Patient leaflets and SmPCs, drug interaction checker, official and paediatric dosages, pregnancy and breastfeeding guidance, and NHS pharmacy opening hours — all in one place.
Patient leaflets and SmPCs, drug interaction checker, official and paediatric dosages, pregnancy and breastfeeding guidance, and NHS pharmacy opening hours — all in one place.
OPDIVO is a medicine used to treat:
• advanced melanoma (a type of skin cancer) in adults
• melanoma after complete resection in adults (treatment after surgery is called adjuvant therapy)
• non-small cell lung cancer (a type of lung cancer) prior to resection or prior to and after resection in adults (treatment prior to surgery is called neoadjuvant therapy; treatment after surgery is called adjuvant therapy)
• advanced non-small cell lung cancer (a type of lung cancer) in adults
• advanced renal cell carcinoma (advanced kidney cancer) in adults
• advanced cancer of the head and neck in adults
• advanced urothelial carcinoma (bladder and urinary tract cancer) in adults
• urothelial carcinoma after complete resection in adults
• advanced colorectal cancer (colon or rectal cancer) in adults
• advanced oesophageal cancer (gullet cancer) in adults
• oesophageal (gullet) or gastro-oesophageal junction cancer with residual disease after chemoradiation followed by surgery in adults
• advanced gastric, gastro-oesophageal junction or oesophageal adenocarcinoma (stomach or gullet cancer) in adults.
• unresectable or advanced hepatocellular carcinoma (liver 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, head and neck, bladder and urinary tract, colon, rectal, stomach, oesophageal or gastro-oesophageal junction cancer cells.
OPDIVO may be given in combination with other anti-cancer medicines. It is important that you also read the package leaflet for these other medicines. If you have any questions about these medicines, please ask your doctor.
You should not be given OPDIVO • if you are allergic to nivolumab or any of the other ingredients of this medicine (listed in section 6 "Contents of the pack and other information"). Talk to your doctor if you are not sure.
Warnings and precautions Talk to your doctor before using OPDIVO as it may cause:
• Problems with your heart such as a change in the rhythm or rate of the heartbeat or an abnormal heart rhythm.
• Problems with your lungs such as breathing difficulties or cough. These may be signs of inflammation of the lungs (pneumonitis or interstitial lung disease).
• Diarrhoea (watery, loose or soft stools) or any symptoms of inflammation of the intestines (colitis), such as stomach pain and mucus or blood in stool.
• Inflammation of the liver (hepatitis). Signs and symptoms of hepatitis may include abnormal liver function tests, eye or skin yellowing (jaundice), pain on the right side of your stomach area, or tiredness.
• Inflammation or problems with your kidneys. Signs and symptoms may include abnormal kidney function tests, or decreased volume of urine.
• Problems with your hormone producing glands (including the pituitary, the thyroid, the parathyroid and adrenal glands) that may affect how these glands work. Signs and symptoms that these glands are not working properly may include fatigue (extreme tiredness), weight change or headache, decreased blood levels of calcium and visual disturbances.
• Diabetes including a serious, sometimes life-threatening problem due to acid in the blood produced from diabetes (diabetic ketoacidosis). Symptoms may include feeling more hungry or thirsty than usual, need to urinate more often, weight loss, feeling tired or having difficulty thinking clearly, breath that smells sweet or fruity, a sweet or metallic taste in your mouth, or a different odour to your urine or sweat, feeling sick or being sick, stomach pain, and deep or fast breathing.
• Inflammation of the skin that can lead to severe skin reaction (known as toxic epidermal necrolysis and Stevens-Johnson syndrome). Signs and symptoms of severe skin reaction may include rash, itching, and peeling of the skin (possibly fatal).
• Inflammation of the muscles such as myocarditis (inflammation of the heart muscle), myositis (inflammation of the muscles) and rhabdomyolysis (stiffness in muscles and joints, muscle spasm). Signs and symptoms may include muscle pain, stiffness, weakness, chest pain, or severe fatigue.
• Solid organ transplant rejection.
• Graft-versus-host disease.
• Haemophagocytic lymphohistiocytosis . A rare disease in which our immune system makes too many of otherwise normal infection fighting cells called histiocytes and lymphocytes. Symptoms may include enlarged liver and/or spleen, skin rash, lymph node enlargement, breathing problems, easy bruising, kidney abnormalities, and heart problems.
• Myocarditis-Myositis-Myasthenia Gravis Overlap Syndrome: an overlap of either two or three conditions including inflammation of the heart muscle (myocarditis) that may cause chest pain, shortness of breath, irregular and/or rapid heartbeat, inflammation of the muscles (myositis) that may cause muscle pain, and a condition that may cause muscle weakness and tiredness (myasthenia gravis).
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 taking medicines to suppress your immune system.
OPDIVO acts on your immune system. It may cause inflammation in parts of your body. Your risk of these side effects may be higher if you already have an autoimmune disease (a condition where the body attacks its own cells). You may also experience frequent flares of your autoimmune disease, which in the majority of cases are mild.
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 solution for injection 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 OPDIVO gets into breast milk. A risk to the breast-fed infant cannot be excluded. Ask your doctor if you can breast-feed during or after treatment with OPDIVO.
Driving and using machines OPDIVO or OPDIVO in combination with ipilimumab may have a minor influence on the ability to drive and use machines; however, use caution when performing these activities until you are sure that OPDIVO does not adversely affect you.
OPDIVO contains polysorbate 80 (E433) This medicine contains 1.25 mg of polysorbate 80 in each 2.5 mL and 2.5 mg of polysorbate 80 in each 5 mL vial which is equivalent to 5 mg/10 mL. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.
You will also find key messages from this package leaflet in the patient card you have been given by your doctor. It is important that you keep this patient card and show it to your partner or caregivers.
How much OPDIVO is given When OPDIVO is given on its own as an injection under your skin (subcutaneous injection), the recommended dose is either 600 mg given every 2 weeks or 1200 mg given every 4 weeks.
When OPDIVO is given intravenously in combination with ipilimumab for the treatment of skin cancer, 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 given as an injection under your skin is 600 mg every 2 weeks or 1200 mg every 4 weeks (single-agent phase).
When OPDIVO is given intravenously in combination with ipilimumab for the treatment of advanced kidney cancer the recommended dose of OPDIVO is 3 mg of nivolumab per kilogram of your body weight for the first 4 doses (combination phase). Thereafter, the recommended dose of OPDIVO given as an injection under your skin is 600 mg every 2 weeks or 1200 mg every 4 weeks (single-agent phase).
