Mounjaro Drug Information

® is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. MOUNJARO ® is a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus.

Recommended Dosage

The recommended starting dosage of MOUNJARO is 2.5 mg injected subcutaneously once weekly . Follow the dosage escalation below to reduce the risk of gastrointestinal adverse reactions . The 2.5 mg dosage is for treatment initiation and is not intended for glycemic control. After 4 weeks, increase the dosage 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 in adults. 10 mg injected subcutaneously once weekly in pediatric patients. If a dose is missed, instruct patients to administer MOUNJARO 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 Inform patients and their caregiver(s) which MOUNJARO presentation (e.g., vial, pre-filled single-dose pen, single-patient-use KwikPen) they will receive and ensure they receive training appropriate for that specific presentation. If the prescribed MOUNJARO presentation changes, ensure patients and caregivers receive appropriate training and instruct them to consult the Instructions for Use for the newly prescribed presentation. Prior to initiation, train patients and their caregiver(s) on proper injection technique for the prescribed MOUNJARO presentation . After training, a patient may self-inject MOUNJARO if the healthcare provider determines that it can be properly administered, except for the following: MOUNJARO KwikPen is not recommended for self-administration by pediatric patients.

MOUNJARO KwikPen is not recommended for self-administration by those who are visually impaired. Instruct patients using MOUNJARO vials to use a syringe appropriate for dose administration (e.g., a 1 mL syringe capable of measuring a 0.5 mL or 0.6 mL dose) and always use a new syringe and needle for each injection. Administer MOUNJARO once weekly, any time of day, with or without meals.

Inject MOUNJARO subcutaneously in the abdomen, thigh, or another person should inject in the back of the upper arm. Rotate injection sites with each dose. Inspect MOUNJARO visually before use.

It should appear 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.

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. Adverse Reactions in the Clinical Trials of Adults with Type 2 Diabetes Mellitus Pool of Two Placebo-Controlled Clinical Trials in Adults The data in Table 1 are derived from 2 placebo-controlled trials in adult patients with type 2 diabetes mellitus . These data reflect exposure of 718 patients to MOUNJARO and a mean duration of exposure to MOUNJARO of 36.6 weeks. The mean age of patients was 58 years, 4% were 75 years or older and 54% were male.

The population was 57% White, 27% Asian, 13% American Indian or Alaska Native, and 3% Black or African American; 25% identified as Hispanic or Latino ethnicity. At baseline, patients had type 2 diabetes mellitus for an average of 9.1 years with a mean HbA1c of 8.1%. As assessed by baseline fundoscopic examination, 13% of the population had retinopathy. At baseline, eGFR was ≥90 mL/min/1.73 m 2 in 53%, 60 to 90 mL/min/1.73 m 2 in 39%, 45 to 60 mL/min/1.73 m 2 in 7%, and 30 to 45 mL/min/1.73 m 2 in 1% of patients.

Pool of Seven Controlled Clinical Trials Adverse reactions were also evaluated in a larger pool of adult patients with type 2 diabetes mellitus participating in seven controlled clinical trials which included two placebo-controlled trials (SURPASS-1 and -5), three trials of MOUNJARO in combination with metformin, sulfonylureas, and/or SGLT2 Inhibitors (SURPASS-2, -3, -4) and two additional trials conducted in Japan. In this pool, a total of 5119 adult patients with type 2 diabetes mellitus were treated with MOUNJARO for a mean duration of 48.1 weeks. The mean age of patients was 58 years, 4% were 75 years or older and 58% were male.

The population was 65% White, 24% Asian, 7% American Indian or Alaska Native, and 3% Black or African American; 38% identified as Hispanic or Latino ethnicity. At baseline, patients had type 2 diabetes mellitus for an average of 9.1 years with a mean HbA1c of 8.3%. As assessed by baseline fundoscopic examination, 15% of the population had retinopathy. At baseline, eGFR was ≥90 mL/min/1.73 m 2 in 52%, 60 to 90 mL/min/1.73 m 2 in 40%, 45 to 60 mL/min/1.73 m 2 in 6%, and 30 to 45 mL/min/1.73 m 2 in 1% of patients.

Common Adverse Reactions Table 1 shows common adverse reactions, not including hypoglycemia, associated with the use of MOUNJARO in the pool of placebo-controlled trials in adults. These adverse reactions occurred more commonly on MOUNJARO than on placebo and occurred in at least 5% of patients treated with MOUNJARO. Table 1: Adverse Reactions in Pool of Placebo-Controlled Trials Reported in ≥5% of MOUNJARO-treated Adult Patients with Type 2 Diabetes Mellitus Note: Percentages reflect the number of patients who reported at least 1 occurrence of the adverse reaction. Adverse Reaction Placebo (N=235) % MOUNJARO 5 mg (N=237) % MOUNJARO 10 mg (N=240) % MOUNJARO 15 mg (N=241) % Nausea 4 12 15 18 Diarrhea 9 12 13 17 Decreased Appetite 1 5 10 11 Vomiting 2 5 5 9 Constipation 1 6 6 7 Dyspepsia 3 8 8 5 Abdominal Pain 4 6 5 5 In the pool of seven clinical trials in adults, the types and frequency of common adverse reactions, not including hypoglycemia, were similar to those listed in Table 1. Gastrointestinal Adverse Reactions In the pool of placebo-controlled trials in adults, 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 majority of reports of nausea, vomiting, and/or diarrhea occurred during dose escalation and decreased over time.

