Quick summary
Terlipressin (Terlivaz) is the first FDA-approved treatment for hepatorenal syndrome with rapid kidney function reduction (HRS-AKI), approved September 2022. It is a vasopressin analog prodrug that produces splanchnic vasoconstriction to restore renal perfusion in advanced liver disease.
Overview
Terlipressin is a synthetic vasopressin analogue and the first FDA-approved medication (approved September 2022) for hepatorenal syndrome with rapid reduction of kidney function (HRS-AKI). It acts as a prodrug that is cleaved in vivo to release lysine-vasopressin, producing potent splanchnic vasoconstriction and improving renal perfusion in the setting of advanced liver disease.
Mechanism of action
Terlipressin is a prodrug consisting of three glycine residues attached to lysine-vasopressin (N-triglycyl-8-lysine-vasopressin). Tissue peptidases cleave the N-terminal glycyl residues, releasing the active moiety lysine-vasopressin. Lysine-vasopressin binds to V1 receptors in splanchnic and peripheral vascular smooth muscle, causing potent vasoconstriction. In hepatorenal syndrome, the underlying pathology is severe splanchnic vasodilation driven by portal hypertension and circulatory dysfunction; by reversing this vasodilation, terlipressin reduces effective arterial blood volume depletion, suppresses the renin-angiotensin-aldosterone and sympathetic nervous systems, and restores renal perfusion. This mechanism is distinct from other vasopressors in its preferential splanchnic action and prolonged duration.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| hepatorenal syndrome (HRS-AKI) | intravenous | 0.85–1.7 mg | every 6 hours for up to 14 days | Start at 0.85 mg IV q6h. After 2 days, if serum creatinine has not decreased by ≥25%, increase to 1.7 mg q6h. Discontinue if no response by day 4 at higher dose. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
In the pivotal CONFIRM trial (Phase 3, 300 patients), 29% of terlipressin-treated patients achieved verified reversal of HRS-AKI versus 16% on placebo. It has been used in Europe and Asia for over two decades prior to FDA approval. A meta-analysis of multiple RCTs confirms superiority over albumin alone and comparable or superior outcomes versus norepinephrine. Risk of respiratory failure is a significant safety signal; patients with SBP below 82 mmHg or baseline hypoxia are at elevated risk.[1][2][3][4]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Terlipressin for synergistic effects.
Legal status
FDA-approved September 2022 (NDA 022231) for hepatorenal syndrome with rapid reduction in kidney function in adults. Available only in hospital settings under clinical supervision. Previously approved in 40+ countries including EU member states.
Sourcing & access
Prescription required
Terlipressin is an FDA-approved prescription medication available through licensed healthcare providers, telehealth platforms, and 503A/503B compounding pharmacies.
Frequently asked questions
Terlipressin (brand name Terlivaz) is a synthetic vasopressin analog prodrug approved by the FDA in September 2022 for hepatorenal syndrome with rapid reduction in kidney function (HRS-AKI). It had been used in Europe and Asia for over two decades prior to US approval.
Terlipressin is cleaved by tissue peptidases to release lysine-vasopressin, which binds V1 receptors causing splanchnic vasoconstriction. In hepatorenal syndrome, this reverses the severe splanchnic vasodilation driven by portal hypertension, suppresses the renin-angiotensin system, and restores renal perfusion.
Serious risks include respiratory failure (potentially fatal), peripheral ischemia, and skin necrosis. Other side effects include abdominal pain, nausea, diarrhea, dyspnea, hyponatremia, and bradycardia. Patients with low blood pressure or baseline hypoxia are at elevated risk.
In the pivotal CONFIRM Phase 3 trial of 300 patients, 29% of terlipressin-treated patients achieved verified reversal of HRS-AKI versus 16% on placebo. A meta-analysis of multiple RCTs confirms superiority over albumin alone.