Dosage & Administration
Recommended Dose Escalation Schedule
Recommended Maintenance and Maximum Dosage
Maximum Recommended Dosage: 15 mg injected subcutaneously once weekly.
Administration Instructions
See full prescribing information for administration instructions.
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Zepbound Prescribing Information
- 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 and Nonclinical Toxicology ].
- 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 ]. 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 and Warnings and Precautions ].
ZEPBOUND® is indicated in combination with a reduced-calorie diet and increased physical activity:
- to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition.
- to treat moderate to severe obstructive sleep apnea (OSA) in adults with obesity.
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.
Recommended Dose Escalation Schedule
- The recommended starting dosage of ZEPBOUND for all indications is 2.5 mg injected subcutaneously once weekly for 4 weeks.
- The 2.5 mg dosage is for treatment initiation and is not approved as a maintenance dosage.
- Follow the dosage escalation below for all indications to reduce the risk of gastrointestinal adverse reactions [see Warnings and Precautions and Adverse Reactions ].
- After 4 weeks, increase the dosage to 5 mg injected subcutaneously once weekly. The dosage may be increased in 2.5 mg increments, after at least 4 weeks on the current dose [see Dosage and Administration ].
- Consider treatment response and tolerability when selecting the maintenance dosage. If patients do not tolerate a maintenance dosage, consider a lower maintenance dosage.
Recommended Maintenance and Maximum Dosage
Recommended Maintenance Dosage
Weight Reduction and Long-Term Maintenance
The recommended maintenance dosage is 5 mg, 10 mg, or 15 mg, injected subcutaneously once weekly.
OSA
The recommended maintenance dosage is 10 mg or 15 mg injected subcutaneously once weekly.
Maximum Recommended Dosage
The maximum dosage of ZEPBOUND for all indications is 15 mg injected subcutaneously once weekly.
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).
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.
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
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.
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.
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 and Clinical Pharmacology ].
Pediatric Use
The safety and effectiveness of ZEPBOUND have not been established in pediatric patients.
Geriatric Use
In a pool of two fixed dose ZEPBOUND clinical studies for weight reduction (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.
ZEPBOUND clinical studies in OSA (Study 5 and Study 6) did not include sufficient numbers of patients age 65 years or older to determine whether they respond differently from younger adult patients. Other reported clinical experience with tirzepatide has not identified differences in responses between the elderly and younger patients.
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 ]. Monitor renal function in patients reporting adverse reactions to ZEPBOUND that could lead to volume depletion [see Warnings and Precautions ].
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 ].
ZEPBOUND is contraindicated in patients with:
- A personal or family history of MTC or in patients with MEN 2 [see Warnings and Precautions ].
- 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 and Adverse Reactions ].