Tirzepatide — Important Safety Information (ISI)

Read this information carefully before starting tirzepatide. Discuss any questions with your provider.

What Is Tirzepatide?

Tirzepatide is a dual GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) receptor agonist used for chronic weight management and type 2 diabetes management. It is available under the brand names Mounjaro® (FDA-approved for type 2 diabetes) and Zepbound® (FDA-approved for chronic weight management) and as compounded formulations from FDA-registered pharmacies.

Boxed Warning — Thyroid C-Cell Tumors

WARNING: RISK OF THYROID C-CELL TUMORS. In rodent studies, tirzepatide caused dose-dependent thyroid C-cell tumors. It is unknown whether tirzepatide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans. Tirzepatide is contraindicated in patients with a personal or family history of MTC or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the risk and symptoms of thyroid tumors (lump in neck, hoarseness, dysphagia, dyspnea).

Contraindications

• Personal or family history of medullary thyroid carcinoma (MTC)
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• Known serious hypersensitivity to tirzepatide or any excipients
• Pregnancy

Warnings and Precautions

• Pancreatitis: Acute pancreatitis has been reported. Discontinue if suspected. Use with caution in patients with history of pancreatitis.
• Hypoglycemia: Risk increases when used with insulin or insulin secretagogues. Dose reduction may be required.
• Acute Kidney Injury: Cases reported in association with dehydration from GI adverse reactions. Monitor renal function in patients with severe GI symptoms.
• Hypersensitivity: Serious reactions including anaphylaxis reported. Discontinue immediately if suspected.
• Diabetic Retinopathy: Worsening reported in patients with type 2 diabetes. Monitor patients with history of retinopathy.
• Gallbladder Disease: Cholelithiasis and cholecystitis reported. Evaluate patients with gallbladder symptoms.
• Heart Rate Increase: Mean increase in resting heart rate observed. Monitor periodically.
• Suicidal Behavior: Monitor for depression and suicidal ideation. Discontinue if symptoms develop.

Most Common Adverse Reactions

Most common adverse reactions (5% or more incidence) in SURMOUNT-1 trial:

• Nausea (33%)
• Diarrhea (23%)
• Vomiting (12%)
• Constipation (17%)
• Abdominal pain (10%)
• Injection site reactions (7%)
• Fatigue (9%)
• Hypersensitivity reactions (5%)

GI adverse reactions are most common during dose escalation. Slow titration significantly reduces their severity.

Drug Interactions

Tirzepatide slows gastric emptying and may affect absorption of oral medications. Monitor oral medications requiring consistent absorption. Increased hypoglycemia risk with insulin and insulin secretagogues.

Use in Specific Populations

• Pregnancy: Discontinue tirzepatide at least 2 months before planned pregnancy. May cause fetal harm.
• Lactation: Unknown if present in human milk. Consider risk/benefit.
• Renal Impairment: No dose adjustment for mild to moderate impairment. Limited data for severe impairment.