ZEPBOUND- tirzepatide injection, solution ZEPBOUND- tirzepatide injection, solution

Zepbound by

Drug Labeling and Warnings

Zepbound by is a Prescription medication manufactured, distributed, or labeled by Eli Lilly and Company. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • BOXED WARNING (What is this?)

    WARNING: RISK OF THYROID C-CELL TUMORS

    • In rats, tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether ZEPBOUND causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions (5.1) and Nonclinical Toxicology (13.1)].
    • ZEPBOUND is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Contraindications (4)]. 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 [see Contraindications (4) and Warnings and Precautions (5.1)].
  • 1 INDICATIONS AND USAGE

    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.

    Limitations of Use

    • ZEPBOUND contains tirzepatide. Coadministration with other tirzepatide-containing products or with any glucagon-like peptide-1 (GLP-1) receptor agonist is not recommended.
  • 2 DOSAGE AND ADMINISTRATION

    2.1 Recommended Dosage

    • The recommended starting dosage of ZEPBOUND is 2.5 mg injected subcutaneously once weekly. Follow the dosage escalation below to reduce the risk of gastrointestinal adverse reactions [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)]. The 2.5 mg dosage is for treatment initiation and is not approved as a maintenance dosage.
    • 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.
    • The recommended maintenance dosages of ZEPBOUND in adults are 5 mg, 10 mg, or 15 mg, injected subcutaneously once weekly.
    • Consider treatment response and tolerability when selecting the maintenance dosage [see Adverse Reactions (6.1) and Clinical Studies (14.1)]. If patients do not tolerate a maintenance dosage, consider a lower maintenance dosage.
    • The maximum dosage of ZEPBOUND is 15 mg injected subcutaneously once weekly.

    2.2 Recommendations Regarding Missed Dose

    • If a dose is missed, instruct patients to administer ZEPBOUND as soon as possible within 4 days (96 hours) after the missed dose. If more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule.
    • The day of weekly administration can be changed, if necessary, as long as the time between the two doses is at least 3 days (72 hours).

    2.3 Important Administration Instructions

    • Prior to initiation of ZEPBOUND, train patients and caregivers on proper injection technique. Refer to the accompanying Instructions for Use for complete administration instructions with illustrations.
    • Instruct patients using the single-dose vial to use a syringe appropriate for dose administration (e.g., a 1 mL syringe capable of measuring a 0.5 mL dose).
    • Inspect ZEPBOUND visually before use. It should appear clear and colorless to slightly yellow. Do not use ZEPBOUND if particulate matter or discoloration is seen.
    • Administer ZEPBOUND in combination with a reduced-calorie diet and increased physical activity.
    • Administer ZEPBOUND once weekly at any time of day, with or without meals.
    • Inject ZEPBOUND subcutaneously in the abdomen, thigh, or upper arm.
    • Rotate injection sites with each dose.
  • 3 DOSAGE FORMS AND STRENGTHS

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

    • 2.5 mg/0.5 mL
    • 5 mg/0.5 mL
    • 7.5 mg/0.5 mL
    • 10 mg/0.5 mL
    • 12.5 mg/0.5 mL
    • 15 mg/0.5 mL
  • 4 CONTRAINDICATIONS

    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)].
    • 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) and Adverse Reactions (6.2)].
  • 5 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.

    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 (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%).

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

    5.3 Acute Kidney Injury

    Use of ZEPBOUND has been associated with acute kidney injury, which can result from dehydration due to gastrointestinal adverse reactions to ZEPBOUND, including nausea, vomiting, and diarrhea [see Adverse Reactions (6.1)].

    In patients treated with GLP-1 receptor agonists, there have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis. Some of these events have been reported in patients without known underlying renal disease. A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. Monitor renal function in patients reporting adverse reactions to ZEPBOUND that could lead to volume depletion.

    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 (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. If cholecystitis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated.

    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 tirzepatide.

    In clinical trials of tirzepatide for a different indication, 14 events of acute pancreatitis were confirmed by adjudication in 13 tirzepatide-treated patients (0.23 patients per 100 years of exposure) versus 3 events in 3 comparator-treated patients (0.11 patients per 100 years of exposure). In a pool of two ZEPBOUND clinical trials (Studies 1 and 2), 0.2% of ZEPBOUND-treated patients had acute pancreatitis confirmed by adjudication (0.14 patients per 100 years of exposure) versus 0.2% of placebo-treated patients (0.15 patients per 100 years of exposure). ZEPBOUND has not been studied in patients with a prior history of pancreatitis. It is unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on ZEPBOUND.

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

    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 trials (Studies 1 and 2), 0.1% of ZEPBOUND-treated patients had severe hypersensitivity reactions compared to no placebo-treated patients. 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.

    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).

    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.

    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.

    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.

  • 6 ADVERSE REACTIONS

    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)]
    • Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.2)]
    • Acute Kidney Injury [see Warnings and Precautions (5.3)]
    • Acute Gallbladder Disease [see Warnings and Precautions (5.4)]
    • Acute Pancreatitis [see Warnings and Precautions (5.5)]
    • Hypersensitivity Reactions [see Warnings and Precautions (5.6)]
    • Hypoglycemia [see Warnings and Precautions (5.7)]
    • Diabetic Retinopathy Complications in Patients with Type 2 Diabetes Mellitus [see Warnings and Precautions (5.8)]
    • Suicidal Behavior and Ideation [see Warnings and Precautions (5.9)]
    • Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions (5.10)]

    6.1 Clinical Trials Experience

    Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

    Pool of Placebo-Controlled Weight Reduction Trials in Adults with Obesity or Overweight, with or without Type 2 Diabetes (Study 1 and Study 2)

    ZEPBOUND was evaluated for safety in a pool of two randomized, double-blind, placebo-controlled trials that included 2,519 adult patients with obesity or overweight treated with ZEPBOUND for up to 72 weeks and a 4-week off drug follow-up period (Study 1 and Study 2) [see Clinical Studies (14.1)]. The mean age of patients was 47 years and 37% were male. The population was 72% White, 12% Asian, 8% Black or African American, and 7% American Indian or Alaska Native; 51% identified as Hispanic or Latino ethnicity. Baseline characteristics included an average BMI of 37.4 kg/m2, 29% with a BMI ≥40 kg/m2, 41% with hypertension, 37% with dyslipidemia, 25% with type 2 diabetes mellitus, 7% with obstructive sleep apnea, and 4% with cardiovascular disease.

    Across both trials, 4.8%, 6.3%, and 6.7% of patients treated with 5 mg, 10 mg, and 15 mg of ZEPBOUND, respectively, permanently discontinued treatment as a result of adverse reactions compared to 3.4% of patients treated with placebo. The majority of patients who discontinued ZEPBOUND due to adverse reactions did so during the first few months of treatment due to gastrointestinal adverse reactions.

    Common Adverse Reactions

    Table 1 shows common adverse reactions associated with the use of ZEPBOUND in the pool of two placebo-controlled trials for weight reduction (Study 1 and Study 2). These adverse reactions occurred more commonly with ZEPBOUND than with placebo and occurred in at least 2% of patients treated with ZEPBOUND.

    Table 1: Adverse Reactions (≥2% and Greater than Placebo) in ZEPBOUND-Treated Adults with Obesity or Overweight (Study 1 and Study 2)

    a Includes diarrhea, frequent bowel movements.

    b Includes constipation, feces hard.

    c Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness.

    d Includes multiple related adverse event terms, such as injection site bruising, injection site erythema, injection site pruritus, injection site pain, injection site rash, injection site reaction.

    e Includes asthenia, fatigue, lethargy, malaise.

    f Includes blood pressure decreased, hypotension, orthostatic hypotension.




    Adverse Reaction
    Placebo
    (N=958)
    %    		ZEPBOUND
    5 mg
    (N=630)
    %    		ZEPBOUND
    10 mg
    (N=948)
    %    		ZEPBOUND
    15 mg
    (N=941)
    %
    Nausea 8 25 29 28
    Diarrheaa8 19 21 23
    Vomiting 2 8 11 13
    Constipationb5 17 14 11
    Abdominal Painc5 9 9 10
    Dyspepsia 4 9 9 10
    Injection Site Reactionsd2 6 8 8
    Fatiguee3 5 6 7
    Hypersensitivity Reactions 3 5 5 5
    Eructation 1 4 5 5
    Hair Loss 1 5 4 5
    Gastroesophageal Reflux Disease 2 4 4 5
    Flatulence 2 3 3 4
    Abdominal Distension 2 3 3 4
    Dizziness 2 4 5 4
    Hypotensionf0 1 1 2

    In a clinical trial that included an intensive lifestyle intervention lead-in period (Study 3), 287 patients were treated with ZEPBOUND for up to 72 weeks. In a randomized withdrawal trial (Study 4), 783 patients were treated with ZEPBOUND for up to 36 weeks, and 335 of these patients were treated for up to 88 weeks [see Clinical Studies (14.1)]. In Study 3, 10% of ZEPBOUND-treated patients and 2% of placebo-treated patients discontinued drug due to adverse reactions. In Study 4, 7% of patients discontinued ZEPBOUND treatment before randomized withdrawal at Week 36 due to adverse reactions. In Study 3 and Study 4, adverse reactions were similar to those reported in the two pooled ZEPBOUND clinical trials (Study 1 and Study 2).

    Gastrointestinal Adverse Reactions

    In a pool of Study 1 and 2, gastrointestinal adverse reactions occurred more frequently among patients receiving ZEPBOUND (5 mg 56%, 10 mg 56%, 15 mg 56%) than placebo (30%). More patients receiving ZEPBOUND 5 mg (1.9%), ZEPBOUND 10 mg (3.3%), and ZEPBOUND 15 mg (4.3%) discontinued treatment due to gastrointestinal adverse reactions than patients receiving placebo (0.5%). The majority of nausea, vomiting, and/or diarrhea events occurred during dose escalation and decreased over time.

    Hypotension

    In a pool of Study 1 and 2, hypotension occurred more frequently among patients taking ZEPBOUND (1.6%) than patients taking placebo (0.1%). Hypotension was more frequently seen in ZEPBOUND-treated patients on concomitant antihypertensive therapy (2.2%) compared to ZEPBOUND-treated patients not on antihypertensive therapy (1.2%). Hypotension also occurred in association with gastrointestinal adverse events and dehydration.

    Hypersensitivity Reactions

    In a pool of Study 1 and 2, immediate hypersensitivity reactions (within one day after drug administration) occurred in 2.1% of ZEPBOUND-treated patients compared to 0.4% of placebo-treated patients, while non-immediate hypersensitivity reactions occurred in 3.5% of ZEPBOUND-treated patients compared to 2.7% of placebo-treated patients. Among ZEPBOUND-treated patients, hypersensitivity reactions were more frequent in those with anti-tirzepatide antibodies (6.2%) compared to those who did not develop anti-tirzepatide antibodies (3%) [see Clinical Pharmacology (12.6)]. The majority of the hypersensitivity reactions in trials were skin reactions (e.g., rash, itching).

    Injection Site Reactions

    In ZEPBOUND-treated patients in a pool of Study 1 and 2, injection site reactions were more frequent in those with anti-tirzepatide antibodies (11.3%) compared to those who did not develop anti-tirzepatide antibodies (1%) [see Clinical Pharmacology (12.6)].

    Hair Loss

    Hair loss adverse reactions in ZEPBOUND-treated patients were associated with weight reduction. In a pool of Study 1 and 2, hair loss was reported more frequently in female than male patients in the ZEPBOUND (7.1% female versus 0.5% male) and placebo (1.3% female versus 0% male) treatment groups. No ZEPBOUND-treated patients and one placebo-treated patient discontinued study treatment due to hair loss.

    Other Adverse Reactions

    Acute Kidney Injury

    In a pool of Study 1 and 2, acute kidney injury was reported in 0.5% of ZEPBOUND-treated patients compared to 0.2% of placebo-treated patients.

    Acute Gallbladder Disease

    In a pool of Study 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.

