NULOJIX (Belatacept)
Selective Immunosuppressant for Kidney Transplant Rejection Prevention
Quick Facts About NULOJIX
Key Takeaways About NULOJIX
- Prevents kidney transplant rejection: NULOJIX is a selective T-cell costimulation blocker that prevents the immune system from attacking a transplanted kidney, used in combination with mycophenolic acid and corticosteroids
- EBV status must be confirmed positive: Treatment must not be started in patients who have not been exposed to Epstein-Barr virus (EBV) due to significantly increased risk of post-transplant lymphoproliferative disorder (PTLD)
- Administered as IV infusion: Given over 30 minutes by healthcare professionals in a clinical setting – not a medication you take at home
- Serious infection risk: NULOJIX weakens the immune system and can increase susceptibility to serious infections, including tuberculosis, CMV infections, and progressive multifocal leukoencephalopathy (PML)
- Avoid live vaccines: Live vaccines must not be given during treatment; inform your transplant team before receiving any vaccinations
What Is NULOJIX and What Is It Used For?
NULOJIX (belatacept) is a selective immunosuppressant that prevents kidney transplant rejection by blocking T-cell activation. It is used in adult kidney transplant recipients in combination with other immunosuppressive medications, including mycophenolic acid and corticosteroids.
NULOJIX contains the active substance belatacept, which belongs to a group of medicines known as selective immunosuppressants. These are medications that reduce the activity of the immune system – the body's natural defence mechanism. In the context of organ transplantation, suppressing the immune system is essential because the body would otherwise recognise the transplanted kidney as foreign tissue and mount an immune response to destroy it, a process known as transplant rejection.
Belatacept works through a highly targeted mechanism of action. It is a fusion protein that binds to two specific molecules called CD80 and CD86 on the surface of antigen-presenting cells (APCs). Under normal circumstances, these molecules interact with a receptor called CD28 on T lymphocytes (T cells), providing a critical "second signal" that is required for full T-cell activation. By blocking this costimulatory pathway, belatacept effectively prevents T cells from becoming fully activated and mounting an immune attack against the transplanted kidney.
This mechanism distinguishes NULOJIX from calcineurin inhibitors (such as ciclosporin and tacrolimus), which are the traditional cornerstone of immunosuppressive regimens in transplant medicine. While calcineurin inhibitors are effective at preventing rejection, they are associated with significant long-term nephrotoxicity – meaning they can damage the very organ they are intended to protect. Clinical trials, notably the BENEFIT and BENEFIT-EXT studies, have demonstrated that belatacept-based regimens can provide superior long-term kidney function (as measured by glomerular filtration rate) compared to ciclosporin-based regimens, while maintaining similar rates of patient and graft survival.
NULOJIX is used exclusively in adults who have undergone kidney transplantation. It is not approved for use in other types of organ transplants (such as liver or heart transplants) and should not be used in these settings. The medication is always used as part of a multi-drug immunosuppressive regimen, never as monotherapy.
NULOJIX was approved by the European Medicines Agency (EMA) in 2011 and by the US Food and Drug Administration (FDA) in the same year. It represents the first selective T-cell costimulation blocker approved for use in kidney transplantation and is manufactured by Bristol-Myers Squibb at their biologics facility in Dublin, Ireland.
What Should You Know Before Taking NULOJIX?
Before starting NULOJIX, your EBV serostatus must be confirmed positive. The medication is contraindicated in EBV-seronegative or unknown-status patients due to the high risk of PTLD. Inform your transplant team about all medical conditions, infections, and medications.
Contraindications
You must not receive NULOJIX if any of the following apply:
- Allergy to belatacept or any excipients – allergic reactions have been reported in clinical trials, including serious hypersensitivity reactions
- Unknown or negative Epstein-Barr virus (EBV) serostatus – this is the most critical contraindication. Patients who have not been previously exposed to EBV are at substantially higher risk of developing post-transplant lymphoproliferative disorder (PTLD), a potentially fatal type of lymphoma. Your doctor must confirm your EBV status before treatment can begin
Post-transplant lymphoproliferative disorder (PTLD) is a type of cancer that occurs more frequently with NULOJIX treatment. PTLD associated with NULOJIX more often involves the central nervous system (brain) and can be fatal. The risk is highest in patients who are EBV-seronegative. NULOJIX must never be used in patients with unknown or negative EBV serostatus.
