250 mg powder for concentrate for solution for infusion
belatacept
What NULOJIX is and what it is used for
NULOJIX contains the active substance belatacept, which belongs to a group of medicines called immunosuppressants. It is a drug that reduces the activity of the immune system, the body’s natural defenses.
NULOJIX is used in adults to prevent the immune system from attacking the transplanted kidney and causing a rejection reaction. It is used in combination with other immunosuppressive drugs, including mycophenolic acid and corticosteroids.
What you need to know before using NULOJIX
Do not use NULOJIX
- if you are allergic to belatacept or any of the other ingredients of this medicine (listed in section 6). Allergic reactions related to belatacept treatment have been reported in clinical trials .
- if you have not been exposed to Epstein-Barr virus ( EBV ) or are unsure if you have been exposed, do not treat with NULOJIX. EBV causes glandular fever. If you have not been exposed to it, you are at higher risk of developing a type of cancer called post-transplant lymphoproliferative disease (PTLD). Ask your doctor if you are unsure if you have been infected with the virus before.
Warnings and cautions
Lymphoproliferative disease after transplantation:
Treatment with NULOJIX increases the risk of developing a type of cancer called post-transplant lymphoproliferative disease (PTLD). With NULOJIX treatment, this occurs more often in the brain and can lead to death. People are at higher risk of developing PTLD in the following cases:
- If you have not been exposed to EBV before transplantation
- If you are infected with a virus called cytomegalovirus ( CMV )
- If you have been treated for acute rejection, such as antitymocyte globulin to reduce the number of T cells . T cells are cells that are responsible for your body’s ability to resist diseases and infections . They can cause rejection of your transplanted kidney.
- Ask your doctor if you are unsure about any of these conditions.
Serious infection you
Serious infections can occur with NULOJIX treatment and can lead to death.
NULOJIX weakens the body’s ability to resist infection. Serious infections can include:
- Tuberculosis
- Cytomegalovirus ( CMV ), a virus that can cause serious tissue and blood infections
- Shingles
- Other herpes virus infections.
There have been reports of a rare type of brain infection called progressive multifocal leukoencephalopathy (PML) in patients receiving NULOJIX. PML often leads to severe disability or death.
Tell your family or carer about your treatment. You may have symptoms that you may not be aware of. Your doctor may need to examine your symptoms to rule out PML, PTLD, or other infections. See section 4, Possible side effects, for a list of symptoms.
Skin cancer
Limit your exposure to sunlight and ultraviolet (UV) rays when using NULOJIX. Wear protective clothing and use sunscreen with a high sun protection factor. People who use NULOJIX are at higher risk of getting certain types of cancer, especially skin cancer.
Blood clots in your transplanted kidney
Depending on the type of kidney transplant you have received, you may have a higher risk of getting blood clots in your transplanted kidney.
Use when switching from another type of immunosuppressive maintenance therapy
If healthcare professionals change your maintenance treatment to a NULOJIX-based immunosuppressive treatment, your kidney function may be checked more often for some time after the change. This is done to monitor for signs of rejection.
Use in liver transplants
The use of NULOJIX is not recommended if you have had a liver transplant.
Use with other immunosuppressive drugs
Normally Nulojix is given with steroids. Too rapid a reduction in the dose of one of the steroids can increase the risk of your body rejecting your transplanted kidney. Take exactly the dose of steroid you have been prescribed by your doctor.
Children and young people
NULOJIX has not been studied in children and adolescents under the age of 18 and is therefore not recommended for this age group.
Other medicines and NULOJIX
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.
Ask your doctor or pharmacist for advice before taking any other medicine while you are using NULOJIX.
The use of live vaccines should be avoided during treatment with NULOJIX. Tell your doctor if you need vaccinations. Your doctor will advise you on what to do.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using this medicine.
Tell your doctor if you become pregnant during NULOJIX treatment.
Do not use NULOJIX if you are pregnant unless your doctor specifically recommends it. The effect of NULOJIX in pregnant women is unknown. You must not become pregnant during treatment with NULOJIX. If you are of childbearing potential, you should use effective contraception during treatment with NULOJIX and up to 8 weeks after the last dose of treatment, as the potential risk of developing embryo/fetus is unknown. Your doctor will advise you on reliable contraception.
You must stop breastfeeding if you are being treated with NULOJIX. It is not known if the active substance belatacept is excreted in human milk.