    Hypoglycemia

    In Study 2, a trial of patients with type 2 diabetes mellitus and BMI ≥27 kg/m2, hypoglycemia (plasma glucose <54 mg/dL) was reported in 4.2% of ZEPBOUND-treated patients versus 1.3% of placebo-treated patients.

    In Study 1, a trial of ZEPBOUND in adults with obesity/overweight without type 2 diabetes mellitus, there was no systematic capturing of hypoglycemia, but plasma glucose <54 mg/dL was reported in 0.3% of ZEPBOUND-treated patients versus no placebo-treated patients.

    Heart Rate Increase

    In a pool of Study 1 and 2, treatment with ZEPBOUND resulted in a mean increase in heart rate of 1 to 3 beats per minute compared to no increase in placebo-treated patients.

    Dysesthesia

    In a pool of Study 1 and 2, dysesthesia occurred more frequently among patients receiving ZEPBOUND (5 mg 0.2%, 10 mg 0.2%, 15 mg 0.4%) than placebo (0.1%).

    Dysgeusia

    In a pool of Study 1 and 2, dysgeusia was reported by 0.4% of ZEPBOUND-treated patients and no placebo-treated patients.

    Dry Mouth

    In a pool of Study 1 and 2, dry mouth or dry throat was reported by 1% of ZEPBOUND-treated patients and 0.1% of placebo-treated patients.

    Laboratory Abnormalities

    Amylase and Lipase Increase

    In a pool of Study 1 and 2, treatment with ZEPBOUND resulted in mean increases from baseline in serum pancreatic amylase concentrations of 20% to 25% and serum lipase concentrations of 28% to 35%, compared to mean increases from baseline in pancreatic amylase of 2.1% and serum lipase of 5.8% in placebo-treated patients. The clinical significance of elevations in amylase or lipase with ZEPBOUND is unknown in the absence of other signs and symptoms of pancreatitis.

    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.

    Hypersensitivity: anaphylaxis, angioedema

    Gastrointestinal: ileus

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

  • 7 DRUG INTERACTIONS

    7.1 Concomitant Use with Insulin or an Insulin Secretagogue (e.g., Sulfonylurea)

    ZEPBOUND lowers blood glucose. When initiating ZEPBOUND, consider reducing the dose of concomitantly administered insulin or insulin secretagogues (e.g., sulfonylureas) to reduce the risk of hypoglycemia [see Warnings and Precautions (5.7)].

    7.2 Oral Medications

    ZEPBOUND delays gastric emptying and thereby has the potential to impact the absorption of concomitantly administered oral medications. Caution should be exercised when oral medications are concomitantly administered with ZEPBOUND.

    Monitor patients on oral medications dependent on threshold concentrations for efficacy and those with a narrow therapeutic index (e.g., warfarin) when concomitantly administered with ZEPBOUND.

    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. Hormonal contraceptives that are not administered orally should not be affected [see Use in Specific Populations (8.3) and Clinical Pharmacology (12.2, 12.3)].

  • 8 USE IN SPECIFIC POPULATIONS

    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, F1 pups from F0 maternal 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.

    8.2 Lactation

    Risk Summary

    There are no data on the presence of tirzepatide or its metabolites in animal or human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ZEPBOUND and any potential adverse effects on the breastfed infant from ZEPBOUND or from the underlying maternal condition.

    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)].

    8.4 Pediatric Use

    The safety and effectiveness of ZEPBOUND have not been established in pediatric patients.

    8.5 Geriatric Use

    In a pool of two fixed dose ZEPBOUND clinical trials (Study 1 and Study 2), 226 (9%) ZEPBOUND-treated patients were 65 years of age or older, and 13 (0.5%) ZEPBOUND-treated patients were 75 years of age or older at baseline.

    No overall differences in safety or effectiveness of ZEPBOUND have been observed between patients 65 years of age and older and younger adult patients.

    8.6 Renal Impairment

    No dosage adjustment of ZEPBOUND is recommended for patients with renal impairment. In subjects with renal impairment including end-stage renal disease (ESRD), no change in tirzepatide pharmacokinetics (PK) was observed [see Clinical Pharmacology (12.3)]. Monitor renal function in patients reporting adverse reactions to ZEPBOUND that could lead to volume depletion [see Warnings and Precautions (5.3)].

    8.7 Hepatic Impairment

    No dosage adjustment of ZEPBOUND is recommended for patients with hepatic impairment. In a clinical pharmacology study in subjects with varying degrees of hepatic impairment, no change in tirzepatide PK was observed [see Clinical Pharmacology (12.3)].

  • 10 OVERDOSAGE

    In the event of an overdosage, contact the Poison Help Line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Appropriate supportive treatment should be initiated according to the patient's clinical signs and symptoms. A period of observation and treatment for these symptoms may be necessary, taking into account the half-life of tirzepatide of approximately 5 days.

  • 11 DESCRIPTION

    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:

    Structural Formula

    ZEPBOUND is a clear, colorless to slightly yellow, sterile solution for subcutaneous use. Each single-dose pen or single-dose vial contains preservative-free 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. Hydrochloric acid solution and/or sodium hydroxide solution may have been added to adjust the pH. ZEPBOUND has a pH of 6.5 – 7.5.

  • 12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    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.

    12.2 Pharmacodynamics

    Tirzepatide lowers body weight with greater fat mass loss than lean mass loss.

    Tirzepatide decreases calorie intake. The effects are likely mediated by affecting appetite.

    Tirzepatide stimulates insulin secretion in a glucose-dependent manner and reduces glucagon secretion. Tirzepatide increases insulin sensitivity, as demonstrated in a hyperinsulinemic euglycemic clamp study in patients with type 2 diabetes mellitus after 28 weeks of treatment. These effects can lead to a reduction of blood glucose.

    Tirzepatide delays gastric emptying. The delay is largest after the first dose and this effect diminishes over time.

    12.3 Pharmacokinetics

    The pharmacokinetics of tirzepatide is similar between healthy subjects and patients with overweight or obesity. Steady-state plasma tirzepatide concentrations were achieved following 4 weeks of once weekly administration. Tirzepatide exposure increases in a dose-proportional manner.

    Absorption

    Following subcutaneous administration, the median time (range) to maximum plasma concentration of tirzepatide is 24 hours (8 to 72 hours). The mean absolute bioavailability of tirzepatide following subcutaneous administration is 80%. Similar exposure was achieved with subcutaneous administration of tirzepatide in the abdomen, thigh, or upper arm.

    Distribution

    The mean [coefficient of variation (CV)%] apparent steady-state volume of distribution of tirzepatide following subcutaneous administration in patients with overweight or obesity is approximately 9.7 L (28.5%). Tirzepatide is highly bound to plasma albumin (99%).

    Elimination

    The apparent population mean clearance (CV%) of tirzepatide in patients with overweight or obesity is 0.056 L/h (20.9%) with an elimination half-life of approximately 5 days.

    Metabolism

    Tirzepatide is metabolized by proteolytic cleavage of the peptide backbone, beta-oxidation of the C20 fatty diacid, and amide hydrolysis.

    Excretion

    The primary excretion routes of tirzepatide metabolites are via urine and feces. Intact tirzepatide is not observed in urine or feces.

    Specific Populations

    The intrinsic factors of age (18 to 84 years), sex, race (71% White, 11% Asian, 9% American Indian or Alaska Native, and 8% Black or African American), ethnicity, or body weight do not have a clinically relevant effect on the PK of tirzepatide.

    Patients with Renal Impairment

    Renal impairment does not impact the pharmacokinetics of tirzepatide. The pharmacokinetics of tirzepatide after a single 5 mg dose were evaluated in patients with different degrees of renal impairment (mild, moderate, severe, ESRD) compared with subjects with normal renal function. Data from clinical studies have also shown that renal impairment in patients with overweight or obesity does not impact the pharmacokinetics of tirzepatide [see Use in Specific Populations (8.6)].

    Patients with Hepatic Impairment

    Hepatic impairment does not impact the pharmacokinetics of tirzepatide. The pharmacokinetics of tirzepatide after a single 5 mg dose were evaluated in patients with different degrees of hepatic impairment (mild, moderate, severe) compared with subjects with normal hepatic function [see Use in Specific Populations (8.7)].

    Drug Interaction Studies

    Potential for Tirzepatide to Influence the Pharmacokinetics of Other Drugs

    In vitro studies have shown low potential for tirzepatide to inhibit or induce CYP enzymes, and to inhibit drug transporters.

    ZEPBOUND delays gastric emptying and thereby has the potential to impact the absorption of concomitantly administered oral medications [see Drug Interactions (7.2)].

    The impact of tirzepatide on gastric emptying was greatest after a single dose of 5 mg and diminished after subsequent doses.

    Following a first dose of tirzepatide 5 mg, acetaminophen maximum concentration (Cmax) was reduced by 55%, and the median peak plasma concentration (tmax) occurred 1 hour later. After coadministration at Week 6 with tirzepatide 15 mg, there was no meaningful impact on acetaminophen Cmax and tmax. Overall acetaminophen exposure (AUC0-24hr) was not influenced.

    Following administration of a combined oral contraceptive (0.035 mg ethinyl estradiol and 0.25 mg norgestimate) in the presence of a single dose of tirzepatide 5 mg, mean Cmax of ethinyl estradiol, norgestimate, and norelgestromin was reduced by 59%, 66%, and 55%, while mean AUC was reduced by 20%, 21%, and 23%, respectively. A delay in tmax of 2.5 to 4.5 hours was observed.

    12.6 Immunogenicity

    The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the trials described below with the incidence of anti-drug antibodies in other trials.

    During the 72-week treatment period with anti-drug antibodies (ADA) sampling in Studies 1 and 2 [see Clinical Studies (14)], 64.5% (1591/2467) of ZEPBOUND-treated patients developed anti-tirzepatide antibodies. In these trials, anti-tirzepatide antibody formation in 40% and 16.5% of ZEPBOUND-treated patients showed cross-reactivity to native GIP or native GLP-1, respectively.

    Of the ZEPBOUND-treated patients, 2.8% and 2.7% developed neutralizing antibodies against tirzepatide activity on the GIP or GLP-1 receptors, respectively, and 0.8% and 0.1% developed neutralizing antibodies against native GIP or GLP-1, respectively.

    There was no identified clinically significant effect of anti-tirzepatide antibodies on pharmacokinetics or effectiveness of ZEPBOUND. More ZEPBOUND-treated patients who developed anti-tirzepatide antibodies experienced hypersensitivity reactions or injection site reactions than those who did not develop these antibodies [see Adverse Reactions (6.1)].

  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    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.

  • 14 CLINICAL STUDIES

    14.1 Weight Reduction and Long-term Maintenance Studies in Adults with Obesity or Overweight

    Weight Reduction in Adults with Obesity or Overweight, with or without Type 2 Diabetes Mellitus (Study 1 and Study 2)

    Overview of Study 1 and Study 2

    The efficacy of ZEPBOUND for weight reduction in conjunction with a reduced-calorie diet and increased physical activity was studied in two randomized, double-blind, placebo-controlled fixed-dosage trials (Study 1 and Study 2) in adults aged 18 years and older. In Studies 1 and 2, all patients received a standard lifestyle intervention which included instruction on a reduced-calorie diet (approximately 500 kcal/day deficit) and increased physical activity counseling (recommended minimum of 150 min/week) that began with the first dose of study medication or placebo and continued throughout the trial. Patients also received counseling on behavior modification strategies to adhere to diet and exercise recommendations. In both trials, weight reduction was assessed after 72 weeks of treatment (at least 52 weeks at maintenance dose).

    Study 1 (NCT04184622) was a 72-week trial that enrolled 2,539 adult patients with obesity (BMI ≥30 kg/m2), or with overweight (BMI 27 to <30 kg/m2) and at least one weight-related comorbid condition, such as dyslipidemia, hypertension, obstructive sleep apnea, or cardiovascular disease; patients with type 2 diabetes mellitus were excluded. Patients were randomized in a 1:1:1:1 ratio to once weekly fixed dosage of ZEPBOUND 5 mg, ZEPBOUND 10 mg, ZEPBOUND 15 mg, or placebo, with an escalation period of up to 20 weeks followed by the maintenance period. At baseline, mean age was 45 years (range 18-84 years), 68% were female, 71% were White, 11% were Asian, 9% were American Indian/Alaska Native, and 8% were Black or African American. A total of 48% were Hispanic or Latino ethnicity. Mean baseline body weight was 104.8 kg and mean BMI was 38 kg/m2. Baseline characteristics included 32% with hypertension, 30% with dyslipidemia, 8% with obstructive sleep apnea, and 3% with cardiovascular disease.

