Opdivo
nivolumab
nivolumab
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 OPDIVO is and what it is used for
What you need to know before you use OPDIVO
How to use OPDIVO
Possible side effects
How to store OPDIVO
Contents of the pack and other information
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)
advanced non-small cell lung cancer (a type of lung cancer) in adults
malignant pleural mesothelioma (a type of cancer that affects the lining of the lung) 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
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 pathologic disease after chemoradiation followed by surgery in adults
advanced gastric, gastro-oesophageal junction or oesophageal adenocarcinoma (stomach or gullet 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, bladder, 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.
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.
Talk to your doctor before using OPDIVO as it may cause:
(colitis), such as stomach pain and mucus or blood in stool.
kidney function tests, or decreased volume of urine.
(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.
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.
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
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.
OPDIVO should not be used in children and adolescents below 18 years of age.
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.
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.
You will also find key messages from this package leaflet in the patient alert card you have been given by your doctor. It is important that you keep this patient alert card and show it to your partner or caregivers.
When OPDIVO is given on its own, the recommended dose is either 240 mg given every 2 weeks or 480 mg given every 4 weeks depending on indication.
When OPDIVO is given 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 is 240 mg given every 2 weeks or 480 mg given every 4 weeks (single-agent phase).
When OPDIVO is given 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 is 240 mg given every 2 weeks or 480 mg given every 4 weeks (single-agent phase).
When OPDIVO is given 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 for the first 4 doses (combination phase). Thereafter, the recommended dose of OPDIVO is 240 mg given every 2 weeks (single-agent phase).
When OPDIVO is given in combination with ipilimumab for the treatment of malignant pleural mesothelioma, the recommended dose of OPDIVO is 360 mg every 3 weeks.
When OPDIVO is given in combination with ipilimumab for the treatment of advanced oesophageal cancer, the recommended dose of OPDIVO is 3 mg of nivolumab per kilogram of your body weight every 2 weeks or 360 mg every 3 weeks.
When OPDIVO is given in combination with chemotherapy for the treatment of advanced oesophageal cancer, the recommended dose of OPDIVO is 240 mg every 2 weeks or 480 mg every 4 weeks.
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 360 mg every 3 weeks or 240 mg every 2 weeks.
When OPDIVO is given in combination with ipilimumab and chemotherapy for the treatment of advanced non-small cell lung cancer, the recommended dose of OPDIVO is 360 mg every 3 weeks. After completion of 2 cycles of chemotherapy, OPDIVO is given in combination with ipilimumab, the recommended dose of OPDIVO is 360 mg every 3 weeks.
When OPDIVO is given in combination with cabozantinib for the treatment of advanced kidney cancer, the recommended dose of OPDIVO is 240 mg given every 2 weeks or 480 mg given every 4 weeks.
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.
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 30 or 60 minutes, every 2 weeks or 4 weeks, depending on the dose you are receiving. 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 for the treatment of skin, advanced kidney or advanced colon or rectal cancer, you will be given an infusion over a period of 30 minutes,
every 3 weeks for the first 4 doses (combination phase). Thereafter it will be given as an infusion over a period of 30 or 60 minutes, every 2 weeks or 4 weeks, depending on the dose you are receiving (single-agent phase).
When OPDIVO is given in combination with ipilimumab for the treatment of malignant pleural mesothelioma, you will be given an infusion over a period of 30 minutes, every 3 weeks.
When OPDIVO is given in combination with ipilimumab for the treatment of advanced oesophageal cancer, you will be given an infusion over a period of 30 minutes, every 2 or 3 weeks, depending on the dose you are receiving.
When OPDIVO is given in combination with chemotherapy for the treatment of advanced oesophageal cancer, you will be given an infusion over a period of 30 minutes, every 2 or 4 weeks, depending on the dose you are receiving.
When OPDIVO is given in combination with chemotherapy for the treatment of advanced gastric, gastro-oesophageal junction or oesophageal adenocarcinoma, you will be given an infusion over a period of 30 minutes every 3 weeks or every2 weeks, depending on the dose you are receiving.
