How to Initiate Mounjaro (Tirzepatide)
Start Mounjaro at 2.5 mg subcutaneously once weekly for the first 4 weeks, then increase to 5 mg once weekly. 1
Starting Dose and Initial Titration
- Begin with 2.5 mg subcutaneously once weekly for 4 weeks as the initial dose, which serves as a dose-escalation step rather than a therapeutic dose 1
- After completing 4 weeks at 2.5 mg, increase to 5 mg once weekly, which represents the first therapeutic maintenance dose 1
- Administer the injection subcutaneously in the abdomen, thigh, or upper arm 2
- The injection can be given at any time of day, with or without meals 1, 2
Subsequent Dose Escalation
- After at least 4 weeks on the 5 mg dose, consider increasing to 10 mg once weekly based on clinical response and tolerability 1
- After at least 4 weeks on the 10 mg dose, the maximum dose of 15 mg once weekly can be considered if additional glycemic control or weight loss is needed 1
- Each dose escalation requires a minimum of 4 weeks at the current dose before advancing 1
Administration Logistics
- Inject on the same day each week, though the time of day and injection site can be changed as needed 2
- The medication comes as a pre-filled pen for subcutaneous self-administration 1
Managing Common Side Effects
- Gastrointestinal side effects are most common during the dose-escalation period in the first 20 weeks: nausea (10-31%, dose-dependent), diarrhea (7-23%), vomiting (2-12%), constipation (3-5%), and abdominal pain (3-5%) 1, 3
- These adverse events are typically mild to moderate in severity and occur primarily during dose escalation 3, 4
Special Population Considerations
- No dose adjustments are required for any level of renal impairment, including severe renal dysfunction 1, 5
- However, use caution when initiating or escalating doses in patients with kidney disease due to potential risk of acute kidney injury from gastrointestinal side effects 1
Critical Safety Monitoring
- Screen for contraindications before initiating: personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia type 2 (black box warning) 1
- Monitor for signs of pancreatitis (severe persistent abdominal pain) and discontinue immediately if suspected 1, 6
- Be particularly vigilant in patients with pre-existing gallstones or metabolic risk factors, as pancreatitis risk may be elevated 6
Assessing Treatment Response
- If no response after 6-8 weeks (defined as <1-2 g/dL increase in hemoglobin A1c reduction or inadequate weight loss), attempt appropriate dose escalation per FDA labeling before discontinuing 7
- For weight loss indication, evaluate response after 12 weeks at maintenance dose and consider discontinuation if patient has not lost at least 5% of initial body weight 2
Perioperative Considerations
- Consider the 5-day elimination half-life and effects on gastric emptying when planning surgical procedures 1