    Study 2 (NCT04657003) was a 72-week trial that enrolled 938 adult patients with BMI ≥27 kg/m2 and type 2 diabetes mellitus. Patients included in the trial had HbA1c 7-10% and were treated with either diet and exercise alone, or any oral anti-hyperglycemic agent except dipeptidyl peptidase-4 (DPP-4) inhibitors or GLP-1 receptor agonists. Patients who were taking insulin or injectable GLP-1 receptor agonists for type 2 diabetes mellitus were excluded. Patients were randomized in a 1:1:1 ratio to once weekly fixed dosage of ZEPBOUND 10 mg, ZEPBOUND 15 mg, or placebo with an escalation period of up to 20 weeks followed by the maintenance period. At baseline, mean age was 54 years (range 18-85 years), 51% were female, 76% were White, 13% were Asian, and 8% were Black or African American. A total of 60% were Hispanic or Latino ethnicity. Mean baseline body weight was 100.7 kg and mean BMI was 36.1 kg/m2. Baseline characteristics included 66% with hypertension, 61% with dyslipidemia, 8% with obstructive sleep apnea, and 10% with cardiovascular disease.

    Results for Study 1 and Study 2

    The proportions of patients who discontinued study drug in Study 1 were 14.3%, 16.4%, and 15.1% for the 5 mg, 10 mg, and 15 mg ZEPBOUND-treated groups, respectively, and 26.4% for the placebo-treated group. The proportions of patients who discontinued study drug in Study 2 were 9.3% and 13.8% for the 10 mg and 15 mg ZEPBOUND-treated groups, respectively, and 14.9% for the placebo-treated group.

    For Studies 1 and 2, weight reduction was assessed after 72 weeks of treatment (at least 52 weeks at maintenance dose). In both studies, the primary efficacy parameters were mean percent change in body weight and the percentage of patients achieving ≥5% weight reduction from baseline to Week 72 (see Table 2).

    After 72 weeks of treatment, ZEPBOUND resulted in a statistically significant reduction in body weight compared with placebo, and greater proportions of patients treated with ZEPBOUND 5 mg, 10 mg, and 15 mg achieved at least 5% weight reduction compared to placebo. Among patients treated with ZEPBOUND 10 mg and 15 mg, greater proportions of patients achieved at least 10%, 15%, and 20% weight reduction compared to placebo (see Table 2). A reduction in body weight was observed with ZEPBOUND irrespective of age, sex, race, ethnicity, baseline BMI, and glycemic status.

    Table 2: Changes in Body Weight at Week 72 in Studies 1 and 2 in Patients with Obesity or Overweight

    Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; N = number of patients randomly assigned to study drug.

    a The intention-to-treat population includes all randomly assigned patients. For Study 1 at Week 72, body weight was missing for 21.6%, 10.2%, 10.5%, and 9.4% of patients randomly assigned to placebo, ZEPBOUND 5 mg, 10 mg, and 15 mg, respectively. For Study 2 at Week 72, body weight was missing for 11.1%, 4.8%, and 8.4% of patients randomly assigned to placebo, ZEPBOUND 10 mg, and 15 mg, respectively. The missing values were imputed by a hybrid approach using retrieved dropouts from the same treatment group (if missing not due to COVID-19) or using all non-missing data assuming missing at random (for missing solely due to COVID-19).

    b Least-squares mean from ANCOVA adjusted for baseline value and other stratification factors.

    c Analyzed using logistic regression adjusted for baseline value.

    d p-value<0.001 (unadjusted 2-sided) for superiority, controlled for type I error rate.

    e Not controlled for type I error rate.

    Study 1Study 2
    Intention-to-Treat (ITT) Populationa
    Placebo
    N = 643    		ZEPBOUND
    5 mg
    N = 630    		ZEPBOUND
    10 mg
    N = 636    		ZEPBOUND
    15 mg
    N = 630
    Placebo
    N = 315    		ZEPBOUND
    10 mg
    N = 312    		ZEPBOUND
    15 mg
    N = 311
    Body Weight
       Baseline mean (kg) 104.8 102.9 105.8 105.6 101.7 100.9 99.6
       % Change from baselineb-3.1 -15.0 -19.5 -20.9 -3.2 -12.8 -14.7
       % Difference from placebob
        (95% CI)     		-11.9
    (-13.4, _10.4)d    		-16.4
    (_17.9, -14.8)d    		-17.8
    (_19.3, -16.3)d    		-9.6
    (-11.1, -8.1)d    		-11.6
    (-13.0, -10.1)d
    % of Patients losing ≥5% body weight 34.5 85.1 88.9 90.9 32.5 79.2 82.8
       % Difference from placebo
        (95% CI)     		50.3
    (44.3, 56.2)c,d    		54.6
    (49.1, 60.0)c,d    		56.4
    (50.9, 62.0)c,d    		46.8
    (39.5, 54.1)c,d    		50.4
    (43.1, 57.8)c,d
    % of Patients losing ≥10% body weight 18.8 68.5 78.1 83.5 9.5 60.5 64.8
       % Difference from placebo
        (95% CI)     		49.3
    (43.6, 54.9)c,e    		59.5
    (54.2, 64.9)c,d    		64.8
    (59.6, 70.1)c,d    		51.0
    (44.4, 57.7)c,d    		55.3
    (48.6, 62.0)c,d
    % of Patients losing ≥15% body weight 8.8 48.0 66.6 70.6 2.7 39.7 48.0
       % Difference from placebo
        (95% CI)     		38.7
    (33.6, 43.7)c,e    		58.1
    (53.2, 63.0)c,d    		62.0
    (57.2, 66.8)c,d    		37.0
    (31.1, 42.9)c,d    		45.4
    (39.4, 51.4)c,d
    % of Patients losing ≥20% body weight 3.1 30.0 50.1 56.7 1.0 21.5 30.8
       % Difference from placebo
        (95% CI)     		26.6
    (22.4, 30.7)c,e    		47.3
    (42.7, 51.9)c,d    		53.8
    (49.3, 58.3)c,d    		20.5
    (15.7, 25.4)c,d    		29.7
    (24.3, 35.0)c,d

    The cumulative frequency distributions of change in body weight are shown in Figure 1 for Study 1 and Figure 2 for Study 2. One way to interpret this figure is to select a change in body weight of interest on the horizontal axis and note the corresponding proportions of patients (vertical axis) in each treatment group who achieved at least that degree of weight reduction. For example, note that the vertical line arising from -10% in Figure 1 intersects the ZEPBOUND 15 mg and placebo curves at approximately 83.5%, and 18.8%, respectively, which correspond to the values shown in Table 2.

    Figure 1: Changes in Body Weight (%) from Baseline to Week 72 in Study 1 in Patients with Obesity or Overweight (without Type 2 Diabetes)

    Figure 1

    Note: Based on average percent weight change of each randomized patient within each specific treatment arm from 100 imputed datasets including observed data and imputed data using hybrid approach for missing values.

    Figure 2: Changes in Body Weight (%) from Baseline to Week 72 in Study 2 in Patients with Obesity or Overweight and Type 2 Diabetes

    Figure 2

    Note: Based on average percent weight change of each randomized patient within each specific treatment arm from 100 imputed datasets including observed data and imputed data using hybrid approach for missing values.

    The time courses of weight reduction with ZEPBOUND and placebo from baseline through Week 72 are depicted in Figure 3 for Study 1 and Figure 4 for Study 2.

    Figure 3: Change from Baseline (%) in Body Weight in Study 1 in Patients with Obesity or Overweight (without Type 2 Diabetes)

    Figure 3

    Note: Displayed results are from the Intent-to-Treat Population. (1) Observed mean value from Week 0 to Week 72, and (2) least-squares mean ± standard error at Week 72 hybrid imputation (HI).

    Figure 4: Change from Baseline (%) in Body Weight in Study 2 in Patients with Obesity or Overweight and Type 2 Diabetes

    Figure 4

    Note: Displayed results are from the Intent-to-Treat Population. (1) Observed mean value from Week 0 to Week 72, and (2) least squares mean ± standard error at Week 72 hybrid imputation (HI).

    Changes in waist circumference and cardiometabolic parameters with ZEPBOUND are shown in Table 3 for Study 1 and Study 2.

    Table 3: Changes in Anthropometry and Cardiometabolic Parameters at Week 72 in Studies 1 and 2 in Patients with Obesity or Overweight

    Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; N = number of patients randomly assigned to study drug.

    a The intention-to-treat population includes all randomly assigned patients. The missing values were imputed by a hybrid approach using retrieved dropouts from the same treatment group (if missing not due to COVID-19) or using all non-missing data assuming missing at random (for missing solely due to COVID-19).

    b Least-squares mean from ANCOVA adjusted for baseline value and other stratification factors.

    c Analyzed using log-transformed data.

    d p-value<0.001 (unadjusted 2-sided) for superiority, controlled for type I error rate.

    e Not controlled for type I error rate.

    f Least-squares mean from mixed model for repeated measures adjusted for baseline value and other stratification factors.

    g Baseline value is the geometric mean.