When OPDIVO is given intravenously in combination with ipilimumab for the treatment of advanced colon or rectal cancer, the recommended dose of OPDIVO is 3 mg of nivolumab per kilogram of your body weight or 240 mg for the first 4 doses (combination phase) depending on your treatment.
Thereafter, the recommended dose of OPDIVO is 600 mg every 2 weeks or 1200 mg every 4 weeks (single-agent phase) given as an injection under your skin, depending on your treatment.
When OPDIVO is given in combination with ipilimumab for the treatment of unresectable or advanced liver cancer, the recommended dose of OPDIVO given as an infusion into a vein is 1 mg of nivolumab per kilogram of your body weight for up to 4 doses (combination phase) depending on your treatment. Thereafter, the recommended dose of OPDIVO given as an injection under your skin is 600 mg every 2 weeks or 1200 mg every 4 weeks (single-agent phase) depending on your treatment
When OPDIVO is given in combination with chemotherapy for the neoadjuvant treatment (before surgery) of non-small cell lung cancer, the recommended dose of OPDIVO given as an injection under your skin is 900 mg every 3 weeks for 3 cycles.
When OPDIVO is given in combination with chemotherapy for the neoadjuvant (before surgery) and adjuvant (after surgery) treatment of non-small cell lung cancer, the recommended dose of OPDIVO given as an injection under your skin is 900 mg every 3 weeks for 4 cycles (combination phase) prior to resection and 1200 mg every 4 weeks (single-agent phase) as an injection under your skin.
When OPDIVO is given in combination with chemotherapy for the treatment of advanced oesophageal cancer, the recommended dose of OPDIVO is 600 mg every 2 weeks or 1200 mg every 4 weeks as an injection under your skin.
When OPDIVO is given in combination with chemotherapy for the treatment of advanced gastric, gastro-oesophageal junction or oesophageal adenocarcinoma, the recommended dose of OPDIVO is either 600 mg every 2 weeks or 900 mg every 3 weeks as an injection under your skin.
When OPDIVO is given in combination with chemotherapy for the treatment of urothelial carcinoma (bladder and urinary tract cancer), the recommended dose of OPDIVO is 900 mg every 3 weeks as an injection under your skin, for up to 6 cycles. Thereafter, the recommended dose of OPDIVO is 600 mg every 2 weeks or 1200 mg every 4 weeks (single agent phase) given as an injection under your skin.
When OPDIVO is given in combination with cabozantinib for the treatment of advanced kidney cancer, the recommended dose of OPDIVO is 600 mg given every 2 weeks or 1200 mg given every 4 weeks as an injection under your skin.
More than one vial of OPDIVO may be necessary to obtain the required dose.
How OPDIVO is given You will receive treatment with OPDIVO under the supervision of an experienced doctor.
OPDIVO is given as an injection under the skin (subcutaneously) of the abdomen or thigh over a period of 3 to 5 minutes, every 2 weeks, 3 weeks, or 4 weeks, depending on the dose you are receiving. Treatment with OPDIVO will continue for as long as you keep benefitting from it or until you no longer tolerate the treatment.
When OPDIVO is given intravenously in combination with ipilimumab for the treatment of skin, advanced kidney, advanced colon or rectal cancer, or unresectable or advanced liver cancer, you will be given an infusion over a period of 30 minutes, every 3 weeks for the first 4 doses (combination phase) depending on your treatment. Thereafter, OPDIVO will be given as an injection under the skin of the abdomen or thigh over a period of 3 to 5 minutes, every 2 weeks or 4 weeks, depending on the dose you are receiving (single-agent phase).
When OPDIVO is given as an injection under the skin of the abdomen or thigh in combination with chemotherapy for the neoadjuvant (before surgery) treatment of non-small cell lung cancer it will be given over a period of 3 to 5 minutes, every 3 weeks. After surgery, OPDIVO will be given as an injection under the skin of the abdomen or thigh over a period of 3 to 5 minutes, every 4 weeks, depending on the dose you are receiving (single agent phase).
When OPDIVO is given as an injection under the skin of the abdomen or thigh in combination with chemotherapy for the treatment of advanced oesophageal cancer, OPDIVO will be given over a period of 3 to 5 minutes, every 2 weeks or 4 weeks, depending on the dose you are receiving.
When OPDIVO is given in combination with chemotherapy for the treatment of urothelial carcinoma (bladder or urinary tract cancer), OPDIVO will be given as an injection under the skin of the abdomen or thigh over a period of 3 to 5 minutes, every 3 weeks (combination phase), and then it will be given every 2 or 4 weeks, depending on the dose you are receiving (single-agent phase).
When OPDIVO is given as an injection under the skin of the abdomen or thigh in combination with chemotherapy for the treatment of advanced gastric, gastro-oesophageal junction or oesophageal adenocarcinoma, it will be given over a period of 3 to 5 minutes every 2 weeks or 3 weeks, depending on the dose you are receiving.
When OPDIVO is given as an injection under the skin of the abdomen or thigh in combination with cabozantinib, it will be given over a period of 3 to 5 minutes, every 2 weeks or 4 weeks, depending on the dose you are receiving.
If you miss a dose of OPDIVO It is very important for you to keep all your appointments to receive OPDIVO. If you miss an appointment, ask your doctor when to schedule your next dose.
If you stop using OPDIVO Stopping your treatment may stop the effect of the medicine. Do not stop treatment with OPDIVO unless you have discussed this with your doctor.
If you have any further questions about your treatment or on the use of this medicine, ask your doctor.
When OPDIVO is given in combination with other anti-cancer medicines, you will first be given OPDIVO followed by the other medicine.
Please refer to the package leaflet of these other medicines in order to understand the use of these medicines. If you have questions about them, please ask your doctor.
Like all medicines, this medicine can cause side effects, although not everybody gets them. Your doctor will discuss these with you and will explain the risks and benefits of your treatment.
Be aware of important symptoms of inflammation. OPDIVO acts on your immune system and may cause inflammation in parts of your body. Inflammation may cause serious damage to your body and some inflammatory conditions may be life-threatening and need treatment or withdrawal of OPDIVO.
