Get your patient on Zepbound (Tirzepatide)

ZEPBOUND^® is indicated in combination with a reduced-calorie diet and increased physical activity:

• to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition.
• to treat moderate to severe obstructive sleep apnea (OSA) in adults with obesity.

• The recommended starting dosage is 2.5 mg injected subcutaneously once weekly for 4 weeks. Increase the dosage in 2.5 mg increments after at least 4 weeks until recommended maintenance dosage is achieved. (
  2.1 Recommended Dose Escalation Schedule

  • The recommended starting dosage of ZEPBOUND for all indications is 2.5 mg injected subcutaneously once weekly for 4 weeks.
  • The 2.5 mg dosage is for treatment initiation and is not approved as a maintenance dosage.
  • Follow the dosage escalation below for all indications to reduce the risk of gastrointestinal adverse reactions
    [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)]
    .
  • After 4 weeks, increase the dosage to 5 mg injected subcutaneously once weekly. The dosage may be increased in 2.5 mg increments, after at least 4 weeks on the current dose
    [see Dosage and Administration (2.2)]
    .
  • Consider treatment response and tolerability when selecting the maintenance dosage. If patients do not tolerate a maintenance dosage, consider a lower maintenance dosage.
  )
• Consider treatment response and tolerability when selecting the maintenance dosage. (
  2.1 Recommended Dose Escalation Schedule

  • The recommended starting dosage of ZEPBOUND for all indications is 2.5 mg injected subcutaneously once weekly for 4 weeks.
  • The 2.5 mg dosage is for treatment initiation and is not approved as a maintenance dosage.
  • Follow the dosage escalation below for all indications to reduce the risk of gastrointestinal adverse reactions
    [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)]
    .
  • After 4 weeks, increase the dosage to 5 mg injected subcutaneously once weekly. The dosage may be increased in 2.5 mg increments, after at least 4 weeks on the current dose
    [see Dosage and Administration (2.2)]
    .
  • Consider treatment response and tolerability when selecting the maintenance dosage. If patients do not tolerate a maintenance dosage, consider a lower maintenance dosage.
  )

• Weight Reduction and Long-Term Maintenance:
  5 mg, 10 mg, or 15 mg injected subcutaneously once weekly. (
  2.2 Recommended Maintenance and Maximum Dosage

  Recommended Maintenance Dosage

  Weight Reduction and Long-Term Maintenance

  The recommended maintenance dosage is 5 mg, 10 mg, or 15 mg, injected subcutaneously once weekly.

  OSA

  The recommended maintenance dosage is 10 mg or 15 mg injected subcutaneously once weekly.

  Maximum Recommended Dosage

  The maximum dosage of ZEPBOUND for all indications is 15 mg injected subcutaneously once weekly.
  )
• Obstructive Sleep Apnea:
  10 mg or 15 mg injected subcutaneously once weekly. (
  2.2 Recommended Maintenance and Maximum Dosage

  Recommended Maintenance Dosage

  Weight Reduction and Long-Term Maintenance

  The recommended maintenance dosage is 5 mg, 10 mg, or 15 mg, injected subcutaneously once weekly.

  OSA

  The recommended maintenance dosage is 10 mg or 15 mg injected subcutaneously once weekly.

  Maximum Recommended Dosage

  The maximum dosage of ZEPBOUND for all indications is 15 mg injected subcutaneously once weekly.
  )

See full prescribing information for administration instructions. (

Injection: Clear, colorless to slightly yellow solution in pre-filled single-dose pens, single-dose vials, or multi-dose vials, each available in the following strengths:

• Pregnancy:
  May cause fetal harm. When pregnancy is recognized, discontinue ZEPBOUND. (
  8.1 Pregnancy

  Pregnancy Exposure Registry

  There will be a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ZEPBOUND (tirzepatide) during pregnancy. Pregnant patients exposed to ZEPBOUND and healthcare providers are encouraged to contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979).

