Tirzepatide
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alen Antony Pathil, M.D.[2]
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Black Box Warning
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Risk of Thyroid C-Cell tumor
See full prescribing information for complete Boxed Warning.
It has been shown in animal study that tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures among male and female rats.
Tirzepatide is contraindicated in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
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Overview
Tirzepatide is a glucagon-like peptide-1 (GLP-1) receptor agonist that is FDA approved for the treatment of type 2 diabetes mellitus in adults in adjunct to diet and exercise.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include pancreatitis, hypoglycemia with concomitant use of insulin or insulin secretagogues, acute kidney injury, severe gastrointestinal disease, acute gallbladder disease, diabetic retinopathy complication, risk of thyroid C-cell tumor and hypersensitivity reaction..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
MOUNJARO is indicated for improving high blood glucose levels in adults with type 2 diabetes mellitus in adjunct to diet and exercise. MOUNJARO is not indicated for treating type 1 diabetes mellitus.
recommended dosage:
- recommended starting dosage of MOUNJARO is 2.5 mg injected subcutaneously once weekly.
- After 4 weeks, the dosage is increased to 5 mg injected subcutaneously once weekly.
- If additional glycemic control is needed, increase the dosage in 2.5 mg increments after at least 4 weeks on the current dose (The maximum dosage of MOUNJARO is 15 mg injected subcutaneously once weekly).
- if a dose of MOUNJARO is missed, the next dose is given immediately with 4 days of the last dose. However, if more than 4 days have passed, it is advised to follow the next dose on the regularly scheduled day (the duration for between 2 doses should be at least 72 hours apart).
Off-Label Use and Dosage (Adult)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Safety and effectiveness of MOUNJARO have not been established in pediatric patients (younger than 18 years of age).
Off-Label Use and Dosage (Pediatric)
Contraindications
- patients with personal and family history of medullary thyroid carcinoma and multiple endocrine neoplasia (MEN2)
- patients who are sensitive to Tirzepatide or excipients of Tirzepatide, as they hypersensitive reactions like anaphylaxis or angioedema.
Warnings
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Risk of Thyroid C-Cell tumor
See full prescribing information for complete Boxed Warning.
It has been shown in animal study that tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures among male and female rats.
Tirzepatide is contraindicated in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
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- Risk of Thyroid tumor
In a clinical study involving both sexes of rats, tirzepatide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) at clinically relevant plasma exposures. MOUNJARA is contraindicated in patients with personal and family history of medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia (MEN2). Patients are counseled about the potential risk of MTC and symptoms of thyroid tumors like mass in the neck, dyspnea, dysphagia, and hoarsness. However, routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with MOUNJARO.
- Pancreatitis
In clinical studies, 14 events of acute pancreatitis were confirmed by adjudication in 13 MOUNJARO-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). MOUNJARO has not been studied in patients with a history of pancreatitis, therefore it is unknown if MOUNJARO increases the risk of pancreatitis in patients with a history of pancreatitis. Patients are carefully observed for signs of pancreatitis (nausea, vomiting, epigastric pain radiating to the back) after initiating MOUNJARO.
- Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues like sulfonylurea. Patients are advised on the potential risk of hypoglycemia and counseled on the symptoms of hypoglycemia.
- Acute Kidney Injury
In patients treated with GLP1 agonists, there have been post-marketing reports of renal impairment or worsening of chronic kidney disease. Majority of the event occurred in patients with complaints of nausea, vomiting, diarrhea or dehydration. Monitor patients renal function test on initiating or increasing the dosage of MOUNJARO for those having severe gastrointestinal reactions.
- Diabetic Retinopathy Complications
Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Patients with a history with history diabetic retinopathy should be monitored for progression of the existing retinopathy
- Acute Gallbladder disease
cholecystitis and cholelithiasis have been observed in post-marketing surveillance and trials in patients taking GLP-1 agonists.
- Hypersensitivity reaction
life-threatening reaction like angioedema and anaphylaxis has been observed in patients taking MOUNJARO. do not use MOUNJARO in patients with prior history hypersensitivity reactions.
- Severe Gastrointestinal Disease
nausea, vomiting, diarrhea, constipation, dyspepsia, abdominal pain and decreased appetite
Adverse Reactions
Clinical Trials Experience
- Gastrointestinal adverse reaction
In the pool of placebo-controlled trials, gastrointestinal adverse reactions occurred more frequently among patients receiving MOUNJARO than placebo (placebo 20.4%, MOUNJARO 5 mg 37.1%, MOUNJARO 10 mg 39.6%, MOUNJARO 15 mg 43.6%). More patients receiving MOUNJARO 5 mg (3.0%), MOUNJARO 10 mg (5.4%), and MOUNJARO 15 mg (6.6%) discontinued treatment due to gastrointestinal adverse reactions than patients receiving placebo (0.4%) the most commonly presented adverse reactions were: eructation, gastroesophageal reflux disease, constipation,and flatulence.
- Hypoglycemia
- tachycardia
- hypersensitivity reaction
- injection site reaction
- acute gallbladder disease
- elevation of amylase and lipase enzyme - laboratory abnormalities
Postmarketing Experience
- Hypersensitivity reaction- angioedema and anaphylaxis
- gastrointestinal- ileus
- acute kidney injury or worsening of chronic kidney disease requiring dialysis.
Drug Interactions
- MOUNJARO concomitantly administered with insulin and insulin secretagogues can cause hypoglycemia.
- MOUNJARO can delay gastric emptying, as a result, this may delay the absorption of the concomitantly orally administered drugs.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): C
Available data with MOUNJARO use in pregnant women are insufficient to evaluate for a drug-related risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. However, based on animal reproduction studies, there may be risks to the fetus from exposure to tirzepatide during pregnancy.
