What is a Patient Information Leaflet and why is it useful?

The Patient Information Leaflet (PIL) is the leaflet included in the pack with a medicine. It is written for patients and gives information about taking or using a medicine. It is possible that the leaflet in your medicine pack may differ from this version because it may have been updated since your medicine was packaged.

Black triangle. This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information.

Below is a text only representation of the Patient Information Leaflet, the original can be viewed in PDF format using the link above.

The text only version may be available from RNIB in large print, Braille or audio CD. For further information call RNIB Medicine Leaflet Line on 0800 198 5000. The product code(s) for this leaflet are: EU/1/15/1014/001, EU/1/15/1014/002.

OPDIVO 10 mg/mL concentrate for solution for infusion

Package leaflet: Information for the user

OPDIVO 10 mg/mL concentrate for solution for infusion

nivolumab

▼This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

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.
  • It is important that you keep the Alert Card with you during treatment.
  • If you have any further questions, ask your doctor.
  • If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

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

1. What OPDIVO is and what it is used for

OPDIVO is a medicine used to treat:

  • advanced melanoma (a type of skin cancer) in adults
  • advanced non-small cell lung cancer (a type of lung cancer) 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.

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 or bladder cancer cells.

OPDIVO may be given in combination with ipilimumab. It is important that you also read the package leaflet for this medicine. If you have any questions about ipilimumab, please ask your doctor.

2. What you need to know before you use OPDIVO

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 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 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 and visual disturbances.
  • Diabetes (symptoms include excessive thirst, the passing of a greatly increased amount of urine, increase in appetite with a loss of weight, feeling tired, drowsy, weak, depressed, irritable and generally unwell) or diabetic ketoacidosis (acid in the blood produced from diabetes).
  • 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.

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.

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 nivolumab 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

Nivolumab is unlikely to affect your ability to drive or use machines; however, use caution when performing these activities until you are sure that nivolumab 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 per mL of concentrate.

You will also find this information in the Patient Alert Card you have been given by your doctor. It is important that you keep this Alert Card and show it to your partner or caregivers.

3. How to use OPDIVO

How much OPDIVO is given

The amount of OPDIVO you will be given will be calculated based on your body weight. The recommended dose is 3 mg of nivolumab per kilogram of your body weight.

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.

When OPDIVO is given in combination with ipilimumab 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 is 3 mg of nivolumab per kilogram of your body weight (single-agent phase).

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 60 minutes, every 2 weeks. 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, you will be given an infusion over a period of 60 minutes, every 3 weeks for the first 4 doses (combination phase). Thereafter it will be given as an infusion over a period of 60 minutes, every 2 weeks (single-agent phase).

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 ipilimumab, you will first be given OPDIVO followed by ipilimumab.

Please refer to the package leaflet of ipilimumab in order to understand the use of this medicine. If you have questions about this medicine, please ask your doctor.

4. Possible side effects

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 nivolumab.

The following side effects have been reported in clinical trials with nivolumab alone:

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

  • Decrease in some white blood cells
  • Diarrhoea (watery, loose or soft stools), nausea
  • Skin rash sometimes with blisters, itching
  • Feeling tired or weak

Common (may affect up to 1 in 10 people)

  • Infections of the upper respiratory tract
  • Allergic reaction, reactions related to the infusion of the medicine
  • 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
  • Inflammation of the nerves (causing numbness, weakness, tingling or burning pain of the arms and legs), headache, dizziness
  • High blood pressure (hypertension)
  • Inflammation of the lungs (pneumonitis, characterised by coughing and difficulty breathing), shortness of breath (dyspnoea), cough
  • Inflammation of the intestines (colitis), mouth ulcers and cold sores (stomatitis), vomiting, stomach pain, constipation, dry mouth
  • Skin colour change in patches (vitiligo), dry skin, redness of the skin, unusual hair loss or thinning
  • Pain in the muscles, bones (musculoskeletal pain) and joints (arthralgia)
  • Fever, oedema (swelling)

Uncommon (may affect up to 1 in 100 people)

  • Serious lung infection (pneumonia), bronchitis
  • Increase in some white blood cells
  • 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, increased acid levels in the blood
  • Inflammation of the liver (hepatitis)
  • 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), blurred vision, dry eyes
  • Fast heart rate
  • Fluid around the lungs
  • Inflammation of the pancreas (pancreatitis), inflammation of the stomach (gastritis)
  • 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), 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), hives (itchy, bumpy rash)
  • Inflammation of the muscles causing pain or stiffness (polymyalgia rheumatica), inflammation of the joints (arthritis)
  • Inflammation of the kidney, kidney failure (including abrupt loss of kidney function)
  • Pain, chest pain

Rare (may affect up to 1 in 1000 people)

