What is the difference between terlipressin and vasopressin (Vasoconstrictor Hormone)?

Key Differences Between Terlipressin and Vasopressin

Terlipressin is a synthetic vasopressin analogue with a longer half-life (0.9 hours vs. minutes for vasopressin), fewer systemic side effects, and superior clinical efficacy—it is the only vasoactive drug proven to reduce mortality in variceal bleeding and is the preferred agent for hepatorenal syndrome. 1, 2, 3

Pharmacological Differences

Half-Life and Administration

• Terlipressin has a terminal half-life of 0.9 hours, while its active metabolite lysine-vasopressin has a half-life of 3.0 hours, providing sustained biological activity 2, 3
• Vasopressin has an extremely short half-life (minutes) and requires continuous IV infusion, typically in an ICU setting 1
• Terlipressin can be administered as intermittent IV boluses every 6 hours through a peripheral line without ICU monitoring, making it far more practical 1, 3

Receptor Selectivity and Mechanism

• Terlipressin has twice the selectivity for V1 receptors versus V2 receptors compared to natural vasopressin 3
• Terlipressin functions as both a prodrug (converted to lysine-vasopressin by tissue peptidases) and has direct pharmacologic activity 3, 4
• Both agents cause splanchnic vasoconstriction, reducing portal blood flow and pressure, but terlipressin achieves this with less systemic vasoconstriction 1, 2, 4

Safety Profile

Adverse Effects

• Vasopressin causes significant systemic vasoconstriction leading to mesenteric or myocardial ischemia, which limits its clinical use 1
• Terlipressin has a substantially safer adverse event profile with fewer vasoconstrictive complications 1, 2, 4
• Common terlipressin side effects include hyponatremia, abdominal pain, and diarrhea, but mortality or withdrawal due to adverse events occurs in <1% of cases 2, 4
• Vasopressin is rarely used in modern practice specifically because terlipressin offers comparable efficacy with reduced toxicity 1

Clinical Efficacy

Variceal Bleeding

• Terlipressin is the only vasoactive drug proven to reduce mortality in acute variceal hemorrhage, with a 34% relative risk reduction (RR 0.66,95% CI 0.49-0.88) 1, 5
• Terlipressin decreases failure of initial hemostasis by 34% and is considered first-line treatment when available 4, 5
• No mortality benefit has been demonstrated for vasopressin in variceal bleeding 1

Hepatorenal Syndrome (HRS-AKI)

• Terlipressin is the vasoactive drug of choice for HRS-AKI, supported by placebo-controlled RCTs including the pivotal CONFIRM trial 1
• The CONFIRM trial demonstrated that terlipressin with albumin achieved 29.1% reversal of HRS versus 15.8% with placebo (P=0.012) 1
• Terlipressin reverses type 1 HRS in 33-60% of cases and is the only treatment with proven efficacy in randomized trials 4, 6
• Norepinephrine appears equally effective to terlipressin but requires ICU admission and continuous monitoring 1

Practical Considerations

Dosing and Monitoring

• Terlipressin is administered as 1 mg IV boluses every 6 hours initially, increased to 2 mg every 6 hours on day 4 if inadequate response (<30% creatinine decrease) 1, 3
• Treatment continues up to 14 days or until creatinine decreases to <1.5 mg/dL 1, 3
• Vasopressin requires continuous infusion with intensive hemodynamic monitoring due to its short half-life and unpredictable effects 1

Contraindications

• Terlipressin is contraindicated in patients with hypoxemia, ongoing coronary/peripheral/mesenteric ischemia, and should be used cautiously in ACLF grade 3 1
• Patients with creatinine >5 mg/dL have low response rates and are unlikely to benefit from vasoconstrictors 1

Geographic Availability

• Terlipressin is FDA-approved in the United States as of the CONFIRM trial and widely available internationally 1, 3
• In regions where terlipressin is unavailable, norepinephrine serves as an alternative but requires ICU-level care 1