  Risk Summary

  Weight loss offers no benefit to a pregnant patient and may cause fetal harm. Advise pregnant patients that weight loss is not recommended during pregnancy and to discontinue ZEPBOUND when a pregnancy is recognized

  (see Clinical Considerations)

  . Available data with tirzepatide in pregnant patients are insufficient to evaluate for a drug-related risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Based on animal reproduction studies, there may be risks to the fetus from exposure to tirzepatide during pregnancy.

  In pregnant rats administered tirzepatide during organogenesis, fetal growth reductions and fetal abnormalities occurred at clinical exposure in maternal rats based on AUC. In rabbits administered tirzepatide during organogenesis, fetal growth reductions were observed at clinically relevant exposures based on AUC. These adverse embryo/fetal effects in animals coincided with pharmacological effects on maternal weight and food consumption

  (see Data)

  .

  The estimated background risk of major birth defects and miscarriage for the indicated population is increased when compared to the general population. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

  Clinical Considerations

  Disease-Associated Maternal and/or Embryo/Fetal Risk

  Appropriate weight gain based on pre-pregnancy weight is currently recommended for all pregnant patients, including those with obesity or overweight, due to the obligatory weight gain that occurs in maternal tissues during pregnancy.

  Data

  Animal Data

  In pregnant rats given twice weekly subcutaneous doses of 0.02, 0.1, and 0.5 mg/kg tirzepatide [0.03-, 0.07-, and 0.5-fold the maximum recommended human dose (MRHD) of 15 mg once weekly based on AUC] during organogenesis, increased incidences of external, visceral, and skeletal malformations, increased incidences of visceral and skeletal developmental variations, and decreased fetal weights coincided with pharmacologically-mediated reductions in maternal body weights and food consumption at 0.5 mg/kg. In pregnant rabbits given once weekly subcutaneous doses of 0.01, 0.03, or 0.1 mg/kg tirzepatide (0.01-, 0.06-, and 0.2-fold the MRHD) during organogenesis, pharmacologically mediated effects on the gastrointestinal system resulting in maternal mortality or abortion in a few rabbits occurred at all dose levels. Reduced fetal weights associated with decreased maternal food consumption and body weights were observed at 0.1 mg/kg. In a pre- and post-natal study in rats administered subcutaneous doses of 0.02, 0.10, or 0.25 mg/kg tirzepatide twice weekly from implantation through lactation, F₁pups from F₀maternal rats given 0.25 mg/kg tirzepatide had statistically significant lower mean body weight when compared to controls from post-natal day 7 through post-natal day 126 for males and post-natal day 56 for females.
  )
• Females of Reproductive Potential:
  Advise females using oral contraceptives to switch to a non-oral contraceptive method or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation. (
  8.3 Females and Males of Reproductive Potential

  Contraception

  Use of ZEPBOUND may reduce the efficacy of oral hormonal contraceptives due to delayed gastric emptying. This delay is largest after the first dose and diminishes over time. Advise patients using oral hormonal contraceptives to switch to a non-oral contraceptive method, or add a barrier method of contraception, for 4 weeks after initiation with ZEPBOUND and for 4 weeks after each dose escalation

  [see Drug Interactions (7.2) and Clinical Pharmacology (12.2,12.3)]

  .
  )

ZEPBOUND is contraindicated in patients with:

• A personal or family history of MTC or in patients with MEN 2
  [see Warnings and Precautions (

  5.1 Risk of Thyroid C-Cell Tumors

  In rats, tirzepatide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) in a 2-year study at clinically relevant plasma exposures

  [see Nonclinical Toxicology (13.1)]

  . It is unknown whether ZEPBOUND causes thyroid C-cell tumors, including MTC, in humans as human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined.

  ZEPBOUND is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of ZEPBOUND and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness).

  Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with ZEPBOUND. Such monitoring may increase the risk of unnecessary procedures, due to the low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin values may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.