The following side effects have been reported with OPDIVO alone:
Very common (may affect more than 1 in 10 people)
• Infections of the upper respiratory tract
• A decreased number of red blood cells (which carry oxygen), white blood cells (which are important in fighting infection) or platelets (cells which help the blood to clot)
• Decreased appetite, high sugar levels in the blood (hyperglycaemia)
• Headache
• Shortness of breath (dyspnoea), cough
• Diarrhoea (watery, loose or soft stools), vomiting, nausea, stomach pain, constipation
• Skin rash sometimes with blisters, itching
• Pain in the muscles, bones (musculoskeletal pain) and joints (arthralgia)
• Feeling tired or weak, fever
Common (may affect up to 1 in 10 people)
• Serious lung infection (pneumonia), bronchitis
• Reactions related to the infusion of the medicine, allergic reaction, (including life-threatening allergic reaction)
• Underactive thyroid gland (which can cause tiredness or weight gain), overactive thyroid gland (which can cause rapid heart rate, sweating and weight loss), swelling of the thyroid gland
• Dehydration, decrease in body weight, low sugar levels in the blood (hypoglycaemia)
• Inflammation of the nerves (causing numbness, weakness, tingling or burning pain of the arms and legs), dizziness
• Blurred vision, dry eyes
• Fast heart rate, abnormal heart rhythm
• High blood pressure (hypertension)
• Inflammation of the lungs (pneumonitis, characterised by coughing and difficulty breathing), fluid around the lungs
• Inflammation of the intestines (colitis), mouth ulcers and cold sores (stomatitis), dry mouth
• Skin colour change in patches (vitiligo), dry skin, redness of the skin, unusual hair loss or thinning
• Inflammation of the joints (arthritis)
• Kidney failure (including abrupt loss of kidney function)
• Pain, chest pain, oedema (swelling)
• Reaction at site of injection
Uncommon (may affect up to 1 in 100 people)
• Increase in some white blood cells
• Chronic diseases associated with a build-up of inflammatory cells in various organs and tissues, most commonly the lungs (sarcoidosis)
• Decreased secretion of hormones produced by adrenal glands (glands situated above the kidneys), underactive function (hypopituitarism) or inflammation (hypophysitis) of the pituitary gland situated at the base of the brain, diabetes
• Increased acid levels in the blood (metabolic acidosis)
• Damage to nerves causing numbness and weakness (polyneuropathy), inflammation of the nerves caused by the body attacking itself, causing numbness, weakness, tingling or burning pain (autoimmune neuropathy)
• Inflammation of the eye (which causes pain and redness)
• Inflammation of the heart muscle, inflammation of the covering of the heart and accumulation of fluid around the heart (pericardial disorders), changes in the rhythm or rate of the heartbeat
• Fluid in the lungs
• Inflammation of the pancreas (pancreatitis), inflammation of the stomach (gastritis)
• Inflammation of the liver (hepatitis), blockage of bile ducts (cholestasis)
• Skin disease with thickened patches of red skin, often with silvery scales (psoriasis), severe condition of the skin that causes red, often itchy spots, similar to the rash of measles, which starts on the limbs and sometimes on the face and the rest of the body (erythema multiforme), hives (itchy, bumpy rash)
• Inflammation of the muscles causing pain or stiffness (polymyalgia rheumatica)
• Myocarditis-Myositis-Myasthenia Gravis Overlap Syndrome: an overlap of either two or three conditions, including inflammation of the heart muscle (myocarditis), inflammation of the muscles (myositis), and a condition that may cause muscle weakness and tiredness (myasthenia gravis)
Rare (may affect up to 1 in 1000 people)
• A temporary and reversible non-infectious inflammation of the protective membranes surrounding the brain and spinal cord (aseptic meningitis)
• A disease causing the inflammation or enlargement of a lymph node (Kikuchi lymphadenitis)
• Acid in the blood produced from diabetes (diabetic ketoacidosis), decreased function of the parathyroid gland
• A temporary inflammation of the nerves that causes pain, weakness, and paralysis in the extremities (Guillain-Barré syndrome), loss of the protective sheath around nerves (demyelination), a condition in which the muscles become weak and tire easily (myasthenic syndrome)
• An inflammation of the optic nerve that may cause a complete or partial loss of vision (optic neuritis)
• Inflammation of the brain
• Inflammatory disease of blood vessels
• Ulcer of the small intestines
• Severe and possibly fatal peeling of the skin (toxic epidermal necrolysis or Stevens-Johnson syndrome), skin condition of the face where the nose and cheeks are unusually red (rosacea)
• Disease in which the immune system attacks the glands that make moisture for the body, such as tears and saliva (Sjogren’s syndrome), aching muscles, muscle tenderness or weakness, not caused by exercise (myopathy), inflammation of the muscles (myositis), stiffness in muscles and joints, muscle spasm (rhabdomyolysis)
• Inflammation of the kidney, inflammation of the bladder, signs and symptoms may include frequent and/or painful urination, urge to pass urine, blood in urine, pain or pressure in lower abdomen
• Lack or reduction of digestive enzymes made by the pancreas (pancreatic exocrine insufficiency)
• Coeliac disease (characterised by symptoms such as stomach pain, diarrhoea, and bloating after consuming gluten-containing foods)
Other side effects that have been reported with frequency not known (cannot be estimated from the available data):
• A condition where the immune system makes too many infection-fighting cells called histiocytes and lymphocytes that may cause various symptoms (called haemophagocytic lymphohistiocytosis)
• Solid organ transplant rejection
• A group of metabolic complications occurring after cancer treatment characterised by high blood levels of potassium and phosphate, and low blood levels of calcium (tumour lysis syndrome)
• An inflammatory disorder (most likely of autoimmune origin) affecting the eyes, skin and the membranes of the ears, brain and spinal cord (Vogt-Koyanagi-Harada syndrome)
• Pain, numbness, tingling, or weakness in the arms or legs; bladder or bowel problems including needing to urinate more frequently, urinary incontinence, difficulty urinating and constipation (myelitis/transverse myelitis)
• Changes in any area of the skin and/or genital area that are associated with drying out, thinning, itching and pain (lichen sclerosus or other lichen disorders)
The following side effects have been reported with OPDIVO in combination with other anti-cancer medicines (the frequency and severity of side effects may vary with the combination of anti-cancer medicines received):
Very common (may affect more than 1 in 10 people)
• Infections of the upper respiratory tract
• A decreased number of red blood cells (which carry oxygen), white blood cells (which are important in fighting infection) or platelets (cells which help the blood to clot)
• Underactive thyroid gland (which can cause tiredness or weight gain), overactive thyroid gland (which can cause rapid heart rate, sweating and weight loss)
