What is the treatment for a rash caused by amoxicillin (amoxicillin)?

Treatment for Amoxicillin Rash

For mild maculopapular amoxicillin rash, discontinue the drug if bothersome, treat symptomatically with oral antihistamines and topical corticosteroids, and use acetaminophen or ibuprofen for fever or discomfort. 1

Immediate Assessment: Rule Out Life-Threatening Conditions

Before treating symptomatically, you must first exclude severe reactions and dangerous mimics:

• Stop amoxicillin immediately if any skin rash develops 2
• Urgent evaluation required if fever accompanies the rash with palmar/plantar involvement—this demands immediate assessment for Rocky Mountain Spotted Fever or meningococcemia, not drug reaction 3
• Transfer to emergency care immediately if any of these features are present: blistering, skin exfoliation, mucosal involvement (Stevens-Johnson syndrome/toxic epidermal necrolysis), respiratory symptoms, cardiovascular symptoms, or angioedema 1, 4, 2

Symptomatic Treatment for Uncomplicated Maculopapular Rash

For the typical benign maculopapular rash without concerning features:

• Oral antihistamines for pruritus 1
• Topical corticosteroids for local inflammation 1
• Acetaminophen or ibuprofen for associated fever or discomfort 1, 4
• Monitor closely over 24-48 hours for progression; if lesions progress, discontinue monitoring and seek emergency evaluation 4, 2

Antibiotic Management During Active Infection

If the patient still requires antibiotic therapy for a concurrent bacterial infection:

• Switch to a non-beta-lactam antibiotic such as a macrolide 1, 4
• The American Academy of Otolaryngology-Head and Neck Surgery recommends this approach for patients with mild maculopapular rash being treated for active infection 1
• Important caveat: Most cases of mononucleosis are self-limiting and do not require antibacterial therapy—the rash itself does not indicate bacterial infection requiring antibiotics 4

Critical Distinction: Viral Interaction vs. True Allergy

Understanding the mechanism is essential for future management:

• 30-100% of patients with infectious mononucleosis (Epstein-Barr virus) develop a non-pruritic morbilliform rash when given amoxicillin—this is NOT a true drug allergy but rather a unique virus-drug interaction 1, 4, 2
• Over 90% of children with reported amoxicillin rashes tolerate the drug on re-exposure 4
• Do NOT label patients as "penicillin allergic" based solely on a maculopapular rash during viral illness 4
• The vast majority of delayed amoxicillin rashes are not true drug allergies and do not require permanent penicillin avoidance 4

Documentation and Future Use

Patients who develop maculopapular rash during mononucleosis can typically take penicillins safely after the EBV infection resolves 4

For appropriate documentation:

• Document the reaction in the medical record 1
• Specify the type of rash (maculopapular vs. urticarial), timing, and associated symptoms 1, 4
• Note whether concurrent viral illness (especially mononucleosis) was present 4

Allergy Testing and Rechallenge

For patients with past maculopapular rash without systemic symptoms:

• Direct amoxicillin challenge (single dose under medical observation) is recommended when the infection resolves to confirm tolerance 4, 3
• Reaction rates on rechallenge are 5-10%, generally no more severe than the original reaction 4
• Penicillin skin testing has limited utility for non-IgE-mediated reactions like maculopapular rashes and should NOT be used for this purpose 4, 3

When to Refer to Allergy/Immunology

• Severe reactions (anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis) require formal allergy evaluation and permanent avoidance of penicillins 1, 2
• Consider allergy consultation for clarification of true allergy status when there is uncertainty 1, 4
• Immediate-onset reactions (within 1 hour) with urticaria, angioedema, or anaphylaxis suggest true IgE-mediated drug allergy requiring specialist evaluation 4

Common Pitfalls to Avoid

• Do not permanently label children as penicillin-allergic based on rashes during viral illnesses—this leads to unnecessary use of broader-spectrum, less effective antibiotics with increased healthcare costs and antibiotic resistance 4
• Do not perform penicillin skin testing for maculopapular rashes—it has poor sensitivity/specificity for delayed reactions 4, 3
• Do not continue amoxicillin in patients with known mononucleosis—the FDA label specifically warns that a high percentage develop erythematous skin rash, and amoxicillin should not be administered to these patients 2
• If a patient had a negative strep test and developed a rash, the original indication for antibiotics was likely inappropriate (viral illness), and the child should not receive future amoxicillin restrictions 4