FDA approves Zepbound label update removing suicidal ideation warning and adding intestinal obstruction

The FDA has approved a labeling change for Zepbound (tirzepatide) injection and Zepbound KwikPen that removes the drug's suicidal ideation and behavior warning and adds intestinal obstruction and severe constipation, including fecal impaction, to the list of postmarketing adverse reactions ^[1]. The approval letter for supplement S-042 was signed February 25, 2026, and the agency said the application is approved effective on the date of the letter ^[1].

Eli Lilly and Company submitted the supplemental new drug application on November 14, 2025 ^[1]. The supplement carried two sets of labeling changes that trace back to separate FDA safety reviews.

On April 28, 2025, the FDA emailed Lilly about a newly identified safety signal for intestinal obstruction and fecal impaction involving the GLP-1 receptor agonist class, of which Zepbound is a member, and followed with a supplement request letter on October 14, 2025 ^[1]. In response, the label now includes this sentence in Section 5, Warnings and Precautions, under Severe Gastrointestinal Adverse Reactions: "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 second change concerns suicidal ideation. The FDA said it notified Lilly on July 21, 2023, that it was evaluating a safety signal for suicidal ideation for the GLP-1 receptor agonist class ^[1]. On January 13, 2026, the agency sent a supplement request letter asking that information about suicidal ideation be removed from the Zepbound label, and the letter states those changes were made during review of S-042 rather than in a separate supplement ^[1].

As a result, subsection 5.9, Suicidal Ideation and Behavior, has been removed from the Warnings and Precautions section of the prescribing information, with corresponding updates to the Highlights of Prescribing Information, the table of contents, Section 6, Section 17 and the Recent Major Changes section ^[1]. The line "depression or thoughts of suicide" has also been removed from the possible side effects section of the Medication Guide ^[1].

The approval letter does not give numbers of reported cases, rates or clinical trial data behind either change. How often intestinal obstruction, fecal impaction or severe constipation occur among people taking Zepbound is not stated in the letter. The letter also does not describe the evidence the FDA reviewed before concluding that the suicidal ideation information should be removed. Postmarketing experience reflects reports submitted after a drug is approved, and such reports do not by themselves establish that a drug caused the event.

The letter notes that the pediatric assessment requirement under the Pediatric Research Equity Act does not apply to this supplement ^[1].

Why it matters for patients

For people taking or considering Zepbound, the documents their clinicians and pharmacists rely on have changed. Suicidal ideation and behavior are no longer listed as a warning in the prescribing information, and the Medication Guide no longer names depression or thoughts of suicide among possible side effects ^[1]. At the same time, the label now discloses that intestinal obstruction and severe constipation, including fecal impaction, have been reported after the drug reached the market ^[1].

Because the letter does not report how many of these gastrointestinal events occurred or how frequently, patients and clinicians cannot use it to estimate individual risk. The letter also does not say whether the same labeling changes are being made to other GLP-1 receptor agonist products, only that the safety signals it cites applied to the class and that this action covers Zepbound ^[1].

What happens next

Within 14 days of the approval letter, Lilly must submit the content of labeling in structured product labeling format through the FDA's automated drug registration and listing system, and must amend pending supplemental applications that include labeling changes for this application, providing a marked-up copy showing all changes ^[1].

Within 7 days of receiving the letter, the company must submit a statement of intent to comply with requirements that promotional materials be revised to match the approved labeling and prominently disclose the new safety information ^[1]. Patent information required for listing in the Orange Book is due within 30 days of approval ^[1]. The date by which updated labels will appear in public labeling repositories has not been disclosed.