Contraindications of Mounjaro (Tirzepatide)
Mounjaro is absolutely contraindicated in only two clinical scenarios: patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), and patients with known serious hypersensitivity to tirzepatide or its excipients. 1
Absolute Contraindications
Thyroid Malignancy Risk
- Personal or family history of medullary thyroid carcinoma (MTC) is an absolute contraindication 1
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) is an absolute contraindication 1
- This stems from rodent studies demonstrating thyroid C-cell tumors, though human relevance remains undetermined 2
Hypersensitivity Reactions
- Known serious hypersensitivity to tirzepatide or any excipients constitutes an absolute contraindication 1
- Serious reactions including anaphylaxis and angioedema have been documented 1
Critical Precautions Requiring Extreme Caution
Pregnancy and Lactation
- Pregnancy is an absolute contraindication in clinical practice 2
- Breastfeeding is contraindicated 2
- Safety has not been established in these populations 3
Pancreatitis History
- Use with extreme caution in patients with prior pancreatitis 2, 4
- Acute pancreatitis has been reported in clinical trials, with temporal correlation between drug initiation and symptom onset 5, 6
- Discontinue immediately if pancreatitis is suspected 4
- Cases have occurred even after switching from other GLP-1 agonists like semaglutide 6
Severe Gastroparesis
- Not recommended in patients with clinically meaningful gastroparesis 3
- Tirzepatide delays gastric emptying and will worsen existing symptoms 3
Renal Impairment
- Use with caution when initiating or escalating doses in patients with kidney disease 4
- Risk of acute kidney injury from dehydration secondary to gastrointestinal side effects 4
- Unlike some GLP-1 agonists, no dose adjustment is required, but careful monitoring is essential 4
Important Clinical Considerations
Gallbladder Disease
- May cause cholelithiasis and gallstone-related complications 4
- Monitor for gallbladder disease throughout treatment 4
Drug Interactions
- Delays gastric emptying, affecting absorption of oral medications 4
- Monitor medications with narrow therapeutic indices (e.g., warfarin) closely 4
- For oral hormonal contraceptive users: advise non-oral contraception or addition of non-oral method for 4 weeks after initiation and each dose escalation 4
Hypoglycemia Risk
- When combined with insulin or sulfonylureas, dose reduction of these agents is required 4
- Tirzepatide alone carries low intrinsic hypoglycemia risk 4
G6PD Deficiency Screening
- While not a contraindication for tirzepatide specifically, screening for G6PD deficiency is important when considering GLP-1 class medications, particularly in patients of African American, Mediterranean, or Southeast Asian descent 7
Common Pitfall to Avoid
Do not confuse relative precautions with absolute contraindications. Only MTC/MEN 2 history and serious hypersensitivity are FDA-labeled absolute contraindications 1. Conditions like renal impairment, pancreatitis history, and pregnancy require extreme caution or avoidance but are managed differently in clinical practice 2, 4.