Medication Guide App

Belatacept

Pronunciation: bel-AT-a-sept
Class: Immunologic agent

Trade Names

Nulojix
- Injection, lyophilized powder for solution 250 mg

Pharmacology

Decreases T-cell proliferation and inhibits the production of the cytokines, tumor necrosis factor (TNF)–alpha, interferon-gamma, interleukin-2, and interleukin-4.

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Pharmacokinetics

Absorption

C max and AUC are 247 mcg/mL and 22,252 mcg•h/mL, respectively, for a 10 mg/kg dose, and 139 mcg/mL and 14,090 mcg•h/mL, respectively, for a 5 mg/kg dose.

Distribution

Vd is approximately 0.11 L/kg.

Elimination

Systemic Cl is approximately 0.5 mL/h/kg; terminal half-life is 8 to 10 days.

Special Populations

Renal Function Impairment

Cl of belatacept was not affected.

Hepatic Function Impairment

Cl of belatacept was not affected.

Elderly

Cl of belatacept was not affected.

Gender

Cl of belatacept was not affected.

Race

Cl of belatacept was not affected.

Body weight

There was a trend toward higher Cl with increasing body weight.

Indications and Usage

Prophylaxis of organ rejection in patients receiving kidney transplantation.

Contraindications

Transplant patients who are Epstein-Barr virus seronegative or with unknown Epstein-Barr virus serostatus.

Dosage and Administration

Adults Initial phase

IV 10 mg/kg on day of transplantation (prior to implantation), day 5 (approximately 96 h after day 1 dose), and at end of wk 2, 4, 8, and 12 after transplantation.

Maintenance phase

IV 5 mg/kg at end of wk 16 after transplantation and every 4 wk (plus or minus 3 days) thereafter. Recommended doses should not be exceeded and dosage should not be modified during the course of therapy unless there is a change in body weight of more than 10%.

General Advice

  • Used in combination with basiliximab induction, mycophenolate mofetil, and corticosteroids.
  • For IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration.
  • Administer each dose as a 30-min infusion with an infusion set and a low-protein-binding filter (pore size 0.2 to 1.2 mcm).
  • The dose prescribed should be evenly divisible by 12.5 mg.
  • Reconstitute powder for injection with 10.5 mL of sterile water for injection, sodium chloride 0.9%, or dextrose 5% in water using only the silicone-free disposable syringe provided. Rotate vial and invert with gentle swirling until contents completely dissolve. Avoid prolonged or vigorous agitation. Do not shake.
  • Reconstituted solution must be further diluted to 50 to 250 mL; final concentration should be between 2 to 10 mg/mL. Discard any unused portions in vials.
  • Do not infuse concurrently in the same IV line with other agents.

Storage/Stability

Store unopened vials in a refrigerator (36° to 46°F). Protect from light. Infusion of fully diluted belatacept solution must be completed within 24 h of reconstitution of the belatacept vials. If not used immediately, fully diluted belatacept solution may be stored for up to 24 h in refrigerator before use (a max of 4 h may be between 68° and 77°F).

Drug Interactions

Mycophenolate mofetil

Mycophenolic acid C max and AUC may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Coadminister with caution and closely monitor the clinical response.

Vaccines (eg, bacille Calmette-Guérin, intranasal influenza, measles, mumps, oral polio, rubella, TY21a typhoid, varicella, and yellow fever vaccines)

Vaccinations may be less effective while patients are treated with belatacept. Live vaccines should be avoided.

Adverse Reactions

Cardiovascular

Hypertension (32%); hypotension (18%); atrial fibrillation, hematoma, lymphocele (less than 10%).

CNS

Headache (21%); insomnia (15%); anxiety (10%); dizziness (9%); tremor (8%).

Dermatologic

Alopecia, hyperhidrosis (less than 10%); acne (8%); nonmelanoma skin cancer (2%).

EENT

Nasopharyngitis (13%).

GI

Diarrhea (39%); constipation (33%); nausea (24%); vomiting (22%); abdominal pain (19%); stomatitis, including aphthous stomatitis (less than 10%); upper abdominal pain (9%).

Genitourinary

UTI (37%); proteinuria (33%); hematuria (16%); dysuria (11%); chronic allograft nephropathy, renal impairment, including acute renal failure, renal artery stenosis, urinary incontinence, and hydronephrosis (less than 10%); renal tubular necrosis (9%).

Hematologic

Anemia (45%); leukopenia (20%); neutropenia (less than 10%).

Lab Tests

Blood creatinine increased (15%).

Metabolic

Hypokalemia (21%); hyperkalemia (20%); dyslipidemia, hypophosphatemia (19%); hyperglycemia (16%); hypocalcemia (13%); hypercholesterolemia (11%); new-onset diabetes after transplant (8%); hypomagnesemia (7%); hyperuricemia (5%).

