What are the contraindications to Zepbound (generic name)?

Contraindications to Zepbound (Tirzepatide)

Zepbound is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). 1

Absolute Contraindications

1. Personal history of medullary thyroid carcinoma (MTC)

   • Tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors in rats at clinically relevant exposures
   • Human relevance has not been determined, but caution is warranted

2. Family history of MTC

   • Genetic predisposition increases risk

3. Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)

   • Genetic syndrome associated with high risk of developing MTC

4. Concomitant use with other tirzepatide-containing products

   • Increases risk of adverse effects due to duplicate therapy

5. Concomitant use with other GLP-1 receptor agonists

   • Not recommended due to overlapping mechanisms and potential for additive adverse effects

Relative Contraindications and Precautions

1. Monoamine Oxidase Inhibitors (MAOIs)

   • Tirzepatide contains bupropion which is contraindicated with MAOIs
   • Requires 14-day washout period between stopping MAOIs and starting treatment 2

2. Unmanaged hypertension

   • May exacerbate cardiovascular risk

3. Risk of hypoglycemia

   • Particularly when used with insulin or sulfonylureas
   • Dose adjustments of concomitant medications may be required

4. Patients at high risk for glaucoma

   • Risk of acute angle-closure glaucoma

5. Pregnancy

   • Limited data on safety in pregnancy

Clinical Considerations and Monitoring

Patient Counseling

• Inform patients about potential risk for MTC and symptoms of thyroid tumors:
  • Mass in the neck
  • Dysphagia
  • Dyspnea
  • Persistent hoarseness

Monitoring

• Routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Zepbound
• Monitor for gastrointestinal adverse reactions, especially during dose escalation
• For patients using oral hormonal contraceptives:
  • Consider switching to a non-oral contraceptive method or
  • Add a barrier method for 4 weeks after initiation and for 4 weeks after each dose escalation

Special Populations

• Patients with renal impairment: Use caution when initiating or increasing dose due to increased risk of gastrointestinal side effects and potential risk of acute kidney injury from dehydration
• Patients with history of suicidal behavior: Risk of suicidal behavior/ideation in people younger than 24 years

Dosing Considerations

• Starting dose should be 2.5 mg injected subcutaneously once weekly for 4 weeks
• Gradual dose escalation is recommended to reduce gastrointestinal adverse reactions
• Maximum recommended dose is 15 mg injected subcutaneously once weekly

By carefully screening for contraindications before prescribing Zepbound and monitoring patients appropriately during treatment, clinicians can maximize the benefits of this medication while minimizing potential risks to patient safety.