Research information only. PrecisePep is an educational library. It is not medical advice and is not intended to assist, encourage or enable self-administration. The compounds documented here are research chemicals — most are not approved for human use. Read the full disclaimer.
PrecisePep/Peptide Library/Terlipressin
Endocrine & Reproductive Axis
Terlivaz® · Glypressin® · triglycyl-lysine-vasopressin
A vasopressin prodrug that constricts the splanchnic circulation for hours from a single injection — the first drug ever approved in the United States for hepatorenal syndrome, and one that can cause fatal respiratory failure.
In advanced cirrhosis the splanchnic circulation dilates. Blood pools in the gut vasculature, effective arterial volume falls, and the kidney — sensing underfilling despite a normally functioning nephron — clamps down its own perfusion. That is hepatorenal syndrome: kidney failure in a structurally normal kidney, driven entirely by circulatory failure elsewhere. It carries a very high short-term mortality, and until 2022 the United States had no approved treatment for it.
Terlipressin attacks the circulatory problem rather than the kidney. It constricts the splanchnic vasculature through V1 receptors, redistributing blood back into the systemic circulation, restoring effective arterial volume and renal perfusion. The molecule itself is inactive — three glycyl residues on the N-terminus are cleaved by endopeptidases over hours, releasing lysine-vasopressin gradually.[1] That prodrug design is what turns a hormone with a minutes-long half-life into something that can be given as an intermittent bolus rather than a continuous infusion.
The FDA approved it as Terlivaz on 14 September 2022 to improve kidney function in adults with hepatorenal syndrome and rapid reduction in kidney function.[2] It is also used widely outside the United States for acute variceal haemorrhage, where the same splanchnic vasoconstriction lowers portal pressure.
Terlipressin is a hospital intravenous medicine given to critically ill patients with decompensated cirrhosis. It appears here because the conditions index names hepatorenal syndrome, and because the vasopressin family is worth understanding as a whole alongside desmopressin and oxytocin.
It carries a boxed warning for serious or fatal respiratory failure, and respiratory failure occurred in roughly one in six patients in the pivotal trial. There is no context in which this drug is used outside a hospital, and this page publishes no dosing.
Prodrug activation. Terlipressin itself has low intrinsic receptor activity. Tissue endopeptidases progressively remove the three glycyl residues, liberating lysine-vasopressin over several hours. The result is a sustained, relatively flat exposure from an intermittent bolus.
V1-preferring vasoconstriction. Unlike desmopressin, which was engineered to avoid V1, terlipressin is used precisely for it. Splanchnic arteriolar constriction reduces portal inflow and pressure and redistributes volume centrally.
Restoration of renal perfusion. Improved effective arterial volume reduces activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system, which is what was constricting the renal circulation. Glomerular filtration recovers without any direct renal action — the kidney was never the lesion.
Why the lungs are the problem. Redistributing volume from the splanchnic bed into the central circulation raises pulmonary capillary pressure. In patients who are already volume-overloaded or who have acute-on-chronic liver failure, that produces pulmonary oedema and respiratory failure. The boxed warning is not an idiosyncratic reaction — it is the haemodynamic consequence of the drug doing what it is given to do.[2]
Effects that have been reported. A study-tier entry means a result was published — not that the effect is established, reproducible, or transferable from a rodent to a person.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Randomised placebo-controlled evidence supported approval on a verified reversal endpoint — improvement in serum creatinine with survival without renal replacement therapy. The first agent approved for this indication in the United States.
Used widely outside the United States alongside endoscopic therapy and antibiotics in acute variceal bleeding, with evidence supporting bleeding control and, in some analyses, mortality benefit.
The prodrug design permits intermittent intravenous bolus dosing, which is operationally simpler than the continuous infusions required for octreotide or vasopressin in the same settings.
Where renal recovery improves candidacy or reduces the need for combined liver-kidney transplantation, the clinical value extends beyond the creatinine number.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Studied as a catecholamine-sparing vasopressor. Results have been mixed and the digital ischaemia signal is a real limitation. Not an approved use.
Response is poorer in acute-on-chronic liver failure grade 3 and at very high baseline creatinine, and that is also the group at greatest risk of respiratory failure. The risk-benefit balance shifts sharply across the population it is used in.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
There is no patient-directed use, no outpatient use, and no grey market. Reporting comes from clinical literature and case series rather than from users.
Adverse effects, contraindications and unknowns. The grey-market tier is where under-reporting is worst: uncontrolled use produces no systematic safety surveillance at all, so absence of a reported harm is not evidence of safety.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Patients with volume overload or with acute-on-chronic liver failure grade 3 are at increased risk. Oxygen saturation must be assessed before starting, and treatment should not be initiated in a patient who is hypoxic — for example SpO₂ below 90% — until oxygenation improves.
