Anti-human T-lymphocyte immunoglobulin

Approved Indications:

• Renal Transplantation:
• Induction Therapy: To prevent acute rejection in renal allograft recipients, especially in high immunologic risk patients.
• Treatment of Acute Rejection: For treatment of moderate to severe corticosteroid-resistant acute rejection episodes in organ transplant patients.
• Severe Aplastic Anemia (SAA):
• In combination with cyclosporine, it is used as first-line therapy in patients ineligible for bone marrow transplantation.

Clinically Accepted Off-label Uses:

• Graft-versus-Host Disease (GVHD): For prophylaxis or treatment, especially in steroid-refractory cases after hematopoietic stem cell transplantation.
• Liver or Heart Transplantation: In some protocols as induction or rejection management agent.
• Autoimmune Disorders (rare): Occasionally used for conditions such as pure red cell aplasia or refractory systemic lupus erythematosus, under specialist supervision.

Adult Dosage:

• Renal Transplantation (Induction):
  1.5 mg/kg/day IV infusion for 4–7 days, starting intraoperatively or immediately post-transplant.
• Acute Rejection Episodes:
  1.5 mg/kg/day IV infusion for 7–14 days, depending on response.
• Severe Aplastic Anemia:
  40 mg/kg/day IV over 4 days (total 160 mg/kg), usually with concurrent cyclosporine.

Pediatric Dosage:

• Similar to adult dosing on a weight-based basis (e.g., 15–40 mg/kg/day), especially in aplastic anemia.

Elderly:
No specific adjustment required, but close monitoring is essential due to comorbidities and polypharmacy.

Special Populations:

• Renal or Hepatic Impairment:
  No dose adjustment typically required, but monitor closely for toxicities.

Administration Route & Method:

• Administer IV via central or peripheral vein over 4–12 hours.
• Always premedicate with antihistamines, corticosteroids, and antipyretics 30–60 minutes before infusion.
• Close monitoring during and after infusion is mandatory for signs of infusion reactions.

Anti-human T-lymphocyte immunoglobulin is a polyclonal antibody derived from animals (usually rabbits or horses) immunized with human thymocytes. The preparation contains immunoglobulins targeting various T-cell surface antigens. It depletes circulating T lymphocytes through complement-dependent lysis and antibody-dependent cellular cytotoxicity. Additionally, it impairs T-cell activation and proliferation by binding to multiple surface receptors. This profound immunosuppressive effect reduces immune-mediated graft rejection and mitigates T-cell-driven bone marrow suppression in aplastic anemia.

• Absorption: Not applicable; administered intravenously.
• Distribution: Extensively binds to lymphoid tissues; large volume of distribution.
• Metabolism: Broken down by proteolytic enzymes into amino acids and peptides.
• Half-life: Terminal half-life ranges from 2 to 4 days; can extend with repeated dosing.
• Excretion: Cleared by the reticuloendothelial system (not renal-dependent); not excreted via kidneys.

• Pregnancy:
• Previously categorized as FDA Pregnancy Category C.
• Risk cannot be ruled out; animal data are limited and not conclusive.
• Should be used during pregnancy only if the potential benefit justifies the risk to the fetus.
• Lactation:
• Unknown whether it is excreted in human breast milk.
• Due to the potential for serious adverse effects in nursing infants (e.g., immunosuppression), breastfeeding is not recommended during and for a period after therapy.

• Primary Class: Immunosuppressive Agent
• Subclass: Polyclonal Anti-thymocyte Globulin (ATG)
• Source: Derived from rabbit or horse serum immunized with human thymocytes

• Hypersensitivity to anti-thymocyte globulin or any excipients
• Known allergy to rabbit (or horse) proteins
• Uncontrolled acute infections (bacterial, viral, or fungal)
• Severe thrombocytopenia or leukopenia not related to the underlying disease

• Infusion Reactions:
• Can be severe (e.g., hypotension, bronchospasm, anaphylaxis); premedication and slow infusion required.
• Infection Risk:
• Profound immunosuppression increases risk of opportunistic infections (CMV, fungal, bacterial).
• Malignancy:
• Long-term use associated with increased risk of post-transplant lymphoproliferative disorder (PTLD).
• Hematologic Toxicity:
• May cause leukopenia, thrombocytopenia, or anemia requiring treatment interruption.
• Serum Sickness:
• Delayed hypersensitivity reaction (fever, arthralgia, rash) may occur; corticosteroids are often needed.
• Monitoring Required:
• CBC, renal/liver function, infection surveillance, and vital signs during infusion.

Common (>10%):

• Fever, chills, hypotension
• Rash, nausea, vomiting
• Leukopenia, thrombocytopenia, anemia
• Arthralgia, headache

Less Common (1–10%):

• Dyspnea, chest pain, tachycardia
• Serum sickness (7–14 days post-infusion)
• Elevated liver enzymes

Rare/Serious (<1%):

• Anaphylaxis
• Sepsis or septic shock
• Post-transplant lymphoproliferative disorder (PTLD)
• Pulmonary edema, ARDS

• Live Vaccines:
• Avoid use during and after therapy due to suppressed immune response.
• Other Immunosuppressants (e.g., Cyclosporine, Tacrolimus):
• Increased risk of infection and additive hematologic toxicity.
• Myelosuppressive Chemotherapy or Radiotherapy:
• Potential for synergistic bone marrow suppression.

Enzymatic Interactions:

• Not metabolized via CYP450 pathways; minimal risk of enzyme-related drug interactions.

• EMA & FDA Updates (2023–2024):
• Enhanced warnings on premedication to prevent fatal infusion reactions.
• Updated infection monitoring protocols, including CMV prophylaxis strategies.
• KDIGO & EBMT Guidelines:
• Favor use in high-risk transplant patients over IL-2 receptor antagonists.
• Continued recommendation as first-line treatment for severe aplastic anemia when bone marrow transplant is unavailable.

• Temperature: Store at 2°C to 8°C (refrigerator). Do not freeze.
• Light: Protect from direct light.
• After Reconstitution/Dilution:
• Use immediately, or store refrigerated (2°C–8°C) for up to 24 hours if aseptic conditions maintained.
• Handling Precautions:
• Use sterile technique. Discard unused portions; do not shake.