milk and affect a baby that is breast-fed. Talk to your doctor about the benefits and risks before breast-feeding during or after treatment with Opdualag.

Driving and using machines Opdualag has a minor influence on the ability to drive and use machines; however, use caution when performing these activities until you are sure that Opdualag does not adversely affect you.

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

How much Opdualag is given The recommended dose by infusion in adults and adolescents 12 years of age and older is 480 mg nivolumab and 160 mg relatlimab every 4 weeks. This dose is established for adolescent patients weighing at least 30 kg.

Depending on your dose, the appropriate amount of Opdualag may be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 50 mg/mL (5%) solution for injection before use. Opdualag may also be used undiluted.

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

Opdualag will be given to you as an infusion (a drip) into a vein, every 4 weeks. Each infusion takes about 30 minutes to give.

Your doctor will continue treating you with Opdualag for as long as you keep benefitting from it or until side effects become too severe.

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

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

If you have any further questions on the use of this medicine, 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 (described in section 2 under warnings and precautions ). Opdualag 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 Opdualag.

The following side effects have been reported with Opdualag:

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

• infection of the urinary tract (the parts of the body that collect and pass out urine)
• decreased number of red blood cells (which carry oxygen) and white blood cells (lymphocytes, neutrophils, leucocytes; which are important in fighting infection)
• underactive thyroid gland (which can cause tiredness or weight gain)
• decreased appetite
• headache
• difficulty breathing, cough
• diarrhoea (watery, loose or soft stools), vomiting; nausea; stomach pain; constipation
• skin rash (sometimes with blisters), skin colour change in patches (vitiligo), itching
• pain in the muscles, bones and joints
• feeling tired or weak, fever. Changes in the results of tests carried out by your doctor may show:
• abnormal liver function (increased amounts of the liver enzymes alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase in your blood)
• abnormal kidney function (increased amounts of creatinine in your blood)
• decrease of sodium and magnesium, and decrease or increase of calcium and potassium.

Common (may affect up to 1 in 10 people)

• infections of the upper respiratory tract (nose and upper airways)
• decreased number of platelets (cells which help the blood to clot), increase in some white blood cells
• decreased secretion of hormones produced by adrenal glands (glands situated above the kidneys), inflammation of the pituitary gland situated at the base of the brain, overactive thyroid gland, inflammation of the thyroid gland
• diabetes, low sugar levels in the blood; weight loss, high levels of the waste product uric acid in the blood, decreased levels of the protein albumin in the blood, dehydration
• state of confusion
• inflammation of the nerves (causing numbness, weakness, tingling or burning pain of the arms and legs), dizziness, changes in the sense of taste
• inflammation of the eye (which causes pain and redness, vision problems or blurry vision), vision problems, dry eyes, excessive tear production
• inflammation of the heart muscle
• inflammation of a vein, which can cause redness, tenderness and swelling
• inflammation of the lungs (pneumonitis), characterised by coughing and difficulty breathing; nasal congestion (blocked nose)
• inflammation of the intestines (colitis), inflammation of the pancreas, inflammation of the stomach (gastritis), difficulty swallowing, mouth ulcers and cold sores; dry mouth
• inflammation of the liver (hepatitis)
• unusual hair loss or thinning (alopecia), isolated area of skin growth that becomes red and itchy (lichenoid keratosis), sensitivity to light, dry skin
• painful joints (arthritis), muscle spasms, muscle weakness
• kidney failure (changes in amount or colour of urine, blood in urine, swelling ankles, loss of appetite), high levels of proteins in the urine
• oedema (swelling), flu-like symptoms, chills
• reactions related to the administration of the medicine. Changes in the results of tests carried out by your doctor may show:
• abnormal liver function (higher blood levels of the waste product bilirubin, higher blood levels of the liver enzyme gamma-glutamyl transferase)
• increase in sodium and magnesium
• increased level of troponin (a protein released into the blood when the heart is damaged)
• increased level of the enzyme that breaks down glucose (sugar) (lactate dehydrogenase), the enzyme that breaks down fats (lipase), the enzyme that breaks down starch (amylase)

Uncommon (may affect up to 1 in 100 people)

• inflammation and infection in the hair follicles
• disorder in which red blood cells are destroyed faster than they can be made (haemolytic anaemia)
• underactive function of the pituitary gland situated at the base of the brain; underactive function of the glands producing sex hormones
• inflammation of the brain, which may include confusion, fever, memory problems or seizures (encephalitis), a temporary inflammation of the nerves that causes pain, weakness, and paralysis in the extremities (Guillain-Barr syndrome), inflammation of the optic nerve that may cause a complete or partial loss of vision
• an inflammatory disorder affecting the eyes, skin and the membranes of the ears, brain and spinal cord (Vogt-Koyanagi-Harada disease), red eye
• fluid around the heart
• asthma
• inflammation of the oesophagus (passage between throat and stomach)
• inflammation of the bile duct
• skin rashes and blistering on the legs, arms, and abdomen (pemphigoid), skin disease with thickened patches of red skin, often with silvery scales (psoriasis), hives (itchy, bumpy rash)
• inflammation of the muscles causing weakness, swelling, and pain, disease in which the immune system attacks the glands that make moisture for the body, such as tears and saliva (Sjogren s syndrome), inflammation of muscles causing pain or stiffness, inflammation of the joints (painful joint disease), disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs, such as joints, skin, brain, lungs, kidneys, and blood vessels (systemic lupus erythematosus)
• inflammation of the kidney
• absence of sperm in the semen. Changes in the results of tests carried out by your doctor may show:
• increase in level of c-reactive protein
• red blood cell sedimentation rate increased.

