Label:information for the user

NULOJIX 250mg powder for concentrate for solution for infusion

belatacept

Read this label carefully before starting to use the medicine, because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this label. See section 4.

1.What NULOJIX is and for what it is used

2.What you need to know before starting to use NULOJIX

3.How to use NULOJIX

4.Possible adverse effects

5.Storage of NULOJIX

6.Contents of the package and additional information

NULOJIX contains the active ingredient belatacept, which belongs to a group of medicines called immunosuppressants. These are medicines that reduce the activity of the immune system, the body's natural defenses.

NULOJIX is used in adults to prevent the immune system from attacking their transplanted kidney and causing transplant rejection. It is used with other immunosuppressant medicines, such as mycophenolic acid and corticosteroids.

Do not use NULOJIX

• If you are allergicto belatacept or to any of the other ingredients of this medicine (listed in section 6). Cases of allergic reactions associated with the use of belatacept have been reported in clinical trials.
• If you have not been exposed to the Epstein-Barr virus(EBV) or are unsure if you have been exposed, you should not receive treatment with NULOJIX. EBV is the virus that causes infectious mononucleosis. If you have never been exposed to this virus, your risk of developing a cancer called post-transplant lymphoproliferative disorder (PTLD) is higher. If you are unsure if you have been infected with the virus before, consult your doctor.

Warnings and precautions

Post-transplant lymphoproliferative disorder

The treatment with NULOJIX increases the risk of developing a cancer called post-transplant lymphoproliferative disorder (PTLD). With NULOJIX, this cancer develops more frequently in the brain and can be fatal. The risk of developing a PTLD is higher in the following cases:

• If you have not been exposed to EBV before your transplant
• If you have an infection with a virus called cytomegalovirus (CMV)
• If you have received treatment for acute rejection, for example, antithymocyte globulin to reduce T lymphocytes.T lymphocytes are responsible for maintaining the body's ability to resist diseases and infections. They can cause rejection of the transplanted kidney.
• If you are unsure about any of these situations, consult your doctor.

Severe infections

During treatment with NULOJIX, you may contract severe infections that can be fatal.

NULOJIX weakens the body's ability to fight infections.Severe infections can be

• Tuberculosis
• Cytomegalovirus (CMV), a virus that can cause severe infections in the blood and tissues
• Herpes zoster
• Other herpes virus infections.

Cases of a rare type of brain infection called progressive multifocal leukoencephalopathy (PML) have been reported in patients who received NULOJIX. PML often causes severe disability or death.

Inform your family or caregiver about your treatment.You may experience symptoms that you are not aware of. Your doctor may need to study your symptoms to rule out PML, PTLD, or other infections. For a list of symptoms, see section 4 "Possible side effects".

Skin cancer

Limit your exposure to sunlight and ultraviolet (UV) light while using NULOJIX. Wear protective clothing and use high-protection sunscreen. People receiving treatment with NULOJIX have a higher risk of contracting certain types of cancer, especially skin cancer.

Blood clots in the transplanted kidney

Depending on the type of kidney transplant you received, you may have a higher risk of having blood clots in your transplanted kidney.

Use in conversion from another type of immunosuppressive treatment

If your doctor changes your maintenance treatment to an immunosuppressive treatment with NULOJIX, they will monitor your kidney function more frequently for a period of time after the change, to monitor rejection.

Use in liver transplants

NULOJIX is not recommended for use in liver transplants.

Use with other immunosuppressive medications

NULOJIX is usually administered with steroids. A too rapid reduction in steroid intake may increase the risk of your body rejecting the transplanted kidney. Please take the exact dose of steroid established by your doctor.

Children and adolescents

NULOJIX has not been studied in children or adolescents under 18 years of age, therefore, it is not recommended for this age group.

Use of NULOJIX with other medications

Inform your doctor or pharmacist if you are using or have recently used other medications, including those purchased without a prescription.

While using NULOJIX, consult your doctor or pharmacist before using any medication.

Live vaccines should be avoided while using NULOJIX. If you need a vaccine, inform your doctor. Your doctor will advise you on what to do.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medicine.

If you become pregnant while using NULOJIX, inform your doctor.