  )]
  .
• Known serious hypersensitivity to tirzepatide or any of the excipients in ZEPBOUND. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with tirzepatide
  [see Warnings and Precautions (

  5.6 Hypersensitivity Reactions

  There have been postmarketing reports of serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) in patients treated with tirzepatide. In a pool of two ZEPBOUND clinical studies for weight reduction (Studies 1 and 2), 0.1% of ZEPBOUND-treated patients had severe hypersensitivity reactions compared to no placebo-treated patients. Similar rates of severe hypersensitivity reactions were observed in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND trials for OSA. If hypersensitivity reactions occur, advise patients to promptly seek medical attention and discontinue use of ZEPBOUND. Do not use in patients with a previous serious hypersensitivity reaction to tirzepatide or any of the excipients in ZEPBOUND

  [see Contraindications (4) and Adverse Reactions (6.2)]

  .

  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 ZEPBOUND.

  ) and Adverse Reactions (

  6.2 Postmarketing Experience

  The following adverse reactions have been reported during post-approval use of tirzepatide, the active ingredient in ZEPBOUND. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure.

  Gastrointestinal:

  acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death, ileus

  Hypersensitivity:

  anaphylaxis, angioedema

  Pulmonary:

  Pulmonary aspiration has occurred in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation.

  Renal:

  acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis

  )]
  .

• Severe Gastrointestinal Adverse Reactions:
  Use has been associated with gastrointestinal adverse reactions, sometimes severe. ZEPBOUND is not recommended in patients with severe gastroparesis. (
  5.2 Severe Gastrointestinal Adverse Reactions

  Use of ZEPBOUND has been associated with gastrointestinal adverse reactions, sometimes severe

  [see Adverse Reactions (6.1)]

  . In a pool of two ZEPBOUND clinical trials for weight reduction (Studies 1 and 2), severe gastrointestinal adverse reactions were reported more frequently among patients receiving ZEPBOUND (5 mg 1.7%, 10 mg 2.5%, 15 mg 3.1%) than placebo (1%). Similar rates of severe gastrointestinal adverse reactions were observed in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND clinical trials for OSA.

  ZEPBOUND is not recommended in patients with severe gastroparesis.
  )
• Acute Kidney Injury Due to Volume Depletion:
  Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. (
  5.3 Acute Kidney Injury Due to Volume Depletion

  There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with GLP-1 receptor agonists, or ZEPBOUND

  [see Adverse Reactions (6.2)]

  . The majority of the reported events occurred in patients who experienced gastrointestinal adverse reactions leading to dehydration such as nausea, vomiting, or diarrhea

  [see Adverse Reactions (6.1)]

  . Monitor renal function in patients reporting adverse reactions to ZEPBOUND that could lead to volume depletion, especially during dosage initiation and escalation of ZEPBOUND.
  )
• Acute Gallbladder Disease:
  Has been reported in clinical trials. If cholecystitis is suspected, gallbladder studies and clinical follow-up are indicated. (
  5.4 Acute Gallbladder Disease

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

  In a pool of two ZEPBOUND clinical trials for weight reduction (Studies 1 and 2), cholelithiasis was reported in 1.1% of ZEPBOUND-treated patients and 1% of placebo-treated patients, cholecystitis was reported in 0.7% of ZEPBOUND-treated patients and 0.2% of placebo-treated patients, and cholecystectomy was reported in 0.2% of ZEPBOUND-treated patients and no placebo-treated patients. Acute gallbladder events were associated with weight reduction. Similar rates of cholelithiasis were reported in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND trials for OSA. If cholecystitis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated.
  )
• Acute Pancreatitis:
  Has been observed in patients treated with GLP-1 receptor agonists, or ZEPBOUND. Discontinue if pancreatitis is suspected. (
  5.5 Acute Pancreatitis

  Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, or ZEPBOUND

  [see Adverse Reactions (6.1)]

  .

