What is the recommended IV (intravenous) infusion dose of terlipressin?

IV Infusion Dose of Terlipressin

For hepatorenal syndrome (HRS-AKI), terlipressin should be administered as a continuous IV infusion starting at 2 mg/day, which provides similar efficacy to bolus dosing but with significantly fewer adverse events. 1

Continuous Infusion Dosing (Preferred Method)

Initial dose: 2 mg/day as continuous IV infusion 1

Dose escalation: Increase every 24-48 hours up to a maximum of 12 mg/day if serum creatinine does not decrease 1

Advantages of continuous infusion:

• Lower rate of adverse events (35% vs 62% with bolus dosing) 2
• More stable lowering effect on portal pressure 1
• Effective at lower total daily doses than bolus administration (mean 2.23 mg/day vs 3.51 mg/day) 2
• Similar efficacy to bolus dosing for HRS reversal 1, 2

Alternative Bolus Dosing (FDA-Approved in US)

Initial dose: 1 mg IV bolus every 6 hours (total 4 mg/day) 1, 3, 4

Dose escalation: If serum creatinine decreases <30% by day 4, increase to 2 mg every 6 hours (total 8 mg/day) 1, 3, 4

Traditional European dosing: Start at 0.5-1 mg every 4-6 hours, increase to maximum of 2 mg every 4-6 hours (total 8-12 mg/day) if serum creatinine reduction <25% after 2-3 days 1

Mandatory Concomitant Albumin Administration

Day 1: 1 g/kg IV (maximum 100 g) 1

Subsequent days: 20-40 g/day IV for duration of terlipressin therapy 1

Critical caveat: Judicious albumin use is essential—excessive albumin administration increases risk of respiratory failure, particularly in patients with ACLF grade 3 1

Treatment Duration and Response Assessment

Continue treatment until:

• Complete response: serum creatinine ≤1.5 mg/dL for at least 48 hours 1, 3
• Maximum duration: 14 days 1, 3
• Discontinue if serum creatinine remains at or above baseline on day 4 3, 4

Response definitions:

• Complete response: serum creatinine <1.5 mg/dL 1
• Partial response: ≥50% decrease in serum creatinine but still >1.5 mg/dL 1

Administration Requirements

Route: Peripheral IV line (central line not required) 1

Monitoring location: Regular ward acceptable for most patients; ICU not mandatory unless ACLF grade 3 1

Vital signs monitoring: Every 2-4 hours including pulse oximetry 1

Absolute Contraindications

• SpO2 <90% or hypoxemia 1, 3
• Ongoing coronary, peripheral, or mesenteric ischemia 1, 3
• Serum creatinine >5 mg/dL (unlikely to benefit) 1

Relative Contraindications and High-Risk Situations

Use with extreme caution in:

• ACLF grade 3 (≥3 organ failures)—increased risk of respiratory failure 1
• MELD score ≥35—benefits may not outweigh risks 1
• Significant cardiovascular disease 1

Pre-treatment screening required:

• Electrocardiogram 1
• Assessment of volume status to avoid circulatory overload 1

Common Adverse Events

Cardiovascular/ischemic complications:

• Abdominal pain, diarrhea (45-46% with bolus dosing) 1
• Cardiac, intestinal, or peripheral ischemia 1
• Discontinuation rate due to adverse events: ~20% 1

Respiratory complications:

• Respiratory failure (14% vs 5% with placebo) 1, 4
• Death from respiratory failure (11% vs 2% with placebo) 4
• Risk increased with excessive albumin administration 1

Predictors of Response

Favorable predictors:

• Baseline bilirubin <10 mg/dL 1
• Baseline serum creatinine <5 mg/dL 1
• Lower ACLF grade 1
• Systemic inflammatory response syndrome present (37% response vs 6% with placebo) 4

Key Clinical Pearls

Dose adjustment strategy: If serum creatinine decreases ≥25%, continue current dose; if <25% reduction, escalate dose 1

Early response predicts survival: Each 1 mg/dL reduction in creatinine reduces mortality risk by 27% 5

Recurrence rate: Only 17% of complete responders experience HRS recurrence after treatment discontinuation 6

Survival benefit: HRS reversal significantly improves 180-day survival 7, 4