• Decreased appetite, decrease in body weight, high (hyperglycaemia) or low (hypoglycaemia) sugar levels in the blood
• Inflammation of the nerves (causing numbness, weakness, tingling or burning pain of the arms and legs), headache, dizziness, altered sense of taste
• High blood pressure (hypertension)
• Shortness of breath (dyspnoea), cough, abnormal speaking sound (dysphonia)
• Diarrhoea (watery, loose or soft stools), constipation, vomiting, nausea, stomach pain, mouth ulcers and cold sores (stomatitis), indigestion (dyspepsia)
• Skin rash sometimes with blisters, itching, pain of the hands or soles of the feet: rash or redness of the skin, tingling and tenderness developing to symmetrical redness, swelling and pain primarily on the palm of the hand and sole of the foot (palmar-plantar erythrodysaesthaesia syndrome)
• Pain in the joints (arthralgia), pain in the muscles and bones (musculoskeletal pain), muscle spasm
• Excess protein in urine
• Feeling tired or weak, fever, oedema (swelling)
Common (may affect up to 1 in 10 people)
• Serious lung infection (pneumonia), bronchitis, inflammation of the eye (conjunctivitis)
• Increase in some white blood cells, decrease in neutrophils with fever
• Allergic reaction (including life-threatening allergic reaction), reactions related to the infusion of the medicine
• Decreased secretion of hormones produced by adrenal glands (glands situated above the kidneys), underactive function (hypopituitarism) or inflammation (hypophysitis) of the pituitary gland situated at the base of the brain, swelling of the thyroid gland, diabetes
• Dehydration, decreased levels of albumin in the blood, decreased levels of phosphate in the blood
• Sensations like numbness and tingling (paraesthesia)
• Hearing a persistent sound in your ear when no sound exists (tinnitus)
• Blurred vision, dry eye
• Fast heart rate, abnormal heart rhythm
• Formation of a blood clot within a blood vessel (thrombosis), inflammatory disease of blood vessels
• Inflammation of the lungs (pneumonitis, characterised by coughing and difficulty breathing), fluid around the lungs, blood clots, nose bleeding
• Inflammation of the intestines (colitis), inflammation of the pancreas (pancreatitis), dry mouth, inflammation of the stomach (gastritis), oral pain, haemorrhoids (piles)
• Inflammation of the liver
• Skin colour change in patches (including vitiligo), redness of the skin, unusual hair loss or thinning, hair colour change, hives (itchy rash), discolouration or abnormal darkening of the skin (skin hyperpigmentation), dry skin
• Inflammation of the joints (arthritis), muscle weakness, aching muscles
• Kidney failure (including abrupt loss of kidney function)
• Pain, chest pain, chills
• Feeling generally unwell (malaise)
Uncommon (may affect up to 1 in 100 people)
• Acid in the blood produced from diabetes (diabetic ketoacidosis)
• Increased acid levels in the blood
• A temporary inflammation of the nerves that causes pain, weakness and paralysis in the extremities (Guillain-Barré syndrome); damage to nerves causing numbness and weakness (polyneuropathy); foot drop (peroneal nerve palsy); inflammation of the nerves caused by the body attacking itself, causing numbness, weakness, tingling or burning pain (autoimmune neuropathy); muscle weakness and tiredness without atrophy (myasthenia gravis or syndrome)
• Inflammation of the brain
• Inflammation of the eye (which causes pain and redness)
• Changes in the rhythm or rate of the heartbeat, slow heart rate, inflammation of the heart muscle
• Intestinal perforation, inflammation of the duodenum, burning or painful sensation in the tongue (glossodynia)
• Severe and possibly fatal peeling of the skin (Stevens-Johnson syndrome), skin disease with thickened patches of red skin, often with silvery scales (psoriasis), severe condition of the skin that causes red, often itchy spots, similar to the rash of measles, which starts on the limbs and sometimes on the face and the rest of the body (erythema multiforme), changes in any area of the skin and/or genital area that are associated with drying out, thinning, itching and pain (other lichen disorders)
• Muscle tenderness or weakness, not caused by exercise (myopathy), inflammation of the muscles (myositis), stiffness in muscles and joints, inflammation of the muscles causing pain or stiffness (polymyalgia rheumatica), bone damage in the jaw, abnormal opening between two body parts, such as an organ or blood vessel and another structure (fistula)
• Inflammation of the kidney, inflammation of the bladder, signs and symptoms may include frequent and/or painful urination, urge to pass urine, blood in urine, pain or pressure in lower abdomen
• Myocarditis-Myositis-Myasthenia Gravis Overlap Syndrome: an overlap of either two or three conditions, including inflammation of the heart muscle (myocarditis), inflammation of the muscles (myositis), and a condition that may cause muscle weakness and tiredness (myasthenia gravis)
Rare (may affect up to 1 in 1000 people)
• Temporary and reversible non-infectious inflammation of the protective membranes surrounding the brain and spinal cord (aseptic meningitis)
• Chronic diseases associated with a build-up of inflammatory cells in various organs and tissues, most commonly the lungs (sarcoidosis)
• Decreased function of the parathyroid gland
• A group of metabolic complications occurring after cancer treatment characterised by high blood levels of potassium and phosphate, and low blood levels of calcium (tumour lysis syndrome)
• An inflammatory disorder (most likely of autoimmune origin) affecting the eyes, skin and the membranes of the ears, brain and spinal cord (Vogt-Koyanagi-Harada syndrome)
• An inflammation of the optic nerve that may cause a complete or partial loss of vision (optic neuritis)
• Inflammation of the nerves
• Pain, numbness, tingling, or weakness in the arms or legs; bladder or bowel problems including needing to urinate more frequently, urinary incontinence, difficulty urinating and constipation (myelitis/transverse myelitis)
• Severe and possibly fatal peeling of the skin (toxic epidermal necrolysis), changes in any area of the skin and/or genital area that are associated with drying out, thinning, itching and pain (lichen sclerosus)
• Chronic disease of joints (spondyloarthropathy), disease in which the immune system attacks the glands that make moisture for the body, such as tears and saliva (Sjogren’s syndrome), muscle spasm (rhabdomyolysis)
• Lack or reduction of digestive enzymes made by the pancreas (pancreatic exocrine insufficiency)
• Coeliac disease (characterised by symptoms such as stomach pain, diarrhoea, and bloating after consuming gluten-containing foods)
Other side effects that have been reported with frequency not known (cannot be estimated from the available data):
• A condition where the immune system makes too many infection-fighting cells called histiocytes and lymphocytes that may cause various symptoms (called haemophagocytic lymphohistiocytosis)
• Solid organ transplant rejection
• Inflammation of the covering of the heart and accumulation of fluid around the heart (pericardial disorders)
Tell your doctor immediately if you get any of the side effects listed above. Do not try to treat your symptoms with other medicines on your own.
