Terlipressin

A synthetic twelve-residue vasopressin analog and prodrug of lysine-vasopressin that constricts splanchnic vessels through V1 receptors, used for decades in Europe for variceal bleeding and FDA approved since September 2022 for hepatorenal syndrome.

Also referenced as: Terlipressin acetate, Terlivaz, Glypressin, Triglycyl-lysine vasopressin, Triglycyl lysine vasopressin, TGLVP, N-triglycyl-8-lysine-vasopressin, Remestyp, Variquel, Lucassin, Haemopressin

Also appears in: Cardiovascular

COA Public product evidence No certificate records are bound to a tracked Terlipressin product page A record counts here only when a vendor publishes a certificate against one of its own tracked Terlipressin product pages. Other certificates naming this compound may still exist — search the wider certificate database. →

---

What is Terlipressin?

Terlipressin is a synthetic dodecapeptide built from lysine-vasopressin (the porcine form of the antidiuretic hormone, with lysine rather than arginine at position 8) by adding three glycine residues to its N-terminus; the common chemical name is N-triglycyl-8-lysine-vasopressin (the U.S. label writes it as N-[N-(N-glycylglycyl)glycyl]-8-L-lysinevasopressin, a 12-amino-acid peptide), and the marketed form is the acetate salt. The glycyl extension makes it a prodrug: terlipressin itself has little activity, and tissue peptidases strip the glycines over hours to release lysine-vasopressin, which gives the molecule a slow onset and a long enough duration to be dosed by intermittent intravenous bolus. It is a different drug from vasopressin (the native arginine hormone) and from desmopressin (a V2-selective analog with no pressor activity), both profiled separately.

It has been a standard hospital drug in Europe and much of the rest of the world since the 1980s, first for bleeding esophageal varices and later for hepatorenal syndrome. In the United States a single application, first filed in 2009 under the name Lucassin, drew three complete response letters before it was approved as Terlivaz in September 2022. It appears in the research-peptide market only at the margin, as a reagent-grade reference peptide for vasopressin-receptor and splanchnic-hemodynamics work; it has no consumer-facing wellness narrative.

How it works

Terlipressin is a splanchnic vasoconstrictor, and everything it does clinically follows from redirecting blood out of a dilated splanchnic bed.

• Prodrug conversion to lysine-vasopressin — after intravenous injection the parent peptide disappears from plasma with a half-time of roughly 24 minutes while biologically active lysine-vasopressin peaks between 60 and 120 minutes; the diastolic pressure rose, the antidiuresis lasted about five hours, and less than 1% of the dose appeared unchanged in urine (Forsling et al., Journal of Endocrinology, 1980, 85(2):237–244). Single-dose kinetics in healthy volunteers gave distribution and elimination half-lives of 8 and 50 minutes for terlipressin and suggested a 4-hour interval between injections, which became the basis for the 4- to 6-hour bolus schedules used clinically (Nilsson et al., Drugs Under Experimental and Clinical Research, 1990, 16(6):307–314). The current U.S. label gives terminal half-lives of 0.9 hours for terlipressin and 3.0 hours for lysine-vasopressin.
• V1 receptor agonism on vascular smooth muscle — lysine-vasopressin acts through Gq-coupled V1 receptors to constrict splanchnic arterioles, which lowers portal venous inflow and portal pressure; the label describes the molecule as having twice the selectivity for V1 over V2 receptors. In a rat portal-hypertension study that used terlipressin and vasopressin as benchmarks for the highly V1-selective peptide F-180, the vascular-to-antidiuretic (V1/V2) selectivity ratio was 2.2 for terlipressin against 1.0 for vasopressin, and both reduced portal pressure and superior mesenteric artery blood flow, at the cost of larger rises in arterial pressure than the selective agonist produced (Bernadich et al., Hepatology, 1998, 27(2):351–356).
• Reversal of the hepatorenal circulation — in decompensated cirrhosis, splanchnic pooling lowers effective arterial volume, activates the sympathetic and renin-angiotensin systems, and leaves the kidney intensely vasoconstricted; raising systemic and splanchnic vascular tone with a V1 agonist, given with intravenous albumin to restore volume, is the rationale for its use in hepatorenal syndrome (Belcher et al., American Journal of Kidney Diseases, 2022, 79(5):737–745).
• Residual V2 activity — because the active metabolite is a full vasopressin, terlipressin retains antidiuretic action. That is clinically relevant: fluid retention and hyponatremia in a patient already receiving large albumin volumes are part of the mechanism behind the respiratory-failure signal discussed below.

Research status

Terlipressin carries a genuine FDA approval with an unusually contested regulatory history, two negative or equivocal U.S. trials before the positive one, and a boxed warning that came directly from the pivotal study.