Therefore, MOUJARO may only be used in pregnancy if the benefits outweigh the potential risk to the fetus.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Tirzepatide in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Tirzepatide during labor and delivery.
Nursing Mothers
There are no data on the presence of tirzepatide in animal or human milk, the effects on the breastfed infant, or the effects on milk production
Pediatric Use
Safety and effectiveness of MOUNJARO have not been established in pediatric patients (younger than 18 years of age).
Geriatic Use
In the pool of seven clinical trials, 1539 (30.1%) MOUNJARO-treated patients were 65 years of age or older, and 212 (4.1%) MOUNJARO-treated patients were 75 years of age or older at baseline. There were no overall differences in safety or efficacy detected between these patients and younger patients.
Gender
There is no FDA guidance on the use of Tirzepatide with respect to specific gender populations.
Race
There is no FDA guidance on the use of Tirzepatide with respect to specific racial populations.
Renal Impairment
The MOUNJARO dosage was not required to be changed in patients with renal impairment. However, renal function has to be monitored for patients with severe gastrointestinal reaction while initiating or increasing the dosage of MOUNJARO.
Hepatic Impairment
There is no FDA guidance on the use of Tirzepatide in patients with hepatic impairment.
Females of Reproductive Potential and Males
females on oral contraceptives are advised to change a non-oral contraception or barrier method for 4 weeks after initiation and for 4 weeks after increasing each dosage.
Immunocompromised Patients
There is no FDA guidance one the use of Tirzepatide in patients who are immunocompromised.
Administration and Monitoring
Administration
- Before administration, patients, and caregivers are trained on proper injection techniques.
- 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).
- Administer MOUNJARO once weekly, any time of day, with or without meals.
- Inject MOUNJARO subcutaneously in the abdomen, thigh, or upper arm.
- Rotate injection sites with each dose.
- Inspect MOUNJARO visually before use, which usually appears clear and colorless to slightly yellow. Do not use MOUNJARO if particulate matter or discoloration is seen.
When using MOUNJARO with insulin, administer as separate injections and never mix. It is acceptable to inject MOUNJARO and insulin in the same body region, but the injections should not be adjacent to each other.
Monitoring
There is limited information regarding Tirzepatide Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Tirzepatide and IV administrations.
Overdosage
A period of observation and treatment for these symptoms may be necessary, taking into account the half-life of tirzepatide of approximately 5 days.
Pharmacology
There is limited information regarding Tirzepatide Pharmacology in the drug label.
Mechanism of Action
Tirzepatide selectively binds to and activates both the GIP and GLP-1 receptors, which enhances the first- and second-phase insulin secretion and reduces glucagon levels, both in a glucose-dependent manner.
Structure
Tirzepatide is a 39-amino-acid modified peptide with a C20 fatty diacid moiety that enables albumin binding and prolongs the half-life.
Pharmacodynamics
Tirzepatide lowers fasting and postprandial glucose concentration, decreases food intake, and reduces body weight in patients with type 2 diabetes mellitus
It enhances the fist and second phase of insulin secretion and increases the insulin sensitivity.
Tirzepatide delays gastric emptying.This delay is largest after the first dose and the effect diminishes over time. Tirzepatide slows post-meal glucose absorption, reducing postprandial glucose.
Pharmacokinetics
Absorption - Following subcutaneous administration, the time to maximum plasma concentration of tirzepatide ranges from 8 to 72 hours.
Distribution - The mean apparent steady-state volume of distribution of tirzepatide following subcutaneous administration in patients with type 2 diabetes mellitus is approximately 10.3 L. Tirzepatide is highly bound to plasma albumin (99%).
Elimination - The apparent population mean clearance of tirzepatide is 0.061 L/h with an elimination half-life of approximately 5 days, leading to once-weekly dosing.
Tizepatide is metabolized by cleavage of peptide backbone, beta-oxidation CD20 fatty diacid moiety and amide hydrolysis.
The final metabolites of Tirzepatide is excreted via feces and urine.
Nonclinical Toxicology
There is limited information regarding Tirzepatide Nonclinical Toxicology in the drug label.
Clinical Studies
Five trials were conducted to establish the effectiveness of MOUNJARO as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. In these trials, MOUNJARO was studied as monotherapy (SURPASS-1); as an add-on to metformin, sulfonylureas, and/or sodium-glucose co-transporter 2 inhibitors (SGLT2 inhibitors) (SURPASS-2, -3, and -4); and in combination with basal insulin with or without metformin (SURPASS-5). In these trials, MOUNJARO (5 mg, 10 mg, and 15 mg given subcutaneously once weekly) was compared with placebo, semaglutide 1 mg, insulin degludec, and/or insulin glargine.
In adults with tyep2 Diabetes mellitus, MOUNJARO has produced a significant decrease in the HbA1C from the baseline. Furthermore, this effectiveness was not impacted by age, gender, race, ethnicity, region, or by baseline BMI, HbA1c, diabetes duration, or renal function.
How Supplied
MOUNJARO is a clear, colorless to slightly yellow solution available in cartons containing 4 pre-filled single-dose pens or 1 single-dose vial
Storage
- Store MOUNJARO 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 30ºC (86ºF) for up to 21 days.
- Do not freeze MOUNJARO. Do not use MOUNJARO if frozen.
- Store MOUNJARO in the original carton to protect from light.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Tirzepatide Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Tirzepatide interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
MOUNJARO
Look-Alike Drug Names
There is limited information regarding Tirzepatide Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.