    Study 1Study 2
    Intention-to-Treat (ITT) Populationa
    Placebo
    N = 643    		ZEPBOUND
    5 mg
    N = 630    		ZEPBOUND
    10 mg
    N = 636    		ZEPBOUND
    15 mg
    N = 630
    Placebo
    N = 315    		ZEPBOUND
    10 mg
    N = 312    		ZEPBOUND
    15 mg
    N = 311
    Waist Circumference (cm)
       Baseline mean 114.0 113.2 114.8 114.4 116.0 114.2 114.6
       Change from baselineb-4.0 -14.0 -17.7 -18.5 -3.3 -10.8 -13.1
       Difference from placebob (95% CI) -10.1
    (-11.6, -8.6)e    		-13.8
    (-15.2, -12.3)d    		-14.5
    (-15.9, -13.0)d    		-7.4
    (-9.0, -5.9)d    		-9.8
    (-11.2, -8.3)d
    Systolic Blood Pressure (mmHg)
       Baseline mean 122.9 123.6 123.8 123.0 131.0 130.6 130.0
       Change from baselineb-1.0 -6.6 -7.7 -7.4 -1.2 -5.6 -7.1
       Difference from placebob (95% CI) -5.6
    (-7.2, -3.9)e    		-6.7
    (-8.4, -5.0)e    		-6.4
    (-8.0, -4.8)e    		-4.4
    (-6.7, -2.1)e    		-5.9
    (-8.3, -3.6)e
    Diastolic Blood Pressure (mmHg)
       Baseline mean 79.6 79.3 79.9 79.3 79.4 80.2 79.7
       Change from baselineb-0.8 -4.9 -5.0 -4.5 -0.3 -2.1 -2.9
       Difference from placebob (95% CI) -4.1
    (-5.2, -3.0)e    		-4.2
    (-5.3, -3.0)e    		-3.7
    (-4.8, -2.7)e    		-1.8
    (-3.3, -0.4)e    		-2.7
    (-4.2, -1.2)e
    Pulse Rate (beats per minute)
       Baseline mean 72.9 72.4 71.8 72.4 74.8 75.9 75.6
       Change from baselinef0.1 0.6 2.3 2.6 -0.5 0.6 1.0
       Difference from placebof (95% CI) 0.5
    (-0.5, 1.5)e    		2.2
    (1.2, 3.2)e    		2.5
    (1.5, 3.4)e    		1.2
    (-0.1, 2.5)e    		1.5
    (0.2, 2.8)e
    Total Cholesterol (mg/dL)
       Baseline meang187.5 187.1 190.6 187.5 174.9 173.9 167.0
       % change from baselineb-1.8 -3.8 -4.4 -6.3 2.8 -2.8 -1.0
       Relative difference from placebob (95% CI) -2.1
    (-4.5, 0.4)c,e    		-2.7
    (-5.1, -0.2)c,e    		-4.6
    (-6.8, -2.2)c,e    		-5.5
    (-8.7, -2.2)c,e    		-3.8
    (-7.1, -0.3)c,e
    LDL Cholesterol (mg/dL)
       Baseline meang109.4 108.7 112.3 109.3 92.4 90.5 85.7
       % change from baselineb-1.7 -4.6 -5.6 -7.1 7.4 1.8 4.1
       Relative difference from placebob (95% CI) -2.9
    (-6.6, 0.9)c,e    		-4.0
    (-7.5, -0.5)c,e    		-5.5
    (-8.9, -2.0)c,e    		-5.2
    (-10.1, 0.1)c,e    		-3.0
    (-8.4, 2.6)c,e
    HDL Cholesterol (mg/dL)
       Baseline meang46.6 47.6 47.6 47.6 42.7 43.8 42.2
       % change from baselineb-0.7 6.9 9.2 8.0 0.2 8.2 9.7
       Relative difference from placebob (95% CI) 7.7
    (4.6, 10.8)c,e    		9.9
    (6.7, 13.2)c,e    		8.7
    (5.7, 11.8)c,e    		8.0
    (4.2, 11.8)c,e    		9.5
    (5.6, 13.5)c,e
    Non-HDL Cholesterol (mg/dL)
       Baseline meang138.3 137.0 140.4 137.5 129.6 127.2 121.9
       % change from baselineb-2.3 -8.0 -9.4 -11.7 3.7 -6.6 -5.2
       Relative difference from placebob (95% CI) -5.8
    (-8.9, -2.6)c,e    		-7.2
    (-10.3, -4.1)c,e    		-9.6
    (-12.4, -6.6)c,e    		-9.9
    (-14.1, -5.6)c,e    		-8.5
    (-12.9, -4.0)c,e
    Triglycerides (mg/dL)
       Baseline meang130.8 128.7 125.7 128.1 165.0 158.8 158.5
       % change from baselineb-5.6 -21.2 -23.8 -29.1 -3.3 -27.1 -27.3
       Relative difference from placebob (95% CI) -16.5
    (-21.2, -11.4)c,e    		-19.3
    (-23.9, -14.4)c,e    		-24.9
    (-29.1, -20.4)c,e    		-24.6
    (-30.0, -18.7)c,e    		-24.8
    (-30.3, -18.9)c,e
    HbA1c (%)
       Baseline mean 5.6 5.6 5.5 5.6 8.0 8.0 8.1
       Change from baselineb-0.1 -0.4 -0.4 -0.4 -0.5 -2.1 -2.1
       Difference from placebob (95% CI) -0.3
    (-0.3, -0.2)e    		-0.4
    (-0.4, -0.3)e    		-0.4
    (-0.4, -0.3)e    		-1.6
    (-1.7, -1.4)d    		-1.6
    (-1.8, -1.4)d

    Weight Reduction Following Intensive Lifestyle Intervention in Adults with Obesity or Overweight (Study 3)

    Overview of Study 3

    Study 3 (NCT04657016) was an 84-week trial with a 12-week intensive lifestyle intervention lead-in period (Week -12 to Week 0), followed by a 72-week randomized treatment period of ZEPBOUND versus placebo (Week 0 to Week 72) with a standard lifestyle intervention. Only patients who lost ≥5% body weight during the 12-week intensive lifestyle lead-in period entered the 72-week randomized treatment period. The trial initially enrolled 806 adult patients (aged 18 years and older) with obesity (BMI ≥30 kg/m2), or with overweight (BMI 27 to <30 kg/m2) and at least one weight-related comorbid condition, such as dyslipidemia, hypertension, obstructive sleep apnea, or cardiovascular disease; patients with type 2 diabetes mellitus were excluded. During the intensive lifestyle intervention lead-in period, lifestyle instruction was delivered 8 times over 12 weeks by a dietician or dietician-equivalent, with all patients receiving instruction to exercise for at least 150 minutes per week and to reduce their caloric intake to approximately 1,200 kcal/day (females) or 1,500 kcal/day (males). Patients also received counseling on behavior modification strategies to adhere to diet and exercise recommendations. At the end of the 12-week intensive lifestyle intervention lead-in period, 579 patients who achieved ≥5% weight reduction were randomized in a 1:1 ratio to ZEPBOUND or placebo for 72 weeks. ZEPBOUND dosages were escalated over a period of up to 20 weeks to a maximum tolerated dosage (MTD) of 10 mg or 15 mg subcutaneous once weekly. During the randomized treatment period, patients received a standard lifestyle instruction every 12 weeks on reduced-calorie diet (approximately 500 kcal/day deficit) and increased physical activity (recommended minimum of 150 min/week) that began with the first dose of ZEPBOUND or placebo and continued throughout the 72-week treatment period; behavior modification strategies were recommended as needed. Weight reduction was assessed after 72 weeks of treatment (at least 52 weeks at maintenance dose).

    For the 579 patients who were randomized, mean body weight at enrollment prior to entering the 12-week lifestyle lead-in period (Week -12) was 109.5 kg and mean BMI was 38.6 kg/m2. At randomization (Week 0), after the 12-week intensive lifestyle lead-in period, mean body weight was 101.9 kg and mean BMI was 35.9 kg/m2. The mean age of patients randomized to treatment was 46 years (range 18-77 years), 63% were female, 86% were White, 11% were Black or African American, and 1% were Asian. A total of 54% were Hispanic or Latino ethnicity. Baseline characteristics for the 579 randomized patients included 34% with hypertension, 26% with dyslipidemia, 10% with obstructive sleep apnea, and 2% with cardiovascular disease.

    Results for Study 3

    At the end of the 12-week intensive lifestyle intervention lead-in, for patients who subsequently entered the randomized treatment period (n=579), the average body weight loss due to lifestyle was 6.9% (Week -12 to Week 0). Eighty-six percent (86%) of ZEPBOUND-treated patients had a maximum tolerated dosage of 15 mg weekly based on their final dose during the double-blind treatment period. The time course of weight reduction during the lead-in and from Week 0 to Week 72 with ZEPBOUND and placebo are depicted in Figure 5.

    Figure 5: Change in Body Weight (%) After 12-Week Intensive Lifestyle Intervention Lead-In Followed by Randomized Treatment and a Standard Lifestyle Intervention (Study 3) in Patients with Obesity or Overweight

    Figure 5

    Note: Displayed results are from the randomized Population. (1) Observed mean value from Week -12 to Week 72, and (2) least squares mean ± standard error at Week 72 hybrid imputation (HI). Change from Week -12 is not a primary endpoint in Study 3.

    The proportions of patients who discontinued study drug after randomization were 21.3% for the ZEPBOUND-treated group and 30.5% for the placebo-treated group.

    For Study 3, the primary efficacy parameters were mean percent change in body weight from randomization (Week 0) to Week 72 and the percentage of patients achieving ≥5% weight reduction from randomization (Week 0) to Week 72. Amongst randomized patients who already lost ≥5% body weight during the 12-week intensive lifestyle lead-in period, subsequent treatment with ZEPBOUND resulted in a statistically significant reduction in body weight compared to placebo from randomization (Week 0) to Week 72. A greater proportion of patients treated with ZEPBOUND achieved at least 5%, 10%, 15%, and 20% weight reduction from Week 0 to Week 72 compared to placebo (see Table 4).

    Table 4: Changes in Body Weight After 12-Week Intensive Lifestyle Intervention Lead-In Followed by Randomized Treatment and a Standard Lifestyle Intervention (Study 3) in Patients with Obesity or Overweight

    Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; MTD = maximum tolerated dose; N = number of patients randomly assigned to study drug.

    a The intent-to-treat population included only randomized patients with ≥5% weight loss at Week 0 after 12 weeks of intensive lifestyle intervention. During the 12-week lead-in period, 227 of 806 patients (28.2%) discontinued from the study. Of these 141 (17.5%) discontinued due to not achieving the randomization criteria of ≥5% weight reduction.

    b The intent-to-treat population includes all randomly assigned patients. For Study 3 at Week 72, body weight was missing for 23.6% and 8.7% of patients randomly assigned to placebo and ZEPBOUND MTD (10 or 15 mg). The missing values were imputed by a hybrid approach using retrieved dropouts from the same treatment group (if missing not due to COVID-19) or using all non-missing data assuming missing at random (for missing solely due to COVID-19).

    c Least-squares mean from ANCOVA adjusted for baseline value and other stratification factors.

    d Analyzed using logistic regression adjusted for baseline value.

    e p-value<0.001 (unadjusted 2-sided) for superiority, controlled for type I error rate.

    Study 3
    N = 579    a
    Body weight
       Mean (kg) at Week -12 109.5
    Intention-to-Treat (ITT) Populationa,b
    Placebo
    N = 292    		ZEPBOUND
    MTD (10 mg or 15 mg)
    N = 287
    Body Weight
       Mean (kg) at Week 0 101.3 102.5
       % Change from randomization at Week 72c2.5 -18.4
       % Difference from placebo, at Week 72c
        (95% CI)     		-20.8
    (-23.2, -18.5)e
       % of Patients losing ≥5% body weight 16.5 87.5
       % Difference from placebo
        (95% CI)     		71.1
    (63.6, 78.5)d,e
       % of Patients losing ≥10% body weight 8.9 76.7
       % Difference from placebo
        (95% CI)     		67.9
    (60.7, 75.1)d,e
       % of Patients losing ≥15% body weight 4.2 65.4
       % Difference from placebo
        (95% CI)     		61.3
    (54.5, 68.1)d,e
       % of Patients losing ≥20% body weight 2.2 44.7
       % Difference from placebo
        (95% CI)     		42.6
    (36.0, 49.1)d,e

    Changes in waist circumference and cardiometabolic parameters are shown in Table 5.

    Table 5: Changes in Anthropometry and Cardiometabolic Parameters After 12-Week Intensive Lifestyle Intervention Lead-In Followed by Randomized Treatment and a Standard Lifestyle Intervention (Study 3) in Patients with Obesity or Overweight

    Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; N = number of patients randomly assigned to study drug.

    a The intent-to-treat population included all randomly assigned patients. The missing values were imputed by a hybrid approach using retrieved dropouts from the same treatment group (if missing not due to COVID-19) or using all non-missing data assuming missing at random (for missing solely due to COVID-19).

    b Least-squares mean from ANCOVA adjusted for baseline value and other stratification factors.

    c Analyzed using log-transformed data.

    d p-value<0.001 (unadjusted 2-sided) for superiority, controlled for type I error rate.

    e Not controlled for type I error rate.

    f Least-squares mean from mixed model for repeated measures adjusted for baseline value and other stratification factors.

    g Baseline and randomization values are the geometric mean.

    h Observed means are shown for change from Week -12 to Week 0. Least-square means are shown for change from Week 0 to Week 72.