Driving and using machines
Belatacept has a minor influence on the ability to drive and use tools and machines. However, if you get tired or feel unwell after receiving NULOJIX, do not drive or use any tools or machines.
Important information about some of the ingredients of NULOJIX
Tell your doctor if you have been prescribed a low-salt diet (low sodium) before you are treated with NULOJIX.
This medicine contains 0.65 mmol (or 15 mg) sodium per vial, which is equivalent to 1.95 mmol (or 45 mg) sodium per maximum dose of three vials. This corresponds to 2.25% of the maximum recommended daily sodium intake for adults.
How to use NULOJIX
Treatment with NULOJIX is prescribed and monitored by a kidney transplant specialist. NULOJIX will be given to you by healthcare professionals.
It will be given to you by infusion (as a drip) into one of your veins over 30 minutes.
The recommended dose is based on your body weight (in kg) and is calculated by healthcare professionals. Dosage one and the frequency of treatment can be seen below.
| Initial treatment | Dose |
| Transplant day, before implantation (day 1) | 10 mg / kg |
| Day 5, day 14, and day 28 | |
| End of week 8 and week 12 after transplantation | |
| Maintenance treatment | Dose |
| Every 4 weeks (± 3 days) starting at the end of week 16 after transplantation | 5 mg / kg |
In connection with your kidney transplant, you can receive NULOJIX in combination with other types of immunosuppressive drugs, to prevent your immune system from attacking your transplanted kidney.
Your doctor may decide to change your immunosuppressive treatment to treatment with NULOJIX during the maintenance phase after your kidney transplant.
Information for healthcare professionals on dose calculation, preparation, and administration of NULOJIX is provided at the end of this leaflet.
If you use more NULOJIX than you should
Should this occur you will be monitored by a doctor for any signs or symptoms of side effects and if necessary these symptoms will be treated.
If you forget to use NULOJIX
You must appear at all times booked for the administration of NULOJIX. If you miss an opportunity, ask your doctor when you should receive the next dose.
If you stop using NULOJIX
Your body may reject the transplanted kidney if you stop using NULOJIX. The decision to stop using NULOJIX should be discussed with your doctor and usually, other treatments will be started.
If you stop using NULOJIX for a long period, do not take any other medicines to prevent your body from rejecting your transplanted kidney, and then start treatment with NULOJIX again, it is unknown if belatacept has the same effect as before.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
However, NUJOJIX can cause serious side effects that may require treatment.
Tell your family or carer about your treatment, as you may have symptoms that you may not be aware of.
Tell your doctor immediately if you or your family notice any of the symptoms listed below:
Symptoms from the central and peripheral nervous system may include memory problems; language and communication difficulties; change in your mood or behavior; confusion or inability to control your muscles; weakness in one side of the body; visual changes; headache.
Infectious symptoms may include fever; unexplained weight loss; swollen glands; cold symptoms such as the runny nose or sore throat; cough with mucus or blood-mixed mucus; earache; cuts or abrasions that are red, hot, and with warts.
Kidney and urinary tract symptoms may include tenderness at the transplant site; difficulty urinating; changes in the amount of urine you produce (urine production); blood in the urine; pain or burning when urinating (urination).
Symptoms of the gastrointestinal tract may include pain when swallowing; painful cold sores; white spots in the mouth or throat; stomach upset; abdominal pain; vomiting; diarrhea.
Skin changes may include an increased tendency for bruising or bleeding; brown or black skin changes with uneven edges or that one part of the change does not look like the other; a change in the size and color of a birthmark; a new skin change or lump.
Allergic reactions may include, but are not limited to; rash; reddening of the skin; hives; itching; swelling of the lips, tongue, or face; swelling all over the body; chest pain; shortness of breath; rustling/wheezing or dizziness.