Respiratory failure was reported in about 15.5% of patients in the trial data supporting approval — a rate that has to be weighed against the mortality of untreated hepatorenal syndrome.
The other commonly observed adverse reactions, each occurring in more than one in ten patients in the approval dataset.
Splanchnic, peripheral and cardiac ischaemia are recognised consequences of systemic vasoconstriction. Digital and skin necrosis have been reported.
Residual V2 activity means water retention can occur despite the V1-preferring profile. Sodium is monitored during treatment.
Can cause fetal harm and may induce uterine contractions. Pregnancy status should be established before use.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Following review, European authorities issued revised recommendations on patient selection and administration in hepatorenal syndrome, reflecting the same respiratory signal. The direction of travel across regulators has been toward narrower use rather than broader.
Some centres favour continuous infusion over bolus dosing on the reasoning that lower peak concentrations reduce ischaemic and haemodynamic adverse effects. Studied, plausible, not settled.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Practice discussion consistently reflects hesitancy in the sickest patients, which matches both the response data and the risk data.
Figures below are documented, not recommended. Study ranges come from published protocols in the stated model; grey-market ranges are what the research community reports using and carry no safety validation of any kind.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
The label specifies an intermittent intravenous bolus regimen with reassessment of renal function at set intervals and rules for continuation, escalation and discontinuation. Doses are not reproduced here — this is an inpatient protocol for a critically ill population, not a dose to look up.
SpO₂ before initiation, with treatment withheld in hypoxia until oxygenation improves, and monitoring for new or worsening respiratory symptoms during treatment.
Concomitant albumin is standard in the hepatorenal syndrome protocols this drug was studied within, and volume status must be assessed carefully because overload is the principal risk factor for the boxed warning.
Treatment is stopped for lack of response by a defined day, for a serum creatinine rise above baseline, or for respiratory or ischaemic complications.
| Aspect | Detail | Note |
|---|---|---|
| Setting | Inpatient, intravenous | Not an outpatient drug |
| Before first dose | Assess SpO₂ | Do not start if hypoxic (e.g. SpO₂ <90%) |
| During treatment | Monitor oxygenation and volume status | Boxed-warning risk factor |
| Concomitant | Albumin | Part of the studied protocol |
| Highest-risk group | ACLF grade 3, volume overload | Worse response, higher risk |
| Stop for | Non-response, creatinine rise, respiratory or ischaemic events | Defined in the label |
| Pregnancy | Can cause fetal harm | Establish status first |
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Because fluid overload is the identified risk factor for fatal respiratory failure, careful volume management is the intervention most likely to prevent it.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
An intravenous drug for critically ill cirrhotic patients, carrying a boxed warning for fatal respiratory failure and requiring oxygen saturation monitoring, has no unsupervised use to document.
Combination effects. Almost no peptide combination has been studied as a combination in humans; stack logic is overwhelmingly mechanistic inference and community practice. Each linked compound has its own page.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
The combination, not the drug alone, is what the trial protocols tested. Albumin supports effective arterial volume while terlipressin redistributes it.
Vasoactive therapy, band ligation and prophylactic antibiotics together form the standard bundle. Antibiotic prophylaxis independently improves survival in this setting.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Octreotide is used off-label for variceal bleeding through a different mechanism — reduced splanchnic blood flow via somatostatin receptors rather than V1 vasoconstriction. Terlipressin has the stronger position for hepatorenal syndrome specifically.
Desmopressin was engineered to keep V2 and lose V1. Terlipressin exists for V1. Same nine-residue hormone, two drugs built from opposite halves of its pharmacology.
Combined vasopressor exposure raises ischaemic risk, and the ischaemic complications of this drug are already its second most serious problem.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
There is no community use of this compound to report.
Whole schedules — dosing, titration, cycle length, and off-time — as documented in trials, as proposed from mechanism, and as circulated in the research community. Reproduced for study and comparison only.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Randomised placebo-controlled trials in hepatorenal syndrome with albumin in both arms, using verified reversal of renal function as the primary endpoint.
Oxygen saturation before initiation, ongoing respiratory and volume monitoring, and defined stopping rules for non-response and for adverse events.
Revised recommendations narrowing use and reinforcing monitoring, issued after review of the respiratory failure signal.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Because hepatorenal syndrome reflects advanced liver disease, the definitive question is usually transplantation. Pharmacological reversal buys time and improves candidacy rather than resolving the underlying problem.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
No community protocols exist for this compound.
The approved indication is covered above. This is a hospital intravenous drug for critically ill patients with decompensated cirrhosis, and there is no community use to document — so this section covers the off-label hospital uses and the check that its boxed warning turns on.
Boxed warning: serious or fatal respiratory failure. Respiratory failure occurred in roughly one in six patients in the data supporting approval. Patients with volume overload or acute-on-chronic liver failure grade 3 are at increased risk, and treatment should not be started in someone who is hypoxic until oxygenation improves.
