FDA approves Mounjaro labeling update on aspiration risk and gastrointestinal reactions

The FDA approved three labeling supplements for Mounjaro (tirzepatide) injection on Nov. 1, 2024, adding a serious risk warning about pulmonary aspiration during general anesthesia or deep sedation and updating information on severe gastrointestinal reactions, taste distortion (dysgeusia) and abnormal sensations (dysesthesia) ^[1].

The agency's approval letter to Eli Lilly and Company covers supplemental new drug applications S-010, S-015 and S-022, received Dec. 8, 2023, April 19, 2024 and Oct. 3, 2024 ^[1].

S-010 updates the Prescribing Information regarding severe gastrointestinal adverse reactions and adds dysgeusia to Section 6.1, Clinical Trials Experience. It also revises the product description in Sections 11 and 12 ^[1]. S-015 adds dysesthesia to the same clinical trials section ^[1].

S-022 brings the Mounjaro label in line with a Sept. 6, 2024 FDA letter to Lilly, which notified the company under Section 505(o)(4) of the Federal Food, Drug, and Cosmetic Act of new safety information FDA determined should be included in labeling for glucagon-like peptide-1 receptor agonist (GLP-1 RA) products: the serious risk of pulmonary aspiration for patients undergoing elective surgeries or procedures requiring general anesthesia or deep sedation ^[1]. The supplement also reflects Oct. 11 and 16, 2024 email correspondence with the company ^[1].

The letter does not say how often aspiration or the other events occurred, what the new label language states word for word, or how many patients were studied. Those details have not been disclosed in the approval letter ^[1].

This action covers Mounjaro only. The September letter named GLP-1 RA products as a class, but this approval letter does not say whether or when labels for other products were changed ^[1].

Approval was effective the date of the letter, and the document is signed by Monika Houstoun, Pharm.D., M.P.H., deputy director for safety in FDA's Division of Diabetes, Lipid Disorders, and Obesity ^[1].

Why it matters for patients

Pulmonary aspiration means material from the stomach enters the airway, which can cause serious lung injury. The new labeling draws attention to that risk for people taking Mounjaro who are scheduled for elective procedures involving general anesthesia or deep sedation ^[1]. GLP-1 medications are known to slow stomach emptying, which is part of why regulators have examined this question, though the letter does not describe the mechanism or the evidence behind the warning ^[1].

The addition of dysgeusia and dysesthesia to the clinical trials section means patients may see taste changes and unusual skin sensations listed among reported side effects. The letter does not give rates for either event or explain how they were defined in trials ^[1].

Severe gastrointestinal reactions were already a known concern with this drug class, and S-010 changes how that information is presented. The letter does not specify what was altered ^[1].

For patients with an upcoming procedure, the new labeling makes the anesthesia and surgical team's knowledge of GLP-1 use relevant. Whether to pause or continue Mounjaro before a procedure is a clinical judgment, and the approval letter does not address stopping or continuing the drug ^[1].

What happens next

Lilly must submit the updated labeling in structured product labeling format within 14 days of the Nov. 1 letter, which falls around mid-November 2024 ^[1]. Within seven days, the company must file a statement of intent to comply with requirements that promotional materials be revised to match the new labeling and prominently disclose the new safety information ^[1]. Any patent information tied to the changes is due on Form FDA 3542 within 30 days ^[1].

Because FDA classifies Mounjaro as a Part 3 combination product, Lilly must also follow postmarketing safety reporting rules for combination products ^[1].