  After initiation of ZEPBOUND, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue ZEPBOUND and initiate appropriate management.
  )
• Hypersensitivity Reactions:
  Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported postmarketing with tirzepatide. If suspected, advise patients to promptly seek medical attention and discontinue ZEPBOUND. (
  5.6 Hypersensitivity Reactions

  There have been postmarketing reports of serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) in patients treated with tirzepatide. In a pool of two ZEPBOUND clinical studies for weight reduction (Studies 1 and 2), 0.1% of ZEPBOUND-treated patients had severe hypersensitivity reactions compared to no placebo-treated patients. Similar rates of severe hypersensitivity reactions were observed in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND trials for OSA. If hypersensitivity reactions occur, advise patients to promptly seek medical attention and discontinue use of ZEPBOUND. Do not use in patients with a previous serious hypersensitivity reaction to tirzepatide or any of the excipients in ZEPBOUND

  [see Contraindications (4) and Adverse Reactions (6.2)]

  .

  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 ZEPBOUND.
  )
• Hypoglycemia:
  Concomitant use with insulin or an insulin secretagogue may increase the risk of hypoglycemia, including severe hypoglycemia. Reducing dose of insulin or insulin secretagogue may be necessary. Inform all patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. (
  5.7 Hypoglycemia

  ZEPBOUND lowers blood glucose and can cause hypoglycemia.

  In a trial of patients with type 2 diabetes mellitus and BMI ≥27 kg/m²(Study 2), hypoglycemia (plasma glucose <54 mg/dL) was reported in 4.2% of ZEPBOUND-treated patients versus 1.3% of placebo-treated patients. In this trial, patients taking ZEPBOUND in combination with an insulin secretagogue (e.g., sulfonylurea) had increased risk of hypoglycemia (10.3%) compared to ZEPBOUND-treated patients not taking a sulfonylurea (2.1%). There is also increased risk of hypoglycemia in patients treated with tirzepatide in combination with insulin

  [see Drug Interactions (7.1)]

  .

  Hypoglycemia has also been associated with ZEPBOUND and GLP-1 receptor agonists in adults without type 2 diabetes mellitus

  [see Adverse Reactions (6.1)]

  .

  Inform patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. In patients with diabetes mellitus, monitor blood glucose prior to starting ZEPBOUND and during ZEPBOUND treatment. The risk of hypoglycemia may be lowered by a reduction in the dose of insulin or sulfonylurea (or other concomitantly administered insulin secretagogue).
  )
• Diabetic Retinopathy Complications in Patients with Type 2 Diabetes Mellitus:
  Has not been studied in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema. Monitor patients with a history of diabetic retinopathy for progression. (
  5.8 Diabetic Retinopathy Complications in Patients with Type 2 Diabetes Mellitus

  Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. 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.
  )
• Suicidal Behavior and Ideation:
  Monitor for depression or suicidal thoughts. Discontinue ZEPBOUND if symptoms develop. (
  5.9 Suicidal Behavior and Ideation

  Suicidal behavior and ideation have been reported in clinical trials with other weight management products. Monitor patients treated with ZEPBOUND for the emergence or worsening of depression, suicidal thoughts or behaviors, and/or any unusual changes in mood or behavior. Discontinue ZEPBOUND in patients who experience suicidal thoughts or behaviors. Avoid ZEPBOUND in patients with a history of suicidal attempts or active suicidal ideation.
  )
• Pulmonary Aspiration During General Anesthesia or Deep Sedation:
  Has been reported in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures. Instruct patients to inform healthcare providers of any planned surgeries or procedures. (
  5.10 Pulmonary Aspiration During General Anesthesia or Deep Sedation

  ZEPBOUND delays gastric emptying

  [see Clinical Pharmacology (12.2)]

  . There have been rare postmarketing 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.

  Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking ZEPBOUND, including whether modifying preoperative fasting recommendations or temporarily discontinuing ZEPBOUND 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 ZEPBOUND.
  )

The following serious adverse reactions are described below or elsewhere in the prescribing information:

• Risk of Thyroid C-cell Tumors
  [see Warnings and Precautions (

  5.1 Risk of Thyroid C-Cell Tumors

  In rats, tirzepatide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) in a 2-year study at clinically relevant plasma exposures

  [see Nonclinical Toxicology (13.1)]

  . It is unknown whether ZEPBOUND causes thyroid C-cell tumors, including MTC, in humans as human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined.

  ZEPBOUND is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of ZEPBOUND and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness).

  Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with ZEPBOUND. Such monitoring may increase the risk of unnecessary procedures, due to the low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin values may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.

  )]
• Severe Gastrointestinal Adverse Reactions
  [see Warnings and Precautions (

  5.2 Severe Gastrointestinal Adverse Reactions

  Use of ZEPBOUND has been associated with gastrointestinal adverse reactions, sometimes severe

  [see Adverse Reactions (6.1)]

  . In a pool of two ZEPBOUND clinical trials for weight reduction (Studies 1 and 2), severe gastrointestinal adverse reactions were reported more frequently among patients receiving ZEPBOUND (5 mg 1.7%, 10 mg 2.5%, 15 mg 3.1%) than placebo (1%). Similar rates of severe gastrointestinal adverse reactions were observed in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND clinical trials for OSA.

  ZEPBOUND is not recommended in patients with severe gastroparesis.

  )]
• Acute Kidney Injury Due to Volume Depletion
  [see Warnings and Precautions (

  5.3 Acute Kidney Injury Due to Volume Depletion

  There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with GLP-1 receptor agonists, or ZEPBOUND

  [see Adverse Reactions (6.2)]

  . The majority of the reported events occurred in patients who experienced gastrointestinal adverse reactions leading to dehydration such as nausea, vomiting, or diarrhea

  [see Adverse Reactions (6.1)]

  . Monitor renal function in patients reporting adverse reactions to ZEPBOUND that could lead to volume depletion, especially during dosage initiation and escalation of ZEPBOUND.

  )]
• Acute Gallbladder Disease
  [see Warnings and Precautions (

  5.4 Acute Gallbladder Disease

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

  In a pool of two ZEPBOUND clinical trials for weight reduction (Studies 1 and 2), cholelithiasis was reported in 1.1% of ZEPBOUND-treated patients and 1% of placebo-treated patients, cholecystitis was reported in 0.7% of ZEPBOUND-treated patients and 0.2% of placebo-treated patients, and cholecystectomy was reported in 0.2% of ZEPBOUND-treated patients and no placebo-treated patients. Acute gallbladder events were associated with weight reduction. Similar rates of cholelithiasis were reported in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND trials for OSA. If cholecystitis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated.

  )]
• Acute Pancreatitis
  [see Warnings and Precautions (

  5.5 Acute Pancreatitis

  Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, or ZEPBOUND

  [see Adverse Reactions (6.1)]

  .

  After initiation of ZEPBOUND, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue ZEPBOUND and initiate appropriate management.

  )]
• Hypersensitivity Reactions
  [see Warnings and Precautions (

  5.6 Hypersensitivity Reactions

  There have been postmarketing reports of serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) in patients treated with tirzepatide. In a pool of two ZEPBOUND clinical studies for weight reduction (Studies 1 and 2), 0.1% of ZEPBOUND-treated patients had severe hypersensitivity reactions compared to no placebo-treated patients. Similar rates of severe hypersensitivity reactions were observed in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND trials for OSA. If hypersensitivity reactions occur, advise patients to promptly seek medical attention and discontinue use of ZEPBOUND. Do not use in patients with a previous serious hypersensitivity reaction to tirzepatide or any of the excipients in ZEPBOUND

  [see Contraindications (4) and Adverse Reactions (6.2)]

  .

