What are the indications and usage of Terlipressin (vasopressin analogue) in clinical practice?

Indications and Usage of Terlipressin in Clinical Practice

Terlipressin is primarily indicated for hepatorenal syndrome with rapid reduction in kidney function and is also used for management of variceal hemorrhage, though the latter is not an FDA-approved indication in the United States. 1, 2

Primary FDA-Approved Indication

Hepatorenal Syndrome (HRS)

• Terlipressin is the vasoactive drug of choice for hepatorenal syndrome with acute kidney injury (HRS-AKI) 2
• Dosing regimen:
  • Initial: 0.85 mg IV every 6 hours for days 1-3
  • Day 4 assessment:
    • If serum creatinine decreased by ≥30% from baseline: continue 0.85 mg IV every 6 hours
    • If serum creatinine decreased by <30% from baseline: increase to 1.7 mg IV every 6 hours
    • If serum creatinine is at or above baseline: discontinue treatment 1
• Continue treatment until 24 hours after two consecutive serum creatinine values ≤1.5 mg/dL at least 2 hours apart, or for a maximum of 14 days 1
• Treatment is effective in 40-50% of patients with HRS 2
• Limitation: Patients with serum creatinine >5 mg/dL are unlikely to benefit 1

Off-Label Indication

Variceal Hemorrhage

• Terlipressin should be initiated as soon as variceal hemorrhage is suspected or confirmed, preferably before endoscopy 2, 3
• Dosing for variceal hemorrhage:
  • Initial: 2 mg IV every 4 hours until bleeding is controlled
  • Maintenance: 1 mg IV every 4 hours
  • Duration: 2-5 days to prevent early rebleeding 2, 3
• Meta-analysis shows terlipressin reduces mortality in variceal hemorrhage with a relative risk reduction of 34% compared to placebo 4

Contraindications

Terlipressin is contraindicated in patients with:

• Hypoxemia (SpO₂ <90%) or worsening respiratory symptoms 1, 2
• Ongoing coronary, peripheral, or mesenteric ischemia 1, 2
• Caution in patients with acute-on-chronic liver failure (ACLF) grade 3 2

Mechanism of Action

Terlipressin is a synthetic vasopressin analogue with:

• Twice the selectivity for vasopressin V1 receptors versus V2 receptors 1
• Acts as a prodrug for lysine-vasopressin while having pharmacologic activity on its own 1
• Increases renal blood flow in HRS by:
  • Reducing portal hypertension
  • Decreasing blood circulation in portal vessels
  • Increasing effective arterial volume and mean arterial pressure 1
• In variceal hemorrhage, it decreases portal pressure and pressure in esophageal varices 5

Adverse Effects

Common adverse effects (≥10%) include:

• Abdominal pain
• Nausea
• Respiratory failure (most serious)
• Diarrhea
• Dyspnea 1

Cardiovascular or ischemic complications occur in approximately 12% of patients 2

Monitoring During Treatment

• Continuous pulse oximetry to monitor for hypoxia (discontinue if SpO₂ <90%) 1, 2
• Serum sodium levels (risk of hyponatremia)
• Signs of cardiac ischemia
• Renal function
• Arterial pressure 3

Clinical Pearls

• Terlipressin treatment does not require intensive care unit monitoring and can be administered through a peripheral line 2
• Response to therapy for HRS is characterized by a slowly progressive reduction in serum creatinine, with a median time to response of 14 days 2
• Predictors of response in HRS include serum bilirubin <10 mg/dL before treatment and an increase in mean arterial pressure of >5 mmHg at day 3 2
• In variceal hemorrhage, treatment duration may be shortened to 2 days in selected patients with Child-Pugh class A and B cirrhosis with no active bleeding during endoscopy 2
• Terlipressin is also being investigated for use in catecholamine-resistant septic shock, though this remains an experimental indication 6, 7