  • A disease causing the inflammation or enlargement of a lymph node (Kikuchi lymphadenitis)
  • Life-threatening allergic reaction
  • Acid in the blood produced from diabetes (diabetic ketoacidosis)
  • Blockage of bile ducts
  • A temporary inflammation of the nerves that causes pain, weakness, and paralysis in the extremities (Guillain- Barré 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
  • Changes in the rhythm or rate of the heartbeat, abnormal heart rhythm, inflammation of the heart muscle
  • Inflammatory disease of blood vessels
  • Fluid in the lungs
  • 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)

The following side effects have been reported in clinical trials with nivolumab in combination with ipilimumab:

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

  • Underactive thyroid gland (which can cause tiredness or weight gain)
  • Decreased appetite
  • Headache
  • Shortness of breath (dyspnoea)
  • Inflammation of the intestines (colitis), diarrhoea (watery, loose or soft stools), vomiting, nausea, stomach pain
  • Skin rash sometimes with blisters, itching
  • Pain in the joints (arthralgia)
  • Feeling tired or weak, fever

Common (may affect up to 1 in 10 people)

  • Serious lung infection (pneumonia), infections of the upper respiratory tract
  • Increase in some white blood cells
  • 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, overactive thyroid gland (which can cause rapid heart rate, sweating and weight loss), inflammation of the thyroid gland, swelling of the thyroid gland
  • Dehydration
  • Inflammation of the liver
  • Inflammation of the nerves (causing numbness, weakness, tingling or burning pain of the arms and legs), dizziness
  • Inflammation of the eye (which causes pain and redness), blurred vision
  • Fast heart rate
  • High blood pressure (hypertension)
  • Inflammation of the lungs (pneumonitis, characterised by coughing and difficulty breathing), blood clots, cough
  • Mouth ulcers and cold sores (stomatitis), inflammation of the pancreas (pancreatitis), constipation, dry mouth
  • Skin colour change in patches (vitiligo), dry skin, redness of the skin, unusual hair loss or thinning, hives (itchy rash)
  • Pain in the muscles and bones (musculoskeletal pain)
  • Kidney failure (including abrupt loss of kidney function)
  • Oedema (swelling), pain

Uncommon (may affect up to 1 in 100 people)

  • Bronchitis
  • Chronic diseases associated with a build-up of inflammatory cells in various organs and tissues, most commonly the lungs (sarcoidosis)
  • Acid in the blood produced from diabetes (diabetic ketoacidosis), diabetes
  • A temporary inflammation of the nerves that causes pain, weakness and paralysis in the extremities (Guillain-Barré syndrome); damage to nerves causing numbness and weakness (polyneuropathy); inflammation of the nerves; foot drop (peroneal nerve palsy); inflammation of the nerves caused by the body attacking itself, causing numbness, weakness, tingling or burning pain (autoimmune neuropathy)
  • Inflammation of the brain
  • Changes in the rhythm or rate of the heartbeat, abnormal heart rhythm, inflammation of the heart muscle
  • Fluid around the lungs
  • Intestinal perforation, inflammation of the stomach (gastritis), inflammation of the duodenum
  • Skin disease with thickened patches of red skin, often with silvery scales (psoriasis)
  • 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), inflammation of the joints (arthritis), aching muscles, muscle tenderness of weakness, not caused by exercise (myopathy), inflammation of the muscles (myositis), stiffness in muscles and joints, muscle spasm (rhabdomyolysis)
  • Inflammation of the kidney
  • Chest pain

Rare (may affect up to 1 in 1000 people)

  • Severe and possibly fatal peeling of the skin (toxic epidermal necrolysis or Stevens-Johnson syndrome)

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 with ipilimumab 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 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)
  • High (hyperglycaemia) or low (hypoglycaemia) sugar levels in the blood
  • 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)
  • 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
  • Decrease in body weight

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 (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

Ireland

HPRA Pharmacovigilance
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.hpra.ie
e-mail: medsafety@hpra.ie

Malta

ADR Reporting
Website: www.medicinesauthority.gov.mt/adrportal

United Kingdom

Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard

or search for MHRA Yellow Card in the Google Play or Apple App Store

5. How to store OPDIVO

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.

6. Contents of the pack and other information

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) or 100 mg (in 10 mL) of nivolumab.

  • The other ingredients are sodium citrate dihydrate, sodium chloride (see section 2 "OPDIVO contains sodium"), mannitol (E421), pentetic acid, polysorbate 80, 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 or 1 vial of 10 mL.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Bristol-Myers Squibb Pharma EEIG
Uxbridge Business Park
Sanderson Road
Uxbridge
UB8 1DH
United Kingdom

Manufacturer

Bristol-Myers Squibb S.r.l.
Loc. Fontana del Ceraso
03012 Anagni (FR)
Italy

Swords Laboratories t/a Bristol-Myers Squibb Cruiserath Biologics
Cruiserath Road
Mulhuddart
Dublin 15
Ireland

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

United Kingdom
Bristol-Myers Squibb Pharmaceuticals Ltd
Tel: + 44 (0800) 731 1736

This leaflet was last revised in January 2018

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu