What is the recommended dosing schedule for Zepbound (generic name) in patients with normal and impaired renal function?

Zepbound Dosing Schedule

Zepbound (tirzepatide) should be initiated at 2.5 mg subcutaneously once weekly for 4 weeks, then escalated by 2.5 mg increments every 4 weeks as tolerated, up to a maximum maintenance dose of 15 mg once weekly, with no dose adjustment required for renal impairment based on available evidence. 1

Standard Dosing Regimen

Initiation and Titration

• Start at 2.5 mg subcutaneously once weekly for the first 4 weeks 1
• Escalate by 2.5 mg every 4 weeks based on tolerability and weight loss response 1
• Available doses: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg 1
• Maximum dose: 15 mg once weekly 1

Maintenance Dosing

• Continue at the dose that provides adequate weight reduction with acceptable tolerability 1
• Most patients in clinical trials achieved optimal results with 10-15 mg weekly doses 1
• The medication is administered as a once-weekly subcutaneous injection 1

Renal Function Considerations

Normal Renal Function

• No dose adjustment required - standard escalation schedule applies 1

Impaired Renal Function

• No specific dose adjustments are recommended in the available evidence for tirzepatide 1
• Unlike some other medications metabolized renally, tirzepatide does not appear to require dose reduction based on creatinine clearance 1
• This contrasts with drugs like metformin (contraindicated when eGFR <30 mL/min/1.73 m²) 2 or lenalidomide (requiring dose reduction to 10 mg daily for CrCl >30 but ≤50 ml/min) 3

Important Clinical Considerations

Gastrointestinal Adverse Effects

• Most common adverse events are gastrointestinal (nausea, diarrhea, vomiting) 1
• These occur primarily during dose-escalation periods in the first 20 weeks 1
• Most GI effects are mild to moderate in severity 1
• The gradual 4-week titration schedule helps minimize these effects 1

Critical Safety Alert

• Severe GI motility complications including functional small bowel obstruction have been reported, even in patients without prior abdominal surgery or conventional risk factors 4
• Monitor closely for severe abdominal pain, persistent vomiting, or signs of obstruction, particularly during dose escalation 4

Duration of Treatment

• Clinical trial data demonstrate sustained efficacy over 176 weeks (3+ years) of continuous treatment 1
• Weight reduction was maintained throughout the treatment period with ongoing therapy 1
• After discontinuation, some weight regain may occur 1

Dosing Flexibility

Missed Doses

• If a dose is missed and the next scheduled dose is more than 72 hours away, administer as soon as possible 1
• If less than 72 hours remain until the next dose, skip the missed dose and resume the regular schedule 1

Dose De-escalation

• If GI adverse effects become intolerable, consider temporarily reducing to the previous dose level for 4 additional weeks before attempting re-escalation 1
• Permanent dose reduction may be appropriate if higher doses are not tolerated 1