Terlipressin
Evidence: B — Meaningful Human EvidenceRenal / Fluid-Balance Signaling
Evidence Snapshot
What this grade covers
Reflects one positive, adequately powered, placebo-controlled pivotal RCT (CONFIRM, PMID 33657294) supporting FDA approval for a narrowly defined indication (HRS with rapid renal decline, excluding patients with serum creatinine >5 mg/dL), with a real but moderate absolute effect size (HRS reversal 29.1% vs 15.8%) and no clearly demonstrated overall-survival benefit in the same trial. This is deliberately NOT graded A: FDA approval alone does not automatically warrant the top grade, and the serious, labeled, boxed-warning respiratory-failure signal (15.5% vs 7.1% in CONFIRM) is a first-order factor in this grade, not a separate afterthought. Additional supportive but smaller/older/secondary-tier evidence does not raise the grade past B on its own. This grade does not transfer to or from AVP, Lypressin, or any other vasopressin-analogue subject.
Regulatory Context
TERLIVAZ (terlipressin) is FDA-approved to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function, carrying a boxed warning for serious or fatal respiratory failure and specific patient-population exclusions/limitations of use. This approval does not extend to any other vasopressin analogue or to unapproved uses of terlipressin itself.
Research Takeaway
Terlipressin is a 12-amino-acid synthetic vasopressin analogue (triglycyl-lysine-vasopressin) that is enzymatically cleaved by tissue peptidases to release the pharmacologically active metabolite lysine-vasopressin, while also retaining measurable, weaker direct receptor activity of its own.
See all 6 evidence claims →Quick Summary
Terlipressin (TERLIVAZ) is an FDA-approved synthetic vasopressin analogue for hepatorenal syndrome with rapid kidney-function decline. Its strongest evidence is the pivotal CONFIRM trial, which showed a real but moderate improvement in kidney-function reversal without a clear survival benefit — and its boxed warning for serious/fatal respiratory failure means the drug's risk profile is as central to its identity as its efficacy.
Mechanism & Research Overview
Terlipressin (TERLIVAZ) is an FDA-approved synthetic vasopressin analogue for hepatorenal syndrome with rapid kidney-function decline. Its strongest evidence is the pivotal CONFIRM trial, which showed a real but moderate improvement in kidney-function reversal without a clear survival benefit — and its boxed warning for serious/fatal respiratory failure means the drug's risk profile is as central to its identity as its efficacy.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
Terlipressin is a 12-amino-acid synthetic vasopressin analogue (triglycyl-lysine-vasopressin) that is enzymatically cleaved by tissue peptidases to release the pharmacologically active metabolite lysine-vasopressin, while also retaining measurable, weaker direct receptor activity of its own.
Sources: FDA Label / DailyMed Record for TERLIVAZ (Terlipressin); In vitro binding and receptor-mediated activity of terlipressin at vasopressin receptors V1 and V2
Supported
TERLIVAZ (terlipressin) is FDA-approved specifically to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function; patients with serum creatinine above 5 mg/dL are labeled as unlikely to benefit.
Sources: FDA Label / DailyMed Record for TERLIVAZ (Terlipressin)
Supported
In the pivotal CONFIRM trial, terlipressin plus albumin achieved verified HRS reversal in 29.1% of patients versus 15.8% with placebo plus albumin (P=0.012).
Does not establish
Evidence boundary: A statistically significant renal-endpoint effect of this absolute size is real but moderate, and the trial did not clearly demonstrate an overall survival benefit.
Sources: Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome (CONFIRM trial)
Supported
TERLIVAZ carries a boxed warning for serious or fatal respiratory failure, occurring in 15.5% of treated patients versus 7.1% on placebo in CONFIRM; patients with volume overload or ACLF Grade 3 are at increased risk, and continuous pulse-oximetry monitoring with a defined discontinuation threshold is required.
Sources: FDA Label / DailyMed Record for TERLIVAZ (Terlipressin); Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome (CONFIRM trial)
Supported
TERLIVAZ is contraindicated in patients with hypoxia, worsening respiratory symptoms, or ongoing coronary, peripheral, or mesenteric ischemia, reflecting a vasoconstriction-mediated ischemic risk distinct from Desmopressin's hyponatremia-dominant safety profile.
