BELATACEPT 
Pronounciation
- (bel-AT-a-sept)
Trade Name(s)
- Nulojix
Ascertain Epstein-Barr virus (EBV) serology before treatment. Testing for latent TB indicated; see Contraindications and Monitor.
Administration of higher-than-recommended doses or more frequent dosing of belatacept is not recommended because of an increased risk of posttransplant lymphoproliferative disorder (PTLD), progressive multifocal leukoencephalopathy (PML), and serious CNS infections.
Premedication is not required. Base the total infusion dose on actual body weight at the time of transplantation.
a The dose prescribed must be evenly divisible by 12.5 mg (evenly divisible increments are 0, 12.5, 25, 37.5, 50, 62.5, 75, 87.5, and 100). For example: At 10 mg/kg/dose, a patient weighing 64 kg would receive 640 mg. The closest doses evenly divisible by 12.5 below and above 640 mg are 637.5 mg and 650 mg. The nearest dose is 637.5 mg, and this would be the actual prescribed dose. | ||||||||||||||||||||||||||||
Regimen includes basiliximab (Simulect) induction, mycophenolate mofetil (MMF, CellCept), and corticosteroids.
20 mg IV on the day of transplantation and 4 days later.
1 Gm twice daily as an initial dose. Adjust dose based on clinical signs of adverse events or efficacy failure.
should be consistent with those used in clinical trials. In Studies 1 and 2, methylprednisolone 500 mg IV was given on arrival to the OR on Day 1. Methylprednisolone 250 mg IV was given on Day 2, and prednisone 100 mg PO was given on Day 3. In clinical trials, the median corticosteroid doses were tapered to approximately 15 mg (10 to 20 mg) per day by the first 6 weeks and remained at approximately 10 mg (5 to 10 mg) per day for the first 6 months posttransplant; see Precautions. Actual corticosteroid dosing in clinical trials is summarized in the following chart.
a Corticosteroid = Prednisone or prednisolone. b Protocols allowed for flexibility in determining corticosteroid dose and rapidity of taper after Day 15. It is not possible to distinguish corticosteroid doses used to treat acute rejection versus doses used in a maintenance regimen. c Q1 and Q3 are the 25th and 75th percentiles of daily corticosteroid doses, respectively. | |||||||||||||||||||||||
Do not modify the dose during the course of therapy unless there is a change in body weight of greater than 10%.
■ Age, gender, race, renal function, hepatic function, diabetes, and concomitant dialysis do not affect the clearance of belatacept.
Belatacept is for IV infusion only. Must be reconstituted/prepared using only the silicone-free disposable syringe provided with each vial. This syringe will be required for both reconstitution and the preparation of the final infusion. Maintain sterility. Any solution prepared with other than the provided silicone-free syringe must be discarded.
Each vial contains 250 mg of belatacept lyophilized powder. Calculate the number of vials needed to provide the total infusion dose. Reconstitute the contents of each vial with 10.5 mL of SWFI, NS, or D5W using the silicone-free disposable syringe and an 18- to 21-gauge needle. Direct the stream of diluent to the glass wall of the vial. To avoid foaming, rotate the vial and swirl gently until contents are completely dissolved. Avoid prolonged or vigorous agitation. Do not shake. Reconstituted solution yields 25 mg/mL and should be clear to slightly opalescent and colorless to pale yellow. Calculate the total volume of reconstituted solution required to provide the prescribed dose:
Volume of 25 mg/mL belatacept solution (in mL) = Prescribed dose (in mg) ÷ 25 mg/mL
The reconstituted solution must be further diluted in infusion fluid. If reconstituted with SWFI, dilute with either NS or D5W. If reconstituted with NS, further dilute with NS. If reconstituted with D5W, further dilute with D5W. From the appropriate-size infusion bag or bottle (typically an infusion volume of 100 mL is appropriate, but volumes from 50 to 250 mL may be used), withdraw a volume of infusion fluid equal to the total volume of reconstituted belatacept required to provide the prescribed dose. Using the same silicone-free disposable syringe used for reconstitution, withdraw the required amount of belatacept and inject it into the infusion bag or bottle. Gently rotate to ensure mixing. Concentration should range from 2 mg/mL to 10 mg/mL.
Must be administered with a nonpyrogenic, low–protein-binding, 0.2- to 1.2-micron filter.
