What is the likelihood of anaphylaxis in a pediatric or young adult patient with a history of peanut allergy and severe allergic reactions when taking Palforzia (peanut oral immunotherapy) and ibuprofen (nonsteroidal anti-inflammatory drug) concurrently?

Risk of Anaphylaxis with Concurrent Palforzia and Ibuprofen Use

The concurrent use of ibuprofen (or other NSAIDs) with Palforzia increases the risk of anaphylaxis, as NSAIDs are recognized cofactors that lower the threshold for anaphylactic reactions during oral immunotherapy. 1

Understanding the Mechanism

NSAIDs, including ibuprofen, function as cofactors that can lower the threshold at which allergen triggers cause anaphylaxis. 1 This means that a patient on Palforzia who takes ibuprofen may experience an anaphylactic reaction to a dose of peanut protein that would otherwise be tolerated. The mechanism involves NSAIDs potentially enhancing mast cell degranulation and increasing intestinal permeability to allergens. 1

Baseline Risk with Palforzia Alone

Palforzia itself carries inherent anaphylaxis risk:

• Palforzia is specifically indicated to mitigate allergic reactions, including anaphylaxis, but paradoxically can also cause anaphylaxis during treatment. 2
• All patients on Palforzia must maintain strict peanut avoidance in their diet and carry injectable epinephrine at all times due to the risk of drug-related anaphylaxis. 2
• In clinical trials, gastrointestinal, respiratory, and dermatologic manifestations consistent with allergic reactions were commonly reported. 2

Quantifying the Added Risk

While specific incidence data for the combination of Palforzia plus NSAIDs is not available in the provided evidence, the clinical significance is clear:

• Cofactors like NSAIDs are documented to increase anaphylaxis risk during allergen immunotherapy. 1
• Other recognized cofactors include exercise, upper respiratory infections, fever, emotional stress, and perimenstrual status. 1
• Adolescents with peanut allergies are already at highest risk for life-threatening anaphylaxis, making additional risk factors particularly concerning. 3

Clinical Management Recommendations

Patients on Palforzia should avoid ibuprofen and other NSAIDs, particularly around the time of Palforzia dosing. 1 If pain or fever management is needed:

• Consider acetaminophen as an alternative analgesic/antipyretic, as it is not classified as an NSAID cofactor. 1
• If NSAID use is unavoidable, ensure the patient takes Palforzia at a different time of day, though this does not eliminate risk entirely. 1
• Maintain heightened vigilance for anaphylaxis symptoms when any cofactor is present. 1

Critical Safety Measures

All patients on Palforzia must have:

• Two epinephrine autoinjectors available at all times (one dose may be insufficient, and a second may be needed before emergency services arrive). 4
• Clear understanding that epinephrine is the first-line treatment for anaphylaxis and must not be delayed. 1, 4
• An anaphylaxis emergency action plan with proper instruction for epinephrine self-administration. 5
• Awareness that delayed epinephrine administration is associated with increased hospitalization risk and fatalities. 1

Common Pitfalls to Avoid

• Never delay epinephrine administration based on symptom severity - oral itching plus gastrointestinal symptoms already constitutes multi-system involvement meeting anaphylaxis criteria. 4
• Do not rely solely on antihistamines for initial treatment, as severe respiratory and cardiovascular symptoms can appear suddenly. 4
• Recognize that many patients fail to use epinephrine autoinjectors even during severe symptoms due to fear of needles or concerns about adverse effects. 5