Very common side effects ( may affect more than 1 user in 10) are:
- Bladder or kidney infection, upper respiratory tract infection, CMV infection ( may cause severe blood and tissue infections), fever, cough, bronchitis
- Shortness of breath
- Constipation, diarrhea, nausea, vomiting, abdominal pain
- High or low blood pressure
- Headache, difficulty sleeping, nervousness or anxiety, swelling of hands and feet
- Joint pain, back pain, pain in the extremities
- Pain when urinating (urination), blood in the urine
Samples may show:
- Decreased number of blood cells or anemia , decreased number of white blood cells
- Increased amount of creatinine in your blood (a blood test used to measure kidney function), increased amount of protein in urine
- Changes in salt and electrolyte levels in the blood
- Increased cholesterol and triglycerides (blood fats)
- High blood sugar
Common side effects ( may affect up to 1 in 10 people) are:
- Cancer or non-cancerous growth of the skin
- Dangerous reduction in blood pressure , which can lead to collapse, coma and death if left untreated
- Stroke
- Tissue death due to blocked blood flow
- Hepatitis (cytolytic hepatitis )
- Kidney damage
- Fluid in the lungs and wheezing, wheezing when breathing, chest pain or angina, enlarged heart muscle (lower part of the heart)
- Infection of blood or tissue , infection of the respiratory tract, pneumonia , influenza , sinusitis, runny nose, sore throat, pain in the mouth and throat region, herpes virus infection, shingles and other viral infections, cold sores, cold sores, kidney infection, fungal and other fungal infections of the skin, nail fungus , skin infection, soft tissue infection, wound infection, infection limited to a specific area, slow healing, bloody bruising, accumulation of lymph fluid around the transplanted kidney
- High and low heart rate, abnormal and irregular heartbeat, weak heart
- Diabetes
- Dehydration
- Inflammation of the stomach and intestines, often caused by viruses
- Stomach upset
- Unusual feeling of tingling, numbness or weakness in arms and legs
- Rash, itching
- Muscle aches, muscle weakness, pain in bone tissue, swollen joints, abnormal cartilage between the vertebrae of the spine, sudden inability to bend joints, muscle spasms, joint inflammation
- Blockage in the blood vessels in the kidney, enlarged kidney due to blockage in the urine flow from the kidney, backflow of urine from the bladder to the ureter , inability to hold urine, incomplete emptying of the bladder, nocturnal urination, blood in the urine
- Weight gain, weight loss
- Cataracts, blood clots in the eye, blurred vision
- Shaking or trembling, dizziness, fainting or loss of consciousness, earache, wheezing, ringing or other persistent sound in the ears
- Acne, hair loss, abnormal skin changes, heavy sweating, night sweats
- Weakness or loosening of the abdominal muscles and bulging of the skin at the healed scar, hernia of the stomach wall
- Depression, fatigue, tiredness, drowsiness, lack of energy, general malaise, difficulty lying down, nosebleeds
- Typical appearance for a person who has high cortisone levels such as moon face, humpback, obesity on the upper body
- Abnormal fluid retention
Samples may show:
- Low platelet count , too many white blood cells , too many red blood cells
- Changes in the level of carbon dioxide in the blood, retaining fluid, low amount of protein in the blood
- Abnormal liver function tests, elevated blood parathyroid hormone
- Increased protein (C-reactive protein ) in the blood which indicates inflammation
- Decreased number of antibodies ( proteins that fight infections ) in the blood
Uncommon side effects ( may affect up to 1 in 100 people) are:
- Lung cancer, rectal cancer, breast cancer, cancer of bone tissue, muscle or fat tissue, tumor of the skin or intestines caused by a herpes virus and seen in patients with a weakened immune system, prostate cancer, cervical cancer, throat cancer, lymph node cancer, bone marrow cancer, kidney cancer , ureter or bladder.
- Fungal infection of the brain, encephalitis, severe brain infection called PML ( progressive multifocal leukoencephalopathy)
- Abnormal swelling of the brain, increased pressure in the skull and brain, cramps, weakness that causes loss of movement in one half of the body, loss of tissue surrounding nerves, inability to move the facial muscles
- Brain disease that causes headache, fever, hallucinations, confusion, abnormal speech or abnormal body movements
- Weak blood flow to the heart, extra beats, changes in the aortic valve, abnormally high heart rate
- Sudden problems with breathing that cause damage to the lungs, increased blood pressure in the lungs, pneumonia , coughing up blood, changes in the ability to transport air in the lungs and airways, fluid around the alveoli, respiratory arrest during sleep, changes in the voice
- Genital herpes
- Inflammation of the colon caused by cytomegalovirus , pancreatitis, gastric ulcer , ulcer of the small or large intestine, blockage of the small intestine, black tar-like stool, bleeding in the rectum, abnormal color of the stool