Variceal bleeding — the original indication (Europe and elsewhere). Terlipressin was marketed in Europe (Glypressin) for bleeding esophageal varices well before any hepatorenal data existed. The Cochrane review of terlipressin for acute esophageal variceal hemorrhage found that it reduced all-cause mortality relative to placebo (relative risk 0.66 across seven trials) but, with only small comparative trials available, could not show a difference against somatostatin, octreotide, or endoscopic therapy (Ioannou et al., Cochrane Database of Systematic Reviews, 2003, (1):CD002147). In the multicenter TEST trial, terlipressin for 6 days and emergency sclerotherapy had identical failure rates (33% vs 32%) with fewer side effects on terlipressin (Escorsell et al., Hepatology, 2000, 32(3):471–476). A 780-patient Korean noninferiority trial found no difference among terlipressin, somatostatin, and octreotide started before endoscopy, with 5-day treatment success of 86.2%, 83.4%, and 83.8% (Seo et al., Hepatology, 2014, 60(3):954–963). Terlipressin is not FDA approved for variceal bleeding; in the United States octreotide fills that role, itself off-label.

Hepatorenal syndrome — three North American trials.

• OT-0401 (NCT00089570) — Sanyal et al. (2008) randomized 112 patients (56 per arm) to terlipressin or placebo, both with albumin; the primary endpoint of treatment success doubled but missed significance (25% vs 12.5%, P = 0.093), while the secondary endpoint of hepatorenal reversal was met (34% vs 13%, P = 0.008) and survival was similar (Gastroenterology, 134(5):1360–1368). The parallel Spanish trial of Martín-Llahí et al. (2008) in 46 patients found improved renal function with terlipressin plus albumin without a survival difference (Gastroenterology, 134(5):1352–1359).
• REVERSE (NCT01143246) — Boyer et al. (2016) randomized 196 patients and missed the primary endpoint: confirmed hepatorenal reversal in 19.6% on terlipressin vs 13.1% on placebo (P = 0.22), with a significantly larger creatinine fall (1.1 vs 0.6 mg/dL) and more ischemic events on terlipressin (Gastroenterology, 150(7):1579–1589.e2). A pooled analysis of OT-0401 and REVERSE (308 patients) reported reversal in 27% vs 14% (Sanyal et al., Alimentary Pharmacology & Therapeutics, 2017, 45(11):1390–1402).
• CONFIRM (NCT02770716) — the pivotal Phase 3 trial, 300 patients randomized 2:1 at 60 U.S. and Canadian sites from July 2016 to July 2019, met its primary endpoint: verified hepatorenal reversal in 32% on terlipressin vs 17% on placebo (P = 0.006). But 90-day mortality was 51% vs 45%, liver transplantation was less frequent on terlipressin (23% vs 29%), and death from respiratory disorders within 90 days occurred in 22 patients (11%) on terlipressin against 2 (2%) on placebo (Wong et al., New England Journal of Medicine, 2021, 384(9):818–828).

The regulatory path. NDA 022231 was filed in May 2009 by Orphan Therapeutics under the name Lucassin on the strength of OT-0401, and the FDA’s complete response letter of November 4, 2009 said the trial had failed its prespecified endpoint and asked for at least one additional adequate and well-controlled study. After CONFIRM, a Cardiovascular and Renal Drugs Advisory Committee voted 8 to 7 in favor of approval on July 15, 2020, yet the FDA issued a second complete response letter on September 11, 2020, agreeing that CONFIRM met its primary endpoint but citing the excess of serious respiratory failure (14% vs 5%) and unresolved questions about the clinical significance of the endpoint (Belcher et al., American Journal of Kidney Diseases, 2022, 79(5):737–745). A third letter on February 18, 2022 concerned product-quality deficiencies at a manufacturing facility rather than the clinical data; once the facility issue was resolved, Terlivaz was approved on September 14, 2022, with priority review, fast-track, and orphan designations, for improving kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function. The label reports the primary endpoint as 29% vs 16% under the FDA’s own analysis. The package insert has been revised several times since, most recently in September 2026 (the current DailyMed version); no new indication has been added through October 2026.

Who gets the respiratory failure. A post hoc analysis of CONFIRM showed the respiratory-failure incidence on terlipressin was 9.4% in patients with grade 1–2 acute-on-chronic liver failure (ACLF) but 30% in grade 3 (P = 0.0002), with no such gradient on placebo; 90-day survival in grade 3 ACLF was 27.6% on terlipressin vs 50.0% on placebo, a difference that did not reach statistical significance (P = 0.122) in that small subgroup (Wong et al., Alimentary Pharmacology & Therapeutics, 2022, 56(8):1284–1293). Excluding patients with grade 3 ACLF or baseline creatinine above 5 mg/dL, a later reanalysis found reversal in 43% vs 17% with similar respiratory-failure rates between arms (11% vs 7%) and still no survival difference (Rockey et al., Liver International, 2025, 45(12):e70399). The same signal prompted a European Article 31 safety referral, opened at Denmark’s request in January 2022 and concluded in November 2022, which added warnings that terlipressin should be avoided in hepatorenal syndrome when serum creatinine is 5 mg/dL or higher or in grade 3 ACLF or a MELD score of 39 or more, and recommended continuous infusion as an alternative to bolus dosing to reduce severe adverse events.