Warnings and Precautions
Talk to your transplant team before receiving NULOJIX if any of the following apply. You may be at increased risk of serious adverse effects:
- Cytomegalovirus (CMV) infection – patients with active or recent CMV infection have a higher risk of PTLD
- Previous treatment with anti-thymocyte globulin (ATG) – this T-cell depleting therapy used to treat acute rejection episodes increases the risk of PTLD when combined with NULOJIX
- History of serious infections – including tuberculosis, fungal infections, or viral infections. NULOJIX weakens the immune system and can make existing infections worse or allow new infections to develop
- Liver transplant recipients – NULOJIX is not recommended for use in liver transplantation
- Corticosteroid tapering – when NULOJIX is given with steroids, excessively rapid reduction of steroid dose may increase the risk of acute kidney rejection
Serious infections: Because NULOJIX suppresses the immune system, it increases the risk of serious and potentially life-threatening infections. These include:
- Tuberculosis (TB) – screening for latent TB is recommended before starting treatment
- CMV disease – a virus that can cause serious tissue and blood infections in immunosuppressed patients
- Herpes zoster (shingles) and other herpesvirus infections
- Progressive multifocal leukoencephalopathy (PML) – a rare but very serious brain infection caused by the JC virus that can lead to severe disability or death. Symptoms may include memory problems, confusion, difficulty with speech or coordination, vision changes, and weakness on one side of the body
Skin cancer risk: Patients taking NULOJIX should limit exposure to sunlight and ultraviolet (UV) radiation. Wear protective clothing and use high-SPF sunscreen. Immunosuppressed transplant patients have a higher risk of developing skin cancers, including squamous cell carcinoma and melanoma.
Blood clots: Depending on the type of kidney transplant you received, you may be at increased risk of blood clots forming in the transplanted kidney.
It is important to inform your family or caregivers about your treatment with NULOJIX. Some symptoms of serious complications – particularly neurological symptoms of PML or PTLD – may not be immediately apparent to the patient themselves. Your doctor may need to perform specific tests to rule out these conditions.
Pregnancy and Breastfeeding
NULOJIX should not be used during pregnancy unless clearly necessary and recommended by your doctor. The effects of belatacept on the developing foetus are not known. Women of childbearing potential must use effective contraception during treatment and for up to 8 weeks after the last dose of NULOJIX.
Breastfeeding must be discontinued during treatment with NULOJIX. It is not known whether belatacept is excreted in human breast milk, and a risk to the nursing infant cannot be excluded.
Use in Children and Adolescents
NULOJIX has not been studied in children and adolescents under 18 years of age and is therefore not recommended for this age group. There is insufficient data on safety and efficacy in paediatric kidney transplant recipients.
Driving and Using Machines
Belatacept has a minor influence on the ability to drive and use machines. If you feel tired or unwell after receiving NULOJIX, you should not drive or operate machinery until you feel better.
Sodium Content
NULOJIX contains 0.55 mmol (13 mg) of sodium per vial, which is equivalent to 0.64% of the WHO-recommended maximum daily intake of 2 g sodium for adults. This should be taken into consideration if you are on a controlled sodium diet.
How Does NULOJIX Interact with Other Drugs?
NULOJIX is always used with other immunosuppressive medications (mycophenolic acid and corticosteroids). Live vaccines must be avoided. Inform your transplant team about all medications, including over-the-counter products and herbal supplements.
Belatacept is a biological protein and is not metabolised by the cytochrome P450 enzyme system, which means it has fewer direct drug-drug interactions compared to many traditional immunosuppressive agents. However, because it profoundly affects immune function, certain interactions and precautions are clinically significant.
Co-administered Immunosuppressants
NULOJIX is designed to be used as part of a multi-drug immunosuppressive regimen. It is typically co-administered with:
- Mycophenolic acid (mycophenolate mofetil or mycophenolate sodium) – an antiproliferative immunosuppressant that inhibits lymphocyte proliferation
- Corticosteroids – such as prednisolone or methylprednisolone. Important: do not reduce your steroid dose faster than your transplant team recommends, as this may increase the risk of rejection
Vaccines
The use of live vaccines must be avoided during treatment with NULOJIX. The immunosuppressive effects of belatacept can increase the risk of infection from live vaccine strains. Examples of live vaccines include measles-mumps-rubella (MMR), varicella, live influenza (nasal spray), oral polio, rotavirus, yellow fever, and BCG.