Changes in test results OPDIVO alone or in combination may cause changes in the results of tests carried out by your doctor.
These include:
• Abnormal liver function tests (increased amounts of the liver enzymes aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, or alkaline phosphatase in your blood, higher blood levels of the waste product bilirubin)
• Abnormal kidney function tests (increased amounts of creatinine in your blood)
• An increased level of the enzyme that breaks down fats and of the enzyme that breaks down starch
• Increased or decreased amount of calcium or potassium
• Increased or decreased blood levels of magnesium or sodium
• Increased amount of thyroid stimulating hormone
• Increase in blood triglyceride levels in the blood
• Increase in cholesterol levels in the blood
Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard, or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and the vial label after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C to 8°C).
Do not freeze.
Store in the original package in order to protect from light.
Do not store any unused portion of the injection solution for reuse. Any unused medicine or waste material should be disposed of in accordance with local requirements.
What OPDIVO contains • The active substance is nivolumab.
Each mL of solution for injection contains 120 mg of nivolumab.
Each 2.5 mL vial contains 300 mg of nivolumab.
Each 5 mL vial contains 600 mg of nivolumab.
• The other ingredients are recombinant human hyaluronidase (rHuPH20), histidine, histidine hydrochloride monohydrate, sucrose, pentetic acid, polysorbate 80 (E433), methionine, and water for injection (see section 2 “OPDIVO contains polysorbate 80 (E433)”).
What OPDIVO looks like and contents of the pack OPDIVO solution for injection is a clear to opalescent, colourless to pale yellow liquid that may contain few light particles.
It is available in packs containing either 1 glass vial of 2.5 mL or 1 glass vial of 5 mL.
Not all pack sizes may be marketed
Marketing Authorisation Holder Bristol-Myers Squibb Pharma EEIG
Plaza 254
Blanchardstown Corporate Park 2
Dublin 15
D15 T867
Ireland
Manufacturer Swords Laboratories Unlimited Company t/a Bristol-Myers Squibb Cruiserath Biologics
Cruiserath Road
Mulhuddart
Dublin 15
D15 H6EF
Ireland
This leaflet was last revised in July 2026
Bristol Myers Squibb Pharmaceuticals limited
Address
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OPDIVO 300 mg Solution for injection comes as solution containing 300 mg. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
The active substance in OPDIVO 300 mg Solution for injection is nivolumab.
Medicines with the same active substance include: OPDIVO 10 mg/mL concentrate for solution for infusion, OPDIVO 600 mg/5 ml solution for injection. They are interchangeable only if your prescriber or pharmacist says so.
This leaflet reproduces the patient information leaflet approved for OPDIVO 300 mg Solution for injection, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
Melanoma
OPDIVO as monotherapy is indicated for the adjuvant treatment of adults with Stage IIB or IIC melanoma, or melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection (see section 5.1).
OPDIVO as monotherapy or in combination with ipilimumab is indicated for the treatment of advanced (unresectable or metastatic) melanoma in adults (see section 4.2).
Relative to nivolumab monotherapy, an increase in progression‑free survival (PFS) and overall survival (OS) for the combination of nivolumab with ipilimumab is established only in patients with low tumour PD‑L1 expression (see sections 4.4 and 5.1).
Non‑small cell lung cancer (NSCLC)
OPDIVO in combination with platinum-based chemotherapy is indicated for the neoadjuvant treatment of resectable (tumours ≥ 4 cm or node positive) non-small cell lung cancer in adults (see section 5.1).
OPDIVO, in combination with platinum-based chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgical resection, is indicated for the treatment of adults with resectable (tumours ≥4 cm or node positive) non-small cell lung cancer and no known EGFR mutations or ALK rearrangements (see section 5.1).
OPDIVO as monotherapy is indicated for the treatment of locally advanced or metastatic non‑small cell lung cancer after prior chemotherapy in adults.
Renal cell carcinoma (RCC)
OPDIVO in combination with ipilimumab is indicated for the first‑line treatment of adult patients with intermediate/poor‑risk advanced renal cell carcinoma (see section 5.1).
OPDIVO in combination with cabozantinib is indicated for the first‑line treatment of adult patients with advanced renal cell carcinoma (see section 5.1).
OPDIVO as monotherapy is indicated for the treatment of advanced renal cell carcinoma after prior therapy in adults.
Squamous cell cancer of the head and neck (SCCHN)
OPDIVO as monotherapy is indicated for the treatment of recurrent or metastatic squamous cell cancer of the head and neck in adults progressing on or after platinum‑based therapy (see section 5.1).
Urothelial carcinoma (UC)
OPDIVO as monotherapy is indicated for the adjuvant treatment of adults with completely resected muscle invasive urothelial carcinoma (MIUC) with tumour cell PD‑L1 expression ≥ 1%, who are at high risk of recurrence after undergoing radical resection of MIUC (see section 5.1).
OPDIVO in combination with cisplatin and gemcitabine is indicated for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma.
OPDIVO as monotherapy is indicated for the treatment of locally advanced unresectable or metastatic urothelial carcinoma in adults after failure of prior platinum‑containing therapy.
Mismatch repair deficient (dMMR) or microsatellite instability‑high (MSI‑H) colorectal cancer (CRC)
OPDIVO in combination with ipilimumab is indicated for the treatment of adult patients with mismatch repair deficient or microsatellite instability‑high colorectal cancer in the following settings:
- first-line treatment of unresectable or metastatic colorectal cancer;
- treatment of metastatic colorectal cancer after prior fluoropyrimidine‑based combination chemotherapy (see section 5.1).
Oesophageal squamous cell carcinoma (OSCC)
OPDIVO in combination with fluoropyrimidine‑ and platinum‑based combination chemotherapy is indicated for the first‑line treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma with tumour cell PD‑L1 expression ≥ 1%.
OPDIVO as monotherapy is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma after prior fluoropyrimidine‑ and platinum‑based combination chemotherapy.
Adjuvant treatment of oesophageal or gastro‑oesophageal junction cancer (OC or GEJC)
OPDIVO as monotherapy is indicated for the adjuvant treatment of adult patients with completely resected oesophageal or gastro‑oesophageal junction cancer who have residual pathologic disease following prior neoadjuvant chemoradiotherapy (see section 5.1).
