Tirzepatide: uses, appearance and warnings

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. ZEPBOUND is a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist 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. ( 1 ) to treat moderate to severe obstructive sleep apnea (OSA) in adults with obesity. ( 1 ) Limitations of Use: Coadministration with other tirzepatide-containing products or with any GLP-1 receptor agonist is not recommended. ( 1 ) 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.

Injection: Clear, colorless to slightly yellow solution in pre-filled single-dose pens, single-dose vials, multi-dose vials, or single-patient-use KwikPens, each available in the following strengths. The multi-dose vials and single-patient-use KwikPen each contain 4 doses: Single-dose Pen or Vial 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 Multi-dose Vial (4 doses per vial) Dose per Injection Total Strength per Total Volume Strength per mL 2.5 mg/0.6 mL 10 mg/2.4 mL 4.17 mg/mL 5 mg/0.6 mL 20 mg/2.4 mL 8.33 mg/mL 7.5 mg/0.6 mL 30 mg/2.4 mL 12.5 mg/mL 10 mg/0.6 mL 40 mg/2.4 mL 16.7 mg/mL 12.5 mg/0.6 mL 50 mg/2.4 mL 20.8 mg/mL 15 mg/0.6 mL 60 mg/2.4 mL 25 mg/mL Single-Patient-Use KwikPen (4 doses per KwikPen) Dose per Injection Total Strength per Total Volume Strength per mL 2.5 mg 10 mg/2.4 mL 4.17 mg/mL 5 mg 20 mg/2.4 mL 8.33 mg/mL 7.5 mg 30 mg/2.4 mL 12.5 mg/mL 10 mg 40 mg/2.4 mL 16.7 mg/mL 12.5 mg 50 mg/2.4 mL 20.8 mg/mL 15 mg 60 mg/2.4 mL 25 mg/mL Injection: Single-dose pen or single-dose vial: 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, or 15 mg/0.5 mL ( 3 ) Multi-dose vial or single-patient-use KwikPen ® : 10 mg/2.4 mL (4.17 mg/mL) for four 2.5 mg/0.6 mL doses, 20 mg/2.4 mL (8.33 mg/mL) for four 5 mg/0.6 mL doses, 30 mg/2.4 mL (12.5 mg/mL) for four 7.5 mg/0.6 mL doses, 40 mg/2.4 mL (16.7 mg/mL) for four 10 mg/0.6 mL doses, 50 mg/2.4 mL (20.8 mg/mL) for four 12.5 mg/0.6 mL doses, or 60 mg/2.4 mL (25 mg/mL) f …

16.1 How Supplied ZEPBOUND (tirzepatide) is a clear, colorless to slightly yellow solution available in cartons containing 4 pre-filled single-dose pens, 1 single-dose vial, 4 single-dose vials, 1 multi-dose vial, or 1 single-patient-use KwikPen as follows: Single-Dose Vial and Prefilled Pen Strength 4 pack Single-dose Pen NDC 1 pack Single-dose Vial NDC 4 pack Single-dose 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 Multi-Dose Vial Doses per Vial Strength 1 pack Multi-Dose Vial NDC 4 doses of 2.5 mg/0.6 mL 10 mg/2.4 mL (4.17 mg/mL) 0002-6052-11 4 doses of 5 mg/0.6 mL 20 mg/2.4 mL (8.33 mg/mL) 0002-6103-11 4 doses of 7.5 mg/0.6 mL 30 mg/2.4 mL (12.5 mg/mL) 0002-6210-11 4 doses of 10 mg/0.6 mL 40 mg/2.4 mL (16.7 mg/mL) 0002-6304-11 4 doses of 12.5 mg/0.6 mL 50 mg/2.4 mL (20.8 mg/mL) 0002-6523-11 4 doses of 15 mg/0.6 mL 60 mg/2.4 mL (25 mg/mL) 0002-6612-11 Single-Patient-Use KwikPen (with four weekly doses) Doses per KwikPen Strength 1 pack Single-Patient-Use KwikPen NDC 4 doses of 2.5 mg 10 mg/2.4 mL (4.17 mg/mL) 0002-3566-11 4 doses of 5 mg 20 mg/2.4 mL (8.33 mg/mL) 0002-3555-11 4 doses of 7.5 mg 30 mg/2.4 mL (12.5 mg/mL) 0002-3544-11 4 doses of 10 mg 40 mg/2.4 mL (16.7 mg/mL) 0002-3533-11 4 doses of 12.5 mg 50 mg/2.4 mL (20.8 mg/mL) 0002-3522-11 4 doses of 15 mg 60 mg/2.4 mL (25 mg/mL) 0002-3511-11 16.2 Storage and Handling Do not freeze ZEPBOUND. Do not use ZEPBOUND if frozen. Protect ZEPBOUND from heat and light. Store ZEPBOUND in the original carton to protect from light. ZEPBOUND Single-dose Pen and Single-dose Vial Store ZEPBOUND single-dose pen and single-dose vial 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 a total of 21 days. Discard single-dose pen and single-dose vial after a total of 21 days at room temperature. ZEPBOUND Multi-dose Vial or Single-Patient-Use KwikPen Unopened vial or single-patient-use KwikPen: Store unopened multi-dose vial or single-patient-use KwikPen in the refrigerator at 2°C to 8°C (36°F to 46°F). …

