What is Terlipressin Used For?
Terlipressin is a vasopressin analogue used to improve kidney function in adults with hepatorenal syndrome (HRS), particularly type 1 HRS, in patients with advanced cirrhosis and ascites. 1, 2
Primary Indication: Hepatorenal Syndrome
Terlipressin is FDA-approved specifically to improve kidney function in adults with hepatorenal syndrome characterized by rapid reduction in kidney function. 2 This represents a functional, potentially reversible form of acute kidney injury in patients with cirrhosis and ascites. 3
Mechanism of Action
Terlipressin acts as a selective vasopressin V1 receptor agonist (with 2:1 selectivity for V1 over V2 receptors) that functions both as a prodrug for lysine-vasopressin and has direct pharmacologic activity. 2
The drug increases renal blood flow by reducing portal hypertension and splanchnic blood circulation while increasing effective arterial volume and mean arterial pressure (MAP). 2
Hemodynamic effects occur within 5 minutes of administration, with MAP increasing by approximately 16.2 mmHg and heart rate decreasing by 10.6 beats/minute, sustained for at least 6 hours. 2
Clinical Efficacy in Hepatorenal Syndrome
Terlipressin combined with albumin reverses type 1 HRS in 36-44% of patients, significantly superior to albumin alone (which achieves only 8.7% reversal). 1, 4
Evidence Supporting Use
The most recent 2024 AASLD guidelines recommend terlipressin as the preferred first-line vasoconstrictor for HRS-AKI in the absence of shock, particularly given its superiority in acute-on-chronic liver failure (ACLF) settings. 1
In ACLF patients, terlipressin demonstrates clear superiority over norepinephrine with day 4 response rates of 26.1% vs 11.7% (p=0.03), day 7 response of 41.7% vs 20% (p=0.01), and 28-day survival of 48.3% vs 20% (p=0.001). 5
Each 1 mg/dL reduction in serum creatinine achieved with terlipressin therapy reduces mortality risk by 27%, even with partial response. 1, 6
Important Limitation
Patients with serum creatinine >5 mg/dL are unlikely to experience benefit and should not receive terlipressin. 2
Secondary Indication: Variceal Bleeding
While not the primary focus of FDA approval in the United States, terlipressin has established efficacy in managing bleeding esophageal varices in cirrhotic patients. 1, 7
Terlipressin decreases failure of initial hemostasis by 34% and decreases mortality by 34% in patients with bleeding esophageal varices, making it a first-line treatment when available. 7
The drug reduces portal flow and pressure within minutes of administration in patients with portal hypertension. 7
Critical Safety Considerations
Black Box Warning: Respiratory Failure
The FDA mandates a black box warning for serious or fatal respiratory failure, particularly in patients with volume overload or ACLF Grade 3. 2
Do not initiate terlipressin in patients with SpO2 <90% until oxygenation improves, and discontinue if SpO2 drops below 90% during treatment. 2
Respiratory failure occurs in 14-30% of patients, with highest risk in ACLF Grade 3 patients due to complex hemodynamic interactions including diastolic dysfunction and volume overload from aggressive albumin administration. 1, 5
Ischemic Complications
Ischemic events (cardiac, peripheral, or mesenteric) occur in approximately 12% of patients due to terlipressin's potent vasoconstrictor effects. 1, 5
Absolute contraindications include ongoing coronary, peripheral, or mesenteric ischemia. 2
Common ischemic manifestations include angina, arrhythmias, digital ischemia, abdominal pain, and diarrhea from intestinal stimulation. 1
Patient Selection Factors
Predictors of favorable response include baseline bilirubin <10 mg/dL, baseline serum creatinine <5 mg/dL, and MAP increase ≥5-10 mmHg by day 3. 1, 5, 6
Patients with total bilirubin >4.3 mg/dL have significantly higher incidences of adverse events (69% vs 24%) and serious adverse events (64% vs 0%) compared to those with lower bilirubin levels. 8
Mandatory Albumin Co-Administration
Terlipressin must always be combined with albumin, as terlipressin alone achieves only 25% response rate versus 77% with combination therapy. 5
Albumin dosing: 1 g/kg IV (maximum 100 g) on day 1, followed by 20-40 g/day until treatment completion. 1, 5, 6
The combination optimizes circulatory function and treatment efficacy, though it increases risk of volume overload requiring careful monitoring. 1, 5
Practical Administration
Terlipressin can be safely administered via peripheral IV line in ward settings without requiring ICU admission or central line placement in most patients (ACLF grade <3). 5
ICU monitoring is mandatory for ACLF Grade 3 patients (≥3 organ failures) due to increased respiratory failure risk. 5