What should be done for a patient with a known allergy to naproxen (nonsteroidal anti-inflammatory drug (NSAID)) who took naproxen 9 hours ago and now presents with a rash and itchy throat?

Immediate Management of Allergic Reaction to Naproxen

This patient is experiencing an active allergic reaction with rash and itchy throat 9 hours after naproxen ingestion and requires immediate epinephrine administration followed by emergency department evaluation. 1, 2

Immediate Actions Required

Administer intramuscular epinephrine 0.3 mg (300 mcg) into the lateral thigh immediately. 3, 1, 4 The presence of both cutaneous symptoms (rash) and mucosal involvement (itchy throat) meets criteria for anaphylaxis, which requires prompt epinephrine as first-line treatment. 3, 1

• Call 911 or arrange immediate emergency transport after epinephrine administration 3, 5
• Position the patient lying flat with legs elevated if tolerated (unless respiratory distress worsens in this position) 3
• Prepare for repeat epinephrine dosing at 5-15 minutes if symptoms persist or progress 3

Why This Requires Urgent Treatment

The combination of rash and itchy throat represents involvement of two organ systems (skin and upper respiratory/mucosal), which defines anaphylaxis by established clinical criteria. 3 This is classified as a non-severe reaction by symptom criteria, but carries significant risk of rapid progression to life-threatening respiratory compromise or cardiovascular collapse. 3, 1

• Systemic allergic reactions can progress from mild to severe within minutes, and early epinephrine administration can prevent escalation 1, 4
• The itchy throat specifically indicates oropharyngeal involvement, which can rapidly progress to laryngeal edema and airway obstruction 3
• Naproxen's FDA labeling explicitly warns that anaphylactoid reactions may occur and can be fatal, requiring immediate emergency intervention 2

Secondary Medications (After Epinephrine)

After epinephrine administration, add:

• H1-antihistamine (diphenhydramine 25-50 mg IV/IM or cetirizine 10 mg PO) to help control urticaria and pruritus 3, 6, 4
• Corticosteroid (methylprednisolone 125 mg IV or prednisone 40-60 mg PO) to prevent biphasic reactions, though this has no role in acute symptom control 3, 6, 4
• Do NOT rely on antihistamines or corticosteroids as primary treatment - these are adjunctive only and will not prevent progression of anaphylaxis 1, 4

Emergency Department Management

The patient requires emergency department observation for minimum 6 hours after symptom resolution due to risk of biphasic reactions (recurrence of symptoms 6-12 hours after initial reaction). 3, 1

Emergency department should:

• Establish IV access and administer crystalloid fluids (500-1000 mL bolus) if any hypotension develops 3
• Monitor vital signs, oxygen saturation, and respiratory status continuously 3
• Have additional epinephrine and airway management equipment immediately available 3
• Consider epinephrine infusion (0.05-0.1 mcg/kg/min) if multiple boluses are required 3

Critical Pitfalls to Avoid

Do not delay epinephrine administration waiting for symptoms to worsen. 1, 4 The presence of itchy throat with rash already meets treatment criteria, and waiting for respiratory distress or hypotension significantly increases morbidity and mortality risk. 1, 7

• Do not give antihistamines first and observe - this is inadequate treatment for anaphylaxis 1, 4
• Do not assume the reaction has peaked because 9 hours have passed since ingestion - NSAID reactions can be delayed and prolonged 2
• Do not administer epinephrine subcutaneously - intramuscular injection into the lateral thigh provides faster, more reliable absorption 3, 8, 4

Post-Emergency Management

Before discharge from emergency care, ensure:

• Prescription for two epinephrine auto-injectors (0.3 mg for adults) with detailed instructions on use 3, 5
• Written anaphylaxis emergency action plan 3, 5
• Strict avoidance instructions for all NSAIDs, not just naproxen, due to high cross-reactivity risk 9, 2
• Referral to allergist-immunologist for formal evaluation within 1-2 weeks 3, 4
• Medical alert identification (bracelet/necklace) indicating NSAID allergy 3, 4

NSAID Cross-Reactivity Warning

This patient must avoid ALL NSAIDs indefinitely. 9, 2 Cross-reactivity between structurally different NSAIDs is common, particularly when respiratory or systemic symptoms occur. 9 This includes:

• Other propionic acids (ibuprofen, ketoprofen) 9
• Acetic acids (diclofenac, indomethacin) 9
• Oxicams (meloxicam, piroxicam) 9
• Aspirin and all COX-1 inhibiting NSAIDs 9, 2

Safe alternatives for pain management include acetaminophen (if tolerated) or selective COX-2 inhibitors (celecoxib), though the latter should only be introduced under allergist supervision with graded challenge. 9