Belatacept
Belatacept Uses, Dosage, Side Effects, Food Interaction and all others data.
Belatacept is a soluble fusion protein, which links the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1). Structurally, abatacept is a glycosylated fusion protein with a MALDI-MS molecular weight of 92,300 Da and it is a homodimer of two homologous polypeptide chains of 357 amino acids each. It is produced through recombinant DNA technology in mammalian CHO cells. The drug has activity as a selective co-stimulation modulator with inhibitory activity on T lymphocytes. It is approved for the treatment of rheumatoid arthritis. Belatacept selectively blocks the process of T-cell activation. It was developed by Bristol-Myers-Squibb. Belatacept is only 2 amino acids different from abatacept (Orencia). FDA approved on June 15, 2011.
Belatacept binds to CD86 with a 4-fold higher affinity than abatacept. It also binds to CD80 with a 2-fold higher affinity than abatacept. It was observed in non-human primates that belatacept prolongs graft survival due to a decrease in antibody production against the donor organ. Furthermore, belatacept also inhibits the primary humoral immune response which is indicated by the decrease in post-transplant levels of IgG, IgM, and IgA. The magnitude of this effect is more significant in belatacept than it is in cyclosporine.
| Trade Name | Belatacept |
| Availability | Prescription only |
| Generic | Belatacept |
| Belatacept Other Names | Belatacept |
| Related Drugs | Myfortic, mycophenolic acid, Nulojix |
| Weight | 250mg, |
| Type | Intravenous Powder For Injection, Intravenous |
| Formula | C3508H5440N922O1096S32 |
| Weight | 92300.0 Da (with glycosylation) |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Belatacept is a selective T-cell costimulation blocker used in the prophylaxis of organ rejection in adult patients receiving a kidney transplant.
For prophylaxis of organ rejection. It is also used concomitantly with basiliximumab for induction therapy, mycophenolate, and corticosteriods in kidney transplant recepients that are seropositive for the Epstein-Barr virus.
Belatacept is also used to associated treatment for these conditions: Kidney Transplant Rejection
How Belatacept works
Belatacept is a fusion protein in which the Fc portion of human IgG1 is attached onto the extracellular portion of human CTLA-4 (CD152). Belatacept specifically binds to CD80 and CD86 receptors that are found on the antigen-presenting cell (B cells, macrophages, dendritic cells) to block selective T-cell lymphocyte costimulation. CD80 and CD86 would normally act as the ligands to the CD28 receptor T-cells in which this interaction triggers the activation of T lymphocytes. However in the presence of belatacept, because the extracellular CTLA-4 component binds to CD28 with higher affinity than CD80 or CD86, T lymphyocyte anergy, a state of antigen specific tolerance, occurs instead. The T cell is also no longer able to respond to their antigen.
Food Interaction
No interactions found.Belatacept Drug Interaction
Unknown: sulfamethoxazole / trimethoprim, mycophenolate mofetil, carvedilol, tacrolimus, omega-3 polyunsaturated fatty acids, cyclobenzaprine, fluticasone nasal, insulin lispro, arginine, levocarnitine, cysteine, lithium, mycophenolic acid, valproic acid, thiamine, cyanocobalamin, pyridoxine, cholecalciferol, phytonadione, menaquinone
Belatacept Disease Interaction
Major: EBV, vaccination, infections, PMLModerate: liver dysfunction, tuberculosis
Volume of Distribution
Vd, steady state, transplant patients, 10 mg/kg = 0.11 L/kg; Vd, steady state, transplant patients, 5 mg/kg = 0.12 L/kg
Elimination Route
Following multiple intravenous doses of an initial 10 mg/kg dose and followed by a maintenance dose of 5 mg/kg in kidney transplant recipients, these are the following pharmacokinetic parameters: Cmax, 10 mg/kg = 247 µg/mL; Cmax, 5 mg/kg = 139 µg/mL; AUC, 10 mg/kg = 22,252 µg · h/mL; AUC, 5 mg/kg = 14,090 µg · h/mL; Belatacept had linear and dose-dependent pharmacokinetic profile.
Half Life
Mean terminal elimination half-life: 10 mg/kg, kidney transplant recipients= 9.8 days; 5 mg/kg, kidney transplant recipient = 8.2 days
Clearance
Increased body weight may increase the clearance rate of belatacept. Mean systemic clearance: 10 mg/kg, kidney transplant recipients= 0.49 mL/h/kg; 5 mg/kg, kidney transplant recipient = 0.51 mL/h/kg.
Innovators Monograph
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