When OPDIVO is given in combination with ipilimumab and chemotherapy for the treatment of advanced non-small cell lung cancer, you will be given an infusion over a period of 30 minutes, every 3 weeks.
When OPDIVO is given in combination with cabozantinib, you will be given an infusion over a period of 30 minutes or 60 minutes, every 2 weeks or 4 weeks, depending on the dose you are receiving.
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.
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.
The following side effects have been reported with OPDIVO alone:
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)
High (hyperglycaemia) or low (hypoglycaemia) sugar levels in the blood
Diarrhoea (watery, loose or soft stools), vomiting, nausea, constipation, stomach pain
Skin rash sometimes with blisters, itching
Feeling tired or weak, fever, oedema (swelling)
Decreased appetite
Headache
Shortness of breath (dyspnoea), cough
Pain in the muscles, bones (musculoskeletal pain) and joints (arthralgia)
Serious lung infection (pneumonia), bronchitis
Allergic reaction, reactions related to the infusion of the medicine 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
Inflammation of the nerves (causing numbness, weakness, tingling or burning pain of the arms and legs), dizziness
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, hives (itchy, bumpy rash)
Inflammation of the joints (arthritis)
Pain, chest pain
Blurred vision, dry eyes
Dehydration, decrease in body weight
Fast heart rate
Kidney failure (including abrupt loss of kidney function)
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, diabetes
Increased acid levels in the blood
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 heart muscle
Inflammation of the eye (which causes pain and redness)
Inflammation of the covering of the heart and accumulation of fluid around the heart (pericardial disorders), abnormal heart rhythm, 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
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), 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)
Inflammation of the muscles causing pain or stiffness (polymyalgia rheumatica)
Chronic diseases associated with a build-up of inflammatory cells in various organs and tissues, most commonly the lungs (sarcoidosis)
A disease causing the inflammation or enlargement of a lymph node (Kikuchi lymphadenitis)
Acid in the blood produced from diabetes (diabetic ketoacidosis)
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
A temporary and reversible non-infectious inflammation of the protective membranes surrounding the brain and spinal cord (aseptic meningitis)
Decreased function of the parathyroid gland
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)
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
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)
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)
A condition where the immune system makes too many infection-fighting cells called histiocytes
and lymphocytes that may cause various symptoms (called haemophagocytic lymphohistiocytosis)
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):
Infections of the upper respiratory tract, serious lung infection (pneumonia)
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), high (hyperglycaemia) or low (hypoglycaemia) sugar levels in the blood
Decreased appetite, decrease in body weight, decreased levels of albumin in the blood, altered sense of taste
Inflammation of the nerves (causing numbness, weakness, tingling or burning pain of the arms and legs), headache, dizziness
High blood pressure (hypertension)
Abnormal speaking sound (dysphonia)
Shortness of breath (dyspnoea), cough
Inflammation of the intestines (colitis), diarrhoea (watery, loose or soft stools), constipation, vomiting, nausea, stomach pain, mouth ulcers and cold sores (stomatitis)
Skin rash sometimes with blisters, itching, pain of the hands or soles of the feet: rash or redness of the skin, dry 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)
Bronchitis, inflammation of the eye (conjunctivitis)
Increase in some white blood cells, decrease in neutrophils with fever
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 phosphate in the blood
Sensations like numbness and tingling (paraesthesia), hearing a persistent sound in your ear when no sound exists (tinnitus)
Inflammation of the eye (which causes pain and redness), blurred vision, dry eye
Fast heart rate, abnormal heart rhythm, inflammation of the heart muscle
Formation of a blood clot within a blood vessel (thrombosis)
Inflammation of the lungs (pneumonitis, characterised by coughing and difficulty breathing), fluid around the lungs, blood clots, nose bleeding
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)
Inflammation of the joints (arthritis), muscle weakness, aching muscles
Kidney failure (including abrupt loss of kidney function)
Pain, chest pain, chills
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)
Increased acid levels in the blood
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); 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); muscle weakness and tiredness without atrophy (myasthenia gravis or syndrome),
Inflammation of the brain
Changes in the rhythm or rate of the heartbeat, slow heart rate
Intestinal perforation, inflammation of the duodenum, burning or painful sensation in the tongue (glossodynia)
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)
Severe and possibly fatal peeling of the skin (Stevens-Johnson syndrome)
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
tenderness of weakness, not caused by exercise (myopathy), inflammation of the muscles (myositis), stiffness in muscles and joints, muscle spasm (rhabdomyolysis), 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
Severe and possibly fatal peeling of the skin (toxic epidermal necrolysis)
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)
Inflammation of the covering of the heart and accumulation of fluid around the heart (pericardial disorders)
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)
A condition where the immune system makes too many infection-fighting cells called histiocytes and lymphocytes that may cause various symptoms (called haemophagocytic lymphohistiocytosis)
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
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 viathenationalreportingsystemlistedin Appendix V. 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.