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 )] . Personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2 ( 4 ) Known serious hypersensitivity to tirzepatide or any of the excipients in ZEPBOUND ( 4 )

Severe Gastrointestinal Adverse Reactions: Use has been associated with gastrointestinal adverse reactions, sometimes severe. ZEPBOUND is not recommended in patients with severe gastroparesis. ( 5.2 ) Acute Kidney Injury Due to Volume Depletion: Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. ( 5.3 ) Acute Gallbladder Disease: Has been reported in clinical trials. If cholecystitis is suspected, gallbladder studies and clinical follow-up are indicated. ( 5.4 ) Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, or ZEPBOUND. Discontinue if pancreatitis is suspected. ( 5.5 ) Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported postmarketing with tirzepatide. If suspected, advise patients to promptly seek medical attention and discontinue ZEPBOUND. ( 5.6 ) Hypoglycemia: Concomitant use with insulin or an insulin secretagogue may increase the risk of hypoglycemia, including severe hypoglycemia. Reducing dose of insulin or insulin secretagogue may be necessary. Inform all patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. ( 5.7 ) Diabetic Retinopathy Complications in Patients with Type 2 Diabetes Mellitus: Monitor patients with a history of diabetic retinopathy for progression. ( 5.8 ) Pulmonary Aspiration During General Anesthesia or Deep Sedation: Has been reported in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures. Instruct patients to inform healthcare providers of any planned surgeries or procedures. ( 5.9 ) Never share a ZEPBOUND KwikPen between patients, even if the pen needle is changed. ( 5.10 ) 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 )] . In a pool of two ZEPBOUND clinical trials for weight reduction (Studies 1 and 2), severe gastrointestinal adverse reactions were reported more frequently among patients receiving ZEPBOUND (5 mg 1.7%, 10 mg 2.5%, 15 mg 3.1%) than placebo (1%). Similar rates of severe gastrointestinal adverse reactions were observed in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND clinical trials for OSA. Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists. ZEPBOUND is not recommended in patients with severe gastroparesis. 5.3 Acute Kidney Injury Due to Volume Depletion There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with GLP-1 receptor agonists, or ZEPBOUND [see Adverse Reactions ( 6.2 )] . The majority of the reported events occurred in patients who experienced gastrointestinal adverse reactions leading to dehydration such as nausea, vomiting, or diarrhea [see Adverse Reactions ( 6.1 )] . Monitor renal function in patients reporting adverse reactions to ZEPBOUND that could lead to volume depletion, especially during dosage initiation and escalation of ZEPBOUND. 5.4 Acute Gallbladder Disease Treatment with ZEPBOUND and GLP-1 receptor agonists is associated with an increased occurrence of acute gallbladder disease. In a pool of two ZEPBOUND clinical trials for weight reduction (Studies 1 and 2), cholelithiasis was reported in 1.1% of ZEPBOUND-treated patients and 1% of placebo-treated patients, cholecystitis was reported in 0.7% of ZEPBOUND-treated patients and 0.2% of placebo-treated patients, and cholecystectomy was reported in 0.2% of ZEPBOUND-treated patients and no placebo-treated patients. Acute gallbladder events were associated with weight reduction. Similar rates of cholelithiasis were reported in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND trials for OSA. If cholecystitis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated. 5.5 Acute Pancreatitis Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, or ZEPBOUND [see Adverse Reactions ( 6 )] . After initiation of ZEPBOUND, observe patients carefully for signs and symptoms of acute pancreatitis which may include persistent or severe abdominal pain (sometimes radiating to the back) and which may or may not be accompanied by nausea or vomiting. If pancreatitis is suspected, discontinue ZEPBOUND and initiate appropriate management. …

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 Due to Volume Depletion [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 )] Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions ( 5.9 )] The most common adverse reactions, reported in ≥5% of patients treated with ZEPBOUND are: nausea, diar …

ZEPBOUND delays gastric emptying and has the potential to impact the absorption of concomitantly administered oral medications. ( 7.2 ) 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. …