What is the difference between terlipressin (Terlipressin) and vasopressin (Vasopressin)?

From the Guidelines

Terlipressin is preferred over vasopressin due to its longer half-life, fewer side effects, and greater selectivity for V1 receptors, resulting in improved morbidity, mortality, and quality of life outcomes in patients with variceal bleeding and hepatorenal syndrome. The main differences between terlipressin and vasopressin lie in their pharmacokinetic and pharmacodynamic properties. Terlipressin has a longer half-life of 4-6 hours, allowing for less frequent dosing, whereas vasopressin has a shorter half-life of 10-20 minutes, requiring continuous infusion 1. Terlipressin is a prodrug that gets converted to lysine-vasopressin in the body, while vasopressin is directly active.

Clinical Use and Efficacy

Regarding clinical use, terlipressin is primarily indicated for hepatorenal syndrome and variceal bleeding in many countries, though it remains unavailable in the US until recently. Vasopressin is more commonly used for septic shock, post-cardiac arrest vasoplegia, and as an antidiuretic for diabetes insipidus. According to a 2024 study published in Gastroenterology, terlipressin has been evaluated for acute variceal hemorrhage (AVH) and is one of the standard regimens outside of the United States, with a recommended initial dose of 2 mg IV every 4 hours until bleeding is controlled, followed by a maintenance dose of 1 mg IV every 4 hours 1.

Adverse Effects and Safety

Both medications can cause similar adverse effects, including ischemic complications, but terlipressin may have a higher risk of severe ischemic events. A 2021 updated systematic review and meta-analysis involving 21 RCTs found that the use of terlipressin or vasopressin compared with octreotide or somatostatin resulted in similar rates of mortality, hemostasis, early rebleeding, late rebleeding, blood transfusion, and hospital stay, but adverse events increased by 2.39-fold in patients receiving terlipressin or vasopressin 1.

Dosing and Administration

Dosing differs significantly between the two medications: terlipressin is typically given as 1-2 mg IV every 4-6 hours, while vasopressin requires continuous infusion at 0.01-0.04 units/minute. The choice of medication and dosing regimen should be individualized based on the patient's specific condition, severity of disease, and potential risk factors for adverse events. According to the 2024 study, it is reasonable to shorten vasoactive drug treatment to 2 days only in selected patients with Child-Pugh class A and B cirrhosis with no active bleeding identified during endoscopy 1.

Key Points

• Terlipressin has a longer half-life and fewer side effects compared to vasopressin
• Terlipressin is preferred over vasopressin for variceal bleeding and hepatorenal syndrome
• Dosing regimens differ between terlipressin and vasopressin
• Adverse events are increased with the use of terlipressin or vasopressin compared to octreotide or somatostatin
• The choice of medication and dosing regimen should be individualized based on the patient's specific condition and potential risk factors for adverse events.

From the FDA Drug Label

Terlipressin is a synthetic vasopressin analogue with twice the selectivity for vasopressin V1 receptors versus V2 receptors. The main difference between terlipressin and vasopressin is that terlipressin has twice the selectivity for V1 receptors.

• Mechanism of action: Terlipressin acts as both a prodrug for lysine-vasopressin and has pharmacologic activity on its own.
• Pharmacodynamics: Terlipressin increases renal blood flow in patients with hepatorenal syndrome by reducing portal hypertension and increasing effective arterial volume and mean arterial pressure (MAP) 2.

From the Research

Difference between Terlipressin and Vasopressin

• Terlipressin is a synthetic analogue of vasopressin, used in the treatment of acute variceal hemorrhage 3.
• Unlike vasopressin, terlipressin can be administered as intermittent injections instead of continuous intravenous infusion and has a safer adverse reactions profile 3.
• Terlipressin exerts its main pharmacological effect through stimulation of vasopressin-1 receptors, leading to vasoconstriction and a decrease in portal flow and pressure 4, 5.
• Vasopressin, on the other hand, has been used for many years to control bleeding from esophageal varices, with its efficacy believed to be due to direct vasoconstrictor activity on splanchnic arterioles and precapillary sphincters 6.
• Terlipressin has been shown to reduce mortality in acute variceal hemorrhage, with a 34% relative risk reduction in mortality compared to placebo 3, 4.
• In contrast, vasopressin has not been shown to prolong survival from esophageal bleeding, but is effective in controlling upper gastrointestinal hemorrhage and is commonly used as a means of buying time to prepare the patient for shunt surgery 6.

Administration and Safety

• Terlipressin can be administered as intermittent injections, whereas vasopressin is typically administered as a continuous intravenous infusion 3, 6.
• Terlipressin has a safer adverse reactions profile compared to vasopressin, with adverse events mostly related to vasoconstriction and occurring in less than 1% of cases 4.
• Vasopressin, on the other hand, can cause cardiovascular complications, including bradycardia, and requires simultaneous infusion of isoproterenol to avoid adverse effects 6.

Clinical Efficacy

• Terlipressin has been shown to be effective in the treatment of acute variceal hemorrhage, hepatorenal syndrome, and norepinephrine-resistant septic shock 4, 5.
• Vasopressin is effective in controlling upper gastrointestinal hemorrhage, but its use is limited by its potential for cardiovascular complications and lack of effect on mortality 6.
• Terlipressin may be considered the vasoactive agent of choice in acute variceal bleeding due to its efficacy and safety profile 3, 4.