- Bacterial infection , inflammation or infection of the inner part of the heart, tuberculosis , infection of bone tissue, inflammation of the lymph nodes, chronic dilation of the airways in the lungs with frequent lung infections
- Infection is with strongyloidasis mask, diarrhea infection with giardia parasite
- Kidney disease caused by virus (polyomavirus-associated nephropathy ), kidney inflammation, scar tissue in the kidney, shrinkage of the small kidney tubes, inflammation of the bladder with bleeding
- Blood clots in the renal artery
- Guillain-Barré syndrome (a condition that causes muscle weakness or paralysis)
- EBV ( Epstein-Barr virus ) lymphoproliferative disease
- Blood clots in veins, inflamed veins, regular cramps in the legs
- Altered arteries , scarring of the arteries , blood clots in the arteries , narrowing of the arteries , temporary flushing / swollen face
- Gallstones , fluid-filled pockets in the liver, fatty liver
- Skin disease with red spots of thickened skin, often scaly, abnormal hair growth, brittle hair, brittle nails, ulcers on the penis
- Abnormal balance of minerals in the body leading to bone problems, bone inflammation, abnormal weakening of bones leading to bone problems, inflammation of joints, unusual diseases of bone tissue
- Testicular inflammation, abnormally prolonged penis erection, abnormal cervical cells, changes in the breasts, testicular pain, wounds in female genitals, weakened vaginal wall, infertility or inability to conceive, swelling of the scrotum
- Seasonal asthma
- Poor appetite, lost sense of taste, impaired hearing
- Abnormal dreams, mood swings, abnormal inability to focus and sit still, difficulty understanding or thinking, poor memory, migraine , irritability
- Numbness or weakness due to poorly controlled diabetes , changes in the foot due to diabetes , difficulty in keeping the legs still
- Swelling of the back of the eye which leads to changes in vision, eye inflammation, troublesome / increased sensitivity to light, swollen eyelids
- Cracked mouth pores, swollen gums, pain in salivary glands
- Increased sex drive
- Burning sensation
- Infusion reaction wound tissue, inflammation , recurrence of disease, feeling hot, wounds
- Decreased urine production
- Insufficient function of the transplanted kidney, problems during or after a transfusion , separation of wound edges, broken bones, total rupture or separation of tendons, low and / or high blood pressure during or after a procedure, bruising / accumulation of blood in soft parts after a procedure , pain and / or headache related to a procedure, bruising in soft tissues
Samples may show:
- Dangerously low red blood cell count , dangerously low white blood cell count , red blood cell degradation , blood clotting problems, acidity in the blood due to diabetes , lack of acid in the blood
- Altered production of hormones in the adrenal gland
- Low vitamin D levels
- Increased levels of pancreatic enzymes in the blood, increased troponin levels in the blood, increased amount of prostate -specific antigen (PSA), high levels of uric acid in the blood, decreased number of CD4 lymphocytes , low blood sugar
How to store NULOJIX
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 vial and carton after EXP. The expiration date is the last day of the specified month.
This medicine is stored in a healthcare facility where it is administered.
Store in a refrigerator (2 ° C – 8 ° C).
Store in the original package. Sensitive to light.
After reconstitution, the solution should be transferred immediately from the vial to the infusion bag or vial.
After dilution and from a microbiological point of view, the drug should be used immediately. If not used immediately, the infusion solution can be stored in a refrigerator (2 ° C – 8 ° C) for up to 24 hours. The infusion solution can be stored below 25 o C for a maximum of 4 hours out of a total of 24 hours. Do not freeze.
Infusion one of NULOJIX ends within 24 hours after reconstitution of the powder.
Do not use NULOJIX if you notice any particles or discoloration in the reconstituted or diluted solution.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
Contents of the package and other information
Content declaration
What NULOJIX contains
- The active substance is belatacept. Each vial contains 250 mg belatacept. After reconstitution , each ml of concentrate contains 25 mg of belatacept.
- The other ingredients are sodium chloride, sodium dihydrogen phosphate monohydrate, sucrose, sodium hydroxide (for pH control) and hydrochloric acid (for pH control). (See section 2.)
What the medicine looks like and contents of the pack
NULOJIX powder for concentrate for solution for infusion (powder for concentrate) is a white to off-white powder that appears in the form of a cake or is broken up into pieces.
Each vial contains 250 mg belatacept.
Packs of either 1 vial and 1 syringe or 2 vials and 2 syringes.
Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorisation Holder:
Bristol-Myers Squibb Pharma EEIG
Plaza 254
Blanchardstown Corporate Park 2
Dublin 15, D15 T867
Ireland
Manufacturer:
Swords Laboratories T / A Bristol-Myers Squibb Cruiserath Biologics
Cruiserath Road, Mulhuddart
Dublin 15, D15 H6EF
Ireland