Musculoskeletal

Arthralgia (17%); back pain (13%); musculoskeletal pain (less than 10%).

Respiratory

Cough (24%); upper respiratory tract infection (15%); dyspnea (12%); bronchitis (10%).

Miscellaneous

Infection (82%); serious infection (36%); peripheral edema (34%); pyrexia (28%); graft dysfunction (25%); herpes (14%); cytomegalovirus (CMV) infection (13%); influenza (11%); complications of transplanted kidney including wound dehiscence and arteriovenous fistula thrombosis, Guillain-Barré syndrome (less than 10%); infusion reaction, including hypertension and hypotension (5%); malignancies other than posttransplant lymphoproliferative disorder or non-melanoma skin cancer, polyoma virus infection (4%); tuberculosis (TB) (2%); posttransplant lymphoproliferative disorder.

Precautions

Warnings

Posttransplant lymphoproliferative disorder, other malignancies, and serious infections

Increased risk of developing posttransplant lymphoproliferative disorder, predominantly involving the CNS. Transplant recipients without immunity to Epstein-Barr virus are at particularly increased risk; therefore, use in Epstein-Barr virus–seropositive patients only. Patients may also have an increased susceptibility to infection and the possible development of malignancies. Only health care providers experienced in immunosuppressive therapy and management of kidney transplant patients should prescribe belatacept. Patients should be managed in facilities with adequate laboratory and supportive medical resources.

Liver transplant

Use in liver transplant patients is not recommended because of an increased risk of graft loss and death.


Monitor

Determine Epstein-Barr virus serostatus and test for latent TB infection prior to initiation of therapy. Monitor patients for signs and symptoms of infection and for new or worsening neurological, cognitive, or behavioral signs and symptoms.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Greater sensitivity or lesser efficacy in older individuals cannot be ruled out.

Live vaccines

Use of live vaccines should be avoided during treatment with belatacept.

Polyoma virus nephropathy

Cases of polyoma virus–associated nephropathy, mostly due to BK virus infection, have been reported.

Progressive multifocal leukoencephalopathy

Has been reported in patients receiving belatacept at higher cumulative doses and more frequently than the recommended regimen. The recommended doses and frequency of belatacept and concomitant immunosuppression should not be exceeded.

Serious infection

Increased risk of developing bacterial, viral (CMV and herpes), fungal, and protozoal infections, including opportunistic infections, that may lead to serious, including fatal, outcomes. CMV prophylaxis for at least 3 mo after transplant and Pneumocystis jiroveci prophylaxis are recommended.

Skin malignancy

Increased risk of developing malignancies in addition to posttransplant lymphoproliferative disorder, including the skin. Exposure to sunlight and UV light should be limited.

Tuberculosis

TB was observed more frequently in patients treated with belatacept in clinical trials. Treat patients with latent TB infection prior to initiation of therapy.

Overdosage

Symptoms

Doses up to 20 mg/kg have been administered to healthy subjects without apparent toxicity. Administration at a higher cumulative dose and more frequent dosing than recommended in kidney transplant patients resulted in a higher frequency of CNS-related adverse reactions.

Patient Information

  • Advise patient that medication will be prepared and administered by health care provider in a medical setting.
  • Advise patient to review the Medication Guide carefully before starting therapy and to read and check for new information prior to each treatment session.
  • Inform patients that the overall risk of posttransplant lymphoproliferative disorder, especially CNS posttransplant lymphoproliferative disorder, was elevated and that cases of progressive multifocal leukoencephalopathy have been reported in belatacept-treated patients. Instruct patients to immediately report any of the following signs and symptoms during or after therapy with belatacept: changes in mood or usual behavior; confusion, problems thinking, or loss of memory; changes in walking or talking; decreased strength or weakness on one side of the body; changes in vision.
  • Inform patients of the increased risk of malignancies, in addition to posttransplant lymphoproliferative disorder, while taking immunosuppressive therapy, especially skin cancer. Instruct patients to limit exposure to sunlight and UV light by wearing protective clothing and using a sunscreen with a high protection factor. Instruct patients to look for signs and symptoms of skin cancer, such as suspicious moles or lesions.
  • Inform patients about the increased risk of infection. Instruct patients to adhere to antimicrobial prophylaxis regimens as prescribed and to immediately report any signs and symptoms of infection during therapy.
  • Inform patients that vaccinations may be less effective while they are being treated with belatacept and that live vaccines should be avoided.
  • Instruct patients to notify their health care provider if they are pregnant, planning to become pregnant, are breast-feeding, or planning to breast-feed.

Copyright © 2009 Wolters Kluwer Health.

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