Gastric, gastro‑oesophageal junction (GEJ) or oesophageal adenocarcinoma
OPDIVO in combination with fluoropyrimidine‑ and platinum‑based combination chemotherapy is indicated for the first‑line treatment of adult patients with HER2‑negative advanced or metastatic gastric, gastro‑oesophageal junction or oesophageal adenocarcinoma whose tumours express PD‑L1 with a combined positive score (CPS) ≥ 5.
Hepatocellular carcinoma (HCC)
OPDIVO in combination with ipilimumab is indicated for the first‑line treatment of adult patients with unresectable or advanced hepatocellular carcinoma.
Treatment must be initiated and supervised by physicians experienced in the treatment of cancer.
Patients currently receiving intravenous nivolumab monotherapy, or in combination with chemotherapy or cabozantinib, may transition to OPDIVO solution for injection.
PD‑L1 testing
If specified in the indication, patient selection for treatment with OPDIVO based on the tumour expression of PD‑L1 should be confirmed by a validated test (see sections 4.1, 4.4, and 5.1).
MSI/MMR testing
If specified in the indication, patient selection for treatment with OPDIVO based on MSI-H/dMMR tumour status should be assessed by a CE-marked IVD with the corresponding intended purpose. If the CE-marked IVD is not available, an alternative validated test should be used (see sections 4.1, 4.4, and 5.1).
Posology
OPDIVO as monotherapy
The recommended dose of OPDIVO solution for injection is either nivolumab 600 mg every 2 weeks or 1200 mg every 4 weeks (see section 5.1).
If patients need to be switched from the 600 mg every 2 weeks schedule to the 1200 mg every 4 weeks schedule, the first 1200 mg dose should be administered two weeks after the last 600 mg dose. Conversely, if patients need to be switched from the 1200 mg every 4 weeks schedule to the 600 mg every 2 weeks schedule, the first 600 mg dose should be administered four weeks after the last 1200 mg dose.
OPDIVO in combination with ipilimumab
Melanoma
Table 1: Recommended doses and infusion times for OPDIVO solution for infusion in combination with ipilimumab followed by OPDIVO solution for injection monotherapy for melanoma (see section 5.1 and 5.2)
| Combination phase OPDIVO solution for infusion, intravenously (IV) and ipilimumab, for 4 dosing cycles | Monotherapy phase OPDIVO solution for injection, subcutaneously (SC) | |
| Nivolumab | 1 mg/kg every 3 weeks over 30 minutes | 600 mg every 2 weeks or 1200 mg every 4 weeks The first dose should be administered: |
| Ipilimumab | 3 mg/kg every 3 weeks over 30 minutes | - |
Renal cell carcinoma (RCC)
Table 2: Recommended doses and infusion times for OPDIVO solution for infusion in combination with ipilimumab followed by OPDIVO solution for injection monotherapy for RCC
| Combination phase OPDIVO solution for infusion, intravenously (IV) and ipilimumab, for 4 dosing cycles | Monotherapy phase OPDIVO solution for injection, subcutaneously (SC) | |
| Nivolumab | 3 mg/kg every 3 weeks over 30 minutes | 600 mg every 2 weeks or 1200 mg every 4 weeks The first dose should be administered: |
| Ipilimumab | 1 mg/kg every 3 weeks over 30 minutes | - |
dMMR or MSI‑H colorectal cancer (CRC)
Table 3: Recommended doses and infusion times for OPDIVO solution for infusion in combination with ipilimumab followed by OPDIVO solution for injection monotherapy for dMMR or MSI‑H CRC
| Combination phase, OPDIVO solution for infusion, intravenously (IV), and ipilimumab for 4 dosing cycles | Monotherapy phase OPDIVO solution for injection, subcutaneously (SC) | ||
| Nivolumab | First-line treatment | 240 mg every 3 weeks over 30 minutes | 600 mg every 2 weeks or 1200 mg every 4 weeks The first dose should be administered 3 weeks after the last dose of the combination of IV nivolumab and ipilimumab. Treatment is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. |
| Treatment after priorfluoropyrimidine‑based combination chemotherapy | 3 mg/kg every 3 weeks over 30 minutes | 600 mg every 2 weeks The first dose should be administered 3 weeks after the last dose of the combination of IV nivolumab and ipilimumab. | |
| Ipilimumab | 1 mg/kg every 3 weeks over 30 minutes | - | |
Hepatocellular carcinoma (HCC)
Table 4: Recommended doses and infusion times for OPDIVO solution for infusion in combination with ipilimumab followed by OPDIVO solution for injection monotherapy for the treatment of HCC (see sections 5.1 and 5.2)
| Combination phase OPDIVO solution for infusion, intravenously (IV) and ipilimumab for up to 4 dosing cycles | Monotherapy phase* OPDIVO solution for injection, subcutaneously (SC) | |
| Nivolumab | 1 mg/kg every 3 weeks over 30 minutes | 600 mg every 2 weeks or 1200 mg every 4 weeks The first dose should be administered 3 weeks after the last dose of the combination of IV nivolumab and ipilimumab. |
| Ipilimumab | 3 mg/kg every 3 weeks over 30 minutes | - |
*Treatment is recommended until disease progression, unacceptable toxicity, or up to 24 months.
OPDIVO in combination with cabozantinib
Renal cell carcinoma (RCC)
Table 5: Recommended doses for OPDIVO solution for injection in combination with cabozantinib for the treatment of RCC
| Combination therapy* | |
| Nivolumab | 600 mg every 2 weeks or 1200 mg of every 4 weeks |
| Cabozantinib | 40 mg every day, orally |
*For OPDIVO in combination with cabozantinib, OPDIVO should be continued until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Cabozantinib should be continued until disease progression or unacceptable toxicity. Refer to the Summary of Product Characteristics (SmPC) for cabozantinib.
