Tirzepatide Safety Information

Absolute Contraindications

Personal or Family History of Medullary Thyroid Carcinoma

Tirzepatide carries a boxed warning regarding thyroid C-cell tumors based on rodent studies. Anyone with personal history of MTC should never use tirzepatide. First-degree relatives of people with MTC should also avoid tirzepatide due to potential hereditary risk.

Multiple Endocrine Neoplasia Syndrome Type 2 (MEN2)

MEN2 dramatically increases MTC risk. Tirzepatide is absolutely contraindicated in anyone with known or suspected MEN2. Genetic testing for RET mutations can confirm or rule out MEN2 in at-risk individuals.

Known Hypersensitivity

Anyone with known serious hypersensitivity reaction to tirzepatide or any components should not use the medication. Previous allergic reaction to other GLP-1 agonists is a relative contraindication.

Pregnancy

Tirzepatide is contraindicated during pregnancy due to potential teratogenic effects in animal studies. Women of reproductive potential should use effective contraception. If pregnancy is planned, tirzepatide should be discontinued at least 2 months before conception attempts. If pregnancy occurs, discontinue immediately.

Relative Contraindications and Precautions

History of Pancreatitis

History of pancreatitis warrants extreme caution. The decision to use tirzepatide should involve careful risk-benefit assessment and informed patient consent. If used, patients should be educated about pancreatitis symptoms and instructed to discontinue and seek immediate care if these occur.

Severe Gastrointestinal Disease

Conditions affecting GI motility (gastroparesis, severe GERD, IBD) may be exacerbated by tirzepatide's effects on gastric emptying. Use cautiously with close monitoring for symptom worsening.

Severe Renal Impairment

While no dose adjustment is required for mild to moderate renal impairment, data in severe renal impairment (eGFR <15 mL/min) are limited. Enhanced monitoring for adverse effects is warranted.

History of Eating Disorders

Tirzepatide's appetite suppression may be problematic in people with history of eating disorders. Use requires careful psychiatric assessment and close monitoring.

Pre-Treatment Evaluation

Medical History

Detailed history should address: personal/family history of MTC or MEN2, pancreatitis history, GI disorders, kidney disease, diabetic complications, cardiovascular disease, gallbladder disease, eating disorders, depression, pregnancy plans, current medications, and allergies.

Physical Examination

Baseline exam should include: weight, height, BMI, blood pressure, heart rate, waist circumference, thyroid palpation, abdominal examination, and cardiovascular examination.

Laboratory Testing

Recommended baseline tests: HbA1c (if diabetes/prediabetes), fasting glucose, comprehensive metabolic panel, lipid panel, thyroid function tests, and pregnancy test for women of reproductive potential.

Safe Initiation and Dose Escalation

Standard Dose Escalation

For diabetes: Start 2.5 mg weekly for 4 weeks, then 5 mg weekly. Can increase to 7.5 mg, 10 mg, 12.5 mg, or 15 mg at 4-week intervals if needed.

For weight management: 2.5 mg weekly for 4 weeks, 5 mg for 4 weeks, 7.5 mg for 4 weeks, 10 mg for 4 weeks, 12.5 mg for 4 weeks, then 15 mg maintenance.

Injection Technique

Inject subcutaneously in abdomen, thigh, or upper arm. Rotate injection sites. Allow medication to reach room temperature. Use proper technique and dispose of needles properly in sharps container.

Ongoing Monitoring

Clinical Monitoring

At each visit: weight, BMI, blood pressure, heart rate, side effect assessment, glucose monitoring review (if applicable), dietary intake assessment, physical activity evaluation, mental health screening, and medication adherence.

Laboratory Monitoring

HbA1c every 3 months until stable, then every 6 months (if diabetes). Comprehensive metabolic panel every 3-6 months. Lipid panel every 6-12 months. Thyroid function annually or if symptoms develop.

Medication Adjustments

Insulin Dose Reduction

When adding tirzepatide to insulin: reduce basal insulin by 20% initially. Monitor glucose closely and adjust further based on response. Some people can discontinue insulin entirely.

Sulfonylurea Dose Reduction

When adding tirzepatide to sulfonylurea: reduce sulfonylurea dose by 50% initially. Monitor for hypoglycemia closely. Many people can discontinue sulfonylureas.

Lifestyle Modifications

Dietary Recommendations

Reduced-calorie diet with 500-1000 calorie deficit. Adequate protein (1.2-1.6 g/kg daily). Balanced macronutrients. Smaller, more frequent meals. Avoid high-fat meals. Adequate hydration. Multivitamin supplementation.

Physical Activity

At least 150 minutes moderate-intensity aerobic exercise weekly. Resistance training 2-3 times weekly to preserve muscle mass. Gradual progression. Consistency over intensity.

Emergency Situations

Seek Emergency Care For:

• Severe persistent abdominal pain (possible pancreatitis)
• Severe right upper quadrant pain with fever (possible cholecystitis)
• Signs of severe allergic reaction
• Severe hypoglycemia with confusion or loss of consciousness
• Chest pain or pressure
• Severe dehydration
• Signs of bowel obstruction

Long-Term Safety Considerations

Clinical trials have followed participants for up to 2-3 years. Questions remain about very long-term safety (decades of use), particularly regarding thyroid cancer risk, bone health, and muscle mass preservation. Ongoing post-marketing surveillance will provide additional data.

Quality Assurance: Brand vs Compounded

FDA-Approved Formulations

Brand-name tirzepatide (Mounjaro, Zepbound) undergoes rigorous FDA review ensuring consistent purity, potency, sterility, and quality.

Compounded Tirzepatide

Compounded tirzepatide is not FDA-approved and may vary in quality. If using compounded product, ensure the pharmacy is licensed, follows USP standards, provides certificates of analysis, and uses pharmaceutical-grade ingredients.