Sources: FDA Label / DailyMed Record for TERLIVAZ (Terlipressin)
Supported
TERLIVAZ's safety profile (respiratory failure, ischemia) is specific to Terlipressin and must not be generalized as a class-wide warning for all vasopressin analogues (e.g., Desmopressin, AVP, Lypressin), which have materially different risk profiles.
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Higher-Priority Safety Consideration
15.5% vs 7.1% placebo in CONFIRM; disproportionate in volume overload/ACLF Grade 3.Higher-Priority Safety Consideration
Direct contraindication in patients with ongoing ischemic disease; mechanism consistent with vasoconstrictor pharmacology.Higher-Priority Safety Consideration
Explicitly named in the boxed warning as a risk-amplifying population; efficacy is also limited in severe renal impairment (creatinine >5 mg/dL).Safety Consideration
29.1% vs 15.8% HRS reversal is real but should not be inflated into an unqualified 'terlipressin saves lives in HRS' claim.
Research Areas Being Studied
Research areas discussed on this page reflect the Renal / Fluid-Balance Signaling category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
- Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome (CONFIRM trial) (2021):
- Terlipressin plus hydroxyethyl starch in the treatment of hepatorenal syndrome ():
Study Tables by Evidence Type
Human Studies & Clinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome (CONFIRM trial) | 2021 | 2:1 randomized, placebo-controlled, double-blind, terlipressin + albumin vs. placebo + albumin, up to 14 days, hepatorenal syndrome type 1 (HRS-1) | Verified HRS reversal occurred in 29.1% of the terlipressin arm versus 15.8% of the placebo arm (P=0.012) — a real but moderate absolute effect. No clearly demonstrated overall-survival difference was reported between arms. | ||
| Terlipressin plus hydroxyethyl starch in the treatment of hepatorenal syndrome | Terlipressin combined with hydroxyethyl starch volume expansion was evaluated in hepatorenal syndrome, contributing to the terlipressin/HRS clinical evidence base. |
Animal / Cell / Preclinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| In vitro binding and receptor-mediated activity of terlipressin at vasopressin receptors V1 and V2 | 2018 | Terlipressin itself has measurable but weak (roughly 100-fold lower binding affinity than lysine-vasopressin/AVP) direct V1/V2 receptor activity, behaving as a partial agonist — i.e. genuine, if modest, intrinsic activity, not purely inert prodrug behavior. |
Regulatory Documents & Official Trial Registries
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| FDA Label / DailyMed Record for TERLIVAZ (Terlipressin) | TERLIVAZ is indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function; patients with serum creatinine >5 mg/dL are labeled as unlikely to benefit. Boxed warning: TERLIVAZ may cause serious or fatal respiratory failure; patients with volume overload or ACLF Grade 3 are at increased risk. | CONFIRM-trial adverse-event rates (TERLIVAZ vs. placebo): respiratory failure 15.5% vs 7.1%; abdominal pain 19.5% vs 6.1%; nausea 16.0% vs 10.1%; diarrhea 13.0% vs 7.1%; dyspnea 12.5% vs 5.1%. Contraindicated in patients with hypoxia, worsening respiratory symptoms, or ongoing coronary/peripheral/mesenteric ischemia. | No source link available |
Review Articles / Secondary Sources
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Role of Terlipressin in Cirrhotic Patients with Ascites and without Hepatorenal Syndrome: A Systematic Review of Current Evidence | Systematic review of terlipressin evidence in cirrhotic ascites without hepatorenal syndrome, used as discovery/context-tier supporting literature. | No source link available | |||
| Terlipressin for the Prevention and Treatment of Renal Decline in Hepatorenal Syndrome: A Drug Profile | Notes terlipressin acts as both a prodrug for lysine-vasopressin and has some pharmacologic activity of its own, with a measurable pressor effect reported within 3 minutes of administration, before lysine-vasopressin levels rise. | No source link available |
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes FDA-approved labeling and published clinical-trial research about Terlipressin and does not provide medical advice, an individualized treatment recommendation, or dosing/monitoring instructions.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated .
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