OPDIVO in combination with chemotherapy
Oesophageal squamous cell carcinoma (OSCC)
Table 6: Recommended doses for administration of OPDIVO solution for injection in combination with fluoropyrimidine- and platinum‑based chemotherapy for the treatment of OSCC (see section 5.1)*
| Combination therapy | |
| Nivolumab | 600 mg every 2 weeks or 1200 mg every 4 weeks |
| Fluoropyrimidine- and platinum-based chemotherapy | Every 4 weeks |
*Treatment with nivolumab is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Gastric, gastro‑oesophageal junction (GEJ) or oesophageal adenocarcinoma
Table 7: Recommended doses for administration of OPDIVO solution for injection in combination with fluoropyrimidine‑ and platinum‑based chemotherapy for the treatment of gastric, GEJ or oesophageal adenocarcinoma (see section 5.1)*
| Combination therapy | |
| Nivolumab | 600 mg every 2 weeks or 900 mg every 3 weeks |
| Fluoropyrimidine- and platinum-based chemotherapy | Every 2 weeks or every 3 weeks, depending on the nivolumab regimen |
*Treatment with nivolumab is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Urothelial carcinoma (UC)
Table 8: Recommended doses for OPDIVO solution for injection in combination with cisplatin and gemcitabine followed by OPDIVO monotherapy for UC (see section 5.1)
| Combination phase for up to 6 dosing cycles | Monotherapy phase* | |
| Nivolumab | 900 mg every 3 weeks | 600 mg every 2 weeks or 1200 mg every 4 weeks |
| Cisplatin and gemcitabine | Every 3 weeks | - |
*Treatment with nivolumab is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Neoadjuvant treatment of NSCLC
Table 9: Recommended doses for OPDIVO solution for injection in combination with platinum‑based chemotherapy for neoadjuvant treatment of NSCLC (see section 5.1)
| Combination therapy for 3 cycles | |
| Nivolumab | 900 mg every 3 weeks |
| Platinum‑based chemotherapy | Every 3 weeks |
Neoadjuvant and adjuvant treatment of non‑small cell lung cancer (NSCLC)
Table 10: Recommended doses for OPDIVO solution for injection in combination with platinum‑based chemotherapy for neoadjuvant treatment followed by OPDIVO monotherapy for adjuvant treatment of NSCLC
| Combination phase (neoadjuvant treatment) for up to 4 cycles | Monotherapy phase* (adjuvant treatment) | |
| Nivolumab | 900 mg every 3 weeks | 1200 mg every 4 weeks |
| Platinum‑based chemotherapy | Every 3 weeks | - |
*Treatment is recommended until disease progression or recurrence, unacceptable toxicity, or up to 13 cycles (see section 5.1).
Duration of treatment
Treatment with OPDIVO, either as a monotherapy or in combination with other therapeutic agents, should be continued as long as clinical benefit is observed or until treatment is no longer tolerated by the patient (and up to maximum duration of therapy if specified for an indication).
For adjuvant therapy, the maximum treatment duration with OPDIVO is 12 months.
Atypical responses (i.e., an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed. It is recommended to continue treatment with nivolumab or nivolumab in combination with ipilimumab for clinically stable patients with initial evidence of disease progression until disease progression is confirmed.
Dose escalation or reduction is not recommended for OPDIVO as monotherapy or in combination with other therapeutic agents. Dosing delay or discontinuation may be required based on individual safety and tolerability. Guidelines for permanent discontinuation or withholding of doses are described in Table 11. Detailed guidelines for the management of immune‑related adverse reactions are described in section 4.4. When nivolumab is administered in combination with other therapeutic agents, refer to the SmPC of these other combination therapeutic agents regarding dosing.
Table 11: Recommended treatment modifications for OPDIVO or OPDIVO in combination
| Immune-related adverse reaction | Severity | Treatment modification |
| Immune-related pneumonitis | Grade 2 pneumonitis | Withhold dose(s) until symptoms resolve, radiographic abnormalities improve, and management with corticosteroids is complete |
| Grade 3 or 4 pneumonitis | Permanently discontinue treatment | |
| Immune-related colitis | Grade 2 diarrhoea or colitis | Withhold dose(s) until symptoms resolve and management with corticosteroids, if needed, is complete |
| Grade 3 diarrhoea or colitis - OPDIVO monotherapy
- OPDIVO+ipilimumaba |
Withhold dose(s) until symptoms resolve and management with corticosteroids is complete Permanently discontinue treatment | |
| Grade 4 diarrhoea or colitis | Permanently discontinue treatment | |
| Immune-related hepatitis NOTE: for RCC patients treated with OPDIVO in combination with cabozantinib with liver enzyme elevations, see dosing guidelines following this table. | Grade 2 elevation in aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin | Withhold dose(s) until laboratory values return to baseline and management with corticosteroids, if needed, is complete |
| Grade 3 or 4 elevation in AST, ALT, or total bilirubin | Permanently discontinue treatment | |
| Immune-related nephritis and renal dysfunction | Grade 2 or 3 creatinine elevation | Withhold dose(s) until creatinine returns to baseline and management with corticosteroids is complete |
| Grade 4 creatinine elevation | Permanently discontinue treatment | |
| Immune-related endocrinopathies | Symptomatic Grade 2 or 3 hypothyroidism, hyperthyroidism, hypophysitis, Grade 2 adrenal insufficiency Grade 3 diabetes | Withhold dose(s) until symptoms resolve and management with corticosteroids (if needed for symptoms of acute inflammation) is complete. Treatment should be continued in the presence of hormone replacement therapyb as long as no symptoms are present |
| Grade 4 hypothyroidism Grade 4 hyperthyroidism Grade 4 hypophysitis Grade 3 or 4 adrenal insufficiency Grade 4 diabetes | Permanently discontinue treatment | |
| Immune-related skin adverse reactions | Grade 3 rash | Withhold dose(s) until symptoms resolve and management with corticosteroids is complete |
| Grade 4 rash | Permanently discontinue treatment | |
| Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) | Permanently discontinue treatment (see section 4.4) | |
| Immune-related myocarditis | Grade 2 myocarditis | Withhold dose(s) until symptoms resolve and management with corticosteroids is completec |
| Grade 3 or 4 myocarditis | Permanently discontinue treatment | |
| Other immune-related adverse reactions | Grade 3 (first occurrence) | Withhold dose(s) |
| Grade 4 or recurrent Grade 3; persistent Grade 2 or 3 despite treatment modification; inability to reduce corticosteroid dose to 10 mg prednisone or equivalent per day | Permanently discontinue treatment | |
| Myocarditis-Myositis-Myasthenia Gravis Overlap Syndromed | Grade 2 Myocarditis-Myositis-Myasthenia Gravis Overlap Syndrome | Withhold dose(s) until symptoms resolve and management with corticosteroids is complete |
| Grade 3 or 4 Myocarditis-Myositis-Myasthenia Gravis Overlap Syndrome | Permanently discontinue treatment |
Note: Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4).
a During administration of the second phase of treatment (nivolumab monotherapy) following combination treatment, permanently discontinue treatment if Grade 3 diarrhoea or colitis occurs.
b Recommendation for the use of hormone replacement therapy is provided in section 4.4.
c The safety of re-initiating nivolumab or nivolumab in combination with ipilimumab therapy in patients previously experiencing immune-related myocarditis is not known.
d Presenting as an overlap of either two or all three conditions. The most severe CTCAE grade from the individual events should be considered to assess the recommended treatment modification.
