What are the contraindications to starting Zepbound (tirzepatide)?

Contraindications to Starting Zepbound (Tirzepatide)

Zepbound (tirzepatide) 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

• Personal history of medullary thyroid carcinoma (MTC) 1
• Family history of medullary thyroid carcinoma (MTC) 1
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1

Important Precautions (Not Absolute Contraindications)

Gastrointestinal Conditions

• Severe gastrointestinal disease
  • Severe constipation
  • Small-bowel obstruction/ileus progression 1
  • Gastroparesis (not recommended) 1

Pregnancy Considerations

• Pregnancy or planning pregnancy
  • Women using oral contraceptives should:
    • Switch to a non-oral contraceptive method OR
    • Add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation 1

Medication Interactions

• Medications with narrow therapeutic index
  • Monitor effects closely due to potential delayed absorption 1
  • Oral medication absorption may be impaired during dose titration 1

Other Precautions

• Gallbladder disease
  • May cause cholelithiasis and gallstone-related complications 1
  • Avoid use in high-risk individuals 1
• Pancreatitis
  • Acute pancreatitis has been reported with GLP-1 receptor agonists 1
  • Consider avoiding in patients at high risk for pancreatitis

Clinical Considerations

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that has shown significant efficacy for weight loss and glycemic control 1. When prescribing Zepbound, it's important to:

• Screen for thyroid disorders: The black box warning regarding thyroid C-cell tumors is based on rodent studies, but human relevance has not been determined 1

• Assess gastrointestinal function: GI side effects are the most common adverse events (nausea, vomiting, diarrhea, constipation) and are primarily mild to moderate in severity, occurring mainly during dose escalation 2

• Consider surgical timing: Provide guidance on discontinuation prior to surgical procedures due to potential ileus risk 1

• Monitor for gallbladder disease: Evaluate for gallbladder disease if cholelithiasis or cholecystitis is suspected 1

• Assess for diabetic retinopathy: Close monitoring is recommended in those at high risk (older individuals and those with longer duration of T2D ≥10 years) 1

The contraindications to Zepbound are relatively few compared to its potential benefits in appropriate patients. The medication has demonstrated substantial weight reduction and improvement in cardiometabolic parameters 2, 3, with a safety profile primarily characterized by gastrointestinal effects that tend to be transient during dose escalation.

Human Medical Consultant Note: While the FDA black box warning about thyroid C-cell tumors is based on animal studies, the contraindication for patients with personal or family history of MTC or MEN2 must be strictly observed as a matter of patient safety.

Human Medical Consultant Note: While the FDA black box warning about thyroid C-cell tumors is based on animal studies, the contraindication for patients with personal or family history of MTC or MEN2 must be strictly observed as a matter of patient safety.