Drug information of Belatacept

Mechanism of effect

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.

Pharmacodynamic

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.

Pharmacokinetics

Absorption

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.

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

Metabolism

The cytochrome P450 enzyme system or uridine diphosphate-glucuronosyltransferases are not expected to be involved with the metabolism of belatacept. Because the drug is a protein, belatacept is degraded into smaller peptides and amino acids by proteolytic enzymes.

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.

Drug indications

Kidney Transplant Rejection

Dosage

Usual Adult Dose for Rejection Prophylaxis

Initial phase dose: 10 mg/kg IV on Day 1 (day of transplant, prior to implantation) and Day 5 (approximately 96 hours after Day 1 dose), and at the end of Weeks 2, 4, 8, and 12 after transplantation

Maintenance phase dose: 5 mg/kg IV at the end of Week 16 after transplantation and every 4 weeks (plus or minus 3 days) thereafter

Usual Adult Dose for Renal Transplant

Initial phase dose: 10 mg/kg IV on Day 1 (day of transplant, prior to implantation) and Day 5 (approximately 96 hours after Day 1 dose), and at the end of Weeks 2, 4, 8, and 12 after transplantation

Maintenance phase dose: 5 mg/kg IV at the end of Week 16 after transplantation and every 4 weeks (plus or minus 3 days) thereafter

Side effects

Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of a urinary tract infection (UTI) like blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.
• Signs of electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up.
• Signs of high or low blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• Feeling very tired or weak.
• Shortness of breath.
• Swelling in the arms or legs.
• A big weight loss.
• Night sweats.
• Fever that does not go away.
• Swollen gland.
• Change in color or size of a mole.
• A skin lump or growth.
• Mental, mood, or behavior changes that are new or worse.
• A very bad brain problem called progressive multifocal leukoencephalopathy (PML) has happened with belatacept. It may cause disability or can be deadly. Tell your doctor right away if you have signs like confusion, memory problems, low mood (depression), change in the way you act, change in strength on 1 side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight.
• Some people treated with belatacept have had very bad kidney problems caused by a certain viral infection (BK virus). In people who have had a kidney transplant, BK virus infection may cause loss of the kidney. Call your doctor right away if you have signs of kidney problems like change in the amount of urine passed, difficulty or pain when passing urine, or blood in the urine.

Interactions

adalimumab , baricitinib , bcg vaccine, certolizumab , clozapine , deferiprone , etanercept , fingolimod , golimumab , infliximab , influenza virus vaccine, h1n1, live, influenza virus vaccine, live, trivalent , leflunomide , measles virus vaccine , mumps virus vaccine , natalizumab , poliovirus vaccine, live, trivalent , rotavirus vaccine, rubella virus vaccine , smallpox vaccine , talimogene laherparepvec , teriflunomide , tofacitinib , typhoid vaccine, live , varicella virus vaccine , yellow fever vaccine , zoster vaccine live

Alerts

• You may have a chance of getting post-transplant lymphoproliferative disorder (PTLD). PTLD happens when your white blood cells grow out of control and can lead to cancer and death.
• This medicine may add to the chance of getting some types of cancer. Talk with the doctor.
• This medicine may raise the chance of very bad and sometimes deadly infections. Tell your doctor if you get signs of infection like a fever of 100.4°F (38°C) or higher, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, wound that will not heal, or anal itching or pain.
• Do not use belatacept if you have had a liver transplant or if you have not been exposed to EBV (Epstein Barr virus). Talk with your doctor.

Points of recommendation

• Tell all of your health care providers that you take belatacept. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Have your urine checked as you have been told by your doctor.
• Tell your doctor if you have signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• The chance of skin cancer may be raised. Avoid lots of sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
• You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
• You will need a TB (tuberculosis) test before starting belatacept.
• Talk with your doctor before getting any vaccines. Use of some vaccines with belatacept may either raise the chance of an infection or make the vaccine not work as well.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using belatacept while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Pregnancy level

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