    Intention-to-Treat (ITT) PopulationaAll Randomized Patients
    N=579    		Placebo
    N=292    		ZEPBOUND MTD (10 mg or 15 mg)
    N=287
    Baseline (Week -12)Change from Week -12 to Week 0Randomization (Week 0)Change from Week 0 to Week 72Randomization (Week 0)Change from Week 0 to Week 72Difference from placebo, Week 0 to Week 72
    (95% CI)
    Waist circumference (cm)h116.1 -6.7 109.6 0.2b109.3 -14.6b-14.8b
    (-17.2, -12.5)d
    Systolic Blood Pressure (mmHg)h126.2 -5.0 120.8 3.5b121.7 -5.1b-8.6b
    (-11.3, -6.0)e
    Diastolic Blood Pressure (mmHg)h81.7 -2.9 78.3 2.1b79.3 -3.2b-5.3b
    (-6.9, -3.7)e
    Pulse Rate (beats per minute)h73.0 -1.6 70.7 0.9f72.2 2.7f1.8f
    (0.3, 3.4)e
    HbA1c (%)h5.5 -0.1 5.4 0.0b5.3 -0.4b-0.4b
    (-0.5, -0.3)e
    Total Cholesterol (mg/dL)g,h190.2 -8.6 181.6 4.3 181.7 -2.4 -6.4b
    (-9.0, -3.6)c,e
    LDL Cholesterol (mg/dL)g,h111.6 -3.5 107.5 4.4 108.0 -5.6 -9.6b
    (-13.7, -5.4)c,e
    HDL Cholesterol (mg/dL)g,h48.4 -1.2 47.8 5.4 46.9 15.2 9.3b
    (4.5, 14.2)c,e
    Non-HDL Cholesterol (mg/dL)g,h139.2 -7.4 131.5 4.4 132.4 -8.8 -12.6b
    (-15.9, -9.3)c,e
    Triglycerides (mg/dL)g,h123.1 -19.8 108.8 2.1 111.7 -23.5 -25.1b
    (-30.9, -18.9)c,e

    Weight Reduction Following Randomized Withdrawal in Adults with Obesity or Overweight (Study 4)

    Overview of Study 4

    Study 4 (NCT04660643) was an 88-week randomized withdrawal trial in which all patients received open-label ZEPBOUND during a 36-week lead-in period, followed by randomization to either continue ZEPBOUND or switch to placebo for 52 weeks. The trial enrolled 783 adult patients (aged 18 years and older) with obesity (BMI ≥30 kg/m2), or with overweight (BMI 27 to <30 kg/m2) and at least one weight-related comorbid condition, such as dyslipidemia, hypertension, obstructive sleep apnea, or cardiovascular disease; patients with type 2 diabetes mellitus were excluded. All patients received a standard lifestyle intervention which included instruction on a reduced-calorie diet (approximately 500 kcal/day deficit) and increased physical activity counseling (recommended minimum of 150 min/week) that began with the first dose of ZEPBOUND, during the lead-in period, and continued throughout the trial. During the 36-week open-label ZEPBOUND lead-in period, ZEPBOUND dosages were escalated over a period of up to 20 weeks to an MTD of 10 mg or 15 mg subcutaneous once weekly. After the lead-in period, patients were randomized at Week 36 to continue ZEPBOUND or switch to placebo for 52 weeks.

    Of the 783 patients who started ZEPBOUND at Week 0, 14.4% discontinued treatment before randomization at Week 36, and adverse events were the most common reason for discontinuation (6.8%). At Week 36, a total of 670 patients were randomized in a 1:1 ratio to ZEPBOUND MTD or placebo for 52 weeks. For the 670 randomized patients, at study entry (Week 0) mean body weight was 107.3 kg and mean BMI was 38.4 kg/m2, and at randomization (Week 36, after the open-label ZEPBOUND lead-in period) mean body weight was 85.2 kg and mean BMI was 30.5 kg/m2. Among the randomized patients, the mean age was 49 years (range 19-81 years), 71% were female, 80% were White, 11% were Black or African American, and 7% were Asian. A total of 44% were Hispanic or Latino ethnicity. Baseline characteristics for the 670 randomized patients included 35% with hypertension, 32% with dyslipidemia, 12% with obstructive sleep apnea, and 6% with cardiovascular disease.

    Results for Study 4

    At the end of the 36-week open-label ZEPBOUND lead-in period, of the 670 randomized patients, 93% were on ZEPBOUND MTD of 15 mg weekly and 7% were on MTD of 10 mg weekly. After open-label ZEPBOUND treatment, randomized patients (n=670) had an average body weight loss of 20.9% (Week 0 to Week 36). The time course of weight reduction from Week 0 through Week 88 is depicted in Figure 6.

    Figure 6: Change in Body Weight (%) After 36-Week Open-Label Treatment Followed by Randomized Withdrawal (Study 4) in Patients with Obesity or Overweight

    Figure 6

    Note: Displayed results are from the randomized population. (1) Displayed results are observed mean value from Week 0 to Week 88 and (2) least squares mean ± standard error at Week 88 hybrid imputation (HI). Change from Week 0 was not a primary endpoint in Study 4.

    The proportions of patients who discontinued study drug after randomization at Week 36 were 10.4% for the ZEPBOUND-treated group and 17.9% for the placebo-treated group.

    For Study 4, the primary efficacy parameter was mean percent change in body weight from randomization (Week 36) to Week 88. After weight loss with ZEPBOUND treatment during the open-label lead-in period (Week 0 to Week 36), continued treatment with ZEPBOUND from randomization (Week 36) to Week 88 resulted in a statistically significant reduction in body weight compared with placebo (see Table 6).

    Table 6: Changes in Body Weight After 36-Week Open-Label Treatment Followed by Randomized Withdrawal (Study 4) in Patients with Obesity or Overweight

    Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; MTD = maximum tolerated dose; N = number of patients randomly assigned to study drug.

    a The intent-to-treat population included all randomly assigned patients and did not include 113 patients who were enrolled but not randomized. At Week 88, body weight was missing for 13.7% and 7.5% of patients randomly assigned to placebo and ZEPBOUND MTD (10 or 15 mg), respectively. The missing values were imputed by a hybrid approach using retrieved dropouts from the same treatment group (if missing not due to COVID-19) or using all non-missing data assuming missing at random (for missing solely due to COVID-19).

    b Least-squares mean from ANCOVA adjusted for baseline value and other stratification factors.

    c Analyzed using logistic regression adjusted for baseline value.

    d p-value<0.001 (unadjusted 2-sided) for superiority, controlled for type I error rate.

    Study 4
    N=670    a
    Body weight
       Mean at Week 0 (kg) 107.3
    Intention-to-Treat (ITT) PopulationaPlacebo
    N=335    		ZEPBOUND
    (MTD 10 mg or 15 mg)
    N=335
    Body Weight
       Mean at Week 36 (kg) 85.8 84.6
       % change from Week 36 at Week 88b14.0 -5.5
       % difference from placebo at Week 88
        (95% CI)b    		-19.4
    (-21.2, -17.7)d

    Changes in waist circumference and cardiometabolic parameters in Study 4 are shown in Table 7.

    Table 7: Mean Changes in Anthropometry and Cardiometabolic Parameters After 36-Week Open-Label Treatment Followed by Randomized Withdrawal (Study 4) in Patients with Obesity or Overweight

    Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; N = number of patients randomly assigned to study drug.

    a The intent-to-treat population included all randomly assigned patients. The missing values were imputed by a hybrid approach using retrieved dropouts from the same treatment group (if missing not due to COVID-19) or using all non-missing data assuming missing at random (for missing solely due to COVID-19).

    b Least-squares mean from ANCOVA adjusted for baseline value and other stratification factors.

    c Analyzed using log-transformed data.

    d p-value<0.001 (unadjusted 2-sided) for superiority, controlled for type I error rate.

    e Not controlled for type I error rate.

    f Least-squares mean from mixed model for repeated measures adjusted for baseline value and other stratification factors.

    g Baseline and randomization values are the geometric mean.

    h Observed means are shown for change from Week 0 to Week 36. Least-square means are shown for change from Week 36 to Week 88.

    Intention-to-Treat (ITT) PopulationaAll Randomized Patients
    N=670    		Placebo
    N=335    		ZEPBOUND MTD (10 mg or 15 mg)
    N=335
    Baseline (Week 0)Change from Week 0 to Week 36Randomization (Week 36)Change from Week 36 to Week 88Randomization (Week 36)Change from Week 36 to Week 88Difference from placebo, Week 36 to Week 88
    (95% CI)
    Waist circumference (cm)h115.2 -17.8 98.2 7.8b96.8 -4.3b-12.1b
    (-13.5, -10.6)d
    Systolic Blood Pressure (mmHg)h126.1 -11.2 114.8 8.2b115.0 2.0b-6.2b
    (-8.2, -4.3)e
    Diastolic Blood Pressure (mmHg)h80.9 -5.1 76.2 3.2b75.4 -0.7b-3.8b
    (-5.2, -2.4)e
    Pulse Rate (beats per minute)h72.5 5.0 77.8 -5.2f77.1 -2.1f3.1f
    (1.9, 4.3)e
    HbA1c (%)h5.5 -0.5 5.0 0.3b5.1 -0.0b-0.3b
    (-0.3, -0.2)e
    Total Cholesterol (mg/dL)g,h188.3 -12.4 176.1 8.0 175.9 2.7 -4.9b
    (-7.4, -2.4)c,e
    LDL Cholesterol (mg/dL)g,h108.6 -1.9 107.6 3.2 105.9 -3.5 -6.5b
    (-10.0, -2.9)c,e
    HDL Cholesterol (mg/dL)g,h49.9 -2.7 47.3 14.8 47.7 18.7 3.4b
    (0.2, 6.6)c,e
    Non-HDL Cholesterol (mg/dL)g,h135.8 -9.8 126.3 5.1 126.0 -3.4 -8.1b
    (-11.3, -4.8)c,e
    Triglycerides (mg/dL)g,h121.4 -40.4 85.5 13.5 90.9 -4.8 -16.1b
    (-21.7, -10.0)c,e
  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    16.1 How Supplied

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

    Total Strength per Total Volume4 pack
    Pen NDC    		1 pack
    Vial NDC    		4 pack
    Vial NDC
    2.5 mg/0.5 mL 0002-2506-80 0002-0152-01 0002-0152-04
    5 mg/0.5 mL 0002-2495-80 0002-0243-01 0002-0243-04
    7.5 mg/0.5 mL 0002-2484-80 0002-1214-01 0002-1214-04
    10 mg/0.5 mL 0002-2471-80 0002-1340-01 0002-1340-04
    12.5 mg/0.5 mL 0002-2460-80 0002-1423-01 0002-1423-04
    15 mg/0.5 mL 0002-2457-80 0002-2002-01 0002-2002-04

    16.2 Storage and Handling

    • Store ZEPBOUND in a refrigerator at 2°C to 8°C (36°F to 46°F).
    • If needed, each single-dose pen or single-dose vial can be stored unrefrigerated at temperatures not to exceed 30°C (86°F) for up to 21 days. If ZEPBOUND is stored at room temperature, it should not be returned to the refrigerator.
    • Discard if not used within 21 days after removing from the refrigerator.
    • Do not freeze ZEPBOUND. Do not use ZEPBOUND if frozen.
    • Store ZEPBOUND in the original carton to protect from light.
  • 17 PATIENT COUNSELING INFORMATION

    Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

    Risk of Thyroid C-Cell Tumors

    Inform patients that ZEPBOUND causes thyroid C-cell tumors in rats and that the human relevance of this finding has not been determined. Counsel patients to report symptoms of thyroid tumors (e.g., a lump in the neck, persistent hoarseness, dysphagia, or dyspnea) to their healthcare provider [see Boxed Warning and Warnings and Precautions (5.1)].

    Severe Gastrointestinal Adverse Reactions

    Inform patients of the potential risk of severe gastrointestinal adverse reactions. Instruct patients to contact their healthcare provider if they have severe or persistent gastrointestinal symptoms [see Warnings and Precautions (5.2)].

    Acute Kidney Injury

    Advise patients treated with ZEPBOUND of the potential risk of dehydration due to gastrointestinal adverse reactions and take precautions to avoid fluid depletion. Inform patients of the potential risk for worsening renal function and explain the associated signs and symptoms of renal impairment, as well as the possibility of dialysis as a medical intervention if renal failure occurs [see Warnings and Precautions (5.3)].

    Acute Gallbladder Disease

    Inform patients of the risk of acute gallbladder disease. Instruct patients to contact their healthcare provider for appropriate clinical follow-up if gallbladder disease is suspected [see Warnings and Precautions (5.4)].

    Acute Pancreatitis

    Inform patients of the potential risk for pancreatitis. Instruct patients to discontinue ZEPBOUND promptly and contact their healthcare provider if pancreatitis is suspected (severe abdominal pain that may radiate to the back, and which may or may not be accompanied by vomiting) [see Warnings and Precautions (5.5)].

    Hypersensitivity Reactions

    Inform patients that serious hypersensitivity reactions have been reported with use of tirzepatide. Advise patients on the symptoms of hypersensitivity reactions and instruct them to stop taking ZEPBOUND and seek medical advice promptly if such symptoms occur [see Warnings and Precautions (5.6)].