Inactivated vaccines may be administered, but their effectiveness may be reduced due to the immunosuppressive effects of the treatment. Your transplant team will advise you on which vaccinations are safe and appropriate.
| Drug / Category | Interaction Type | Clinical Significance |
|---|---|---|
| Live vaccines (MMR, varicella, BCG, yellow fever) | Contraindicated | Risk of infection from live vaccine strains; must be avoided during treatment |
| Anti-thymocyte globulin (ATG) | Increased PTLD risk | T-cell depletion combined with costimulation blockade increases risk of PTLD significantly |
| Mycophenolic acid | Therapeutic combination | Part of standard regimen; belatacept may increase mycophenolic acid exposure by approximately 40% |
| Corticosteroids | Therapeutic combination | Essential part of regimen; avoid rapid taper to prevent rejection risk |
| Other immunosuppressants | Additive immunosuppression | Combining with additional immunosuppressants may excessively suppress immune function |
Always tell your transplant team, doctor, or pharmacist about all medications you are taking, including prescription drugs, over-the-counter medicines, vitamins, and herbal supplements. Even if a specific interaction with belatacept is unlikely, other components of your immunosuppressive regimen may be affected.
What Is the Correct Dosage of NULOJIX?
NULOJIX is given as a 30-minute intravenous infusion by a healthcare professional. The dose is calculated based on body weight. During the initial phase (first 12 weeks), 10 mg/kg is given on specific days. During maintenance, 6 mg/kg is given every 4 weeks.
NULOJIX treatment is prescribed and supervised by a specialist in kidney transplantation. The medication is always administered by a healthcare professional in a clinical setting – it is not a medication that patients take at home. The recommended dose is calculated based on the patient's actual body weight in kilograms.
Initial Phase (Day 1 to Week 12)
Initial Phase Dosing – 10 mg/kg body weight
During the initial phase after transplantation, NULOJIX is given at a dose of 10 mg/kg on the following schedule:
- Day 1 (transplant day, before implantation)
- Day 5 after transplant
- Day 14 after transplant
- Day 28 after transplant
- End of week 8 after transplant
- End of week 12 after transplant
Maintenance Phase (From Week 16 Onwards)
Maintenance Phase Dosing – 6 mg/kg body weight
Starting at the end of week 16 after transplantation, NULOJIX is given at a dose of 6 mg/kg every 4 weeks (± 3 days). This maintenance schedule continues for as long as the transplant team determines that treatment is beneficial.
| Phase | Timing | Dose |
|---|---|---|
| Initial | Day 1 (transplant day, before implantation) | 10 mg/kg |
| Initial | Day 5, Day 14, Day 28 | 10 mg/kg |
| Initial | End of Week 8 and Week 12 | 10 mg/kg |
| Maintenance | Every 4 weeks (± 3 days) from Week 16 | 6 mg/kg |
Dose Adjustments
Dose modification is not recommended for body weight changes of less than 10%. If your weight changes significantly, your transplant team will recalculate the dose accordingly. There are no specific dose adjustments recommended for elderly patients or patients with renal impairment.
Missed Dose
It is very important that you attend all scheduled infusion appointments. If you miss an appointment, contact your transplant team as soon as possible to reschedule. Missing doses of NULOJIX may increase the risk that your immune system begins to attack the transplanted kidney, potentially leading to rejection.
Overdose
If an overdose occurs during an infusion session, you will be monitored by your healthcare team for any signs or symptoms of adverse effects. If necessary, appropriate treatment will be provided. Single doses up to 20 mg/kg have been administered in clinical studies without apparent dose-limiting toxicity.
Stopping Treatment
Do not stop NULOJIX treatment without first discussing this with your transplant team. If you stop using NULOJIX, your body may begin to reject the transplanted kidney. The decision to discontinue NULOJIX should always be made in consultation with your transplant specialist, and alternative immunosuppressive therapy will typically be started. If treatment is interrupted for a prolonged period and then restarted, the effectiveness of belatacept may not be the same as before.
What Are the Side Effects of NULOJIX?
Like all immunosuppressive medications, NULOJIX can cause side effects. The most serious risks include post-transplant lymphoproliferative disorder (PTLD), progressive multifocal leukoencephalopathy (PML), and serious infections. Common side effects include infections, anaemia, blood pressure changes, gastrointestinal disturbances, and headache.
NULOJIX may cause serious adverse effects that require immediate medical attention. It is important that your family or caregivers are aware of your treatment, as some symptoms – particularly neurological changes – may not be apparent to the patient themselves.
Neurological symptoms: Memory problems, speech difficulties, mood or behavioural changes, confusion, muscle weakness on one side of the body, vision changes, or severe headache. These may indicate PML or PTLD affecting the brain.
Signs of infection: Unexplained fever, weight loss, swollen lymph nodes, persistent cough (especially with blood), severe sore throat, or wounds that are red, warm, and producing pus.
Kidney symptoms: Pain at the transplant site, difficulty urinating, changes in urine output, blood in urine, or pain during urination.
Allergic reactions: Rash, hives, itching, facial or throat swelling, chest pain, difficulty breathing, or dizziness.
