What is the recommended dose and administration of hydrocortisone (cortisol) as a premedication for patients at high risk of infusion-related reactions prior to receiving liposomal amphotericin B (antifungal medication)?

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Hydrocortisone Premedication Before Liposomal Amphotericin B

Hydrocortisone premedication is NOT routinely recommended before liposomal amphotericin B; instead, use diphenhydramine or acetaminophen as first-line premedication, reserving glucocorticosteroids (such as hydrocortisone 25 mg IV) only for patients who develop severe infusion-related reactions despite standard premedication. 1, 2

Standard Premedication Protocol

The recommended approach for preventing infusion-related reactions with liposomal amphotericin B includes:

  • Diphenhydramine or acetaminophen should be administered prior to infusion as the primary premedication strategy 1, 2
  • Administer 1 L of normal saline before and after the infusion in patients who can tolerate fluids to reduce nephrotoxicity 1, 2
  • This standard premedication approach is effective for most patients receiving liposomal amphotericin B 1

When to Consider Glucocorticosteroids

Glucocorticosteroids like hydrocortisone have a limited role and should only be used in specific circumstances:

  • Reserve glucocorticosteroids for rare cases where severe infusion-related reactions occur despite standard premedication with diphenhydramine and acetaminophen 3
  • If glucocorticosteroids are needed, administer approximately 30 minutes before the infusion 3
  • The typical dose used in clinical practice is hydrocortisone 25 mg IV, based on historical protocols 4

Important Clinical Context

The evidence strongly suggests against routine glucocorticosteroid premedication:

  • Liposomal amphotericin B has significantly fewer infusion-related reactions (20%) compared to conventional amphotericin B (44-54%), making aggressive premedication less necessary 5, 6
  • Empirical premedication regimens (including corticosteroids) showed no superiority over no pretreatment in preventing infusion-related adverse events in a large prospective study of 397 patients 7
  • The recommended strategy is to treat symptoms when they first arise, then premedicate for subsequent infusions rather than using empirical premedication for all patients 7

Monitoring During Infusion

If infusion-related reactions occur despite premedication:

  • Monitor for chest pain, dyspnea, hypoxia, severe abdominal/flank/leg pain, flushing, and urticaria 1, 5
  • Temporarily interrupt the infusion and administer intravenous diphenhydramine if reactions develop 1
  • Consider adding hydrocortisone for subsequent infusions only if reactions were severe 3

Common Pitfalls to Avoid

  • Do not routinely use hydrocortisone premedication as it adds unnecessary medication exposure without proven benefit for most patients receiving liposomal amphotericin B 7
  • Do not assume cross-reactivity between different amphotericin B formulations—patients who react to one lipid formulation may tolerate another 8
  • Distinguish between liposomal amphotericin B and conventional amphotericin B—the latter has much higher rates of infusion reactions and historically required more aggressive premedication strategies 9, 6

References

Guideline

Administration Protocol for Lyophilized Amphotericin B

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Liposomal Amphotericin B Treatment for Severe Fungal Infections

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Side Effects of Liposomal Amphotericin B

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Pretreatment regimens for adverse events related to infusion of amphotericin B.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 1995

Research

Apparent lack of cross-reactivity for infusion-related reactions between two forms of lipid-based amphotericin B.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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