    Hypoglycemia

    Inform patients of the risk of hypoglycemia and educate patients on the signs and symptoms of hypoglycemia. Advise patients on insulin or insulin secretagogue therapy that they may have an increased risk of hypoglycemia when using ZEPBOUND and to report signs and/or symptoms of hypoglycemia to their healthcare provider [see Warnings and Precautions (5.7)].

    Diabetic Retinopathy Complications

    Inform patients with type 2 diabetes mellitus to contact their healthcare provider if changes in vision are experienced during treatment with ZEPBOUND [see Warnings and Precautions (5.8)].

    Suicidal Behavior and Ideation

    Advise patients to report emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Inform patients that if they experience suicidal thoughts or behaviors, they should stop taking ZEPBOUND [see Warnings and Precautions (5.9)].

    Pulmonary Aspiration During General Anesthesia or Deep Sedation

    Inform patients that ZEPBOUND may cause their stomach to empty more slowly which may lead to complications with anesthesia or deep sedation during planned surgeries or procedures. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking ZEPBOUND [see Warnings and Precautions (5.10)].

    Pregnancy

    Advise a pregnant patient of the potential risk to a fetus. Advise patients to inform their healthcare provider if they are pregnant or intend to become pregnant during treatment with ZEPBOUND. Advise patients that there will be a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ZEPBOUND during pregnancy [see Use in Specific Populations (8.1)].

    Contraception

    Use of ZEPBOUND may reduce the efficacy of oral hormonal contraceptives. 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), Use in Specific Populations (8.3), and Clinical Pharmacology (12.3)].

    Administration

    Instruct patients how to prepare and administer the correct dose of ZEPBOUND and assess their ability to inject subcutaneously to ensure the proper administration of ZEPBOUND. Instruct patients using the single-dose vial to use a syringe appropriate for dose administration (e.g., a 1 mL syringe capable of measuring a 0.5 mL dose) [see Dosage and Administration (2.3)].

    Missed Doses

    Inform patients if a dose is missed, it should be administered as soon as possible within 4 days after the missed dose. If more than 4 days have passed, the missed dose should be skipped and the next dose should be administered on the regularly scheduled day. In each case, inform patients to resume their regular once weekly dosing schedule [see Dosage and Administration (2.2)].

    Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA

    Copyright © 2023, 2024, Eli Lilly and Company. All rights reserved.

    ZEP-0006-USPI-20241023

  • MEDICATION GUIDE

    This Medication Guide has been approved by the U.S. Food and Drug Administration.

    Revised: 10/2024

    Medication Guide
    ZEPBOUND® (ZEHP-bownd)
    (tirzepatide)
    injection, for subcutaneous use

    What is the most important information I should know about ZEPBOUND?
    ZEPBOUND may cause serious side effects, including:

    • Possible thyroid tumors, including cancer. Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rats, ZEPBOUND and medicines that work like ZEPBOUND caused thyroid tumors, including thyroid cancer. It is not known if ZEPBOUND will cause thyroid tumors, or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people.
    • Do not use ZEPBOUND if you or any of your family have ever had a type of thyroid cancer called MTC, or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
    What is ZEPBOUND?
    • ZEPBOUND is an injectable prescription medicine that may help adults with obesity, or some adults with overweight who also have weight-related medical problems, to lose excess body weight and keep the weight off.
    • ZEPBOUND should be used with a reduced-calorie diet and increased physical activity.
    • ZEPBOUND contains tirzepatide and should not be used with other tirzepatide-containing products or any GLP-1 receptor agonist medicines.
    • It is not known if ZEPBOUND is safe and effective for use in children.
    Do not use ZEPBOUND if:
    • you or any of your family have ever had a type of thyroid cancer called MTC or if you have an endocrine system condition called MEN 2.
    • you have had a serious allergic reaction to tirzepatide or any of the ingredients in ZEPBOUND. See the end of this Medication Guide for a complete list of ingredients in ZEPBOUND.
    Before using ZEPBOUND, tell your healthcare provider about all of your medical conditions, including if you:
    • have or have had problems with your pancreas or kidneys.
    • have severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems with digesting food.
    • have a history of diabetic retinopathy.
    • are scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation).
    • are pregnant or plan to become pregnant. ZEPBOUND may harm your unborn baby. Tell your healthcare provider if you become pregnant while using ZEPBOUND.
      • Pregnancy Exposure Registry: There will be a pregnancy exposure registry for women who have taken ZEPBOUND during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry, or you may contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979).
      • Birth control pills by mouth may not work as well while using ZEPBOUND. If you take birth control pills by mouth, your healthcare provider may recommend another type of birth control for 4 weeks after you start ZEPBOUND and for 4 weeks after each increase in your dose of ZEPBOUND. Talk to your healthcare provider about birth control methods that may be right for you while using ZEPBOUND.
    • are breastfeeding or plan to breastfeed. It is not known if ZEPBOUND passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby while using ZEPBOUND.
    Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. ZEPBOUND may affect the way some medicines work, and some medicines may affect the way ZEPBOUND works.
    Before using ZEPBOUND, tell your healthcare provider if you are taking medicines to treat diabetes including an insulin or sulfonylurea which could increase your risk of low blood sugar. Talk to your healthcare provider about low blood sugar levels and how to manage them.
    Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
    How should I use ZEPBOUND?
    • Read the Instructions for Use that comes with ZEPBOUND.
    • Use ZEPBOUND exactly as your healthcare provider tells you to. A healthcare provider should show you how to prepare to inject your dose of ZEPBOUND before injecting the first time.
    • Use ZEPBOUND with a reduced-calorie diet and increased physical activity.
    • ZEPBOUND is injected under the skin (subcutaneously) of your stomach (abdomen), thigh, or upper arm.
    • Use ZEPBOUND 1 time each week, at any time of the day.
    • You may change the day of the week you use ZEPBOUND as long as the time between the 2 doses is at least 3 days (72 hours).
    • If you miss a dose of ZEPBOUND, take the missed dose as soon as possible within 4 days (96 hours) after the missed dose. If more than 4 days have passed, skip the missed dose and take your next dose on the regularly scheduled day. Do not take 2 doses of ZEPBOUND within 3 days (72 hours) of each other.
    • ZEPBOUND may be taken with or without food.
    • Change (rotate) your injection site with each weekly injection. You may use the same area of your body but be sure to choose a different injection site in that area. Do not use the same site for each injection.
    • In case of overdose, get medical help or contact a Poison Center expert right away at 1-800-222-1222. Advice is also available online at poisonhelp.org.
    What are the possible side effects of ZEPBOUND?
    ZEPBOUND may cause serious side effects, including:
    • See “What is the most important information I should know about ZEPBOUND?”
    • severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use ZEPBOUND. Tell your healthcare provider if you have stomach problems that are severe or will not go away.
    • kidney problems (kidney failure). Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration) which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration.
    • gallbladder problems. Gallbladder problems have happened in some people who use ZEPBOUND. Tell your healthcare provider right away if you get symptoms of gallbladder problems which may include:
      • pain in your upper stomach (abdomen)
      • fever
      • yellowing of skin or eyes (jaundice)
      • clay-colored stools
    • inflammation of your pancreas (pancreatitis). Stop using ZEPBOUND and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back.
    • serious allergic reactions. Stop using ZEPBOUND and get medical help right away if you have any symptoms of a serious allergic reaction including:
      • swelling of your face, lips, tongue or throat
      • problems breathing or swallowing
      • severe rash or itching
      • fainting or feeling dizzy
      • very rapid heartbeat
    • low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use ZEPBOUND with medicines that can cause low blood sugar, such as an insulin or sulfonylurea. Signs and symptoms of low blood sugar may include:
      • dizziness or light-headedness
      • sweating
      • confusion or drowsiness
      • headache
      • blurred vision
      • slurred speech
      • shakiness
      • fast heartbeat
      • anxiety, irritability, or mood changes
      • hunger
      • weakness
      • feeling jittery
    • changes in vision in patients with type 2 diabetes. Tell your healthcare provider if you have changes in vision during treatment with ZEPBOUND.
    • depression or thoughts of suicide. You should pay attention to any changes in your mood, behaviors, feelings, or thoughts. Call your healthcare provider right away if you have any changes to your mental health that are new, worse, or worry you.
    • food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). ZEPBOUND may increase the chance of food getting into your lungs during surgery or other procedures. Tell all your healthcare providers that you are taking ZEPBOUND before you are scheduled to have surgery or other procedures.
    The most common side effects of ZEPBOUND include:
    • nausea
    • diarrhea
    • vomiting
    • constipation
    • stomach (abdominal) pain
    • indigestion
    • injection site reactions
    • feeling tired
    • allergic reactions
    • belching
    • hair loss
    • heartburn
    Talk to your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of ZEPBOUND. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
    How should I store ZEPBOUND?
    • Store ZEPBOUND in the refrigerator between 36°F to 46°F (2°C to 8°C). Store ZEPBOUND in the original carton until use to protect it from light.
    • If needed, each single-dose pen or single-dose vial can be stored at room temperature up to 86°F (30°C) for up to 21 days. If ZEPBOUND is stored at room temperature, it should not be returned to the refrigerator.
    • Discard if not used within 21 days after removing from the refrigerator.
    • Do not freeze ZEPBOUND. Do not use ZEPBOUND if frozen.
    Keep ZEPBOUND and all medicines out of the reach of children.
    General information about the safe and effective use of ZEPBOUND.
    Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ZEPBOUND for a condition for which it was not prescribed. Do not give ZEPBOUND to other people, even if they have the same condition you have. It may harm them. You can ask your pharmacist or healthcare provider for information about ZEPBOUND that is written for health professionals.
    What are the ingredients in ZEPBOUND?
    Active ingredient: tirzepatide
    Inactive ingredients: sodium chloride, sodium phosphate dibasic heptahydrate, and water for injection. Hydrochloric acid solution and/or sodium hydroxide solution may have been added to adjust the pH.
    ZEPBOUND® is a registered trademark of Eli Lilly and Company.
    Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA
    Copyright © 2023, 2024, Eli Lilly and Company. All rights reserved.
    For more information, go to www.zepbound.com or call 1-800-545-5979.

    ZEP-0003-MG-20241018

  • SINGLE-DOSE PEN INSTRUCTIONS FOR USE

    INSTRUCTIONS FOR USE
    ZEPBOUNDTM (ZEHP-bownd)
    (tirzepatide)
    injection, for subcutaneous use

    Figure


    2.5 mg/0.5 mL single-dose pen
    5 mg/0.5 mL single-dose pen
    7.5 mg/0.5 mL single-dose pen
    10 mg/0.5 mL single-dose pen
    12.5 mg/0.5 mL single-dose pen
    15 mg/0.5 mL single-dose pen
    use 1 time each week

    Important information you need to know before injecting ZEPBOUND

    Read this Instructions for Use and the Medication Guide before using your ZEPBOUND pen and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

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

    • ZEPBOUND is a single-dose prefilled pen.
    • ZEPBOUND is used 1 time each week.
    • Inject under the skin (subcutaneously) only.
    • You or another person can inject into your stomach (abdomen) or thigh.
    • Another person can inject into the back of your upper arm.

    Guide to parts

    Figure

    Preparing to inject ZEPBOUND

    Remove the pen from the refrigerator.
    Leave the gray base cap on until you are ready to inject.
    Check the pen label to make sure you have the right medicine and dose, and that it has not expired.
    Inspect the pen to make sure that it is not damaged.
    Figure
    Make sure the medicine:
    • is not frozen
    • is not cloudy
    • is colorless to slightly yellow
    • does not have particles
    Wash your hands.
    Step
    1    		Choose your injection site

    Figure     		Your healthcare provider can help you choose the injection site that is best for you.

    You or another person can inject the medicine in your stomach (abdomen) or thigh.

