What are the contraindications for Zepbound (generic name)?

Contraindications for Zepbound (Tirzepatide)

Zepbound is absolutely contraindicated in two specific clinical scenarios: patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), and patients with known serious hypersensitivity to tirzepatide or any excipients. 1

Absolute Contraindications

Thyroid C-Cell Tumor Risk

• Do not prescribe Zepbound to any patient with a personal or family history of medullary thyroid carcinoma (MTC). 1
• Do not prescribe Zepbound to patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). 1
• This contraindication is based on animal data showing tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors (adenomas and carcinomas) in rats at clinically relevant plasma exposures. 1
• While human relevance remains uncertain, the FDA has issued a boxed warning emphasizing this risk. 1

Hypersensitivity Reactions

• Do not prescribe Zepbound to patients with known serious hypersensitivity to tirzepatide or any of the excipients. 1
• Serious hypersensitivity reactions including anaphylaxis and angioedema have been documented in postmarketing surveillance. 1

Critical Clinical Screening Before Prescribing

Pre-Treatment Assessment Required

• Obtain detailed personal and family history specifically asking about thyroid cancer, particularly MTC. 1
• Screen for MEN 2 syndrome by asking about family history of pheochromocytoma, hyperparathyroidism, or mucosal neuromas. 1
• Document any prior allergic reactions to GLP-1 receptor agonists or tirzepatide-containing products. 1

Thyroid Monitoring Considerations

• Routine serum calcitonin monitoring or thyroid ultrasound is of uncertain value for early MTC detection and may lead to unnecessary procedures due to low test specificity. 1
• However, if serum calcitonin is measured and significantly elevated (typically >50 ng/L in MTC patients), further evaluation is mandatory. 1
• Counsel all patients about MTC symptoms: neck mass, dysphagia, dyspnea, or persistent hoarseness—and instruct them to report these immediately. 1

Important Clinical Caveats

• Zepbound should not be coadministered with other tirzepatide-containing products or any GLP-1 receptor agonist. 1
• The evidence provided regarding other medications (tuberculosis drugs, tolperisone, dextromethorphan, mirtazapine, benzodiazepines, and Z-drugs) is not relevant to Zepbound contraindications and should be disregarded. 2, 3, 4, 5, 6, 7, 8, 9, 10