What are the contraindications for Zepbound (tirzepatide)?

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Last updated: September 11, 2025View editorial policy

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Contraindications for Zepbound (Tirzepatide)

Zepbound (tirzepatide) is contraindicated in patients with personal or family history of medullary thyroid cancer, multiple endocrine neoplasia syndrome type 2, pregnancy or breastfeeding, and severe gastroparesis. 1

Absolute Contraindications

  • Personal or family history of medullary thyroid carcinoma (MTC)
  • Multiple endocrine neoplasia syndrome type 2 (MEN 2)
  • Pregnancy or women planning pregnancy
  • Breastfeeding
  • Severe gastroparesis

Precautions and Relative Contraindications

Gastrointestinal Conditions

  • History of severe gastrointestinal disease
  • Pancreatitis (history of or active)
  • Inflammatory bowel disease with active symptoms

Endocrine Conditions

  • Diabetic retinopathy requiring monitoring
  • Concurrent use with insulin secretagogues (increased risk of hypoglycemia)

Reproductive Considerations

  • Women of reproductive potential must use reliable contraception methods while on tirzepatide 2
  • All medications for obesity treatment are contraindicated in women who are or may become pregnant 2

Medication Interactions

  • Caution with medications that slow gastric emptying
  • Medications with narrow therapeutic index may require monitoring due to delayed absorption

Safety Considerations

Monitoring Requirements

  • Regular ophthalmologic evaluations in patients with diabetic retinopathy
  • Blood glucose monitoring when used with insulin or insulin secretagogues
  • Renal function in patients with kidney impairment

Adverse Effects Profile

  • Most common adverse effects are gastrointestinal (nausea, vomiting, diarrhea, constipation)
  • Additional side effects include alopecia and abdominal pain 1

Special Populations

Renal Impairment

  • No dose adjustment needed for mild to moderate renal impairment
  • Use with caution in severe renal impairment (eGFR <30 mL/min/1.73m²) 1

Elderly

  • No specific dose adjustment required based on age alone
  • Consider increased sensitivity to gastrointestinal effects

Clinical Pearls

  • Tirzepatide has a black box warning regarding the risk of thyroid C-cell tumors in rodents, though human relevance has not been determined 2
  • The risk of hypoglycemia is low when used without insulin or insulin secretagogues 1
  • Slow dose titration is recommended to minimize gastrointestinal side effects
  • Patients should be counseled about the potential for significant weight loss and the need for ongoing monitoring

Remember that contraindications should be carefully assessed before initiating therapy with Zepbound, and patients should be monitored regularly for potential adverse effects throughout treatment.

References

Guideline

Tirzepatide Therapy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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