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.
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), 100 mg (in 10 mL), 120 mg (in 12 mL) or 240 mg (in 24 mL) of nivolumab.
The other ingredients are sodium citrate dihydrate, sodium chloride (see section 2 "OPDIVO contains sodium"), mannitol (E421), pentetic acid, polysorbate 80 (E433), sodium hydroxide, hydrochloric acid and water for injections.
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, 1 vial of 10 mL, 1 vial of 12 mL or 1 vial of 24 mL.
Not all pack sizes may be marketed.
Blanchardstown Corporate Park 2
Dublin 15, D15 T867 Ireland
Swords Laboratories Unlimited Company t/a Bristol-Myers Squibb Cruiserath Biologics Cruiserath Road, Mulhuddart
Dublin 15, D15 H6EF
Ireland
---------------------------------------------------------------------------------------------------------------------------
Preparation should be performed by trained personnel in accordance with good practices rules, especially with respect to asepsis.
More than one vial of OPDIVO concentrate may be needed to give the total dose for the patient. Nivolumab monotherapy:
The prescribed dose for the patient is 240 mg or 480 mg given regardless of body weight depending on
indication.
Nivolumab in combination with ipilimumab:
The prescribed dose for the patient is given in mg/kg. Based on this prescribed dose, calculate the total dose to be given.
The total nivolumab dose in mg = the patient’s weight in kg × the prescribed dose in mg/kg.
The volume of OPDIVO concentrate to prepare the dose (mL) = the total dose in mg, divided by 10 (the OPDIVO concentrate strength is 10 mg/mL).
Nivolumab in combination with ipilimumab in malignant pleural mesothelioma: The prescribed dose for the patient is 360 mg given regardless of body weight.
Nivolumab in combination with ipilimumab in advanced oesophageal cancer:
The prescribed dose for the patient can be based on body weight (3 mg/kg) or is 360 mg given regardless of body weight.
Nivolumab in combination with chemotherapy in advanced oesophageal cancer:
The prescribed dose for the patient is 240 mg or 480 mg given regardless of body weight.
Nivolumab in combination with chemotherapy in gastric, gastro-oesophageal junction or oesophageal adenocarcinoma:
The prescribed dose for the patient is 360 mg or 240 mg given regardless of body weight.
Nivolumab in combination with ipilimumab and chemotherapy:
The prescribed dose for the patient is 360 mg given regardless of body weight.
Nivolumab in combination with cabozantinib:
The prescribed dose for the patient is nivolumab 240 mg or 480 mg given regardless of body weight.
OPDIVO can be used for intravenous administration either:
the final infusion concentration should range between 1 and 10 mg/mL.
the total volume of infusion must not exceed 160 mL. For patients weighing less than 40 kg, the total volume of infusion must not exceed 4 mL per kilogram of patient weight.
OPDIVO concentrate may be diluted with either:
sodium chloride 9 mg/mL (0.9%) solution for injection; or
50 mg/mL (5%) glucose solution for injection.
Inspect the OPDIVO concentrate for particulate matter or discoloration. Do not shake the vial.