Do not use NULOJIX if you are pregnant unless your doctor recommends it explicitly. The effects of NULOJIX on pregnant women are unknown. You should not become pregnant while using NULOJIX. If you are a fertile woman, you should use a reliable contraceptive during treatment with NULOJIX and for 8 weeks after the last dose of treatment, as the possible risk to the developing embryo or fetus is unknown. Your doctor will advise you on the use of a reliable contraceptive.

You should stop breastfeeding if you are receiving treatment with NULOJIX. The active ingredient, belatacept, is unknown to pass into human milk.

Driving and operating machinery

Belatacept has a small effect on the ability to drive and use machines. However, you should not drive or use machines if you feel tired or unwell after treatment with NULOJIX.

NULOJIX contains sodium

Inform your doctor if you are on a low-sodium diet before being treated with NULOJIX.

This medicine contains 0.55mmol (or 13mg) of sodium per vial. This is equivalent to 0.64% of the maximum daily recommended intake for an adult.

The treatment with NULOJIX will be prescribed and monitored by a kidney transplant specialist.

NULOJIX will be administered by a healthcare professional.

It will be administered through infusion (as a "drip") in a vein for approximately 30 minutes.

The recommended dose is based on body weight (in kg) and will be calculated by a healthcare professional. The following shows the dose and administration frequency.

NULOJIX may be administered at the time of renal transplant in combination with other types of immunosuppressive treatments to help prevent your body from rejecting the transplanted kidney.

Your doctor may decide to change your immunosuppressive treatment to NULOJIX treatment during the maintenance phase after your renal transplant.

Information for the doctor and healthcare professionals on calculating doses, preparing, and administering NULOJIX is provided at the end of this prospectus.

If you are given more NULOJIX than you should

If this happens, your doctor will monitor you for any signs or symptoms of side effects and treat these symptoms if necessary.

If you forget to take NULOJIX

It is very important that you respect all appointments for NULOJIX treatment. If you forget to receive NULOJIX when due, ask your doctor to schedule your next dose.

If you interrupt NULOJIX treatment

If you interrupt NULOJIX treatment, your body may reject the transplanted kidney. The decision to interrupt NULOJIX treatment should be discussed with your doctor, who will usually initiate another treatment.

If you interrupt NULOJIX treatment for a long period of time without taking any other medication to prevent rejection, and then restart it, it is unknown whether belatacept will have the same effect as before.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. However, NULOJIX may cause serious side effects that may require treatment.

Inform your doctor or caregiver about your treatment, as you may be experiencing symptoms of which you may not be aware.

Inform your doctor immediately if you or your family notice any of the following symptoms:

Neurological symptomsmay include loss of memory; difficulties with speech and communication; mood or behavior changes; confusion or inability to control muscles; weakness on one side of the body; changes in vision; or headache.

Infection symptomsmay include fever; unexplained weight loss; swollen lymph nodes; symptoms of a cold such as runny nose or sore throat; cough with mucus; blood in mucus; ear pain; cuts or scratches with red color; heat and pus discharge.

Renal or urinary symptomsmay include discomfort in the transplanted kidney area; difficulty urinating; changes in urine production; blood in urine; pain or burning while urinating.

Gastrointestinal symptomsmay include pain while swallowing; painful sores in the mouth; white patches in the mouth or throat; stomach discomfort; stomach pain; vomiting; or diarrhea.

Skin changesmay include hematoma or unexpected bleeding; skin injury with brown or black color and irregular edges, or a part of the injury that does not resemble the other; change in size and color of a mole; or a new skin injury or a new injury or bruise on the skin.

Allergic reactionsmay include, but are not limited to, rash; skin redness; urticaria; itching; lip swelling; tongue swelling; face swelling; whole body swelling; chest pain; difficulty breathing; whistling; or dizziness.

Very common side effects(may affect more than 1 in 10 people)are:

• Cystitis or renal infection, upper respiratory tract infection, CMV infection (may cause severe blood and tissue infections), fever, cough, bronchitis
• Difficulty breathing
• Constipation, diarrhea, nausea, vomiting, abdominal pain
• High blood pressure, low blood pressure
• Headache, difficulty falling asleep, feeling of nervousness or anxiety, swollen hands and feet
• Pain in joints, back, or limbs
• Pain while urinating, blood in urine

Analyses may reveal:

• Decreased red blood cell count or anemia, decreased white blood cell count
• Increased creatinine levels in blood (blood test to measure kidney function), increased protein levels in urine
• Changes in blood levels of different salts and electrolytes
• Increased levels of cholesterol and triglycerides (fats in blood)
• High blood sugar levels