OPDIVO as monotherapy or in combination with other therapeutic agents should be permanently discontinued for:
• Grade 4 or recurrent Grade 3 adverse reactions;
• Persistent Grade 2 or 3 adverse reactions despite management.
Patients treated with OPDIVO must be given the patient card and be informed about the risks of OPDIVO (see also package leaflet).
When OPDIVO is administered intravenously in combination with ipilimumab, if either agent is withheld, the other agent should also be withheld. If dosing is resumed after a delay, either the intravenous combination treatment or OPDIVO monotherapy administered intravenously or subcutaneously could be resumed based on the evaluation of the individual patient.
When OPDIVO is administered in combination with chemotherapy, refer to the SmPC of the other combination therapy agents regarding dosing. If any agents are withheld, the other agents may be continued. If dosing is resumed after a delay, either the combination treatment, OPDIVO monotherapy or chemotherapy alone could be resumed based on the evaluation of the individual patient.
OPDIVO in combination with cabozantinib in RCC
When OPDIVO is used in combination with cabozantinib, the above treatment modifications in Table 11 also apply to the OPDIVO component. In addition, for liver enzyme elevations, in patients with RCC being treated with OPDIVO in combination with cabozantinib:
• If ALT or AST > 3 times ULN but ≤ 10 times ULN without concurrent total bilirubin ≥ 2 times ULN, both OPDIVO and cabozantinib should be withheld until these adverse reactions recover to Grades 0‑1. Corticosteroid therapy may be considered. Rechallenge with a single medicine or rechallenge with both medicines after recovery may be considered. If rechallenging with cabozantinib, refer to cabozantinib SmPC.
• If ALT or AST > 10 times ULN or > 3 times ULN with concurrent total bilirubin ≥ 2 times ULN, both OPDIVO and cabozantinib should be permanently discontinued and corticosteroid therapy may be considered.
Special populations
Elderly
No dose adjustment is required for elderly patients (≥ 65 years).
Renal impairment
Based on the population pharmacokinetic (PK) results for intravenous nivolumab, no dose adjustment is required in patients with mild or moderate renal impairment (see section 5.2). Data from patients with severe renal impairment are too limited to draw conclusions on this population.
Hepatic impairment
Based on the population PK results for intravenous nivolumab, no dose adjustment is required in patients with mild or moderate hepatic impairment (see section 5.2). Data from patients with severe hepatic impairment are too limited to draw conclusions on this populations. OPDIVO must be administered with caution in patients with severe (total bilirubin > 3 × ULN and any AST) hepatic impairment.
Paediatric population
The safety and efficacy of OPDIVO solution for injection in children below 18 years of age have not been established.
Method of administration
OPDIVO solution for injection (subcutaneous formulation)
It is important to check the vial labels to ensure that the appropriate formulation (intravenous or subcutaneous formulation) and dose is being administered to the patient as prescribed.
OPDIVO solution for injection is not intended for intravenous administration and must be given by subcutaneous injection only using the doses specified.
Administer the full contents of the syringe of OPDIVO solution for injection into the subcutaneous tissue of the abdomen or thigh over a period of 3 to 5 minutes. Alternate injection sites for successive injections. Do not inject into areas where the skin is tender, red, or bruised, or areas where there are scars or moles. If the administration of OPDIVO solution for injection is interrupted, it can be resumed at the same site, or at an alternate site.
During the treatment course with OPDIVO solution for injection, other medicinal products for subcutaneous administration should preferably be injected at different sites.
For instructions on use and handling of the OPDIVO solution for injection before administration, see section 6.6.
OPDIVO solution for infusion (intravenous formulation)
The SmPC of OPDIVO concentrate for solution for infusion should be referred to for information on dosing instructions and method of administration.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Nivolumab is a human monoclonal antibody, as such pharmacokinetic interaction studies have not been conducted. As monoclonal antibodies are not metabolised by cytochrome P450 (CYP) enzymes or other drug metabolising enzymes, inhibition or induction of these enzymes by co‑administered medicinal products is not anticipated to affect the pharmacokinetics of nivolumab.
Other forms of interaction
Systemic immunosuppression
The use of systemic corticosteroids and other immunosuppressants at baseline, before starting nivolumab, should be avoided because of their potential interference with the pharmacodynamic activity. However, systemic corticosteroids and other immunosuppressants can be used after starting nivolumab to treat immune‑related adverse reactions. The preliminary results show that systemic immunosuppression after starting nivolumab treatment does not appear to preclude the response on nivolumab.
Pregnancy
There are no data from the use of nivolumab in pregnant women. Studies in animals have shown embryofoetal toxicity (see section 5.3). Human IgG4 is known to cross the placental barrier and nivolumab is an IgG4; therefore, nivolumab has the potential to be transmitted from the mother to the developing foetus. Nivolumab is not recommended during pregnancy and in women of childbearing potential not using effective contraception unless the clinical benefit outweighs the potential risk. Effective contraception should be used for at least 5 months following the last dose of nivolumab.
Breast‑feeding
It is unknown whether nivolumab is secreted in human milk. Because many medicinal products, including antibodies, can be secreted in human milk, a risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast‑feeding or to discontinue from nivolumab therapy taking into account the benefit of breast‑feeding for the child and the benefit of therapy for the woman.
Fertility
Studies to evaluate the effect of nivolumab on fertility have not been performed. Thus, the effect of nivolumab on male and female fertility is unknown.
Nivolumab or nivolumab in combination with ipilimumab may have a minor influence on the ability to drive and use machines. Because of potential adverse reactions such as fatigue (see section 4.8), patients should be advised to use caution when driving or operating machinery until they are certain that nivolumab does not adversely affect them.
No cases of overdose have been reported in clinical trials. In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted immediately.
Ask anything about OPDIVO 300 mg Solution for injection. The assistant answers only from this leaflet — if the leaflet does not cover it, it will say so. It does not give medical advice.
Answers come from the patient leaflet published on the electronic medicines compendium (emc). They are not medical advice. Ask a pharmacist or your GP if you are unsure. For urgent help call NHS 111, or 999 in an emergency.
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