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.

Opdualag will be given to you in a hospital or clinic and the healthcare professionals will be responsible for its storage.

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

Do not use this medicine after the expiry date 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 - 8 C). Do not freeze. Keep the vial in the outer carton in order to protect from light. The unopened vial can be stored at controlled room temperature (up to 25 C) for up to 72 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 Opdualag contains

• The active substances are nivolumab and relatlimab. Each mL of concentrate for solution for infusion contains 12 mg of nivolumab and 4 mg of relatlimab. One vial of 20 mL concentrate contains 240 mg nivolumab and 80 mg relatlimab.

• The other ingredients are histidine, histidine hydrochloride monohydrate, sucrose, pentetic acid, polysorbate 80 (E433) and water for injections.

What Opdualag looks like and contents of the pack Opdualag concentrate for solution for infusion (sterile concentrate) is a clear to opalescent, colourless to slightly yellow liquid that is essentially free of particles. It is available in cartons containing one glass vial.

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

For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:

Belgique/Belgi /Belgien N.V. Bristol-Myers Squibb Belgium S.A. T l/Tel: + 32 2 352 76 medicalinfo.belgium@bms.com

Lietuva Swixx Biopharma UAB Tel: + 370 52 369medinfo.lithuania@swixxbiopharma.com

Swixx Biopharma EOOD Te .: + 359 2 4942 medinfo.bulgaria@swixxbiopharma.com

Luxembourg/Luxemburg N.V. Bristol-Myers Squibb Belgium S.A. T l/Tel: + 32 2 352 76 medicalinfo.belgium@bms.com

esk republika Bristol-Myers Squibb spol. s r.o. Tel: + 420 221 016 medinfo.czech@bms.com

Magyarorsz g Bristol-Myers Squibb Kft. Tel.: + 36 1 301 9Medinfo.hungary@bms.com

Danmark Bristol-Myers Squibb Denmark Tlf: + 45 45 93 05 medinfo.denmark@bms.com

Malta A.M. Mangion Ltd Tel: + 356 23976pv@ammangion.com

Deutschland Bristol-Myers Squibb GmbH & Co. KGaA Tel: 0800 0752002 (+ 49 89 121 42 350) medwiss.info@bms.com

Nederland Bristol-Myers Squibb B.V. Tel: + 31 (0)30 300 2medischeafdeling@bms.com

Eesti Swixx Biopharma O
Tel: + 372 640 1medinfo.estonia@swixxbiopharma.com

Norge Bristol-Myers Squibb Norway Ltd. Tlf: + 47 67 55 53 medinfo.norway@bms.com

Bristol-Myers Squibb A.E. : + 30 210 6074medinfo.greece@bms.com

sterreich Bristol-Myers Squibb GesmbH Tel: + 43 1 60 14 medinfo.austria@bms.com

Espa a Bristol-Myers Squibb, S.A. Tel: + 34 91 456 53 informacion.medica@bms.com

Polska Bristol-Myers Squibb Polska Sp. z o.o. Tel.: + 48 22 2606informacja.medyczna@bms.com

France Bristol-Myers Squibb SAS T l: + 33 (0)1 58 83 84 infomed@bms.com

Portugal Bristol-Myers Squibb Farmac utica Portuguesa, S.A. Tel: + 351 21 440 70 portugal.medinfo@bms.com

Hrvatska Swixx Biopharma d.o.o. Tel: + 385 1 2078 medinfo.croatia@swixxbiopharma.com

Rom nia Bristol-Myers Squibb Marketing Services S.R.L. Tel: + 40 (0)21 272 16 medinfo.romania@bms.com

Ireland Bristol-Myers Squibb Pharmaceuticals uc Tel: 1 800 749 749 (+ 353 (0)1 483 3625) medical.information@bms.com

Slovenija Swixx Biopharma d.o.o. Tel: + 386 1 2355 medinfo.slovenia@swixxbiopharma.com

sland Vistor hf. S mi: + 354 535 7vistor@vistor.is medical.information@bms.com

Slovensk republika Swixx Biopharma s.r.o. Tel: + 421 2 20833 medinfo.slovakia@swixxbiopharma.com
Italia Bristol-Myers Squibb S.r.l. Tel: + 39 06 50 39 medicalinformation.italia@bms.com

Suomi/Finland Oy Bristol-Myers Squibb (Finland) Ab Puh/Tel: + 358 9 251 21 medinfo.finland@bms.com

Bristol-Myers Squibb A.E. : 800 92666 (+ 30 210 6074300) medinfo.greece@bms.com

Sverige Bristol-Myers Squibb Aktiebolag Tel: + 46 8 704 71 medinfo.sweden@bms.com

Latvija Swixx Biopharma SIA Tel: + 371 66164medinfo.latvia@swixxbiopharma.com

United Kingdom (Northern Ireland) Bristol-Myers Squibb Pharmaceutical Limited Tel: +44 (0)800 731 1medical.information@bms.com

This leaflet was last revised in

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