  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 ZEPBOUND.

  )]
• Hypoglycemia
  [see Warnings and Precautions (

  5.7 Hypoglycemia

  ZEPBOUND lowers blood glucose and can cause hypoglycemia.

  In a trial of patients with type 2 diabetes mellitus and BMI ≥27 kg/m²(Study 2), hypoglycemia (plasma glucose <54 mg/dL) was reported in 4.2% of ZEPBOUND-treated patients versus 1.3% of placebo-treated patients. In this trial, patients taking ZEPBOUND in combination with an insulin secretagogue (e.g., sulfonylurea) had increased risk of hypoglycemia (10.3%) compared to ZEPBOUND-treated patients not taking a sulfonylurea (2.1%). There is also increased risk of hypoglycemia in patients treated with tirzepatide in combination with insulin

  [see Drug Interactions (7.1)]

  .

  Hypoglycemia has also been associated with ZEPBOUND and GLP-1 receptor agonists in adults without type 2 diabetes mellitus

  [see Adverse Reactions (6.1)]

  .

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

  )]
• Diabetic Retinopathy Complications in Patients with Type 2 Diabetes Mellitus
  [see Warnings and Precautions (

  5.8 Diabetic Retinopathy Complications in Patients with Type 2 Diabetes Mellitus

  Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. 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.

  )]
• Suicidal Behavior and Ideation
  [see Warnings and Precautions (

  5.9 Suicidal Behavior and Ideation

  Suicidal behavior and ideation have been reported in clinical trials with other weight management products. Monitor patients treated with ZEPBOUND for the emergence or worsening of depression, suicidal thoughts or behaviors, and/or any unusual changes in mood or behavior. Discontinue ZEPBOUND in patients who experience suicidal thoughts or behaviors. Avoid ZEPBOUND in patients with a history of suicidal attempts or active suicidal ideation.

  )]
• Pulmonary Aspiration During General Anesthesia or Deep Sedation
  [see Warnings and Precautions (

  5.10 Pulmonary Aspiration During General Anesthesia or Deep Sedation

  ZEPBOUND delays gastric emptying

  [see Clinical Pharmacology (12.2)]

  . There have been rare postmarketing 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.

  Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking ZEPBOUND, including whether modifying preoperative fasting recommendations or temporarily discontinuing ZEPBOUND 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 ZEPBOUND.

  )]

ZEPBOUND delays gastric emptying and has the potential to impact the absorption of concomitantly administered oral medications. (

ZEPBOUND (tirzepatide) injection, for subcutaneous use, contains tirzepatide, a GIP receptor and GLP-1 receptor agonist. Tirzepatide is based on the GIP sequence and contains aminoisobutyric acid (Aib) in positions 2 and 13, a C-terminal amide, and Lys residue at position 20 that is attached to 1,20-eicosanedioic acid via a linker. The molecular weight is 4813.53 Da and the empirical formula is C₂₂₅H₃₄₈N₄₈O₆₈.

Structural formula:

ZEPBOUND is a clear, colorless to slightly yellow, sterile solution for subcutaneous use. Each single-dose pen or single-dose vial contains a 0.5 mL solution of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg of tirzepatide and the following excipients: sodium chloride (4.1 mg), sodium phosphate dibasic heptahydrate (0.7 mg), and water for injection. Each multi-dose vial contains 2.4 mL of solution, which provides 4 doses of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg of tirzepatide per 0.6 mL. Each dose contains the following excipients: benzyl alcohol (5.4 mg), glycerin (4.8 mg), phenol (1.08 mg), sodium chloride (1.05 mg), sodium phosphate dibasic heptahydrate (0.8 mg), and water for injection. Hydrochloric acid solution and/or sodium hydroxide solution may have been added to adjust the pH. ZEPBOUND has a pH of 6.5 to 7.5.

