Infusion-associated reactions (IARs) from Thymoglobulin—typically cytokine release–mediated—can present with fever, chills, hypotension, bronchospasm, or anaphylaxis. Proper premedication and supportive response protocols are key to safe administration.

Standard Premedication Regimen

To reduce incidence and severity of IARs, the manufacturer (FDA) and institutional guidelines recommend premedicating 30–60 minutes before each infusion with the following :

Medication Typical Dose Route Timing/Notes
Acetaminophen 650–975 mg Oral 30 min before infusion for fever and chills prophylaxis
Diphenhydramine 25–50 mg PO or IV 30 min before infusion for histamine-mediated symptoms (itching, rash, bronchospasm)
Corticosteroid (e.g., Methylprednisolone) 40–125 mg IV 30 min before infusion to blunt cytokine release and prevent severe reactions

Premedication should be repeated before each daily dose of Thymoglobulin throughout the treatment course.​

Rescue and Management Medications

If infusion reactions occur despite premedication, interventions follow an escalation pathway:

For mild-to-moderate infusion reactions (fever, chills, rash, flushing):

  • Stop or slow the infusion.
  • Administer:
    • Acetaminophen 650–975 mg PO/PRN for persistent fever.
    • Diphenhydramine 25 mg IV for urticaria or rash.
    • Hydrocortisone or methylprednisolone 25–50 mg IV for progressive symptoms.​

For severe cytokine release or anaphylaxis:

  • Stop infusion immediately and initiate emergency protocols.
  • Epinephrine 0.3–0.5 mL of 1 mg/mL (1:1000) SC or IM, repeat every 5–15 min as needed.​
  • Provide oxygen supplementation, establish IV access, and administer normal saline bolus for hypotension.
  • Add additional antihistamines and high-dose corticosteroids (e.g., methylprednisolone 125 mg IV) as needed.
  • Initiate bronchodilators (albuterol nebulization 2.5 mg) for bronchospasm or wheezing.​

Nursing and Monitoring Parameters

  • Continuous monitoring during infusion for vital sign changes, respiratory distress, and hypersensitivity signs.
  • Maintain readiness of crash cart and epinephrine at bedside for all Thymoglobulin infusions.​
  • Resume infusion only when all symptoms resolve and at a slower rate; severe reactions warrant permanent discontinuation.​

Supportive Care Framework

Stage Medication/Intervention Primary Purpose
Premedication Acetaminophen 650–975 mg PO, Diphenhydramine 25–50 mg PO/IV, Methylprednisolone 40–125 mg IV Reduce fever, histamine release, and cytokine storm
Mild Reaction Pause/slower infusion, acetaminophen ± diphenhydramine IV Manage fever, rash, mild hypotension
Moderate Reaction Add corticosteroid IV, IV fluids, oxygen Control bronchospasm or significant hypotension
Anaphylaxis/Severe CRS Epinephrine SC/IM, oxygen, IV fluids, steroids, bronchodilator (albuterol) Reverse life-threatening systemic collapse

Clinical takeaway

Systematic premedication with acetaminophen, diphenhydramine, and corticosteroids, coupled with immediate access to epinephrine, oxygen, and albuterol, forms the cornerstone of Thymoglobulin safe administration. Early recognition and response to cytokine-release symptoms prevent progression to anaphylaxis, ensuring continued therapy tolerance.

References

  1. U.S. Food and Drug Administration. Thymoglobulin (anti-thymocyte globulin [rabbit]) for injection, for intravenous use: package insert. Updated 2024. Accessed October 26, 2025. https://www.fda.gov/media/74641/download
  2. EdRen: The Renal Unit Handbook. ATG (Anti-thymocyte Globulin). Updated 2025. Accessed October 26, 2025. https://edren.org/ren/handbook/transplant-handbook/immunosuppressive-drugs/atg-anti-thymocyte-globulin/
  3. Cooley Dickinson Health Care. Thymoglobulin (Anti-thymocyte Globulin [Rabbit]) Administration Guidelines. Published June 2018. Accessed October 26, 2025. https://www.cooleydickinson.org/wp-content/uploads/2018/06/208-236-THYMOGLOBULIN.pdf
  4. OncoLink. Thymoglobulin® (Antithymocyte Globulin [Rabbit]). Updated 2023. Accessed October 26, 2025. https://www.oncolink.org/cancer-treatment/oncolink-rx/thymoglobulin-r-antithymocyte-globulin-rabbit