Management of Hives Associated with Zepbound (Tirzepatide)

Assessment and Treatment

Assess for signs of anaphylaxis, including respiratory symptoms, hypotension, or gastrointestinal symptoms, which would require immediate intramuscular epinephrine administration, in patients with hives associated with Zepbound (Tirzepatide) 1
Evaluate the severity of hives as mild (<10% body surface area), moderate (10-30% body surface area), or severe (>30% body surface area or any respiratory involvement) in patients taking Zepbound (Tirzepatide) 2

For mild hives, start a non-sedating H1 antihistamine, such as cetirizine 10 mg daily, and apply cooling antipruritic lotions, such as calamine or 1% menthol in aqueous cream, for symptomatic relief in patients with Zepbound (Tirzepatide)-associated hives 2, 3
For moderate hives, increase the non-sedating H1 antihistamine dose up to 4 times the standard dose and add a sedating antihistamine at bedtime, such as hydroxyzine 10-25 mg, in patients with Zepbound (Tirzepatide)-associated hives 2, 3
For severe hives, administer systemic corticosteroids, such as prednisone 0.5-1 mg/kg/day, until hives resolve in patients with Zepbound (Tirzepatide)-associated hives 2

Never rechallenge with tirzepatide after a hypersensitivity reaction, as rechallenge can lead to serious and possibly fatal reactions, according to the British Journal of Pharmacology 4

Hives should begin improving within days of stopping Zepbound (Tirzepatide) and using antihistamines, with complete resolution typically occurring within 6 weeks in patients with Zepbound (Tirzepatide)-associated hives 2
If individual wheals persist >24 hours, skin biopsy is recommended to rule out urticarial vasculitis in patients with Zepbound (Tirzepatide)-associated hives 1

Avoid NSAIDs in all urticaria patients, as they can trigger or worsen urticaria, in patients with Zepbound (Tirzepatide)-associated hives 1
Consider subspecialty referral if urticaria is unresponsive to high-dose second-generation antihistamines (up to 4× standard dose) in patients with Zepbound (Tirzepatide)-associated hives 1