The following gastrointestinal adverse reactions were reported more frequently in MOUNJARO-treated adult patients than placebo-treated patients (frequencies listed, respectively, as: placebo; 5 mg; 10 mg; 15 mg): eructation (0.4%, 3.0%, 2.5%, 3.3%), flatulence (0%, 1.3%, 2.5%, 2.9%), gastroesophageal reflux disease (0.4%, 1.7%, 2.5%, 1.7%), abdominal distension (0.4%, 0.4%, 2.9%, 0.8%). Other Adverse Reactions in Adults Hypoglycemia Table 2 summarizes the incidence of hypoglycemic events in the placebo-controlled trials in adults. Table 2: Hypoglycemia Adverse Reactions in Placebo-Controlled Trials in Adult Patients with Type 2 Diabetes Mellitus Note: Percentages reflect the number of patients who reported at least 1 episode of hypoglycemia in respective categories. * Reflects the study treatment period. Data include events occurring during 4 weeks of treatment-free safety follow up.

Events after introduction of a new glucose-lowering treatment are excluded. ** Episodes requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Placebo % MOUNJARO 5 mg % MOUNJARO 10 mg % MOUNJARO 15 mg % Monotherapy (40 weeks)* N=115 N=121 N=119 N=120 Blood glucose <54 mg/dL 1 0 0 0 Severe hypoglycemia** 0 0 0 0 Add-on to Basal Insulin with or without Metformin (40 weeks)* N=120 N=116 N=119 N=120 Blood glucose <54 mg/dL 13 16 19 14 Severe hypoglycemia** 0 0 2 1 Hypoglycemia was more frequent when MOUNJARO was used in combination with a sulfonylurea . In an adult clinical trial up to 104 weeks of treatment, when administered with a sulfonylurea, hypoglycemia (glucose level <54 mg/dL) occurred in 13.8%, 9.9%, and 12.8%, and severe hypoglycemia occurred in 0.5%, 0%, and 0.6% of patients treated with MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. Acute Pancreatitis In clinical studies, 14 events of acute pancreatitis were confirmed by adjudication in 13 MOUNJARO-treated adult 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). Heart Rate Increase In the pool of placebo-controlled trials, treatment of adults with MOUNJARO resulted in a mean increase in heart rate of 2 to 4 beats per minute compared to a mean increase of 1 beat per minute in placebo-treated patients.

Episodes of sinus tachycardia, associated with a concomitant increase from baseline in heart rate of ≥15 beats per minute, also were reported in 4.3%, 4.6%, 5.9% and 10% of subjects treated with placebo, MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. For patients enrolled in Japan, these episodes were reported in 7% (3/43), 7.1% (3/42), 9.3% (4/43), and 23% (10/43) of patients treated with placebo, MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. The clinical relevance of heart rate increases is uncertain.

Hypersensitivity Reactions Hypersensitivity reactions have been reported with MOUNJARO in the pool of placebo-controlled trials in adults, sometimes severe (e.g., urticaria and eczema); hypersensitivity reactions were reported in 3.2% of MOUNJARO-treated patients compared to 1.7% of placebo-treated patients. In the pool of seven clinical trials in adults, hypersensitivity reactions occurred in 106/2,570 (4.1%) of MOUNJARO-treated adult patients with anti-tirzepatide antibodies and in 73/2,455 (3.0%) of MOUNJARO-treated patients who did not develop anti-tirzepatide antibodies. In the clinical trial in pediatric patients 10 years of age and older, hypersensitivity reactions occurred in 2/50 (4%) of MOUNJARO-treated pediatric patients with anti-tirzepatide antibodies and in 0/43 (0%) of MOUNJARO-treated pediatric patients who did not develop anti-tirzepatide antibodies.

Injection Site Reactions In the pool of placebo-controlled trials in adults, injection site reactions were reported in 3.2% of MOUNJARO-treated patients compared to 0.4% of placebo-treated patients. In the pool of seven clinical trials, injection site reactions occurred in 119/2,570 (4.6%) of MOUNJARO-treated adult patients with anti-tirzepatide antibodies and in 18/2,455 (0.7%) of MOUNJARO-treated adult patients who did not develop anti-tirzepatide antibodies. In the clinical trial in pediatric patients 10 years of age and older, injection site reactions occurred in 3/50 (6%) of MOUNJARO-treated pediatric patients with anti-tirzepatide antibodies and in 0/43 (0%) of MOUNJARO-treated pediatric patients who did not develop anti-tirzepatide antibodies.

Acute Gallbladder Disease In the pool of placebo-controlled clinical trials in adults, acute gallbladder disease (cholelithiasis, biliary colic and cholecystectomy) was reported by 0.6% of MOUNJARO-treated patients and 0% of placebo-treated patients. Dysesthesia In the pool of placebo-controlled clinical trials in adults, dysesthesia was reported by 0.4%, 0.4%, and 0.4% of patients treated with MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. No events were reported by patients receiving placebo.