OPDIVO concentrate is a clear to opalescent, colourless to pale yellow liquid. Discard the vial if the solution is cloudy, is discoloured, or contains particulate matter other than a few
translucent-to-white particles.
Withdraw the required volume of OPDIVO concentrate using an appropriate sterile syringe.
Transfer the concentrate into a sterile, evacuated glass bottle or intravenous container (PVC or polyolefin).
If applicable, dilute with the required volume of sodium chloride 9 mg/mL (0.9%) solution for
injection or 50 mg/mL (5%) glucose solution for injection. For ease of preparation, the concentrate can be transferred directly into a pre-filled bag containing the appropriate volume of sodium chloride 9 mg/mL (0.9%) solution for injection or 50 mg/mL (5%) glucose solution for injection.
Gently mix the infusion by manual rotation. Do not shake.
OPDIVO infusion must not be administered as an intravenous push or bolus injection.
Administer the OPDIVO infusion intravenously over a period of 30 or 60 minutes depending on the dose.
OPDIVO infusion should not be infused at the same time in the same intravenous line with other agents. Use a separate infusion line for the infusion.
Use an infusion set and an in-line, sterile, non-pyrogenic, low protein binding filter (pore size of 0.2 μm to 1.2 μm).
OPDIVO infusion is compatible with:
PVC containers
Polyolefin containers
Glass bottles
PVC infusion sets
In-line filters with polyethersulfone membranes with pore sizes of 0.2 µm to 1.2 µm.
After administration of the nivolumab dose, flush the line with sodium chloride 9 mg/mL (0.9%) solution for injection or 50 mg/mL (5%) glucose solution for injection.
Unopened vial
OPDIVO must be stored in a refrigerator (2°C to 8°C). The vials must be kept in the original package in order to protect from light. OPDIVO should not be frozen.
The unopened vial can be stored at controlled room temperature up to 25°C with room light for up to
48 hours.
Do not use OPDIVO after the expiry date which is stated on the carton and on the vial label after EXP. The expiry date refers to the last day of that month.
OPDIVO infusion
Chemical and physical in-use stability from the time of preparation has been demonstrated as follows (times are inclusive of the administration period):
Infusion preparation | Chemical and physical in-use stability | |
Storage at 2ºC to 8ºC protected from light | Storage at room temperature (≤ 25°C) and room light | |
Undiluted or diluted with sodium chloride 9 mg/mL (0.9%) solution for injection | 30 days | 24 hours (of total 30 days storage) |
Diluted with 50 mg/mL (5%) glucose solution for injection | 7 days | 8 hours (of total 7 days storage) |
From a microbiological point of view the prepared solution for infusion, regardless of the diluent, should be used immediately. If not used immediately, in-use storage times and conditions prior to use
are the responsibility of the user and would normally not be longer than 7 days at 2°C to 8°C or
8 hours (of the total 7 days of storage) at room temperature (≤ 25°C). Aseptic handling should be ensured during the preparation of infusion.
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.
Taking into account the PRAC Assessment Report on the PSUR(s) for nivolumab, the scientific conclusions of the CHMP are as follows:
The PRAC agreed to update the Summary of Product Characteristics (SmPC) section 4.8 to move the adverse reactions: “lymphopenia, leucopenia, neutropenia, thrombocytopenia and anaemia”, from “Investigations” to “Blood and lymphatic system disorders”, and to move the adverse reactions: “hyperglycaemia, hypoglycaemia and weight decreased”, from “Investigations” to “Metabolism and nutrition disorders”. In addition, to ensure that patients are fully informed of what diabetic ketoacidosis (DKA) is and of the particular signs to be aware of, the risk of DKA and relevant symptoms, should be reflected in the Package Leaflet.
The CHMP agrees with the scientific conclusions made by the PRAC.
On the basis of the scientific conclusions for nivolumab the CHMP is of the opinion that the benefit-risk balance of the medicinal product(s) containing nivolumab is unchanged subject to the proposed changes to the product information.
The CHMP recommends that the terms of the marketing authorisation(s) should be varied.