Very Common Side Effects
May affect more than 1 in 10 patients
- Urinary tract infections, upper respiratory tract infections, CMV infection
- Fever, cough, bronchitis
- Shortness of breath (dyspnoea)
- Constipation, diarrhoea, nausea, vomiting, abdominal pain
- High blood pressure (hypertension) or low blood pressure (hypotension)
- Headache, insomnia, anxiety
- Swelling of hands and feet (peripheral oedema)
- Joint pain, back pain, pain in extremities
- Painful urination, blood in urine
- Anaemia, decreased white blood cell count
- Increased blood creatinine, increased protein in urine
- High blood sugar, high cholesterol and triglycerides
- Changes in blood electrolyte levels
Common Side Effects
May affect up to 1 in 10 patients
- Skin cancer, non-cancerous skin growths
- Severe hypotension, stroke, tissue death due to blocked blood flow
- Liver inflammation (cytolytic hepatitis), kidney damage
- Fluid in the lungs, wheezing, chest pain, enlarged heart muscle
- Bloodstream or tissue infections, pneumonia, influenza, sinusitis
- Herpesvirus infections, shingles, oral thrush
- Skin and soft tissue infections, wound infections, fungal infections
- Diabetes, dehydration
- Abnormal heart rate (fast, slow, or irregular), heart failure
- Tingling, numbness, or weakness in arms and legs
- Rash, itching, acne, hair loss, excessive sweating
- Muscle pain, bone pain, joint inflammation, muscle spasms
- Kidney blood vessel blockage, urinary retention, incontinence
- Weight gain or loss, cataracts, blurred vision
- Tremor, dizziness, fainting, tinnitus
- Depression, fatigue, drowsiness, nosebleeds
Uncommon Side Effects
May affect up to 1 in 100 patients
- Lung cancer, rectal cancer, breast cancer, prostate cancer, cervical cancer, kidney cancer, bone marrow cancer, lymph node cancer
- EBV lymphoproliferative disease (PTLD)
- Brain fungal infection, brain inflammation (encephalitis), PML
- Seizures, abnormal brain swelling, increased intracranial pressure
- Weak blood flow to the heart, heart valve abnormalities
- Acute respiratory distress, pulmonary hypertension, coughing up blood
- Pancreatitis, gastrointestinal ulcers, bowel obstruction, rectal bleeding
- Tuberculosis, bone infections, parasitic infections (strongyloides, giardia)
- Polyomavirus-associated nephropathy, kidney inflammation
- Blood clots in kidney artery or veins
- Guillain-Barré syndrome (muscle weakness or paralysis)
- Gallstones, fatty liver, liver cysts
- Bone disorders, testicular inflammation, infertility
- Dangerously low red blood cell or white blood cell counts
If you experience any side effects, including those not listed here, contact your transplant team or doctor immediately. Reporting suspected adverse reactions is important for continuous safety monitoring of all medicines.
How Should You Store NULOJIX?
NULOJIX is stored and administered in a clinical setting by healthcare professionals. The unopened powder must be refrigerated at 2°C–8°C and kept in the original packaging to protect it from light.
As NULOJIX is a hospital-administered medication, patients will not typically need to store it themselves. However, the following storage conditions are important to understand:
- Unopened vials: Store in a refrigerator at 2°C to 8°C. Keep in the original carton to protect from light
- After reconstitution: The solution should be transferred immediately from the vial to the infusion bag or bottle
- After dilution: The infusion solution should be used immediately. If not used immediately, it can be stored refrigerated (2°C–8°C) for up to 24 hours, with a maximum of 4 hours at room temperature (below 25°C) out of the total 24 hours
- Do not freeze the reconstituted or diluted solution
- The infusion must be completed within 24 hours of reconstitution of the powder
- Do not use if the solution contains visible particles or is discoloured
Keep all medicines out of the sight and reach of children. Do not use NULOJIX after the expiry date stated on the vial label and carton. Unused medicine should be disposed of in accordance with local requirements to protect the environment.
What Does NULOJIX Contain?
Each NULOJIX vial contains 250 mg of belatacept as the active ingredient. After reconstitution with 10.5 ml of solvent, each ml of concentrate contains 25 mg of belatacept.
The active substance is belatacept. Each vial contains 250 mg of belatacept. After reconstitution with the appropriate solvent, each ml of concentrate contains 25 mg of belatacept.
