What is the recommended starting dose and titration schedule for Mounjaro (tirzepatide) for the first month of treatment?

Mounjaro (Tirzepatide) First Month Prescription Recommendation

For the first month of Mounjaro therapy, prescribe 2.5 mg subcutaneously once weekly for 4 weeks, then increase to 5 mg once weekly starting in week 5. 1, 2

Initial Dosing Protocol

• Start with 2.5 mg once weekly for the first 4 weeks as the mandatory initial dose 1, 2
• This 2.5 mg dose serves as a dose-escalation period to minimize gastrointestinal side effects, which occur primarily during the first 20 weeks of treatment 3
• After completing 4 weeks at 2.5 mg, increase to 5 mg once weekly beginning in week 5 1, 2

Administration Instructions

• Administer as a subcutaneous injection once weekly, at any time of day, with or without meals 1
• The injection can be given on the same day each week, but the specific time is flexible 1
• Available as single-dose prefilled pens for ease of administration 4

Expected Side Effects During First Month

The most common adverse events during the initial dose-escalation period are gastrointestinal and typically mild to moderate in severity 4, 5:

• Nausea: 17-22% of patients (dose-dependent) 1, 5
• Diarrhea: 13-16% of patients 1, 5
• Vomiting: 6-10% of patients 5
• Constipation: 3-5% of patients 1
• Decreased appetite and abdominal pain: 3-5% each 1

These gastrointestinal symptoms occur primarily during the dose-escalation period and tend to improve with continued use 3.

Critical Safety Monitoring During First Month

Contraindications to verify before prescribing:

• Personal or family history of medullary thyroid carcinoma (MTC) - absolute contraindication 1
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) - absolute contraindication 1

Monitor for the following during the first month:

• Pancreatitis warning signs: Severe persistent abdominal pain radiating to the back, with or without vomiting - discontinue immediately if suspected 1, 6
• Acute kidney injury risk: Use caution when initiating therapy in patients with pre-existing kidney disease, as gastrointestinal side effects (nausea, vomiting, diarrhea) can lead to dehydration and acute kidney injury 1, 2
• Hypoglycemia: Risk is low (0.2-1.7%) when used without insulin or sulfonylureas, but monitor if used with these agents 5

Important Drug Interactions and Precautions

Oral contraceptives:

• Advise patients to switch to a non-oral contraceptive method or add a barrier method for 4 weeks after starting Mounjaro and for 4 weeks after each dose escalation 2
• Tirzepatide delays gastric emptying, which may affect oral contraceptive absorption 2

Medications with narrow therapeutic indices:

• Monitor warfarin and similar drugs closely, as tirzepatide may affect their absorption 2

Renal Impairment Considerations

• No dose adjustment required for any level of renal function, including severe renal impairment 1, 7
• However, exercise caution when initiating therapy due to the risk of dehydration-induced acute kidney injury from gastrointestinal side effects 1, 2

First Month Prescription Summary

Week 1-4: Mounjaro 2.5 mg subcutaneously once weekly (4 doses total)
Week 5 onward: Mounjaro 5 mg subcutaneously once weekly

The 2.5 mg starting dose is not a therapeutic dose but rather a tolerability dose designed to minimize gastrointestinal side effects during the critical initial period 1, 2. The minimum effective maintenance dose is 5 mg once weekly, which provides approximately 10% weight reduction 2.