See important safety information, including boxed warning, in the attached prescribing information.

The use of tirzepatide in patients undergoing surgical procedures or hospitalization has not been evaluated.

Health care providers should use patient medical records and their clinical judgement to make a treatment recommendation. The additional considerations below may be helpful to determine what is best for their patient (Pharmacokinetics and Pharmacodynamics, Drug Interactions, Precautions).

Administer tirzepatide

• once weekly
• any time of day, and
• with or without food.1

Tirzepatide should be injected subcutaneously in the abdomen, thigh, or upper arm.1

Following subcutaneous administration, the median time to maximum plasma concentration of tirzepatide is 24 hours and ranges from 8 to 72 hours.1

Steady-state plasma tirzepatide concentrations were achieved following 4 weeks of once-weekly administration.1

Tirzepatide is highly bound to plasma albumin (99%).1

The elimination half-life of tirzepatide is approximately 5 days.1

For full information on pharmacokinetics, please refer to the enclosed prescribing information.1

Because tirzepatide delays gastric emptying, it has the potential to impact the absorption of concomitantly administered oral medications. The impact of tirzepatide on gastric emptying was greatest after a single dose of 5 mg and diminished after subsequent doses.1

Patients on oral medications dependent on threshold concentrations for efficacy and those with a narrow therapeutic index (eg, warfarin) should be monitored when concomitantly administered with tirzepatide.1

In vitro studies of tirzepatide showed low potential to inhibit or induce CYP enzymes, and to inhibit drug transporters.1

Following first dose of tirzepatide 5 mg, acetaminophen maximum concentration (C_max) was reduced by 55% and the median peak plasma concentration (t_max) occurred 1 hour later. After coadministration at week 6, there was no meaningful impact on acetaminophen C_max and t_max. Overall acetaminophen exposure (AUC_0-24h) was not influenced.1

For full information on drug interactions, please refer to the enclosed prescribing information.1

Tirzepatide is contraindicated in patients with a

• personal or family history of medullary thyroid carcinoma (MTC) or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2), or
• known serious hypersensitivity to tirzepatide or any of the excipients in Zepbound. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with tirzepatide.1

Tirzepatide delays gastric emptying. There have been rare post-marketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations.1

Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking tirzepatide, including whether modifying preoperative fasting recommendations or temporarily discontinuing tirzepatide could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking tirzepatide.1

If pancreatitis is suspected, discontinue tirzepatide and initiate appropriate management. If the diagnosis of pancreatitis is confirmed, tirzepatide should not be restarted.1

Tirzepatide has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients.1

Use of tirzepatide has been associated with acute kidney injury, which can result from dehydration due to gastrointestinal adverse reactions to tirzepatide; including nausea, vomiting, and diarrhea.1

Monitor patients treated with tirzepatide for the emergence or worsening of depression, suicidal thoughts or behaviors, and/or any unusual changes in mood or behavior. Discontinue tirzepatide in patients who experience suicidal thoughts or behaviors. Avoid tirzepatide in patients with a history of suicidal attempts or active suicidal ideation.1

Tirzepatide has not been studied in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy.1

In patients with diabetes mellitus, monitor blood glucose prior to starting tirzepatide and during tirzepatide treatment. The risk of hypoglycemia may be lowered by a reduction in the dose of insulin or sulfonylurea (or other concomitantly administered insulin secretagogue).1

Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with GLP-1 receptor agonists. Use caution in patients with a history of angioedema or anaphylaxis with a GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to these reactions with tirzepatide.1

Treatment with tirzepatide and GLP-1 receptor agonists is associated with an increased occurrence of acute gallbladder disease.1

For full information on precautions, please refer to the enclosed prescribing information.1

ZEPBOUND® (tirzepatide) injection, for subcutaneous use, Lilly