What are the contraindications for Zepbound?

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Zepbound Contraindications

Zepbound is contraindicated in women who are pregnant or actively trying to conceive, and is not recommended for use in individuals who are nursing. 1

Primary Contraindications

  • Pregnancy or attempting to conceive: All weight management medications, including Zepbound (tirzepatide), are contraindicated during pregnancy due to potential risks to the fetus 1
  • Nursing mothers: Not recommended during breastfeeding 1
  • Personal or family history of medullary thyroid cancer: Due to risk of thyroid C-cell tumors observed in rodents (human relevance not determined) 1
  • Multiple endocrine neoplasia syndrome type 2 (MEN 2): Due to increased risk of medullary thyroid cancer 1

Important Precautions and Safety Considerations

Gastrointestinal Effects

  • Risk of pancreatitis: Discontinue if pancreatitis is suspected 1
  • Gastrointestinal disorders: Risk of severe constipation and small bowel obstruction/ileus 1
  • Common side effects: Nausea, vomiting, diarrhea, esophageal reflux 1

Medication Interactions

  • Oral medications with narrow therapeutic index: Monitor for potential consequences of delayed absorption due to Zepbound's effect on gastric emptying 1
  • Oral contraceptives: May reduce efficacy of oral hormonal contraceptives; patients should switch to a non-oral contraceptive method or add a barrier method for 4 weeks after initiation and for 4 weeks after each dose escalation 1

Other Important Precautions

  • Kidney disease: Use caution when initiating or increasing doses due to increased risk of gastrointestinal side effects and potential risk of acute kidney injury from dehydration 1
  • Gallbladder disease: May cause cholelithiasis and gallstone-related complications 1
  • Hypoglycemia: Risk increases when used with insulin or insulin secretagogues 1

Special Population Considerations

Weight Loss Monitoring

  • Patients experiencing significant (>20%) or rapid (>4 kg/month) weight loss should be monitored for malnutrition and sarcopenia 1
  • Healthcare providers should encourage resistance training and sufficient protein intake to prevent muscle loss 1

Medication Continuation

  • Be aware that discontinuation of tirzepatide leads to substantial regain of lost weight, whereas continued treatment maintains and augments initial weight reduction 2

Clinical Decision Algorithm

  1. Screen for absolute contraindications:

    • Pregnancy or attempting to conceive
    • Breastfeeding
    • Personal or family history of medullary thyroid cancer
    • MEN 2 syndrome

  2. Evaluate for relative contraindications:

    • History of pancreatitis
    • Severe gastrointestinal disease
    • Significant kidney disease
    • Use of medications with narrow therapeutic index

  3. Counsel patients on:

    • Need for reliable contraception if of reproductive potential
    • Common side effects and when to seek medical attention
    • Importance of proper hydration to prevent kidney injury
    • Need for continued treatment to maintain weight loss

By carefully screening for contraindications and monitoring patients appropriately, healthcare providers can help ensure the safe and effective use of Zepbound for weight management.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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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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