Tirzepatide warnings and contraindications, in plain language

The frequency table on the side-effects page covers what is common. This page covers what the label treats as serious enough to warn about regardless of frequency: the boxed warning, the contraindications, and sections 5.1 through 5.10 of the Zepbound label as revised in August 2026. Section numbers are Zepbound's; the Mounjaro label has the same warnings under slightly different numbering plus diabetes-specific ones noted below.

The boxed warning: thyroid C-cell tumors

In rats, tirzepatide causes dose-dependent and duration-dependent thyroid C-cell tumors at clinically relevant exposures. Whether it does so in humans, including medullary thyroid carcinoma (MTC), is unknown, because the human relevance of the rodent finding has not been determined. The label instructs prescribers to counsel patients about the potential risk and the symptoms of a thyroid tumor: a mass in the neck, difficulty swallowing, shortness of breath, persistent hoarseness. It also says routine calcitonin monitoring or thyroid ultrasound is of uncertain value for early detection.

Contraindications (section 4)

Two. A personal or family history of MTC, or Multiple Endocrine Neoplasia syndrome type 2. And known serious hypersensitivity to tirzepatide or any excipient; the label notes that anaphylaxis and angioedema have been reported.

Warnings and precautions (section 5)

5.2 Severe gastrointestinal adverse reactions. Use has been associated with GI reactions, sometimes severe. Not recommended in patients with severe gastroparesis. The frequency numbers are on the side-effects page.

5.3 Acute kidney injury due to volume depletion. Reported after GI reactions such as nausea, vomiting and diarrhea that lead to dehydration. Monitor renal function in patients reporting reactions that could cause volume depletion. In the pooled weight trials, acute kidney injury was reported in 0.5% of Zepbound patients.

5.4 Acute gallbladder disease. Reported in clinical trials. If cholecystitis is suspected, gallbladder studies and clinical follow-up are indicated.

5.5 Acute pancreatitis. Observed in patients treated with tirzepatide. Section 6.1 gives the numbers: in the pooled weight trials, 0.2% of Zepbound patients and 0.2% of placebo patients had adjudication-confirmed pancreatitis (0.14 versus 0.15 per 100 patient-years); in the OSA studies, 0.84 per 100 patient-years on Zepbound versus 0 on placebo; in diabetes trials, 14 events in 13 tirzepatide patients (0.23 per 100 patient-years) versus 3 on comparators (0.11). Stop the drug if pancreatitis is suspected; do not restart if confirmed.

5.6 Hypersensitivity reactions. Serious reactions including anaphylaxis and angioedema reported. Immediate reactions occurred in 2.1% of Zepbound patients versus 0.4% on placebo in the pooled trials, mostly skin reactions, and were more common in people who developed anti-tirzepatide antibodies (6.2% versus 3%).

5.7 Hypoglycemia with insulin or insulin secretagogues. Concomitant use raises the risk, including severe hypoglycemia. Reducing the dose of insulin or the secretagogue may be necessary. This is the warning that matters most to people with type 2 diabetes on Mounjaro.

5.8 Diabetic retinopathy complications in patients with type 2 diabetes. Updated 08/2026 in both labels. Patients with a history of diabetic retinopathy should be monitored for progression.

5.9 Pulmonary aspiration during general anesthesia or deep sedation. Reported in patients on GLP-1 receptor agonists undergoing elective surgeries or procedures. Instruct patients to inform healthcare providers of any planned surgery or procedure.

5.10 Never share a KwikPen between patients. Even if the needle is changed; the risk is transmission of blood-borne pathogens. Added 01/2026 when the KwikPen presentation was introduced.

What was removed

The current label's Recent Major Changes section lists "Suicidal Behavior and Ideation (Removed) 02/2026". Earlier versions of the Zepbound label carried a warning to monitor for depression and suicidal thoughts; the February 2026 revision removed it. This site reports the change and does not interpret it beyond that.

Other sections worth knowing

Pregnancy (8.1). There is a pregnancy exposure registry; the label encourages patients exposed during pregnancy and their providers to enrol. The weight-reduction indication has no role in pregnancy, and the label directs a discussion of the risks.

Hypotension. Not a numbered warning, but section 6.1 reports hypotension in 1.6% of Zepbound patients versus 0.1% on placebo, more often in people on antihypertensives (2.2%) and in association with GI events and dehydration. If you are on blood-pressure medication, that is a conversation to have before starting.

Pediatric use (8.4). Zepbound's safety and effectiveness have not been established in pediatric patients. Mounjaro is approved from age 10 for type 2 diabetes, with a 10 mg maximum in that group.

Compounded products

Everything above is from the labels of two FDA-approved products. Compounded tirzepatide has no FDA-approved label, is not reviewed by FDA for safety, effectiveness or quality before sale, and is not interchangeable with Zepbound or Mounjaro. The warnings above are the closest available guide to the molecule's risks, but they were established for products whose identity, purity and concentration FDA has verified. A compounded product's are set by the pharmacy that made it.