Pathophysiology
Terlipressin works by constricting the splanchnic vasculature and redistributing pooled blood back into the central circulation. That raises pulmonary capillary pressure.
Mechanistic rationale
The respiratory failure is not an idiosyncratic reaction — it is the haemodynamic consequence of the drug doing what it is given to do, in patients who are frequently already volume-overloaded. Oxygen saturation is assessed before the first dose, treatment is withheld in hypoxia, and oxygenation and volume status are monitored throughout. Careful volume management is the intervention most likely to prevent the labelled harm.
Community reports
Clinician hesitancy in acute-on-chronic liver failure grade 3 is consistent with both the poorer response and the higher risk in that group.
Components carrying the argument: V1 vasoconstriction → central volume redistribution
Pathophysiology
Portal hypertension causes oesophageal varices, and rupture carries substantial mortality.
Mechanistic rationale
Splanchnic vasoconstriction lowers portal pressure, and terlipressin is used widely for this indication in Europe and elsewhere alongside endoscopic band ligation and prophylactic antibiotics. Octreotide is used for the same purpose through a different mechanism. Antibiotic prophylaxis independently improves survival here and is the component most easily overlooked.
Community reports
Hospital practice only.
Components carrying the argument: Portal pressure reduction
Pathophysiology
Vasodilatory shock requires vasopressor support, and catecholamine-sparing strategies aim to reduce the dose-related harms of those agents.
Mechanistic rationale
Studied as a catecholamine-sparing vasopressor with mixed results, and digital and peripheral ischaemia is a real limitation — ischaemic complications are this drug’s second most serious problem after the respiratory one. Not an approved use.
Community reports
Intensive care setting.
Components carrying the argument: V1-mediated systemic vasoconstriction
| Question | Position |
|---|---|
| Setting | Inpatient intravenous only — no outpatient use exists |
| Before the first dose | Check SpO₂; do not start if hypoxic |
| Why | Redistribution raises pulmonary capillary pressure |
| Highest-risk group | Volume overload, ACLF grade 3 |
| Second serious risk | Ischaemia — digital, peripheral, cardiac |
| Community use | None, and none is possible |
For hepatorenal syndrome: terlipressin with albumin, or noradrenaline with albumin where terlipressin is unavailable, with transplant assessment in parallel — because the definitive question in advanced liver disease is usually transplantation. For variceal bleeding: resuscitation, endoscopic band ligation, vasoactive therapy and prophylactic antibiotics, then secondary prophylaxis with beta-blockade and banding.
Physical-chemistry reference for laboratory handling of the lyophilised material. Reproduced so that stability and concentration mathematics can be studied — see the calculator for the arithmetic and the reconstitution guide for sterile technique.
The licensed product is a lyophilised powder reconstituted by hospital pharmacy or nursing staff with sodium chloride injection immediately before intravenous administration. This site publishes no reconstitution arithmetic for terlipressin.
Store the vial as specified on the label; reconstituted solution is for immediate use and should not be held.
Licensed: 0.85 mg lyophilised powder vial for reconstitution (US presentation).
Single-use, immediate-administration product. The multi-dose bacteriostatic-water logic used elsewhere in this library does not apply.
Regulatory status changes and differs by country. This is a summary for orientation, not legal advice — check your own jurisdiction.
Approved prescription medicine, hospital use only. Approved by the FDA on 14 September 2022 as Terlivaz to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function — the first product approved for this indication in the United States. Long available in Europe and elsewhere as Glypressin, including for acute variceal haemorrhage.
Boxed warning: serious or fatal respiratory failure. Patients with volume overload or acute-on-chronic liver failure grade 3 are at increased risk. Oxygenation must be assessed before initiation and treatment withheld in hypoxia. European regulators have issued revised recommendations narrowing patient selection following review of the same signal.
There is no legitimate unlicensed supply and no outpatient use.
Regulatory and trial claims re-checked against primary sources on 16 August 2026. Checked: Terlivaz approval Sept 2022 and respiratory failure boxed warning. Approvals, trial readouts and compounding decisions move faster than anything else on this page — a date here means someone looked, not that nothing has changed since.
Not a performance compound. Vasopressin analogues can act as plasma volume modifiers; verify against the current WADA Prohibited List if that is relevant.
Links resolve to PubMed records, trial registries, publisher pages or primary documents. Where a body of work rather than a single paper is cited, the link opens a PubMed query so the full result set — including newer papers than this page — can be reviewed. Verify every claim against the primary source before relying on it.
For educational and research reference only. Nothing on this site is medical advice, a recommendation, or an instruction to administer any substance to a human being. Every figure on this page is a record of what has been reported, not a recommendation. Full disclaimer.