Common side effects(may affect up to 1 in 10 people)are:

• Skin cancer and non-cancerous skin lesions
• Potentially life-threatening low blood pressure that, if not treated, may cause collapse, coma, or death
• Stroke
• Tissue necrosis due to lack of blood supply
• Liver inflammation (hepatitis citolítica)
• Kidney damage
• Pulmonary edema, wheezing sounds during breathing (sibilancias), chest pain or angina, increased heart size (lower part of the heart)
• Blood or tissue infections, respiratory infections, pneumonia, flu, sinusitis, runny nose, sore throat, pain in the mouth and throat area, viral infections, herpes, and other viral infections, mouth sores, ulcers, kidney infection, fungal skin infections, fungal nail infections, and other fungal infections, skin infection, soft tissue infection, wound infection, localized infection, slow healing, hematoma with bleeding, accumulation of lymphatic fluid around the transplanted kidney
• Fast or slow heart rate, abnormal heart rhythm, weak heart
• Diabetes
• Dehydration
• Stomach and intestine inflammation, usually caused by a virus
• Abdominal discomfort
• Strange sensation of tingling, numbness, or weakness in arms and legs
• Rash, itching
• Muscle pain, muscle weakness, bone pain, joint inflammation, abnormal cartilage between spine bones, sudden inability to bend joints, muscle spasms, arthritis
• Renal vessel obstruction, kidney enlargement due to urine blockage, urine reflux from bladder to renal tubes, inability to retain urine, incomplete bladder emptying, nocturia, glucose in urine
• Weight gain, weight loss
• Cataracts, increased blood congestion in the eye, blurry vision
• Trembling or shakiness, dizziness, fainting or passing out, ear pain, buzzing, or other persistent sounds in the ears
• Acne, hair loss, abnormal skin changes, excessive sweating, nocturnal sweating
• Abdominal muscle weakness or hernia, hernia in the stomach wall
• Depression, fatigue, feeling of tiredness, somnolence, or lack of energy, general feeling of discomfort, difficulty breathing while lying down, nasal bleeding
• Typical appearance of a person with high steroid levels, such as moon face, curved back, upper body obesity
• Abnormal fluid retention
• Analyses may reveal:
• Low platelet count in blood and excess white blood cells and red blood cells
• Changes in blood levels of carbon dioxide, fluid retention, low protein levels in blood
• Abnormal liver function tests, increased parathyroid hormone levels in blood
• Increased C-reactive protein in blood, indicating inflammation
• Decreased antibodies (proteins that fight infections) in blood

Uncommon side effects(may affect up to 1 in 100 people)are:

• Lung cancer, rectal cancer, breast cancer, a type of bone, muscle, or fatty tissue cancer, skin and intestinal tract tumors caused by herpes virus and in patients with weakened immune systems, prostate cancer, cervical cancer, throat cancer, lymph node cancer, bone marrow cancer, kidney cancer, renal tube or bladder cancer
• Cerebral fungal infection, abnormal brain inflammation, severe brain inflammation called LMP (leucoencefalopatía multifocal progresiva)
• Abnormal brain inflammation, increased intracranial and cerebral pressure, seizures, weakness causing loss of movement or one side of the body, nerve covering loss, inability to move facial muscles
• Any brain disease that causes headache, fever, hallucinations, confusion, speech and movement alterations
• Poor blood circulation to the heart, heart blockage, abnormal aortic valve, abnormal heart rhythm
• Acute respiratory problems causing lung damage, increased pulmonary artery pressure, lung inflammation, cough with blood, abnormal lung and airway abnormalities, fluid in the sac surrounding the lungs, temporary breathing stoppage during sleep, abnormal speech sound
• Genital herpes
• Colitis inflammation caused by cytomegalovirus, pancreatitis, stomach, small intestine, or large intestine ulcers, small intestine obstruction, black tar-like stool, rectal bleeding, abnormal stool color
• Bacterial infections, heart inner layer inflammation or infection, tuberculosis, bone infection, lymph node inflammation, chronic airway dilation with frequent respiratory infections
• Strongyloides worm infection, Giardia diarrhea infections
• Viral kidney disease (nephropatía asociada a poliomavirus), kidney inflammation, kidney scarring, small renal tube retraction, bladder inflammation with hemorrhage
• Renal artery blood clot
• Guillain-Barré syndrome (a disease that causes muscle weakness or paralysis)
• Epstein-Barr virus lymphoproliferative disease
• Vein blood clot, inflamed veins, periodic leg cramps
• Abnormal arteries, artery scarring, artery blood clot, artery narrowing, temporary facial or skin redness, facial swelling
• Gallstones, liver cavity filled with fluid, fatty liver
• Skin disease with thickened skin patches of red color, often with silver scales, abnormal hair growth, excessive hair breakage, nail breakage, genital area ulcers
• Abnormal mineral balance in the body causing bone problems, bone inflammation, abnormal bone weakening causing bone problems, joint capsule inflammation, rare bone disease
• Testicle inflammation, prolonged penile erection, abnormal cervical cell changes, breast lump, testicle pain, vaginal area ulcers, vaginal wall thinning, infertility or inability to become pregnant, scrotum swelling
• Seasonal allergy
• Loss of appetite, taste loss, hearing loss
• Abnormal dreams, mood changes, inability to concentrate or stay still, difficulty understanding or thinking, memory loss, migraine, irritability
• Tingling or weakness due to uncontrolled diabetes, inability to keep legs still
• Posterior eye swelling causing vision changes, inflamed eye, uncomfortable light sensitivity, swollen eyelids
• Cracks in the mouth corner, inflamed gums, gum pain
• Increased libido
• Burning sensation
• Perfusion reaction, scar tissue, inflammation, disease recurrence, heat sensation, ulcer
• Inadequate urine production
• Organ transplant failure, problems during or after a transfusion, wound edge separation before healing, bone fracture, tendon complete or partial separation, low blood pressure during or after a procedure, high blood pressure during or after a procedure, hematomas or blood accumulation in soft tissues after a procedure, procedure-related pain, procedure-related headache, soft tissue contusion
• Analyses may reveal:
• Excessively low red blood cell count, excessively low white blood cell count, red blood cell destruction, blood coagulation problems, diabetic acidosis, lack of acids in blood
• Inadequate hormone production by adrenal glands
• Low vitamin D levels
• Increased pancreatic enzyme levels in blood, increased troponin levels in blood, increased prostate-specific antigen (PSA) levels, high uric acid levels in blood, decreased CD-4 lymphocyte count, low blood sugar levels

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the vial label and on the box after CAD. The expiration date is the last day of the month indicated.

This medication will be stored at the facility where the healthcare professional administers it.

Store in refrigerator (between 2°C-8°C).

Store in the original packaging to protect it from light.

After reconstitution, the reconstituted solution must be transferred immediately from the vial to the bag or infusion container.

After dilution, and from a microbiological point of view, the product must be used immediately. If not used immediately, the infusion solution must be stored in the refrigerator (2°C-8°C) for a maximum of 24hours. The infusion solution can be stored for a maximum of 4hours out of the total 24hours below 25°C. Do not freeze.

NULOJIX infusion must be performed within 24 hours following reconstitution of the powder.

Do not use NULOJIX if you observe particles or color changes in the reconstituted or diluted solution.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications you no longer need. This will help protect the environment.

Composition of NULOJIX

• The active ingredient is belatacept. Each vial contains 250mg of belatacept. After reconstitution, eachml of concentrate contains 25mg of belatacept.
• The other components are sodium chloride, sodium dihydrogen phosphate monohydrate, sucrose, sodium hydroxide (to adjust the pH) and hydrochloric acid (to adjust the pH). (See section 2)

Appearance of the product and contents of the pack

NULOJIX powder for concentrate for solution for infusion (powder for concentrate) is a white to off-white powder that may be presented in a compact or fragmented form.

Each vial contains 250mg of belatacept.

Packaging of 1 vial of glass and 1 syringe or 2 vials of glass and 2 syringes.

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer responsible

Marketing authorization holder:

Bristol‑Myers Squibb Pharma EEIG
254 Plaza
Blanchardstown Corporate Park 2
Dublin 15, D15 T867
Ireland

Manufacturer responsible:

Swords Laboratories Unlimited Company T/A Bristol-Myers Squibb Cruiserath Biologics
Cruiserath Road, Mulhuddart
Dublin 15, D15 H6EF
Ireland

Last review date of this leaflet

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

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This information is intended solely for healthcare professionals:

• Aseptic technique will be used for the reconstitution of vials and for diluting the infusion solution.
• A disposable syringe without silicone provided will be used to reconstitute the vials and add the infusion solution to the infusion. This will prevent the formation of particles.
• Do not agitate the vials. This will prevent the formation of foam.
• The infusion solution must be used with a sterile, apyrogenic, low-protein binding filter (pore size 0.2µm to 1.2µm).