Dysgeusia In the pool of placebo-controlled clinical trials in adults, dysgeusia was reported by 0.1% of MOUNJARO-treated patients and 0% of placebo-treated patients. Laboratory Abnormalities Amylase and Lipase Increase In the pool of placebo-controlled adult clinical trials, treatment with MOUNJARO resulted in mean increases from baseline in serum pancreatic amylase concentrations of 33% to 38% and serum lipase concentrations of 31% to 42%. Placebo-treated patients had a mean increase from baseline in pancreatic amylase of 4% and no changes were observed in lipase. The clinical significance of elevations in lipase or amylase with MOUNJARO is unknown in the absence of other signs and symptoms of pancreatitis.

Adverse Reactions in the Clinical Trial of Pediatric Patients 10 Years of Age and Older with Type 2 Diabetes Mellitus MOUNJARO was administered to 97 pediatric patients 10 years of age and older with type 2 diabetes mellitus for a mean duration of 39.9 weeks . The mean age was 15 years and 61% of patients were female. The population was 58% White, 11% Black or African American, 6% Asian, 20% American Indian or Alaska Native, and 5% were other races; 66% identified as Hispanic or Latino ethnicity. At baseline, pediatric patients had type 2 diabetes mellitus for an average of 2.4 years with a mean HbA1c of 8.0%. The incidences of adverse reactions reported in pediatric patients treated with MOUNJARO 5 mg and 10 mg subcutaneously once-weekly were consistent with those described above for adult patients with type 2 diabetes mellitus with the exception of a higher incidence of vomiting, abdominal pain, and hypoglycemia.

During the 30-week placebo-controlled period of the study, vomiting occurred in 3%, 16%, and 12% of patients and abdominal pain occurred in 9%, 22%, and 15% of patients treated with placebo, MOUNJARO 5 mg, and 10 mg, respectively. No severe hypoglycemia episodes were reported during the trial. Table 3 summarizes the incidence of hypoglycemic events with blood glucose <54 mg/dL in the trial.

Table 3: Hypoglycemia Adverse Reactions in the 30 Week Trial of MOUNJARO Added to Metformin or Basal Insulin, or Both in Pediatric Patients 10 Years of Age and Older with Type 2 Diabetes Mellitus Note: Percentages reflect the number of patients who reported at least 1 episode of blood glucose <54 mg/dL. a Events after the introduction of a new glucose-lowering treatment are excluded. Placebo % MOUNJARO 5 mg % MOUNJARO 10 mg % Add on to basal insulin with or without metformin a N=10 N=10 N=11 Blood glucose <54 mg/dL 10 30 27 Add on to metformin alone a N=24 N=22 N=22 Blood glucose <54 mg/dL 4 9 9

Postmarketing Experience

The following adverse reactions have been reported during post-approval use of MOUNJARO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hypersensitivity : anaphylaxis, angioedema Gastrointestinal : acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death, ileus, intestinal obstruction, severe constipation including fecal impaction Pulmonary : Pulmonary aspiration has occurred in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation Renal : acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis Skin and Subcutaneous Tissue : alopecia

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

When initiating MOUNJARO, consider reducing the dose of concomitantly administered insulin secretagogues (e.g., sulfonylureas) or insulin to reduce the risk of hypoglycemia.

Oral Medications

MOUNJARO 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 MOUNJARO. 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 MOUNJARO. 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 and for 4 weeks after each dose escalation with MOUNJARO. Hormonal contraceptives that are not administered orally should not be affected.

Pregnancy Risk Summary 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. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations). Based on animal reproduction studies, there may be risks to the fetus from exposure to tirzepatide during pregnancy. MOUNJARO should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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 is 6–10% in women with pre-gestational diabetes with an HbA1c >7% and has been reported to be as high as 20–25% in women with an HbA1c >10%. The estimated background risk of miscarriage for the indicated population is unknown. 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 Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications.

Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. 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 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, F 1 pups from F 0 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.

Pediatric Use The safety and effectiveness of MOUNJARO as an adjunct to diet and exercise to improve glycemic control in pediatric patients 10 years of age and older with type 2 diabetes mellitus have been established. Use of MOUNJARO for this indication is supported by a 30-week, randomized, double-blind, placebo-controlled trial with a 22-week open label extension in 99 pediatric patients . Adverse reactions reported in pediatric patients 10 years of age and older treated with MOUNJARO were similar to those reported in adults with the exception of a higher incidence of vomiting, abdominal pain, and hypoglycemia . The safety and effectiveness of MOUNJARO have not been established in pediatric patients less than 10 years of age.

is contraindicated in patients with: A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) . Known serious hypersensitivity to tirzepatide or any of the excipients in MOUNJARO. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with MOUNJARO . Personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2. Known serious hypersensitivity to tirzepatide or any of the excipients in MOUNJARO.

In the event of an overdosage, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Initiate appropriate supportive treatment 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.