    Figure     		Another person should give you the injection in the back of your upper arm.
    Change (rotate) your injection site each week.
    You may use the same area of your body but be sure to choose a different injection site in that area.
    Step
       2    		Pull off the gray base cap

    Figure     		Make sure the pen is locked.
    Do not unlock the pen until you place the clear base on your skin and are ready to inject.
    Pull the gray base cap straight off and throw it away in your household trash.
    Do not put the gray base cap back on – this could damage the needle.
    Do not touch the needle.
    Step
       3    		Place clear base on skin, then unlock

    Figure     		Place the clear base flat against your skin at the injection site.

    Figure     		Unlock by turning the lock ring.

    Step
       4

    		Press and hold up to 10 seconds

    Figure     		Press and hold the purple injection button for up to 10 seconds.
    Listen for:
    • First click = injection started
    • Second click = injection completed

    Figure     		You will know your injection is complete when the gray plunger is visible.
    After your injection, place the used pen in a sharps container.
    See Disposing of your used pen.

    Disposing of your used pen

    • Put your used pen in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) pens 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 recycle your used sharps disposal container.

    • Storage and handling

    Commonly asked questions

    What if I see air bubbles in my pen?

    Air bubbles are normal.

    What if my pen is not at room temperature?

    It is not necessary to warm the pen to room temperature.

    What if I unlock the pen and press the purple injection button before pulling off the gray base cap?

    Do not remove the gray base cap. Throw away the pen and get a new pen.

    What if there is a drop of liquid on the tip of the needle when I remove the gray base cap?

    A drop of liquid on the tip of the needle is normal. Do not touch the needle.

    Do I need to hold the injection button down until the injection is complete?

    This is not necessary, but it may help you keep the pen steady against your skin.

    I heard more than 2 clicks during my injection—2 loud clicks and 1 soft one. Did I get my complete injection?

    Some people may hear a soft click right before the second loud click. That is the normal operation of the pen. Do not remove the pen from your skin until you hear the second loud click.

    I am not sure if my pen worked the right way.


    Figure     		Check to see if you have received your dose. Your dose was delivered the right way if the gray plunger is visible. Also, see Step 4 of the instructions.
    If you do not see the gray plunger, contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) for further instructions. Until then, store your pen safely to avoid an accidental needle stick.

    What if there is a drop of liquid or blood on my skin after my injection?

    This is normal. Press a cotton ball or gauze over the injection site. Do not rub the injection site.

    Other information

    Where to learn more


    Figure     		Scan this code to launch
    www.zepbound.com

    Marketed by:
    Lilly USA, LLC
    Indianapolis, IN 46285, USA

    ZEPBOUND is a trademark of Eli Lilly and Company.

    Copyright © 2023, Eli Lilly and Company. All rights reserved.

    This Instructions for Use has been approved by the U.S. Food and Drug Administration. Revised: November 2023

    ZEP-0002-PEN-IFU-20231109

    Figure

  • SINGLE-DOSE VIAL INSTRUCTIONS FOR USE

    INSTRUCTIONS FOR USE
    ZEPBOUND® [ZEHP-bownd]
    (tirzepatide)
    injection, for subcutaneous use

    2.5 mg/0.5 mL single-dose vial
    5 mg/0.5 mL single-dose vial
    7.5 mg/0.5 mL single-dose vial
    10 mg/0.5 mL single-dose vial
    12.5 mg/0.5 mL single-dose vial
    15 mg/0.5 mL single-dose vial

    Important information you need to know before injecting ZEPBOUND

    Read this Instructions for Use before you start taking ZEPBOUND and each time you get a new vial. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

    Do not share your needles or syringes with other people. You may give other people a serious infection or get a serious infection from them.

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

    Gather supplies needed to give your injection

    Guide to parts

    Vial    		Needle and Syringe (not included)
    Figure Figure

    Note: The needle and syringe are not included. The needle and syringe recommended by your healthcare provider may look different than the needle and syringe in this Instructions for Use.

    Preparing to inject ZEPBOUND

    Remove the vial from the refrigerator.

    Check the vial label to make sure you have the right medicine and dose, and that it has not expired.

    Make sure the medicine:

    • is not frozen
    • is not cloudy
    • is colorless to slightly yellow
    • does not have particles

    Always use a new syringe and needle for each injection to prevent infections and blocked needles. Do not reuse or share your syringes or needles with other people. You may give other people a serious infection or get a serious infection from them.

    Wash your hands with soap and water.

    Step 1:
    Pull off the plastic protective cap. Do not remove the rubber stopper.     		Figure
    Step 2:
    Wipe the rubber stopper with an alcohol swab.     		Figure
    Step 3:
    Remove the outer wrapping from the syringe.     		Figure
    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.     		Figure
    Step 5:
    Place the needle on top of the syringe and turn until it is tight and firmly attached.     		Figure
    Step 6:
    Remove the needle shield by pulling straight off.     		Figure
    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 0.5 mL of air has been drawn into the syringe.     		Figure
    Step 8:
    Push the needle through the rubber stopper of the vial.
    Figure
    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.
    Figure
    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 0.5 mL line.
    If there are air bubbles, tap the syringe gently a few times to let any air bubbles rise to the top.     		Figure Figure
    Step 11:
    Slowly push the plunger up until the plunger tip reaches the 0.5 mL line.     		Figure
    Step 12:
    Pull the syringe out of the rubber stopper of the vial.     		Figure

    Injecting ZEPBOUND

    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.     		Figure Figure
    Step 14:
    Insert the needle into your skin.     		Figure
    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.     		Figure
    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 or an alcohol swab. Do not rub the area.
    • Do not recap the needle. Recapping the needle can lead to a needle stick injury.
    		Figure

    Disposing of used needles and syringes

    Storing ZEPBOUND

    Keep ZEPBOUND vials, syringes, needles, and all medicines out of the reach of children.

    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 © 2024, Eli Lilly and Company. All rights reserved.

    ZEP-0001-VL-IFU-20240328

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

    Issued: March 2024

  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL - ZepboundTM, 2.5 mg/0.5 mL, Carton, 4 Single-Dose Pens

    NDC: 0002-2506-80

    ZepboundTM

    (tirzepatide) injection

    2.5 mg/0.5 mL

    4 x 2.5 mg/0.5 mL prefilled pens

    Rx Only

    For Subcutaneous Use

    Dispense enclosed Medication Guide to each patient.

    Use one pen every week.

    4 Single-dose prefilled pens

    Lilly

    PACKAGE LABEL - Zepbound, 2.5 mg/0.5 mL, Carton, 4 Single-Dose Pens
  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL - ZepboundTM, 5 mg/0.5 mL, Carton, 4 Single-Dose Pens

    NDC: 0002-2495-80

    ZepboundTM

    (tirzepatide) injection

    5 mg/0.5 mL

    4 x 5 mg/0.5 mL prefilled pens

    Rx Only

    For Subcutaneous Use

    Dispense enclosed Medication Guide to each patient.

    Use one pen every week.

    4 Single-dose prefilled pens

    Lilly

    PACKAGE LABEL - Zepbound, 5 mg/0.5 mL, Carton, 4 Single-Dose Pens
  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL - ZepboundTM, 7.5 mg/0.5 mL, Carton, 4 Single-Dose Pens

    NDC: 0002-2484-80

    ZepboundTM

    (tirzepatide) injection

    7.5 mg/0.5 mL

    4 x 7.5 mg/0.5 mL prefilled pens

    Rx Only

    For Subcutaneous Use

    Dispense enclosed Medication Guide to each patient.

    Use one pen every week.

    4 Single-dose prefilled pens

    Lilly

    PACKAGE LABEL - Zepbound, 7.5 mg/0.5 mL, Carton, 4 Single-Dose Pens
  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL - ZepboundTM, 10 mg/0.5 mL, Carton, 4 Single-Dose Pens

    NDC: 0002-2471-80

    ZepboundTM

    (tirzepatide) injection

    10 mg/0.5 mL

    4 x 10 mg/0.5 mL prefilled pens

    Rx Only

    For Subcutaneous Use

    Dispense enclosed Medication Guide to each patient.

    Use one pen every week.

    4 Single-dose prefilled pens

    Lilly

    PACKAGE LABEL - Zepbound, 10 mg/0.5 mL, Carton, 4 Single-Dose Pens
  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL - ZepboundTM, 12.5 mg/0.5 mL, Carton, 4 Single-Dose Pens

    NDC: 0002-2460-80

    ZepboundTM

    (tirzepatide) injection

    12.5 mg/0.5 mL

    4 x 12.5 mg/0.5 mL prefilled pens

    Rx Only

    For Subcutaneous Use

    Dispense enclosed Medication Guide to each patient.

    Use one pen every week.

    4 Single-dose prefilled pens

    Lilly

    PACKAGE LABEL - Zepbound, 12.5 mg/0.5 mL, Carton, 4 Single-Dose Pens
  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL - ZepboundTM, 15 mg/0.5 mL, Carton, 4 Single-Dose Pens

    NDC: 0002-2457-80

    ZepboundTM

    (tirzepatide) injection

    15 mg/0.5 mL

    4 x 15 mg/0.5 mL prefilled pens

    Rx Only

    For Subcutaneous Use

    Dispense enclosed Medication Guide to each patient.

    Use one pen every week.

    4 Single-dose prefilled pens

    Lilly

    PACKAGE LABEL - Zepbound, 15 mg/0.5 mL, Carton, 4 Single-Dose Pens
  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL - Zepbound®, 2.5 mg/0.5 mL, Carton, 4 Single-dose Vials

    NDC: 0002-0152-04

    Zepbound®

    (tirzepatide) injection

    2.5 mg/0.5 mL

    4 x 2.5 mg/0.5 mL single-dose vials

    Discard unused portion

    Rx Only

    For Subcutaneous Use

    Needles and Syringes are not included

    Dispense enclosed Medication Guide to each patient.

    Use one vial every week.

    4 Single-dose vials

    Lilly

    PACKAGE LABEL - Zepbound, 2.5 mg/0.5 mL, 4 count Single-dose Vials
    PACKAGE LABEL - Zepbound, 2.5 mg/0.5 mL, 4 count Single-dose Vials
  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL - Zepbound®, 5 mg/0.5 mL, Carton, 4 Single-dose Vials

    NDC: 0002-0243-04

    Zepbound®

    (tirzepatide) injection

    5 mg/0.5 mL

    4 x 5 mg/0.5 mL single-dose vials

    Discard unused portion

    Rx Only

    For Subcutaneous Use

    Needles and Syringes are not included

    Dispense enclosed Medication Guide to each patient.

    Use one vial every week.

    4 Single-dose vials

    Lilly

    PACKAGE LABEL - Zepbound, 5 mg/0.5 mL, 4 count Single-dose Vials
    PACKAGE LABEL - Zepbound, 5 mg/0.5 mL, 4 count Single-dose Vials
  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL - Zepbound®, 7.5 mg/0.5 mL, Single-dose Vial

    NDC: 0002-1214-01

    Zepbound®

    (tirzepatide) injection

    7.5 mg/0.5 mL

    Single-dose Vial - discard unused portion

    Rx Only

    For Subcutaneous Use

    Needles and Syringes are not included

    Dispense enclosed Medication Guide to each patient.

    Lilly

    PACKAGE LABEL - Zepbound, 7.5 mg/0.5 mL, Single-dose Vial
  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL - Zepbound®, 10 mg/0.5 mL, Carton, Single-dose Vial

    NDC: 0002-1340-01

    Zepbound®

    (tirzepatide) injection

    10 mg/0.5 mL

    Single-dose Vial - discard unused portion

    Rx Only

    For Subcutaneous Use

    Needles and Syringes are not included

    Dispense enclosed Medication Guide to each patient.

    Lilly

    PACKAGE LABEL - Zepbound, 10 mg/0.5 mL, Single-dose Vial
  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL - Zepbound®, 12.5 mg/0.5 mL, Single-dose Vial

    NDC: 0002-1423-01

    Zepbound®

    (tirzepatide) injection

    12.5 mg/0.5 mL

    Single-dose Vial - discard unused portion

    Rx Only

    For Subcutaneous Use

    Needles and Syringes are not included

    Dispense enclosed Medication Guide to each patient.

