FDA asked Lilly to add intestinal obstruction to the Zepbound label
Zepbound's label now lists intestinal obstruction and fecal impaction as postmarketing reports, and drops suicidal ideation language that patients may have seen in the medication guide.
The FDA issued a supplement request letter to Eli Lilly on October 14, 2025, asking the company to update the prescribing information for Zepbound (tirzepatide) to address reports of intestinal obstruction and fecal impaction, according to the approval letter that documents the resulting label change [1].
The request followed a Notification of Newly Identified Safety Signal (NISS) email the agency sent Lilly on April 28, 2025. In that email, FDA said it was evaluating a newly identified safety signal for intestinal obstruction and fecal impaction for the GLP-1 receptor agonist class, of which Zepbound is a member [1]. Zepbound is a tirzepatide injection; the same molecule is sold as Mounjaro, while semaglutide is sold as Ozempic, Wegovy and Rybelsus.
Lilly submitted the resulting supplemental new drug application on November 14, 2025, with amendments, and FDA reviewed it [1]. The letter describes two specific changes to the Zepbound prescribing information [1]:
- Section 5, Warnings and Precautions, under "Severe Gastrointestinal Adverse Reactions," now states: "Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists." [1]
- Section 6, Adverse Reactions, under "Postmarketing Experience," now lists "intestinal obstruction, severe constipation including fecal impaction." [1]
The same supplement also removed suicidal ideation information. FDA said it had sent Lilly a separate safety-signal notification about suicidal ideation for the GLP-1 receptor agonist class on July 21, 2023, and issued a supplement request letter on January 13, 2026, asking that the information be taken out [1]. That removal covers subsection 5.9, Suicidal Ideation and Behavior, in the Warnings and Precautions section, along with updates to the Highlights of Prescribing Information, the table of contents, Section 6, Section 17 and the Recent Major Changes section [1]. The Medication Guide no longer lists "depression or thoughts of suicide" among possible side effects [1]. FDA said those changes were made during review of this supplement rather than in a separate filing [1].
The agency's letter is signed February 25, 2026 [1]. The letter does not say how many reports of intestinal obstruction or fecal impaction were submitted, whether FDA concluded the drug caused those events, or whether labels for other GLP-1 receptor agonists will change. Those details have not been disclosed.
Why it matters for patients
The prescribing information is the document clinicians and patients consult for a drug's known risks, and both changes affect what it says. Intestinal obstruction and severe constipation including fecal impaction are now disclosed as postmarketing reports for Zepbound, and the warnings section now notes that severe gastrointestinal reactions have been reported after approval across the GLP-1 receptor agonist class [1]. Postmarketing reports are voluntary accounts of events that occurred in people taking a drug; they do not by themselves establish that the drug caused the event, and the letter does not give rates or frequencies for either condition [1].
At the same time, the label loses a warning subsection and the Medication Guide loses a side-effect line about depression or thoughts of suicide [1]. That means patients comparing an older copy of the Zepbound label or Medication Guide with the current version may find the two do not match. The letter does not explain the reasoning behind the removal, beyond stating that it followed FDA's evaluation of the 2023 safety signal and a January 13, 2026 request [1].
What happens next
FDA set several deadlines for Lilly in the letter [1]. Within 14 days of the letter, the company must submit the content of labeling in structured product labeling format and amend pending supplements that include labeling changes for this application. Within 7 days, Lilly must file a statement of intent to comply with requirements that promotional materials be revised to match the approved labeling, including prominent disclosure of the new safety information. Within 30 days, any required patent information must be submitted for listing in the Orange Book. The letter does not give a date for when updated labeling will appear in public drug labeling repositories [1].
Sources
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