Tirzepatide is a GIP receptor and GLP-1 receptor agonist. It contains a C20 fatty diacid that enables albumin binding and prolongs the half-life. Tirzepatide selectively binds to and activates both the GIP and GLP-1 receptors, the targets for native GIP and GLP-1.

GLP-1 is a physiological regulator of appetite and caloric intake. Nonclinical studies suggest the addition of GIP may further contribute to the regulation of food intake.

Both GIP receptors and GLP-1 receptors are found in areas of the brain involved in appetite regulation. Animal studies show that tirzepatide distributes to and activates neurons in brain regions involved in regulation of appetite and food intake.

A 2-year carcinogenicity study was conducted with tirzepatide in male and female rats at doses of 0.15, 0.50, and 1.5 mg/kg (0.1-, 0.4-, and 1-fold the MRHD of 15 mg once weekly based on AUC) administered by subcutaneous injection twice weekly. A statistically significant increase in thyroid C-cell adenomas was observed in male rats (≥0.5 mg/kg) and female rats (≥0.15 mg/kg), and a statistically significant increase in thyroid C-cell adenomas and carcinomas combined was observed in male and female rats at all doses examined. In a 6-month carcinogenicity study in rasH2 transgenic mice, tirzepatide at doses of 1, 3, and 10 mg/kg administered by subcutaneous injection twice weekly was not tumorigenic.

Tirzepatide was not genotoxic in a rat bone marrow micronucleus assay.

In fertility and early embryonic development studies, male and female rats were administered twice weekly subcutaneous doses of 0.5, 1.5, or 3 mg/kg (0.3-, 1-, and 2-fold and 0.3-, 0.9-, and 2-fold, respectively, the MRHD of 15 mg once weekly based on AUC). No effects of tirzepatide were observed on sperm morphology, mating, fertility, and conception. In female rats, an increase in the number of females with prolonged diestrus and a decrease in the mean number of corpora lutea resulting in a decrease in the mean number of implantation sites and viable embryos was observed at all dose levels. These effects were considered secondary to the pharmacological effects of tirzepatide on food consumption and body weight.

ZEPBOUND (tirzepatide) is a clear, colorless to slightly yellow solution available in cartons containing 4 pre-filled single-dose pens, 1 single-dose vial, 4 single-dose vials, or 1 multi-dose vial as follows:

Multi-dose vial

Talk to your healthcare provider about how to inject ZEPBOUND the right way.

• ZEPBOUND is a multi-dose vial.
  The vial contains 4 doses, one dose taken weekly.
• Inject
  0.6 mL
  in a single weekly injection, under the skin (subcutaneously).
• You or another person may inject into your stomach (abdomen) or thigh.
• Another person can inject into the back of your upper arm.

• 1 multi-dose ZEPBOUND vial
• 1 syringe and 1 needle, supplied separately (for example, use a 1 mL syringe and needle as recommended by your healthcare provider)
• 1 alcohol swab
• gauze
• 1 sharps container for throwing away used needles and syringes.
  See
  “Disposing of used needles and syringes” at the end of these instructions.

Guide to parts
Vial	Needle and Syringe (not included)

Make sure the medicine:

Step 1: If you are using a new vial, pull off the plastic protective cap. Do not remove the rubber stopper.
Step 2: Wipe the rubber stopper with an alcohol swab.
Step 3: Remove the outer wrapping from the syringe.
Step 4: Remove the outer wrapping from the needle. The syringe that your healthcare provider recommended may have a pre-attached needle. If the needle is attached, skip to step 6.
Step 5: Place the needle on top of the syringe and turn until it is tight and firmly attached.
Step 6: Remove the needle shield by pulling straight off.
Step 7: Hold the syringe in one hand with the needle pointing up. With the other hand pull down on the plunger until the plunger tip reaches the line on the syringe indicating that 0.6 mL of air has been drawn into the syringe.
Step 8: Push the needle through the rubber stopper of the vial.
Step 9: Push the plunger all the way in. This puts air into the vial and makes it easier to pull the solution from the vial.
Step 10: Turn the vial and syringe upside down. Make sure that the tip of the needle is in the liquid and slowly pull the plunger down until the plunger tip is past the 0.6 mL line. If there are air bubbles, tap the syringe gently a few times to let any air bubbles rise to the top.
Step 11: Slowly push the plunger up until the plunger tip reaches the 0.6 mL line.
Step 12: Pull the syringe out of the rubber stopper of the vial.

