FDA label update for Zepbound adds kidney injury and pancreatitis details

The FDA approved a safety-related revision to the Zepbound (tirzepatide) label on Sept. 25, 2025, adding instructions to monitor kidney function in patients with fluid loss and publishing new pancreatitis figures from trials and postmarketing reports ^[1].

The change is recorded in the FDA's safety labeling change log as supplement 031 ^[1]. It revised the label's Warnings and Precautions section on acute kidney injury due to volume depletion. The new text tells prescribers to monitor kidney function in patients who report reactions that could lead to volume depletion, especially while Zepbound is being started and while the dose is being raised ^[1][2]. Zepbound is approved to reduce excess body weight and maintain weight reduction in adults with obesity or with overweight plus at least one weight-related condition, and to treat moderate to severe obstructive sleep apnea in adults with obesity ^[2].

The label's adverse reactions section now lists acute kidney injury due to volume depletion. The postmarketing section adds kidney effects — acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis — and gastrointestinal effects, including acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death, and ileus ^[1]. The Medication Guide states that diarrhea, nausea and vomiting can cause dehydration, which can cause kidney problems ^[1].

On pancreatitis, the revision reports that in clinical trials of tirzepatide for a different indication, 14 events of acute pancreatitis were confirmed by adjudication in 13 tirzepatide-treated patients, or 0.23 patients per 100 years of exposure, versus 3 events in 3 comparator-treated patients, or 0.11 patients per 100 years of exposure ^[1]. In a pool of two Zepbound trials for weight reduction (Studies 1 and 2), 0.2% of Zepbound-treated patients had adjudication-confirmed acute pancreatitis (0.14 patients per 100 years of exposure) versus 0.2% of placebo-treated patients (0.15 patients per 100 years of exposure). In the pooled obstructive sleep apnea studies (Studies 5 and 6), the exposure-adjusted rate was 0.84 patients per 100 years for Zepbound and 0 for placebo ^[1]. The label does not explain why the sleep apnea figure differs from the weight-reduction figure.

The revision also added lactation data. In a single-dose study, 11 healthy lactating adult females received one 5 mg subcutaneous dose of tirzepatide. The drug was undetectable in breast milk (limit of detection 4 ng/mL) in 164 of 171 samples tested ^[1]. The label states there are no available data on the effects of tirzepatide on a breastfed infant or on milk production ^[1].

According to the same FDA log, later revisions followed. One dated Jan. 7, 2026 covered storage and administration instructions, including that a single-dose pen or single-dose vial may be kept at room temperature up to 86°F for up to 21 days ^[1]. A Jan. 20, 2026 revision added a warning never to share a Zepbound KwikPen between patients, even if the needle is changed, because of the risk of transmitting blood-borne pathogens ^[1]. A Feb. 25, 2026 revision added severe gastrointestinal reaction rates from two weight-reduction trials: 1.7% at 5 mg, 2.5% at 10 mg and 3.1% at 15 mg, compared with 1% for placebo, and states Zepbound is not recommended in patients with severe gastroparesis ^[1].

Why it matters for patients

Labels are the instructions doctors, pharmacists and patients work from, so changes here reach routine care. The kidney warning is tied to a common problem: vomiting and diarrhea from the drug can cause fluid loss, and the label now directs providers to check kidney function in patients who report those reactions, particularly around dose increases ^[1][2].

The pancreatitis numbers give context. In the two weight-reduction trials, confirmed pancreatitis rates were essentially the same for Zepbound and placebo, while the sleep apnea trials showed a higher rate on Zepbound. The label directs patients to stop the drug and call a provider if they have severe stomach pain that will not go away, with or without nausea or vomiting, and notes the pain may travel from the abdomen to the back ^[1].

On breastfeeding, the milk study is small — 11 women, one dose — and the label says the effects on a breastfed infant are unknown. What is known is that the drug was undetectable in nearly all samples tested ^[1].

What happens next

No further Zepbound safety revisions or future dates have been disclosed in the FDA log. The log's most recent Zepbound entry at this time is dated Feb. 25, 2026 ^[1].