What is the recommended dose of terlipressin for variceal bleeding?

Terlipressin Dosing for Variceal Bleeding

For acute variceal bleeding, initiate terlipressin at 2 mg IV every 4 hours for the first 48 hours, then reduce to 1 mg IV every 4 hours once bleeding is controlled, continuing for a total duration of 2-5 days. 1, 2

Initial Dosing Regimen

• Start with 2 mg IV every 4 hours during the first 48 hours or until bleeding is controlled 1
• This higher initial dose is critical for achieving rapid hemodynamic response and portal pressure reduction 1
• Begin terlipressin immediately when variceal bleeding is suspected, even before endoscopy 2

Maintenance Dosing

• Reduce to 1 mg IV every 4 hours once hemorrhage is controlled 1
• Continue maintenance dosing for a total treatment duration of 2-5 days 1, 2
• In selected patients with Child-Pugh class A or B cirrhosis with no active bleeding identified during endoscopy, a shorter 2-day course may be reasonable 1

Alternative Dosing: Continuous Infusion

Emerging evidence supports continuous infusion as superior to bolus dosing, though this approach requires HVPG monitoring and is not yet standard practice. 1, 3

• Continuous infusion at 4 mg/24 hours achieves better HVPG reduction (85% vs 58% response at 24 hours) compared to bolus dosing 1, 3
• This approach uses a lower total daily dose and results in fewer adverse events (36% vs 56%) 3
• Rebleeding rates are significantly lower with continuous infusion (2% vs 15% between days 2-5) 1, 3
• Limitation: Requires HVPG measurements at 12 and 24 hours for dose adjustment, which is not feasible in most clinical settings 1

Important Clinical Context

Efficacy Evidence

• Terlipressin is the only vasoactive drug proven to reduce bleeding-related mortality (RR 0.66,95% CI 0.49-0.88) 2
• A single 2 mg IV dose acutely decreases HVPG from 22.2 to 19.1 mmHg 1
• Initial hemostasis rates exceed 95% when combined with endoscopic therapy 4, 5

Safety Considerations vs. Octreotide

Despite superior mortality benefit, octreotide is recommended as first-line in the United States due to terlipressin's adverse event profile. 1

• Terlipressin increases adverse events 2.39-fold compared to octreotide, including abdominal pain, chest pain, diarrhea, and hyponatremia 1
• Contraindications: Hypoxia, worsening respiratory symptoms, ongoing coronary/peripheral/mesenteric ischemia 1
• Common adverse reactions: abdominal pain, nausea, respiratory failure, diarrhea, dyspnea 1
• Myocardial ischemia from coronary vasoconstriction is a serious concern 2

Critical Caveat About FDA Labeling

The FDA-approved terlipressin dosing (0.85 mg IV every 6 hours) is for hepatorenal syndrome, NOT variceal bleeding. 6 The FDA label does not include variceal hemorrhage as an approved indication 1. The dosing regimen for variceal bleeding (2 mg every 4 hours initially, then 1 mg every 4 hours) is based on international guidelines and clinical trials conducted outside the United States 1, 2.

Adjunctive Therapy Requirements

• Always combine with prophylactic antibiotics (ceftriaxone 1g IV daily for up to 7 days) 2
• Perform endoscopic variceal ligation within 12 hours of presentation 2
• Consider early TIPS for high-risk patients (Child-Pugh C score 10-13 or Child-Pugh B with active bleeding despite therapy) 2

Duration Considerations

• Standard duration is 2-5 days, with most guidelines recommending at least 3 days 1, 2
• One high-quality RCT demonstrated that 24 hours of terlipressin is as effective as 72 hours when used as adjunct to successful endoscopic ligation, with no difference in rebleeding (3.1% vs 1.5%) or mortality 7
• However, this shortened duration should only be considered in carefully selected patients with successful initial endoscopic hemostasis 7