What should be done if a patient on Augmentin (amoxicillin/clavulanate) develops hives?

Management of Hives in a Patient on Augmentin

Discontinue Augmentin immediately—this represents an allergic hypersensitivity reaction to amoxicillin/clavulanate that requires stopping the medication and avoiding all penicillin-based antibiotics going forward. 1

Immediate Actions

Stop the medication now. The FDA label explicitly states that if an allergic reaction occurs, amoxicillin should be discontinued and appropriate therapy instituted. 1 This is a hypersensitivity reaction that can progress to more severe manifestations including anaphylaxis. 1

Assess the severity of the urticaria to guide treatment intensity:

• Mild: Less than 3 hives 2
• Moderate: 3-10 hives 2
• Severe: Generalized involvement 2

Screen for signs of anaphylaxis immediately, including respiratory symptoms (wheezing, dyspnea, throat tightness), hypotension, or gastrointestinal symptoms (vomiting, diarrhea, severe abdominal pain). 3, 4 If any of these are present, administer intramuscular epinephrine 0.3-0.5 mg into the lateral thigh and call 911. 4

Treatment Based on Severity

For Mild to Moderate Hives (Most Common Scenario)

Start a non-sedating H1 antihistamine immediately:

• Cetirizine 10 mg daily, OR
• Loratadine 10 mg daily, OR
• Fexofenadine 180 mg daily, OR
• Levocetirizine 5 mg daily 2, 5

If inadequate response within 24-48 hours, increase the antihistamine dose up to 4 times the standard dose (e.g., cetirizine 40 mg daily). 2, 5 This off-label dosing is recommended when benefits outweigh risks.

Add a sedating antihistamine at bedtime if sleep is disrupted by itching:

• Hydroxyzine 10-25 mg at night, OR
• Chlorphenamine 4-12 mg at night 2, 5

For Severe or Generalized Hives

Administer oral corticosteroids:

• Prednisone 0.5-1 mg/kg/day (typically 40-60 mg for adults) for 3-5 days 5, 4
• Continue non-sedating antihistamines as above 2

Monitor closely for progression to more severe cutaneous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS syndrome), which would require immediate hospitalization. 1

Critical Management Points

Warn the patient about recurrent urticaria over the next 1-2 days even after stopping the medication—this is expected and does not indicate treatment failure. 3, 2 Continue antihistamines during this period.

Document the allergy prominently in the medical record as "penicillin allergy" or specifically "amoxicillin/Augmentin allergy." 1

Avoid all penicillin-based antibiotics permanently, including amoxicillin, ampicillin, and penicillin V. 1, 6 Cross-reactivity with cephalosporins occurs in approximately 1-10% of penicillin-allergic patients, so use cephalosporins with caution only if absolutely necessary. 6, 7

Prescribe an alternative antibiotic if the original infection still requires treatment—choose an agent from a completely different class (e.g., azithromycin, doxycycline, or fluoroquinolones depending on the indication). 6

Follow-Up and Patient Education

Provide an emergency action plan that includes instructions to seek immediate care if breathing difficulty, widespread urticaria, or facial/throat swelling develops. 3

Consider prescribing an epinephrine auto-injector if the patient had moderate-to-severe urticaria, as this indicates higher risk for future severe reactions. 3

Schedule follow-up in 3-5 days to ensure complete resolution of hives and adequate symptom control. 2

Expected timeline: Hives should begin improving within 24-48 hours of stopping Augmentin and starting antihistamines, with complete resolution typically within 1-2 weeks. 2, 8

Common Pitfall to Avoid

Do not rechallenge with Augmentin or any penicillin to "test" if the allergy is real—this can precipitate anaphylaxis. 1, 9 The development of hives after 2 days of therapy is a classic presentation of immediate-type penicillin hypersensitivity. 9