Zepbound (Tirzepatide) Injection Site Reactions: Severity Grading Rubric

What does the Zepbound label report?

In the pooled placebo-controlled weight-management trials (SURMOUNT-1 and SURMOUNT-2), injection site reactions were reported in 2% of placebo-treated patients and 6%, 8%, and 8% of patients treated with Zepbound 5 mg, 10 mg, and 15 mg once weekly [1]. The pool included 958 placebo patients and 630, 948, and 941 patients on the three Zepbound doses, with treatment up to 72 weeks [1]. Hypersensitivity reactions were reported in 3% of placebo patients and 5% at each Zepbound dose [1].

Injection site reactions also appear in the label's list of adverse reactions reported in at least 5% of Zepbound-treated patients, alongside nausea, diarrhea, vomiting, constipation, abdominal pain, dyspepsia, fatigue, hypersensitivity reactions, eructation, hair loss, and gastroesophageal reflux disease [1].

Which reactions does the label count at the injection site?

Table 1 of the Zepbound label pools several local terms into a single row: injection site bruising, injection site erythema, injection site pruritus, injection site pain, injection site rash, and injection site reaction [1]. That pooled row is what the 6%, 8%, and 8% figures describe, against 2% on placebo [1].

How severe were injection site reactions in trials?

In an immunogenicity analysis of 5,025 tirzepatide-treated adults with type 2 diabetes across seven phase 3 trials, more patients with treatment-emergent anti-drug antibodies experienced hypersensitivity reactions or injection site reactions than patients without them, and the majority of those reactions were nonserious and nonsevere [2]. Treatment-emergent antibodies developed in 51.1% of patients, and antibody status, titer, and neutralizing antibody status had no effect on pharmacokinetics or efficacy [2].

What serious reactions does the label describe?

Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported postmarketing with tirzepatide [1]. In the pooled weight-management trials, 0.1% of Zepbound-treated patients had severe hypersensitivity reactions compared with no placebo-treated patients [1]. The label says patients should promptly seek medical attention and discontinue Zepbound if a serious hypersensitivity reaction is suspected [1]. Zepbound is contraindicated in patients with a known serious hypersensitivity to tirzepatide or any of the excipients in Zepbound [1].

What injection technique does the label specify?

The label directs injection into the abdomen, thigh, or back of the upper arm, with the upper arm injected by another person, and says to rotate sites [1]. It names vial, prefilled single-dose pen, and single-patient-use KwikPen presentations and says patients should be trained on the specific presentation [1].