Refrigerate vials of lyophilized powder at 2° to 8° C (36° to 46° F) in carton to protect from light. The reconstituted solution should be further diluted in infusion fluid immediately. The infusion must be completed within 24 hours. Infusion solution can be refrigerated protected from light for up to 24 hours. A maximum of 4 hours of those 24 hours can be at RT 20° to 25° C (68° to 77° F) and room light. Discard any unused solution remaining in vials.
Manufacturer states, “Must be reconstituted/prepared using only the silicone-free disposable syringe provided with each vial. Any solution prepared with other than the provided silicone-free syringe must be discarded” and “Infuse in a separate line; should not be infused concomitantly in the same IV line with other agents.”
A selective T-cell costimulation blocker. Produced by recombinant DNA technology. Binds to CD80 and CD86 on antigen-presenting cells, thereby blocking CD28-mediated costimulation of T-lymphocytes. Belatacept-mediated costimulation blockade results in the inhibition of cytokine production by T-cells required for antigen-specific antibody production by B-cells and inhibits T-lymphocyte proliferation. Activated T-lymphocytes are the predominant mediators of immunologic rejection. Half-life ranges from 6.1 to 15.1 days.
Prophylaxis of organ rejection in adult patients receiving a kidney transplant. Used in combination with basiliximab induction, mycophenolate mofetil, and corticosteroids.
Use only in patients who are Epstein-Barr virus (EBV) seropositive.
■ Use for prophylaxis of organ rejection in transplanted organs other than the kidney not established.
Transplant recipients who are Epstein-Barr virus (EBV) seronegative or who have unknown EBV serostatus because of risk of posttransplant lymphoproliferative disorder (PTLD) predominantly involving the CNS.
For IV infusion only.
■ Usually administered by or under the direction of a physician experienced in immunosuppressive therapy and management of kidney transplant patients. Adequate laboratory and supportive medical resources must be available.
■ Increased risk for developing posttransplant lymphoproliferative disorder (PTLD), predominantly involving the CNS, compared with patients on a cyclosporine-based regimen. Recipients without immunity to Epstein-Barr virus (EBV) are at a particularly increased risk; therefore use in EBV-seropositive patients only. Do not use belatacept in transplant recipients who are EBV-seronegative or who have unknown EBV serostatus.
■ Other known risk factors for PTLD include cytomegalovirus (CMV) infection and T-cell–depleting therapy. Use T-cell–depleting therapies to treat acute rejection with caution. CMV prophylaxis is recommended for at least 3 months after transplantation. Patients who are EBV seropositive and CMV seronegative may be at increased risk for PTLD compared with patients who are EBV seropositive and CMV seropositive.
■ Minimization of the corticosteroid dose to 5 mg/day between Day 3 and Week 6 posttransplantation has been associated with an increased rate and grade of acute rejection, particularly Grade III rejection. Graft loss occurred in some patients. Corticosteroid use should be consistent with clinical trial experience; see Usual Dose.
■ Increased susceptibility to infection and possible development of malignancies may result from immunosuppression. Increased risk of developing other malignancies, including malignancies of the skin, appears related to intensity and duration of use. Avoid prolonged exposure to UV light and sunlight. Risk of developing bacterial, viral (e.g., CMV and herpes), fungal, and protozoal infections, including opportunistic infections such as tuberculosis (TB) or polyoma virus–associated nephropathy (PVAN), is increased and may lead to serious (including fatal) outcomes. Prophylaxis for Pneumocystis jiroveci is recommended after transplantation.
■ The coadministration (at the same or nearly the same time) of anti-thymocyte globulin and belatacept may pose a risk for venous thrombosis of the renal allograft; see Drug/Lab Interactions.
■ PML (a rapidly progressive and fatal opportunistic infection of the CNS that is caused by the JC virus) has been reported.
■ Infusion-related reactions have occurred within 1 hour of infusion; however, no serious reactions or anaphylaxis were reported in studies.
■ Use in liver transplant patients is not recommended because of an increased risk of graft loss and death.
■ Anti-belatacept antibody development was not associated with an altered clearance of belatacept. The clinical impact of anti-belatacept antibodies has not been determined.
■ Do not administer live virus vaccines; see Drug/Lab Interactions.
Ascertain EBV serology before starting therapy with belatacept.
■ Monitor for new or worsening neurologic, cognitive, or behavioral signs and symptoms. May indicate PTLD or PML.
