What is the recommended dosage and usage of Thymoglobulin (Anti-thymocyte globulin) for preventing organ rejection in transplant patients?

Thymoglobulin (Anti-thymocyte Globulin) Dosing for Transplant Patients

For kidney transplant patients, Thymoglobulin should be administered at 1.5 mg/kg daily for 4-7 days for prophylaxis of acute rejection and 1.5 mg/kg daily for 7-14 days for treatment of acute rejection, with appropriate premedication and monitoring. 1

Dosing Guidelines by Transplant Type

Kidney Transplantation (FDA-Approved Indication)

Prophylaxis of Acute Rejection

• Dose: 1.5 mg/kg of body weight daily
• Duration: 4-7 days
• Timing: First dose initiated prior to reperfusion of donor kidney
• Administration: First dose over minimum 6 hours; subsequent doses over at least 4 hours

Treatment of Acute Rejection

• Dose: 1.5 mg/kg of body weight daily
• Duration: 7-14 days
• Administration: First dose over minimum 6 hours; subsequent doses over at least 4 hours

Cardiac Transplantation (Off-label Use)

For cardiac transplant patients with antibody-mediated rejection (AMR):

• Dose: 1.5 mg/kg daily
• Duration: 3-7 days
• Use: Consider in severe hemodynamic compromise with plasmapheresis 2

For pediatric heart transplant recipients (St. Louis Children's Hospital protocol):

• Dose: 1.5 mg/kg IV daily
• Duration: 5-7 days
• Administration: First dose over at least 6 hours; subsequent doses over 4 hours if through central line 2

Hematopoietic Stem Cell Transplantation (Off-label Use)

For severe aplastic anemia:

• Dose: 2.5 mg/kg daily
• Duration: 3 days (days -3, -2, and -1)
• Used in combination with: Fludarabine and cyclophosphamide 3

Administration Guidelines

Premedication

Premedicate 1 hour prior to each infusion with:

• Corticosteroids
• Acetaminophen (Tylenol)
• Antihistamine (Benadryl)

For pediatric patients:

• Benadryl 1 mg/kg
• Tylenol 10-15 mg/kg
• Methylprednisolone (dosing varies by day) 2

Monitoring and Dose Adjustments

Monitor during and after infusion:

• White blood cell (WBC) count
• Platelet count

Dose modifications:

• Reduce dose by 50% if WBC count is 2,000-3,000 cells/mm³ or platelet count is 50,000-75,000 cells/mm³
• Consider stopping treatment if WBC count <2,000 cells/mm³ or platelet count <50,000 cells/mm³ 1

Preparation and Administration

1. Reconstitution: Reconstitute each vial with 5 mL Sterile Water for Injection (resulting in 5 mg/mL)
2. Dilution: Transfer contents to infusion bag (saline or dextrose); use 50 mL of infusion solution per vial
3. Administration: Infuse through a 0.22 micron filter under strict medical supervision 1

Concomitant Medications

Thymoglobulin should be used with concomitant immunosuppressants:

• Consider prophylactic antifungal and antibacterial therapy
• Antiviral prophylaxis recommended for CMV-seropositive patients or CMV-seronegative recipients of organs from CMV-seropositive donors 1

Clinical Considerations

• Duration impact: A 7-day regimen (vs. 5-day) in heart transplantation leads to more efficient lymphocyte depletion and significantly less rejection at 1 year without increased CMV infection 4
• Dose-dependent effects: Ultra-low dose regimens (1.5 mg/kg total) deplete peripheral lymphocytes for shorter periods than standard doses (6.0 mg/kg total) 5
• Optimal cumulative dose: 6-7.5 mg/kg for induction therapy in kidney transplantation 6

Cautions and Contraindications

• Should only be used by physicians experienced in immunosuppressive therapy in transplantation
• Increased risk of infection and post-transplant lymphoproliferative disorder
• Monitor for infusion-related reactions, especially with first dose

Thymoglobulin's lack of nephrotoxicity makes it particularly valuable during the early post-transplant period, especially in donation after circulatory death programs 7.