    Lilly

    PACKAGE LABEL - Zepbound, 12.5 mg/0.5 mL, Single-dose Vial
  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL - Zepbound®, 15 mg/0.5 mL, Single-dose Vial

    NDC: 0002-2002-01

    Zepbound®

    (tirzepatide) injection

    15 mg/0.5 mL

    Single-dose Vial - discard unused portion

    Rx Only

    For Subcutaneous Use

    Needles and Syringes are not included

    Dispense enclosed Medication Guide to each patient.

    Lilly

    PACKAGE LABEL - Zepbound, 15 mg/0.5 mL, Single-dose Vial
  • INGREDIENTS AND APPEARANCE
    ZEPBOUND 
    tirzepatide injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 0002-2506
    Route of AdministrationSUBCUTANEOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    tirzepatide (UNII: OYN3CCI6QE) (tirzepatide - UNII:OYN3CCI6QE) tirzepatide2.5 mg  in 0.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    Sodium Phosphate, Dibasic, Heptahydrate (UNII: 70WT22SF4B) 0.7 mg  in 0.5 mL
    Sodium Chloride (UNII: 451W47IQ8X) 4.1 mg  in 0.5 mL
    Hydrochloric Acid (UNII: QTT17582CB)  
    Sodium Hydroxide (UNII: 55X04QC32I)  
    Water (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 0002-2506-804 in 1 CARTON11/08/2023
    1NDC: 0002-2506-010.5 mL in 1 SYRINGE; Type 2: Prefilled Drug Delivery Device/System (syringe, patch, etc.)
    2NDC: 0002-2506-614 in 1 CARTON11/08/2023
    20.5 mL in 1 SYRINGE; Type 2: Prefilled Drug Delivery Device/System (syringe, patch, etc.)
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA21780611/08/2023
    ZEPBOUND 
    tirzepatide injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 0002-2495
    Route of AdministrationSUBCUTANEOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    tirzepatide (UNII: OYN3CCI6QE) (tirzepatide - UNII:OYN3CCI6QE) tirzepatide5 mg  in 0.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    Sodium Phosphate, Dibasic, Heptahydrate (UNII: 70WT22SF4B) 0.7 mg  in 0.5 mL
    Sodium Chloride (UNII: 451W47IQ8X) 4.1 mg  in 0.5 mL
    Hydrochloric Acid (UNII: QTT17582CB)  
    Sodium Hydroxide (UNII: 55X04QC32I)  
    Water (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 0002-2495-804 in 1 CARTON11/08/2023
    1NDC: 0002-2495-010.5 mL in 1 SYRINGE; Type 2: Prefilled Drug Delivery Device/System (syringe, patch, etc.)
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA21780611/08/2023
    ZEPBOUND 
    tirzepatide injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 0002-2484
    Route of AdministrationSUBCUTANEOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    tirzepatide (UNII: OYN3CCI6QE) (tirzepatide - UNII:OYN3CCI6QE) tirzepatide7.5 mg  in 0.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    Sodium Phosphate, Dibasic, Heptahydrate (UNII: 70WT22SF4B) 0.7 mg  in 0.5 mL
    Sodium Chloride (UNII: 451W47IQ8X) 4.1 mg  in 0.5 mL
    Hydrochloric Acid (UNII: QTT17582CB)  
    Sodium Hydroxide (UNII: 55X04QC32I)  
    Water (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 0002-2484-804 in 1 CARTON11/08/2023
    1NDC: 0002-2484-010.5 mL in 1 SYRINGE; Type 2: Prefilled Drug Delivery Device/System (syringe, patch, etc.)
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA21780611/08/2023
    ZEPBOUND 
    tirzepatide injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 0002-2471
    Route of AdministrationSUBCUTANEOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    tirzepatide (UNII: OYN3CCI6QE) (tirzepatide - UNII:OYN3CCI6QE) tirzepatide10 mg  in 0.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    Sodium Phosphate, Dibasic, Heptahydrate (UNII: 70WT22SF4B) 0.7 mg  in 0.5 mL
    Sodium Chloride (UNII: 451W47IQ8X) 4.1 mg  in 0.5 mL
    Hydrochloric Acid (UNII: QTT17582CB)  
    Sodium Hydroxide (UNII: 55X04QC32I)  
    Water (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 0002-2471-804 in 1 CARTON11/08/2023
    1NDC: 0002-2471-010.5 mL in 1 SYRINGE; Type 2: Prefilled Drug Delivery Device/System (syringe, patch, etc.)
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA21780611/08/2023
    ZEPBOUND 
    tirzepatide injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 0002-2460
    Route of AdministrationSUBCUTANEOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    tirzepatide (UNII: OYN3CCI6QE) (tirzepatide - UNII:OYN3CCI6QE) tirzepatide12.5 mg  in 0.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    Sodium Phosphate, Dibasic, Heptahydrate (UNII: 70WT22SF4B) 0.7 mg  in 0.5 mL
    Sodium Chloride (UNII: 451W47IQ8X) 4.1 mg  in 0.5 mL
    Hydrochloric Acid (UNII: QTT17582CB)  
    Sodium Hydroxide (UNII: 55X04QC32I)  
    Water (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 0002-2460-804 in 1 CARTON11/08/2023
    1NDC: 0002-2460-010.5 mL in 1 SYRINGE; Type 2: Prefilled Drug Delivery Device/System (syringe, patch, etc.)
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA21780611/08/2023
    ZEPBOUND 
    tirzepatide injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 0002-2457
    Route of AdministrationSUBCUTANEOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    tirzepatide (UNII: OYN3CCI6QE) (tirzepatide - UNII:OYN3CCI6QE) tirzepatide15 mg  in 0.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    Sodium Phosphate, Dibasic, Heptahydrate (UNII: 70WT22SF4B) 0.7 mg  in 0.5 mL
    Sodium Chloride (UNII: 451W47IQ8X) 4.1 mg  in 0.5 mL
    Hydrochloric Acid (UNII: QTT17582CB)  
    Sodium Hydroxide (UNII: 55X04QC32I)  
    Water (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 0002-2457-804 in 1 CARTON11/08/2023
    1NDC: 0002-2457-010.5 mL in 1 SYRINGE; Type 2: Prefilled Drug Delivery Device/System (syringe, patch, etc.)
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA21780611/08/2023
    ZEPBOUND 
    tirzepatide injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 0002-0152
    Route of AdministrationSUBCUTANEOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    tirzepatide (UNII: OYN3CCI6QE) (tirzepatide - UNII:OYN3CCI6QE) tirzepatide2.5 mg  in 0.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    Sodium Chloride (UNII: 451W47IQ8X) 4.1 mg  in 0.5 mL
    Sodium Phosphate, Dibasic, Heptahydrate (UNII: 70WT22SF4B) 0.7 mg  in 0.5 mL
    Hydrochloric Acid (UNII: QTT17582CB)  
    Sodium Hydroxide (UNII: 55X04QC32I)  
    Water (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 0002-0152-011 in 1 CARTON03/28/2024
    10.5 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    2NDC: 0002-0152-044 in 1 CARTON08/08/2024
    20.5 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA21780611/08/2023
    ZEPBOUND 
    tirzepatide injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 0002-0243
    Route of AdministrationSUBCUTANEOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    tirzepatide (UNII: OYN3CCI6QE) (tirzepatide - UNII:OYN3CCI6QE) tirzepatide5 mg  in 0.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    Sodium Chloride (UNII: 451W47IQ8X) 4.1 mg  in 0.5 mL
    Sodium Phosphate, Dibasic, Heptahydrate (UNII: 70WT22SF4B) 0.7 mg  in 0.5 mL
    Hydrochloric Acid (UNII: QTT17582CB)  
    Sodium Hydroxide (UNII: 55X04QC32I)  
    Water (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 0002-0243-011 in 1 CARTON03/28/2024
    10.5 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    2NDC: 0002-0243-044 in 1 CARTON08/08/2024
    20.5 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA21780611/08/2023
    ZEPBOUND 
    tirzepatide injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 0002-1214
    Route of AdministrationSUBCUTANEOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    tirzepatide (UNII: OYN3CCI6QE) (tirzepatide - UNII:OYN3CCI6QE) tirzepatide7.5 mg  in 0.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    Sodium Chloride (UNII: 451W47IQ8X) 4.1 mg  in 0.5 mL
    Sodium Phosphate, Dibasic, Heptahydrate (UNII: 70WT22SF4B) 0.7 mg  in 0.5 mL
    Hydrochloric Acid (UNII: QTT17582CB)  
    Sodium Hydroxide (UNII: 55X04QC32I)  
    Water (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 0002-1214-011 in 1 CARTON03/28/2024
    10.5 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    2NDC: 0002-1214-044 in 1 CARTON08/08/202408/08/2024
    20.5 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA21780611/08/2023
    ZEPBOUND 
    tirzepatide injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 0002-1340
    Route of AdministrationSUBCUTANEOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    tirzepatide (UNII: OYN3CCI6QE) (tirzepatide - UNII:OYN3CCI6QE) tirzepatide10 mg  in 0.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    Sodium Chloride (UNII: 451W47IQ8X) 4.1 mg  in 0.5 mL
    Sodium Phosphate, Dibasic, Heptahydrate (UNII: 70WT22SF4B) 0.7 mg  in 0.5 mL
    Hydrochloric Acid (UNII: QTT17582CB)  
    Sodium Hydroxide (UNII: 55X04QC32I)  
    Water (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 0002-1340-011 in 1 CARTON03/28/2024
    10.5 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    2NDC: 0002-1340-044 in 1 CARTON08/08/202408/08/2024
    20.5 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA21780611/08/2023
    ZEPBOUND 
    tirzepatide injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 0002-1423
    Route of AdministrationSUBCUTANEOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    tirzepatide (UNII: OYN3CCI6QE) (tirzepatide - UNII:OYN3CCI6QE) tirzepatide12.5 mg  in 0.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    Sodium Chloride (UNII: 451W47IQ8X) 4.1 mg  in 0.5 mL
    Sodium Phosphate, Dibasic, Heptahydrate (UNII: 70WT22SF4B) 0.7 mg  in 0.5 mL
    Hydrochloric Acid (UNII: QTT17582CB)  
    Sodium Hydroxide (UNII: 55X04QC32I)  
    Water (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 0002-1423-011 in 1 CARTON03/28/2024
    10.5 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    2NDC: 0002-1423-044 in 1 CARTON08/08/202408/08/2024
    20.5 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA21780611/08/2023
    ZEPBOUND 
    tirzepatide injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 0002-2002
    Route of AdministrationSUBCUTANEOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    tirzepatide (UNII: OYN3CCI6QE) (tirzepatide - UNII:OYN3CCI6QE) tirzepatide15 mg  in 0.5 mL
    Inactive Ingredients
    Ingredient NameStrength
    Sodium Chloride (UNII: 451W47IQ8X) 4.1 mg  in 0.5 mL
    Sodium Phosphate, Dibasic, Heptahydrate (UNII: 70WT22SF4B) 0.7 mg  in 0.5 mL
    Hydrochloric Acid (UNII: QTT17582CB)  
    Sodium Hydroxide (UNII: 55X04QC32I)  
    Water (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 0002-2002-011 in 1 CARTON03/28/2024
    10.5 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    2NDC: 0002-2002-044 in 1 CARTON08/08/202408/08/2024
    20.5 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA21780611/08/2023
    Labeler - Eli Lilly and Company (006421325)

    • Trademark Results [Zepbound]

    Mark Image

    Registration | Serial
    Company
    Trademark
    Application Date
    ZEPBOUND
    ZEPBOUND
    98427991 not registered Live/Pending
    Eli Lilly and Company
    2024-02-29
    ZEPBOUND
    ZEPBOUND
    97530456 not registered Live/Pending
    Eli Lilly and Company
    2022-08-02
    ZEPBOUND
    ZEPBOUND
    97530451 not registered Live/Pending
    Eli Lilly and Company
    2022-08-02
    ZEPBOUND
    ZEPBOUND
    97362818 not registered Live/Pending
    Eli Lilly and Company
    2022-04-14
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