■ PML is usually diagnosed by brain imaging, CSF testing for JC viral DNA, and/or brain biopsy. Consultation with a specialist (e.g., neurologist and/or infectious disease specialist) should be considered.
■ Evaluate patients for latent tuberculosis (TB). Patients testing positive in TB screening should be treated with a standard TB regimen before initiating belatacept therapy.
■ Monitor for S/S of infection; see Antidote.
■ Monitor renal function closely and consider PVAN if renal function is deteriorating.
■ New-onset diabetes, dyslipidemia, and hypertension may occur; monitor blood sugar, lipid panel, and BP.
■ Monitor for infusion reactions (primarily hypertension and hypotension).
■ See Precautions.
Read manufacturer’s patient information sheet before each infusion.
■ Risk of other malignancies, especially skin cancer, is increased. Report S/S of skin cancer, such as suspicious moles or lesions. Limit exposure to sunlight and UV light. Wear protective clothing and use a sunscreen with a high protection factor.
■ Promptly report confusion, thinking problems, and loss of memory; decreased strength or weakness on one side of the body; and changes in mood or behavior, walking or talking, and vision.
■ Promptly report S/S of infection (e.g., fever, malaise). Adherence to prescribed antimicrobial prophylaxis is imperative.
■ Information on use in pregnant females is not available. Pregnancy registry available to monitor maternal-fetal outcomes.
■ Live vaccines should be avoided.
Insufficient data to inform on drug-associated risk in pregnant females.
■ There are no data on the presence of belatacept in human milk or on the effects on breast-fed infants or human milk production; consider risk versus benefit.
■ Safety and effectiveness for use in pediatric patients under 18 years of age not established.
Safety and effectiveness similar to that seen in younger adults.
A change of mycophenolic acid (MPA) exposure may occur with a crossover from cyclosporine to belatacept or from belatacept to cyclosporine in patients concomitantly receiving MMF. Cyclosporine decreases MPA exposure by preventing enterohepatic recirculation of MPA, whereas belatacept does not. A higher MMF dosage may be needed after switching from belatacept to cyclosporine because cyclosporine may cause lower MPA concentrations and increase the risk of graft rejection. A lower MMF dosage may be needed after switching from cyclosporine to belatacept because this switch may result in higher MPA concentrations and increase the risk for adverse reactions related to MPA.
■ If anti-thymocyte globulin (or any other cell-depleting immunosuppressive induction treatment) and belatacept will be administered concomitantly, a 12-hour interval between the two administrations is suggested to reduce the risk of venous thrombosis of the renal allograft.
■ Avoid the use of live vaccines during treatment with belatacept, including but not limited to intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and Ty21a typhoid vaccines.
Anemia, constipation, cough, diarrhea, fever, graft dysfunction, headache, hyperkalemia, hypertension, hypokalemia, leukopenia, nausea, peripheral edema, urinary tract infection, and vomiting are most common. Posttransplant lymphoproliferative disorder (PTLD), predominantly CNS PTLD; other malignancies; and serious infections, including JC virus–associated progressive multifocal leukoencephalopathy (PML) and polyoma virus–associated nephropathy (PVAN), are the most serious potential side effects and may be life threatening. Abdominal pain, acne, anxiety, arthralgia, back pain, bronchitis, cytomegalovirus (CMV) and herpes infections, dizziness, dyslipidemia, dyspnea, dysuria, hematuria, hypercholesterolemia, hyperglycemia, hyperuricemia, hypocalcemia, hypomagnesemia, hypophosphatemia, hypotension, increased creatinine, influenza, infusion reactions, insomnia, nasopharyngitis, new-onset diabetes, proteinuria, renal tubular necrosis, tremor, tuberculosis, and upper respiratory infections may occur.
Anaphylaxis and venous thrombosis of the renal allograft (with coadministration of anti-thymocyte globulin).
Notify physician of all side effects. Most will be treated symptomatically. In case of overdose, it is recommended that the patient be monitored for any S/S of adverse reactions and appropriate symptomatic treatment instituted. If PML is confirmed or if patient develops evidence of PVAN, consider reducing or discontinuing immunosuppression, taking into account the risk to the allograft. Therapy may need to be interrupted in patients who develop infections. Treat infusion reactions as indicated. Resuscitate as necessary.