What is the recommended dosing of terlipressin (glypressin) for an adult patient with cirrhosis and active variceal hemorrhage?

Terlipressin Dosing for Variceal Hemorrhage

For acute variceal hemorrhage in adults with cirrhosis, administer terlipressin 2 mg IV every 4 hours for the first 48 hours until bleeding is controlled, then reduce to 1 mg IV every 4 hours for a total treatment duration of 2-5 days. 1

Initial Phase Dosing (First 48 Hours)

• Start with 2 mg IV bolus every 4 hours as soon as variceal bleeding is suspected, even before endoscopic confirmation 1
• This higher initial dose is critical for achieving rapid hemodynamic response and portal pressure reduction 1
• A single 2 mg IV dose acutely decreases hepatic venous pressure gradient from 22.2 to 19.1 mmHg 1
• Continue this dose until bleeding is controlled (typically within 48 hours) 1

Maintenance Phase 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
• The drug should be started as soon as variceal hemorrhage is suspected and continued for 3-5 days after diagnosis is confirmed 1

Treatment Duration Considerations

• Standard duration is 2-5 days for most patients 1
• Consider shortening to 2 days in selected patients with Child-Pugh class A or B cirrhosis who have no active bleeding identified during endoscopy 1
• Extend toward 5 days for patients with Child-Pugh class C cirrhosis, active bleeding during endoscopy, or high MELD score (>19) 1

Alternative Dosing: Continuous Infusion

• Emerging evidence supports continuous infusion as an alternative to bolus dosing, starting at 4 mg/24 hours 2
• Continuous infusion achieves higher HVPG response rates (85.4% vs 58.2%) at lower total daily doses with fewer adverse events (36.3% vs 56.4%) compared to bolus administration 2
• However, bolus dosing remains the standard in most guidelines 1

Mandatory Combination Therapy

Terlipressin should never be used as monotherapy. The standard approach requires three simultaneous components: 1

• Vasoactive drug therapy (terlipressin) started immediately
• Endoscopic band ligation performed within 12 hours 1
• Prophylactic antibiotics (ceftriaxone 1 g IV every 24 hours for up to 7 days) 1

This combination achieves 77% five-day hemostasis versus only 58% with endoscopy alone 1

Efficacy and Mortality Benefit

• Terlipressin is the only vasoactive drug proven to reduce bleeding-related mortality (relative risk 0.66) 1
• Initial bleeding control is achieved in 85-90% of patients when combined with endoscopy 1
• The drug significantly reduces early rebleeding rates when combined with endoscopic therapy 1

Safety Profile and Contraindications

Absolute contraindications include: 1

• Hypoxia or oxygen saturation <90% on room air or supplemental oxygen
• Active coronary, peripheral, or mesenteric ischemia
• Worsening respiratory symptoms

Common adverse events include: 1

• Abdominal pain, nausea, and diarrhea
• Respiratory failure (occurs in 30% of patients, particularly those with ACLF grade 3)
• Ischemic complications (occur in ~12% of patients)
• Hyponatremia

Terlipressin increases adverse events 2.39-fold compared to octreotide 1

Administration Details

• Administer as undiluted IV bolus through a peripheral line 3
• No central venous access is required 1
• ICU monitoring is not required for most patients (ACLF grade <3) 1

Comparative Effectiveness

• All vasoactive drugs (terlipressin, octreotide, somatostatin) show similar efficacy for hemostasis and survival 1
• However, terlipressin is the only agent with proven mortality benefit 1
• Octreotide is the only vasoactive drug available in the United States 1

High-Risk Patient Considerations

For carefully selected high-risk patients (Child-Pugh class C with score 10-13, or Child-Pugh class B with active bleeding on endoscopy despite vasoactive therapy), consider early TIPS placement within 72 hours of admission 1

Critical Pitfalls to Avoid

• Do not delay initiation waiting for endoscopic confirmation—start immediately when variceal bleeding is suspected 1
• Do not use as monotherapy—always combine with endoscopy and antibiotics 1
• Do not continue beyond 5 days—prolonged use increases adverse events without additional benefit 1
• Stop the drug if endoscopy reveals non-variceal upper GI bleeding, as vasoactive drugs are not expected to work in other causes 1