Zepbound Initial Dosing
Zepbound (tirzepatide) should be initiated at 2.5 mg subcutaneously once weekly for 4 weeks, then increased to 5 mg once weekly as the first maintenance dose. 1
Dose Titration Schedule
The FDA-approved titration regimen for Zepbound follows a structured 7-day initial period followed by maintenance dosing:
- Days 1-4: 0.23 mg once daily 1
- Days 5-7: 0.46 mg once daily 1
- Day 8 and thereafter: 0.92 mg once daily 1
Administration Guidelines
- Swallow capsules whole with or without food 1
- Do not crush, chew, or open the capsules 1
- The medication can be taken regardless of meal timing, though this differs from ziprasidone which requires administration with a 500 kcal meal for adequate absorption 2
Special Population Considerations
Hepatic Impairment
In patients with mild to moderate hepatic impairment (Child-Pugh class A or B), after completing the standard 7-day titration, the maintenance dose should be 0.92 mg once every other day (not daily) starting on Day 8 1
Reinitiation After Treatment Interruption
- If doses are missed during the first 2 weeks: Restart using the full titration regimen from Day 1 1
- If doses are missed after the first 2 weeks: Continue with the treatment schedule as planned without restarting titration 1
Critical Pre-Treatment Assessments
Before initiating Zepbound, obtain:
- Complete blood count (CBC) including lymphocyte count within the last 6 months 1
- Liver function tests (transaminase and bilirubin levels) within the last 6 months 1
- Electrocardiogram (ECG) to assess for preexisting conduction abnormalities 1
- Baseline ophthalmic examination of the fundus and macula 1
- Baseline skin examination to identify any suspicious lesions 1
Important Safety Considerations
Gastrointestinal motility complications have been reported with Zepbound, including functional small bowel obstruction even in patients without prior abdominal surgery or conventional risk factors, particularly following dose escalation 3. Monitor patients closely for severe constipation, abdominal pain, or signs of obstruction.
The medication causes mean reduction in peripheral lymphocyte count to approximately 45% of baseline due to reversible sequestration in lymphoid tissues, which may increase infection susceptibility 1. Delay initiation if active infection is present until resolved 1.