What are the contraindications for Zepbound (generic name) in patients with impaired liver or kidney function, or a history of severe allergic reactions?

Contraindications for Zepbound (Tirzepatide)

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

Absolute 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 in Zepbound

Liver Impairment Considerations

While not an absolute contraindication, Zepbound should be used with caution in patients with liver impairment:

• The FDA label does not specifically list liver impairment as a contraindication for Zepbound
• This differs from some other medications like galantamine (Reminyl), which is contraindicated in patients with hepatic impairment 2
• However, patients with compromised liver function should be monitored more closely when taking Zepbound, as drug-drug interactions and hepatotoxic chemotherapy may require additional laboratory testing 2

Kidney Impairment Considerations

Similar to liver impairment, kidney dysfunction is not listed as a specific contraindication for Zepbound:

• Unlike medications such as fondaparinux which is contraindicated in patients with CrCl <30 mL/min 2, Zepbound does not have specific renal contraindications
• However, patients with compromised renal function should be monitored more closely, particularly if receiving nephrotoxic medications 2
• This differs from other medications like DOACs which have specific contraindications for various stages of chronic kidney disease 2

Severe Allergic Reactions

• Known serious hypersensitivity to tirzepatide or any excipients in Zepbound is a contraindication 1
• Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with tirzepatide
• If a hypersensitivity reaction is suspected, patients should promptly seek medical attention and discontinue Zepbound

Other Important Warnings (Not Contraindications)

While not contraindications, healthcare providers should be aware of these important warnings:

1. Risk of Thyroid C-Cell Tumors: Tirzepatide causes thyroid C-cell tumors in rats, though human relevance is unknown 1

2. Severe Gastrointestinal Adverse Reactions: Not recommended in patients with severe gastrointestinal disease 1

3. Acute Kidney Injury: Monitor renal function in patients reporting adverse reactions that could lead to volume depletion 1

4. Acute Gallbladder Disease: Has been reported in clinical trials 1

5. Acute Pancreatitis: Discontinue promptly if pancreatitis is suspected 1

6. Hypoglycemia Risk: Particularly when used with insulin or insulin secretagogues 1

7. Diabetic Retinopathy Complications: Monitor patients with history of diabetic retinopathy 1

8. Suicidal Behavior and Ideation: Monitor for depression or suicidal thoughts 1

9. Pulmonary Aspiration Risk: During general anesthesia or deep sedation 1

Special Populations

• Pregnancy: May cause fetal harm; discontinue when pregnancy is recognized 1
• Females of Reproductive Potential: Those using oral contraceptives should switch to a non-oral method or add a barrier method for 4 weeks after initiation and for 4 weeks after each dose escalation 1

Unlike some medications that require specific dose adjustments for renal or hepatic impairment (such as eltrombopag 3), the FDA label for Zepbound does not specify mandatory dose adjustments for these populations, but close monitoring is advised.