FDA issues a section 505(o)(4) letter on pulmonary aspiration

The U.S. Food and Drug Administration notified drugmakers on September 6, 2024 that labeling for glucagon-like peptide-1 receptor agonist (GLP-1 RA) products must include new safety information about "the serious risk of pulmonary aspiration for patients undergoing elective surgeries or procedures requiring general anesthesia or deep sedation" ^[1]. The notice was issued under Section 505(o)(4) of the Federal Food, Drug, and Cosmetic Act, the provision FDA uses when it determines a labeling change is required rather than optional ^[1].

The letter's existence and its scope are documented in an FDA supplement approval letter to Eli Lilly and Company for Mounjaro (tirzepatide) injection, NDA 215866 ^[1]. That approval letter states that supplement S-022 "provides for revisions to the labeling for Mounjaro consistent with our September 6, 2024, letter and October 11 and 16, 2024, email correspondence" ^[1]. The approval was signed electronically by Monika A. Houstoun, Pharm.D., M.P.H., Deputy Director for Safety in FDA's Division of Diabetes, Lipid Disorders, and Obesity, on November 1, 2024 ^[1].

What the label change covers

Pulmonary aspiration means stomach contents entering the lungs. The risk FDA flagged is tied specifically to elective surgeries or procedures that require general anesthesia or deep sedation ^[1]. FDA described the information as applying to GLP-1 receptor agonist products as a class, not to a single brand ^[1].

The Mounjaro approval letter bundled three supplements. S-010 covers "updates to the Prescribing Information (PI) regarding severe gastrointestinal adverse reactions," plus the addition of dysgeusia (altered taste) to Section 6.1, Clinical Trials Experience, and revisions to the product description in Sections 11 and 12 ^[1]. S-015 adds dysesthesia — an abnormal or unpleasant sensation — to Section 6.1 ^[1]. S-022 is the aspiration labeling change ^[1]. Lilly's applications were dated and received December 8, 2023, April 19, 2024 and October 3, 2024 ^[1].

FDA gave Lilly 14 days from the date of the letter to submit the final content of labeling, including the Prescribing Information and Medication Guide, in structured product labeling format so it appears in public labeling repositories ^[1]. The agency also required that "all promotional materials that include representations about your drug product must be promptly revised to be consistent with the labeling changes approved in this supplement, including any new safety-related information," with "prominent disclosure of the important new safety-related information," and asked for a statement of intent to comply within seven days ^[1].

Several details are not in this document. It does not spell out the exact wording added to the Mounjaro label, does not give numbers on how often aspiration has occurred, and does not describe any recommendation about stopping or continuing a GLP-1 before a procedure ^[1]. It also does not list which other GLP-1 products received the same September 6 notice, beyond stating that the determination applies to GLP-1 RA products ^[1].

Why it matters for patients

GLP-1 medicines slow how fast the stomach empties. That is part of how they reduce appetite, but it also means food can remain in the stomach longer than anesthesia teams typically assume after standard fasting. FDA's action puts that concern into the official prescribing information for GLP-1 products rather than leaving it to professional society advisories ^[1].

Practically, a required label warning is the version of a safety issue that shows up in the package insert, in the Medication Guide patients receive at the pharmacy, and in the materials sales representatives and advertisements must use ^[1]. Anesthesiologists, surgeons and endoscopy teams increasingly ask patients whether they take a GLP-1 and when the last dose was. This labeling change is the regulatory basis for that question.

The change also arrived alongside other label updates for Mounjaro on severe gastrointestinal adverse reactions and on two symptoms — dysgeusia and dysesthesia — added to the clinical trials section ^[1]. Those additions reflect FDA's review of accumulated data rather than any new restriction on who can take the drug; the approval letter states the supplements were approved "for use as recommended in the enclosed agreed-upon labeling" ^[1].

What happens next

September 6, 2024: FDA issues the Section 505(o)(4) notification on pulmonary aspiration for GLP-1 receptor agonist products ^[1]. October 11 and 16, 2024: FDA and Lilly exchange email correspondence on the labeling text ^[1]. November 1, 2024: FDA approves supplements S-010, S-015 and S-022, effective on the date of the letter, with final labeling due within 14 days and promotional materials to be revised promptly ^[1]. Because the notice was class-wide, similar labeling updates would be expected for other GLP-1 products, though this document does not name them or give dates ^[1].