Dose selection and vial reconstitution

Calculate the dose and the number of vials of NULOJIX needed. Each vial of NULOJIX provides 250mg of belatacept.

• The total dose of belatacept inmg is equal to the patient's weight inkg multiplied by the belatacept dose inmg/kg (6 or 10mg/kg, see section 3).
• Do not recommend modifying the NULOJIX dose for a weight variation of less than 10%.
• The number of vials needed is equal to the belatacept dose inmg divided by 250, rounded to the nearest whole number of vials.
• Reconstitute each vial with 10.5ml of solution.
• The required volume of the reconstituted solution (ml) is equal to the total dose of belatacept inmg divided by 25.

Practical details for reconstituting vials

Under aseptic conditions, reconstitute each vial with 10.5ml of one of the following solvents (sterile water for injection, sodium chloride 9mg/ml (0.9%) solution for injection or 5% glucose solution for injection), using the disposable syringe provided (necessary to prevent particle formation) and a 18-21 gauge needle. The syringes are marked in units of 0.5ml; therefore, the calculated dose must be rounded to the nearest 0.5ml.

Remove the flip-off(flip-off)cap from the vial and clean the top with a moistened cotton swab. Insert the needle of the syringe into the vial through the center of the rubber stopper. Direct the liquid flow to the glass walls of the vial and not to the powder. Remove the syringe and needle after adding 10.5ml of reconstitution liquid to the vial.

To minimize foam formation, gently turn and invert the vial for at least 30 seconds until the powder is completely dissolved. Do not agitate. Although some foam may remain on the surface of the reconstituted solution, each vial includes a sufficient excess of belatacept to consider possible losses. Therefore, 10ml of a 25mg/ml belatacept solution can be withdrawn from each vial.

The reconstituted solution must be transparent to slightly opaque and colorless to pale yellow. Do not use if opaque particles, color changes, or other foreign particles are observed. It is recommended to transfer the reconstituted solution immediately from the vial to the infusion bag or bottle.

Practical details for preparing the infusion solution

After reconstitution, dilute the product to 100ml with sodium chloride 9mg/ml (0.9%) solution for injection or 5% glucose solution for injection. Withdraw from an infusion bag or bottle of 100ml (usually a volume of infusion of 100ml will be suitable for most patients and doses, although a volume of infusion of 50ml to 250ml may be used) a volume of sodium chloride 9mg/ml (0.9%) solution for injection or 5% glucose solution for injection equal to the volume of the NULOJIX reconstituted solution (ml equal to the total dose inmg divided by 25) needed to provide the dose and discard the remainder. Slowly add the required amount of NULOJIX reconstituted solution from the vial to the infusion bag or bottle using the same disposable syringe used for reconstituting the powder. Mix the infusion container carefully. The final concentration of belatacept in the infusion should be 2mg to 10mg of belatacept perml of solution.

Any unused portion of the vials must be disposed of in accordance with local regulations.

Administration

When reconstitution and dilution are performed under aseptic conditions, the NULOJIX infusion must be initiated immediately or must be completed within 24hours after reconstitution of the powder. If not used immediately, the infusion solution must be stored in the refrigerator (2°C-8°C) for a maximum of 24hours. Do not freeze. The infusion solution may be stored for a maximum of 4hours below 25°C. The infusion must be performed within 24hours after reconstitution of the powder. Before administration, the infusion solution must be visually inspected for the presence of particles or color changes. If particles or color changes are observed, the infusion must be discarded. The completely diluted solution must be administered in 30minutes using an infusion device and a sterile, apyrogenic, low-protein binding filter (pore size 0.2μm to 1.2μm). After administration, it is recommended to clarify the intravenous route with infusion solution to ensure the administration of the entire dose.

NULOJIX must not be administered concomitantly in the same intravenous route as other medications. No compatibility studies of physical or biochemical compatibility have been performed to evaluate the coadministration of NULOJIX with other medications.

Do not store the unused portion of the infusion solution for reuse.

Elimination

The elimination of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.