Dosing route and comparators. A 78-patient randomized trial found continuous infusion better tolerated than boluses (adverse events 35.3% vs 62.2%) at a lower mean daily dose with similar response (Cavallin et al., Hepatology, 2016, 63(3):983–992), and a 49-patient trial found terlipressin plus albumin more effective than the midodrine-octreotide combination that U.S. centers had relied on before approval (70.4% vs 28.6% renal recovery) (Cavallin et al., Hepatology, 2015, 62(2):567–574). The Cochrane review of terlipressin versus placebo in hepatorenal syndrome (nine trials, 534 participants) found a mortality benefit of low-quality evidence (RR 0.85, 95% CI 0.73–0.98) alongside a sevenfold increase in serious cardiovascular adverse events (Allegretti et al., Cochrane Database of Systematic Reviews, 2017, 6(6):CD005162); a companion review compared it with other vasoactive drugs (Israelsen et al., Cochrane Database of Systematic Reviews, 2017, 9(9):CD011532).

Septic shock — investigational and mixed. Terlipressin has been studied as an adjunct vasopressor for years without an approval anywhere for that use. The most recent placebo-controlled trial, in 130 patients with refractory septic shock, increased the share of patients weaned below high-dose catecholamines at 6 hours (22.7% vs 9.4%) but did not change 28-day mortality (60.6% vs 64.1%) (Tongyoo et al., Critical Care, 2025, 29(1):443). ClinicalTrials.gov currently lists about fifteen active or planned studies with terlipressin as a registered intervention, many of them investigator-initiated trials in variceal bleeding, ACLF, transplant anesthesia, and surgical blood loss where it is the comparator or background standard of care, plus an industry Phase 1 program for a long-acting terlipressin derivative.

Common dosage forms

• Approved U.S. product — a single-dose vial of lyophilized powder containing 0.85 mg terlipressin (equivalent to 1 mg terlipressin acetate) with mannitol, reconstituted and given as a slow intravenous bolus in a hospital setting under continuous pulse oximetry. It is refrigerated and light-protected. Strength is expressed as the free base in the United States and as the acetate salt in most other markets, so “0.85 mg” and “1 mg” vials are the same product.
• Ex-U.S. formulations — 1 mg (acetate) lyophilized vials supplied with a solvent ampoule, and a ready-to-use solution of 1 mg terlipressin acetate in 8.5 mL (0.1 mg/mL as terlipressin) that replaced the reconstituted product in several European markets. Both are intravenous-only hospital preparations.
• Continuous infusion — not a separate product; the same vial diluted for infusion pump delivery, used in Europe and in U.S. transplant centers on the strength of the tolerability data above and now named as an option in the European product information.
• Research supply — reagent-grade lyophilized terlipressin acetate in 1 mg to 25 mg quantities from laboratory suppliers, sold as a receptor-pharmacology reference peptide. It is not a common listing in the consumer research-peptide market.

Key considerations

• The approval is narrow and the warning is loud. Terlivaz is approved only to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function; the FDA Approved status reflects that an approved drug product containing the molecule exists. The boxed warning states it may cause serious or fatal respiratory failure, with higher risk in volume overload or grade 3 ACLF; the label contraindicates starting it in hypoxia (SpO2 below 90%) or worsening respiratory symptoms and in ongoing coronary, peripheral, or mesenteric ischemia, warns that its adverse effects can render a listed patient ineligible for liver transplantation, and states that patients with creatinine above 5 mg/dL are unlikely to benefit. Respiratory failure (15.5%) and dyspnea (12.5%) sit among the five most common adverse reactions in the label. Nothing in its record touches metabolic, anti-aging, cognitive, or performance framing, and the research-grade peptide exists for in vitro receptor work, not for self-experimentation.
• It improved a laboratory endpoint, not survival. Across OT-0401, REVERSE, and CONFIRM, terlipressin lowered creatinine and increased hepatorenal reversal, yet no trial has shown a 90-day survival advantage, and CONFIRM showed numerically higher mortality and fewer transplants on the drug. The Cochrane mortality benefit rests on low-quality evidence and older, smaller trials. That gap, more than any doubt about the renal effect, explains the 2020 complete response letter and the later European restrictions.
• The three vasopressins are not interchangeable. Terlipressin is a V1-weighted prodrug of lysine-vasopressin for splanchnic vasoconstriction; vasopressin is the native arginine hormone used as an intravenous vasopressor in vasodilatory shock; desmopressin is a V2-selective analog with no pressor action used for diabetes insipidus and bleeding disorders. Older literature calls terlipressin “triglycyl-lysine vasopressin” or “TGLVP,” and lysine-vasopressin itself appears as lypressin.
• The vasoconstriction is systemic, not just splanchnic. The hepatorenal Cochrane review found a roughly sevenfold increase in serious cardiovascular events, REVERSE recorded more ischemic events, and the label lists cardiac, cerebrovascular, peripheral, and mesenteric ischemia. Digital ischemia occurred in about 28% of both arms of the 2025 septic-shock trial, a reminder that the patients who receive this drug are already on catecholamines.