The other ingredients (excipients) are:
- Sodium chloride
- Sodium dihydrogen phosphate monohydrate
- Sucrose
- Sodium hydroxide (for pH adjustment)
- Hydrochloric acid (for pH adjustment)
Appearance: NULOJIX powder for concentrate for solution for infusion is a white to off-white powder that may appear as a whole or fragmented cake. After reconstitution, the solution should be clear to slightly opalescent and colourless to slightly yellow.
Pack sizes: NULOJIX is available in packs containing either 1 vial and 1 syringe, or 2 vials and 2 syringes. Not all pack sizes may be available in every country.
Marketing Authorisation Holder: Bristol-Myers Squibb Pharma EEIG, Plaza 254, Blanchardstown Corporate Park 2, Dublin 15, D15 T867, Ireland.
Frequently Asked Questions About NULOJIX
NULOJIX (belatacept) is a selective immunosuppressant used in adult kidney transplant recipients to prevent the immune system from rejecting the transplanted kidney. It works by blocking a specific pathway required for T-cell activation (the CD28 costimulatory pathway). It is always used in combination with other immunosuppressive medications, including mycophenolic acid and corticosteroids, and is administered as an intravenous infusion over 30 minutes in a clinical setting.
Unlike calcineurin inhibitors (such as tacrolimus and ciclosporin), which are taken orally and are associated with long-term kidney toxicity (nephrotoxicity), NULOJIX is given as an intravenous infusion and works through a different mechanism – blocking T-cell costimulation rather than calcineurin signalling. Clinical trials have shown that belatacept-based regimens may provide better long-term kidney function compared to ciclosporin-based regimens, potentially because it avoids the nephrotoxic effects of calcineurin inhibitors.
Epstein-Barr virus (EBV) serostatus must be confirmed positive before starting NULOJIX because patients who have not been previously exposed to EBV have a significantly higher risk of developing post-transplant lymphoproliferative disorder (PTLD), a potentially fatal cancer. PTLD associated with NULOJIX more frequently involves the brain (central nervous system) and can lead to death. NULOJIX is absolutely contraindicated in patients with negative or unknown EBV serostatus.
Live vaccines must be avoided during NULOJIX treatment because the immunosuppressive effects increase the risk of infection from live vaccine strains. This includes vaccines such as MMR, varicella, live influenza (nasal spray), oral polio, rotavirus, yellow fever, and BCG. Inactivated vaccines may be given, but their effectiveness may be reduced. Always consult your transplant team before receiving any vaccinations to ensure they are safe for you.
If you miss a scheduled NULOJIX infusion, it is very important to contact your transplant team as soon as possible to reschedule. Missing infusions can reduce the level of immunosuppression and increase the risk of your body rejecting the transplanted kidney. Your doctor will advise you on when to receive your next dose. Never try to make up for a missed dose on your own – the timing and dosing schedule must be managed by your medical team.
No. NULOJIX is approved exclusively for use in adult kidney transplant recipients. It is not recommended for liver transplants, and its use in heart or other organ transplants has not been established. Clinical studies have been conducted only in kidney transplantation, and the safety and efficacy in other types of organ transplants have not been demonstrated.
References
- European Medicines Agency (EMA). NULOJIX Summary of Product Characteristics (SmPC). Last updated 2023. Available at: EMA – NULOJIX
- Vincenti F, Charpentier B, Vanrenterghem Y, et al. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant. 2010;10(3):535-546.
- Durrbach A, Pestana JM, Pearson T, et al. A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study). Am J Transplant. 2010;10(3):547-557.
- Vincenti F, Rostaing L, Grinyo J, et al. Belatacept and long-term outcomes in kidney transplantation. N Engl J Med. 2016;374(4):333-343.
- KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients. Am J Transplant. 2009;9(Suppl 3):S1-S155.
- US Food and Drug Administration (FDA). NULOJIX Prescribing Information. Revised 2023.
- World Health Organization (WHO). Model List of Essential Medicines – 23rd List, 2023.
- Pestana JM, Grinyo JM, Vanrenterghem Y, et al. Three-year outcomes from BENEFIT-EXT: a phase III study of belatacept versus cyclosporine in recipients of extended criteria donor kidneys. Am J Transplant. 2012;12(3):630-639.
Editorial Team
Medical Content
Written by the iMedic Medical Editorial Team – specialists in transplant medicine, nephrology, and clinical pharmacology with documented academic and clinical experience.
Medical Review
Reviewed by the iMedic Medical Review Board according to international guidelines (EMA, FDA, KDIGO). Evidence level: 1A based on randomised controlled trials.
Last reviewed: . Content based on EMA SmPC (2023), FDA Prescribing Information, BENEFIT and BENEFIT-EXT trial data, and KDIGO guidelines. No commercial funding or pharmaceutical sponsorship.