What to do for a patient experiencing hives associated with Mounjaro (tirzepatide)?

Management of Hives Associated with Zepbound (Tirzepatide)

Discontinue Zepbound immediately if hives develop, as serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with tirzepatide, and do not rechallenge with the medication. 1

Immediate Assessment and Drug Discontinuation

• Stop tirzepatide immediately upon recognition of hives, as the FDA label explicitly warns that serious hypersensitivity reactions (anaphylaxis, angioedema) have occurred in patients treated with Mounjaro/Zepbound 1
• Assess for signs of anaphylaxis including respiratory symptoms (dyspnea, wheezing), hypotension, or gastrointestinal symptoms, which would require immediate intramuscular epinephrine administration 2
• Evaluate the severity of hives: mild (<10% body surface area), moderate (10-30% body surface area), or severe (>30% body surface area or any respiratory involvement) 3
• Do not use tirzepatide in patients with a previous serious hypersensitivity reaction to tirzepatide or any excipients, and use caution in patients with a history of angioedema or anaphylaxis with other GLP-1 receptor agonists 1

Treatment Based on Severity

For Mild Hives

• Start a non-sedating H1 antihistamine: cetirizine 10 mg daily, loratadine 10 mg daily, fexofenadine, desloratadine, or levocetirizine 3, 4
• Apply cooling antipruritic lotions such as calamine or 1% menthol in aqueous cream for symptomatic relief 4
• Advise patients to avoid aggravating factors including overheating, stress, and alcohol 4

For Moderate Hives

• Increase the non-sedating H1 antihistamine dose up to 4 times the standard dose when benefits outweigh risks 3, 4
• Add a sedating antihistamine at bedtime (hydroxyzine 10-25 mg or chlorphenamine 4-12 mg) if sleep is disrupted 3, 4
• Consider adding an H2 antihistamine, as combination therapy may provide better control than H1 antihistamine alone 4

For Severe Hives

• Administer systemic corticosteroids such as prednisone 0.5-1 mg/kg/day until hives resolve 3
• Seek immediate medical attention if breathing difficulty, widespread urticaria, or signs of anaphylaxis develop 3
• Consider adding montelukast for refractory cases 4

Critical Management Points

• Never rechallenge with tirzepatide after a hypersensitivity reaction, as rechallenge can lead to serious and possibly fatal reactions occurring much sooner than on first exposure 5, 1
• Treat promptly per standard of care and monitor until signs and symptoms resolve 1
• It is unknown whether patients with a history of angioedema or anaphylaxis with other GLP-1 receptor agonists will be predisposed to these reactions with tirzepatide 1

Expected Timeline and Follow-up

• Hives should begin improving within days of stopping tirzepatide and using antihistamines, with complete resolution typically occurring within 6 weeks 3
• Recurrent urticaria may occur over 1-2 days following the initial episode 3, 4
• Schedule follow-up visits to assess treatment response and discuss alternative diabetes or weight management strategies 3, 4
• If individual wheals persist >24 hours, skin biopsy is recommended to rule out urticarial vasculitis 2

Alternative Medication Considerations

• Avoid NSAIDs in all urticaria patients as they can trigger or worsen urticaria through non-IgE mechanisms 2
• Consider subspecialty referral if urticaria is unresponsive to high-dose second-generation antihistamines (up to 4× standard dose) 2