Mounjaro (Tirzepatide) Injection Site Reactions: Severity Grading Rubric and Management

What does the Mounjaro label say about injection site reactions?

In the label's pool of placebo-controlled adult trials, injection site reactions were reported in 3.2% of Mounjaro-treated patients versus 0.4% of placebo-treated patients; hypersensitivity reactions were reported in 3.2% versus 1.7% [2]. Table 1 of the label lists the adverse reactions reported in at least 5% of patients: nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, and abdominal pain [2].

The label's serious warning covers hypersensitivity. Anaphylaxis and angioedema have been reported with Mounjaro, and the label says to discontinue Mounjaro and promptly seek medical advice if a serious hypersensitivity reaction is suspected [2]. Known serious hypersensitivity to tirzepatide or any excipient is a contraindication [2]. The label also says to use caution in patients with a history of angioedema or anaphylaxis with a GLP-1 receptor agonist, because it is unknown whether such patients will be predisposed to these reactions with Mounjaro [2].

How severe were the reactions in the trials?

In a pooled immunogenicity analysis of 5,025 tirzepatide-treated adults with type 2 diabetes across seven phase 3 trials, treatment-emergent anti-drug antibodies developed in 51.1% of patients [1]. More antibody-positive patients had hypersensitivity or injection-site reactions than antibody-negative patients, but the majority of those reactions were nonserious and nonsevere, and most occurred or resolved regardless of antibody status or titer [1]. The analysis concluded that the majority of hypersensitivity and injection-site reactions in antibody-positive patients were mild to moderate in severity, and that antibody status did not affect pharmacokinetics or efficacy [1]. The label gives 119 of 2,570 antibody-positive adults (4.6%) versus 18 of 2,455 antibody-negative adults (0.7%) for injection site reactions [2].

What the label says to do

The label says to inject Mounjaro subcutaneously in the abdomen, thigh, or back of the upper arm by another person, and to rotate injection sites with each dose [2].

The label's stop point is suspected serious hypersensitivity: it says to discontinue Mounjaro and promptly seek medical advice [2]. Suspected adverse reactions can be reported to Eli Lilly at 1-800-545-5979 or to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch [2].