What is the oral prednisone (corticosteroid) dose to prevent a biphasic reaction after an epinephrine (adrenaline) injection?

From the Guidelines

The use of oral prednisone to prevent biphasic anaphylactic reactions after epinephrine injection is not recommended due to low certainty of evidence and potential harm, as suggested by the most recent study 1. Instead, the focus should be on prompt and adequate treatment of anaphylaxis with epinephrine, as well as education on avoiding known triggers, identification of symptoms, and timely follow-up with an allergist. The management of anaphylaxis should prioritize the administration of epinephrine, with antihistamines and glucocorticoids considered as secondary therapies, but not as a means to prevent biphasic anaphylaxis, as stated in 1. Key considerations in the management of anaphylaxis include:

• Prompt administration of epinephrine
• Education on avoiding known triggers and identifying symptoms
• Timely follow-up with an allergist
• Consideration of extended observation for patients with severe anaphylaxis or those requiring multiple doses of epinephrine, as suggested in 1
• Administration of antihistamines and glucocorticoids as secondary therapies, but with caution due to potential side effects and low certainty of evidence, as noted in 1. It is essential to prioritize the administration of epinephrine and focus on supportive care, rather than relying on oral prednisone to prevent biphasic reactions, as the current evidence does not support its use for this purpose, as indicated by 1.

From the Research

Oral Prednisone Dose to Prevent Biphasic Reaction

• The optimal oral prednisone dose to prevent biphasic reaction after epinephrine injection is not clearly established in the provided studies 2, 3, 4, 5, 6.
• However, some studies suggest that corticosteroids, such as prednisone, may decrease the incidence of biphasic reactions 4, 5.
• A study published in 2024 found that patients who received epinephrine and a corticosteroid had a lower rate of biphasic reactions compared to those who did not receive a corticosteroid 5.
• The dose of prednisone used in these studies is not specified, but a common dose range for oral prednisone in the treatment of anaphylaxis is 1-2 mg/kg/day, with a maximum dose of 50-60 mg/day 3, 4.

Risk Factors for Biphasic Reactions

• Several studies have identified risk factors for biphasic reactions, including:
  • Delayed administration of epinephrine 2, 4
  • Severity of anaphylaxis 3, 4
  • Presence of respiratory symptoms 6
  • Involvement of multiple organ systems 6
• However, the generalizability of these risk factors is questionable, and further research is needed to identify true risk factors associated with biphasic anaphylaxis 2, 4.

Observation Period for Biphasic Reactions

• The optimal observation period for biphasic reactions after epinephrine administration is not clearly established, but most studies recommend an observation period of 4-6 hours 2, 4, 6.
• A study published in 2024 found that extending the observation period beyond 4-6 hours did not reduce the number of patients who experienced a biphasic reaction after discharge 6.
• Another study published in 2025 found that children with anaphylaxis who exhibit symptomatic resolution 4 hours after initiation of therapy have a low risk for subsequently developing a biphasic reaction 5.