antithymocyte globulin equine

Action and Spectrum

Actions and Spectrum: 

anti-thymocyte globulin (ATG) derived from horses, also known as anti-thymocyte globulin equine (ATGAM), is an immunosuppressive medication used in various clinical settings.  

Mechanism of Action:  

ATGAM contains polyclonal antibodies raised against human thymocytes, cells involved in the immune response. The antibodies in ATGAM bind to various cell surface antigens on T lymphocytes (T cells), leading to several immunomodulatory effects: 

• Depletion of T Cells: ATGAM binds to T cells, leading to their depletion or reduction in number. This T-cell depletion is thought to contribute to the immunosuppressive effect of ATGAM. 
• Modulation of T-Cell Function: ATGAM can also modulate the function of T cells by interfering with their activation and ability to respond to antigens. This modulation helps to suppress the immune response, which is beneficial in various clinical conditions. 
• Other Effects: In addition to T-cell targeting, ATGAM may also affect other components of the immune system, such as B cells and natural killer (NK) cells, although the specific mechanisms and their contributions to the overall action of ATGAM are not fully understood. 

Spectrum of Activity: 

 ATGAM is used in various clinical settings that require immunosuppression. Its spectrum of activity includes: 

• Organ Transplantation: ATGAM is commonly used as an induction therapy in solid organ transplantation, such as kidney or liver transplantation. By suppressing the immune response, ATGAM helps to reduce the risk of organ rejection and improve graft survival. 
• Treatment of Immune-Mediated Disorders: ATGAM is also utilized to treat certain immune-mediated disorders, such as aplastic anemia and graft-versus-host disease (GVHD). In these conditions, ATGAM helps to modulate the immune response and reduce the attack on specific tissues or cells. 
• Off-Label Uses: In some cases, ATGAM may be used off-label for other immune-mediated conditions where immunosuppression is required, although the evidence for its effectiveness may vary. 

Drug Interaction

Adverse Reaction

Frequency defined 

Renal Transplant Patients 

>10% 

Thrombocytopenia (11-30%) 

Chills (14-16%) 

Systemic infection (13%) 

Fever (33-51%) 

Rash (27%) 

Leukopenia (14%) 

Dermatologic rxns (12%) 

1-10% 

Headache 

Chest or back pain 

Pain at the infusion site 

Arthralgia, hypotension, peripheral thrombophlebitis 

Nausea or vomiting, stomatitis, diarrhea, 

Night sweats 

Dyspnea  

<1% 

Malaise, weakness or faintness, paresthesia, Dizziness,seizures 

Herpes simplex reactivation, localized infection, systemic infection, serum sickness 

Anaphylaxis, hyperglycemia, laryngospasm 

Hypertension, tachycardia, Edema, Pulmonary edema 

Toxic epidermal necrosis 

Myalgia 

Epigastric pain, hiccoughs 

Aplastic Anemia Patients 

>10% 

Chills (50%) 

HA (16%) 

Arthralgia (50%)  

5-10% 

Chest pain (7%) 

Phlebitis (5%) 

Myalgia (10%) 

Nausea (7%) 

(<5%) 

Diarrhea, vomiting 

Proteinuria 

Anaphylactic reaction 

Agitation, seizures 

Joint stiffness, Lymph node tenderness 

Respiratory distress 

Diaphoresis  

Post-marketing reports 

Serum sickness 

Black Box Warning

Black box warning: 

Only doctors with expertise in immunosuppressive treatment for kidney transplant patients should prescribe it. Patients should only be given the medication in organizations with enough laboratory and accompanying medical resources. 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: ATGAM is contraindicated in patients with known hypersensitivity or severe allergic reaction to antithymocyte globulin equine or any of its components. 
• Prior Serum Sickness: ATGAM should not be used in patients who have previously experienced serum sickness due to ATG or other equine-derived products. 
• Immunization: ATGAM should not be administered to individuals who have received live viral vaccines within the past three months. Live viral vaccines may be less effective in individuals receiving ATGAM due to its immunosuppressive effects. 
• Infection: ATGAM should not be given to patients with active viral, bacterial, fungal, or protozoal infections. Using immunosuppressive medications like ATGAM in the presence of active infections may exacerbate the infection and increase the risk of complications. 

Caution: 

• Vaccination: Live vaccines may have reduced effectiveness in individuals receiving ATGAM due to their immunosuppressive effects. Vaccination with live vaccines should generally be avoided during ATGAM therapy. It is recommended to complete any necessary immunizations before initiating ATGAM treatment, whenever possible. 
• Malignancies: Immunosuppressive therapy, including ATGAM, may increase the risk of developing lymphoproliferative disorders. The potential benefits and risks of ATGAM therapy should be carefully evaluated in patients with a history of cancer or those at increased risk of malignancies. 

Pregnancy / Lactation

Pregnancy consideration: There was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Pregnancy Category: C 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

antithymocyte globulin equine (ATGAM) is an immunosuppressive medication derived from horses. Its pharmacology involves several aspects of its composition, target cells, and immunomodulatory effects.  