• Inject exactly as your healthcare provider has shown you. Your healthcare provider should tell you if you should pinch the skin before injecting.
• Change (rotate) your injection site within the area you choose for each dose
  to reduce your risk of getting lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) at the injection sites.
• Do not
  inject where the skin has pits, is thickened, or has lumps.
• Do not
  inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.
• Do not
  mix ZEPBOUND with any other medicine.
• Do not
  inject ZEPBOUND in the same injection site used for other medicines.

Step 13: Choose your injection site. You can inject ZEPBOUND under the skin (subcutaneously) of your stomach area (abdomen) or thighs. Someone else can inject in your stomach area, thighs, or the back of the upper arms.
Step 14: Insert the needle into your skin.
Step 15: Push down on the plunger to inject your dose. The needle should stay in your skin for at least 5 seconds to make sure you have injected all of your dose.
Step 16: Pull the needle out of your skin. If you see blood after you take the needle out of your skin, press the injection site with a piece of gauze. Do not rub the area. Do not recap the needle. Recapping the needle can lead to a needle stick injury.

• Put your used needle and syringe in an FDA-cleared sharps disposal container right away after use.
  Do not
  throw away (dispose of) loose needles and syringes in your household trash.
• If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
  • -made of a heavy-duty plastic,
  • -can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • -upright and stable during use,
  • -leak-resistant, and
  • -properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at:
  
  http://www.fda.gov/safesharpsdisposal.
• Do not
  dispose of your used sharps disposal container in your household trash unless your community guidelines permit this.
  Do not
  recycle your used sharps disposal container.

• Do not
  freeze.
  Do not
  use if ZEPBOUND has been frozen.
• Store ZEPBOUND in original carton. Keep away from light.

• Store unopened vial in the refrigerator at 36°F to 46°F (2°C to 8°C). It can be used until the expiration date on the label if kept in the refrigerator.
• If stored at room temperature [up to 86°F (30°C)], throw away unopened vial after 30 days.

• Store opened (in-use) vial in the original carton in the refrigerator at 36°F to 46°F (2°C to 8°C) or at room temperature [up to 86°F (30°C)]. Throw away opened vial after a total of 30 days at room temperature, 30 days after first use, or after taking 4 weekly doses, even if there is medicine left in it.

If you have any questions or problems with your ZEPBOUND, contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or call your healthcare provider for help.

Marketed by:

Lilly USA, LLC

Indianapolis, IN 46285, USA

ZEPBOUND is a registered trademark of Eli Lilly and Company.

Copyright © 2026, Eli Lilly and Company. All rights reserved.

ZEP-0001-MDV-IFU-20260107

This Instructions for Use has been approved by the U.S. Food and Drug Administration .

Revised: January 2026

Tirzepatide is a GIP receptor and GLP-1 receptor agonist. It contains a C20 fatty diacid that enables albumin binding and prolongs the half-life. Tirzepatide selectively binds to and activates both the GIP and GLP-1 receptors, the targets for native GIP and GLP-1.

GLP-1 is a physiological regulator of appetite and caloric intake. Nonclinical studies suggest the addition of GIP may further contribute to the regulation of food intake.

Both GIP receptors and GLP-1 receptors are found in areas of the brain involved in appetite regulation. Animal studies show that tirzepatide distributes to and activates neurons in brain regions involved in regulation of appetite and food intake.