When is Mounjaro (tirzepatide) not indicated for use in patients with a history of pancreatitis, thyroid cancer, or multiple endocrine neoplasia syndrome type 2?

When Mounjaro (Tirzepatide) is Not Indicated

Mounjaro is absolutely contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2), and should be used with extreme caution in those with a history of acute pancreatitis. 1, 2

Absolute Contraindications

Thyroid Cancer and MEN2

• Personal or family history of medullary thyroid carcinoma - This is a black box warning based on thyroid C-cell tumor risk demonstrated in animal studies 1, 3, 2
• Multiple endocrine neoplasia syndrome type 2 (MEN2) - This hereditary syndrome includes MTC, pheochromocytoma, and hyperparathyroidism; all GLP-1 receptor agonists and dual GIP/GLP-1 agonists like tirzepatide carry this contraindication 1, 2
• The contraindication applies regardless of whether genetic testing for RET proto-oncogene mutations has been performed 2

Pregnancy and Breastfeeding

• Mounjaro is contraindicated during pregnancy and breastfeeding 1, 3

Severe Hypersensitivity

• History of serious hypersensitivity reaction to tirzepatide or any component of the formulation 1

Relative Contraindications and High-Risk Situations

Pancreatitis History

• Acute pancreatitis history requires extreme caution - While not an absolute contraindication, the medication should be discontinued immediately if pancreatitis is suspected and never restarted if confirmed 1
• Patients should be counseled on pancreatitis symptoms (severe abdominal pain radiating to the back, nausea, vomiting) 1

Severe Gastroparesis

• Not recommended in patients with clinically meaningful gastroparesis - Tirzepatide delays gastric emptying, which can worsen symptoms in these patients 1, 3
• Use caution in patients with prior gastric surgery, including bariatric procedures 1, 3

Renal Impairment Considerations

• Unlike exenatide (contraindicated with eGFR <30 mL/min/1.73 m²), tirzepatide can be used with caution in severe renal impairment but requires careful monitoring for dehydration from gastrointestinal side effects 1, 3
• Monitor renal function closely, especially during dose titration, as severe nausea/vomiting can precipitate acute kidney injury 1, 3

Clinical Situations Requiring Dose Adjustment or Caution

Hypoglycemia Risk

• When combined with insulin or sulfonylureas, reduce doses of these medications to prevent hypoglycemia, as tirzepatide itself carries low intrinsic hypoglycemia risk 1

Diabetic Retinopathy

• Monitor patients with pre-existing diabetic retinopathy closely, as rapid glucose improvement may transiently worsen retinopathy complications 1, 3

Gallbladder Disease Risk

• Increased risk of cholelithiasis and cholecystitis requires monitoring, particularly with rapid weight loss 1, 3

Common Pitfalls to Avoid

• Never prescribe to patients with family history of MTC even without genetic confirmation - The contraindication is absolute and applies to all formulations 2
• Do not assume oral formulations are safer - The MTC/MEN2 contraindication applies to all GLP-1 and dual GIP/GLP-1 receptor agonists regardless of route 2
• Avoid initiating in patients with untreated closed-angle glaucoma - This is a class effect concern 1
• Do not overlook medication interactions - Delayed gastric emptying affects absorption of oral contraceptives and narrow therapeutic index drugs like warfarin; consider non-oral contraception for 4 weeks after initiation and each dose escalation 3

Alternative Considerations

For patients with MTC family history requiring weight loss medication, orlistat is the recommended alternative, as it has no thyroid cancer risk 2. For patients with severe obesity where pharmacotherapy options are limited due to contraindications, bariatric surgery may be considered 2.