ATGAM is a polyclonal antibody preparation obtained by immunizing horses with human thymocytes. It contains a mixture of immunoglobulins (IgG) raised against multiple cell surface antigens found on human T lymphocytes (T cells). 

Pharmacodynamics: 

The pharmacodynamics of antithymocyte globulin equine (ATGAM) involves its immunomodulatory effects on the immune system. Here are the critical pharmacodynamic aspects of ATGAM: 

• T-Cell Depletion: ATGAM contains polyclonal antibodies that target and bind to specific antigens present on T lymphocytes (T cells). This binding leads to the depletion or reduction of circulating T cells. T-cell depletion is a critical pharmacodynamic effect of ATGAM and contributes to its immunosuppressive properties. 
• Modulation of T-Cell Function: In addition to T-cell depletion, ATGAM can modulate the function of T cells. ATGAM interferes with T-cell activation and their ability to respond to antigens by binding to specific cell surface antigens on T cells. This modulation helps to dampen the immune response and reduce T-cell-mediated immune reactions. 
• Effects on Other Immune Cells: ATGAM may also affect other immune cells, such as B and natural killer (NK). However, the exact mechanisms and contributions to its pharmacodynamics are not fully understood. These effects on other immune cells further contribute to the overall immunomodulatory actions of ATGAM. 
• Immunomodulation of Acute Inflammation: ATGAM’s immunomodulatory effects are particularly relevant in acute inflammation that can lead to systemic organ failure. ATGAM acts early in the host immune response to modulate acute inflammation by targeting and modulating T-cell function, which can help prevent or reduce systemic organ dysfunction. 

Pharmacokinetics: 

Absorption 

ATGAM is typically administered intravenously (IV), allowing for rapid and complete absorption into the systemic circulation. IV administration ensures the direct delivery of the medication into the bloodstream. 

Distribution 

Once in the bloodstream, ATGAM distributes throughout the body. Its distribution is influenced by factors such as blood flow, vascular permeability, and the presence of specific target antigens on T cells. ATGAM’s polyclonal antibodies target and bind to T cells, leading to their depletion or modulation of function. 

Metabolism 

ATGAM is a biological product derived from horses. The body undergoes protein metabolism and catabolism, like other endogenous proteins. However, specific information regarding the metabolism of ATGAM in humans is limited. 

Elimination and Excretion 

As a protein-based medication, ATGAM is primarily eliminated from the body through renal excretion. It is filtered by the kidneys and excreted in the urine. The exact elimination half-life of ATGAM can vary among individuals and may depend on factors such as renal function and the presence of antibodies against the horse-derived immunoglobulins. 

Adminstartion

Administration: 

• Dilution: ATGAM is supplied as a concentrated solution and requires dilution before administration. According to the manufacturer’s instructions or the healthcare provider’s guidance, it is usually diluted in a compatible diluent, such as normal saline or 5% dextrose in water. 
• Infusion Rate: The infusion rate of ATGAM can vary depending on the patient’s condition, tolerance, and the healthcare provider’s recommendation. It is typically administered as a slow IV infusion over several hours to minimize the risk of infusion reactions. The healthcare provider will determine the specific infusion rate and duration. 
• Pre-Medication: To reduce the risk of infusion-related reactions, patients may receive pre-medication with antipyretics, antihistamines, and corticosteroids before ATGAM administration. The choice and use of pre-medication may vary based on individual patient factors and the healthcare provider’s discretion. 
• Monitoring: During the ATGAM infusion, patients are closely monitored for any signs of infusion reactions or adverse events. Vital signs, including heart rate, blood pressure, and temperature, are monitored regularly. Healthcare providers also assess the patient’s overall condition and may perform laboratory tests to monitor immune function and response to therapy. 
• Facility Requirements: Due to the potential for infusion reactions and the need for appropriate medical resources, ATGAM should be administered in facilities equipped and staffed with adequate laboratory and supportive medical resources. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: antithymocyte globulin equine 

Why do we use antithymocyte globulin equine? 

antithymocyte globulin equine (ATGAM) is an immunosuppressive medication with several uses in clinical practice. Here are some typical indications for the use of ATGAM: 

• Transplantation: ATGAM is used in solid organ transplantation, particularly kidney transplantation, to prevent graft rejection. It is typically administered with other immunosuppressive medications to induce immunosuppression and reduce the risk of rejection. 
• Aplastic Anemia: ATGAM may be used to treat severe aplastic anemia, a condition characterized by a decrease in the production of red blood cells, white blood cells, and platelets in the bone marrow. ATGAM can help suppress the immune system, which is overactive in aplastic anemia, allowing the bone marrow to recover and resume average blood cell production. 
• Graft-Versus-Host Disease (GVHD): ATGAM is part of the treatment regimen for graft-versus-host disease, a complication that can occur after stem cell transplantation. It helps to suppress the immune response of the transplanted cells against the recipient’s tissues, reducing the severity and progression of GVHD. 
• Investigational Uses: ATGAM may be used in clinical trials or under specific circumstances for other immune-mediated conditions or diseases, such as certain autoimmune disorders or refractory immune thrombocytopenic purpura (ITP).