Terlipressin
A vasopressin analogue that saves kidneys in liver failure and can take the lungs with it
Terlipressin constricts blood vessels in the gut circulation, which raises blood pressure to the failing kidney in hepatorenal syndrome. Approved in the US in 2022, it carries a boxed warning for serious or fatal respiratory failure, and its pivotal trial is where that warning comes from.
What is it?
Hepatorenal syndrome is kidney failure driven by the circulation of advanced liver disease. Terlipressin constricts the splanchnic vessels, redirecting blood and restoring pressure to the kidney. It is a prodrug: the label's pharmacokinetics describe terlipressin and its active metabolite lysine-vasopressin measured together in 69 patients.
The label is unusually specific about who it will not help: patients with a serum creatinine above 5 mg/dL are unlikely to benefit. On days 1 to 3, 0.85 mg (one vial) is given intravenously every six hours. On day 4 the creatinine is compared with baseline: if it has fallen by at least 30% the dose continues, if it has fallen by less the dose may be doubled to 1.7 mg every six hours, and if it is at or above baseline the drug is stopped. Treatment continues until 24 hours after two consecutive creatinine values of 1.5 mg/dL or less, for at most 14 days.
CONFIRM, the trial it was approved on, randomised 300 adults with cirrhosis and type 1 hepatorenal syndrome 2:1 to terlipressin or placebo, both with albumin. Verified reversal of hepatorenal syndrome occurred in 32% on terlipressin against 17% on placebo, and any creatinine of 1.5 mg/dL or less in 39% against 18%. Survival did not improve: by day 90, 51% on terlipressin and 45% on placebo had died, and deaths from respiratory disorders were 22 (11%) against 2 (2%).
The boxed warning is the heart of this entry. The drug may cause serious or fatal respiratory failure, the risk is higher in volume overload and in grade 3 acute-on-chronic liver failure, oxygen saturation must be measured before starting, and it must not be started in a hypoxic patient.
Against other vasoconstrictors the picture is mixed. A randomised trial found kidney function recovered in 70.4% on terlipressin plus albumin against 28.6% on midodrine and octreotide plus albumin, and a study in acute-on-chronic liver failure found noradrenaline predicted non-response and higher mortality compared with terlipressin. A 2017 Cochrane review of ten trials (474 participants), mostly against noradrenaline, found no difference in mortality and a possible benefit on reversing hepatorenal syndrome, with very low quality evidence. Giving it as a continuous infusion rather than boluses was better tolerated at a lower daily dose.
Outside hepatorenal syndrome it has been tested in variceal bleeding and septic shock. In a 1996 trial against somatostatin for acute variceal haemorrhage, control was similar (80% against 84%), as were rebleeding and six-week mortality, with more side effects on terlipressin (38.8% against 23.5%). A 2024 non-inferiority trial found two days of terlipressin with ceftriaxone as good as five for preventing early rebleeding, with shorter hospital stays. In refractory septic shock, adding terlipressin got more patients off high-dose catecholamines at six hours (22.7% against 9.4%) without changing 28-day mortality (60.6% against 64.1%), and digital ischaemia was common in both groups.
The label's other warnings follow from the mechanism. Its adverse reactions, respiratory failure and ischaemia, may make a listed patient ineligible for a liver transplant, and for patients with high transplant priority (MELD 35 or more) the benefits may not outweigh the risks. It can cause cardiac, cerebrovascular, peripheral or mesenteric ischaemia, should be avoided in people with severe cardiovascular or cerebrovascular disease, and can cause fetal harm.
Mechanism of Action
Terlipressin is a prodrug of lysine-vasopressin that constricts splanchnic vessels, redirecting blood to restore kidney perfusion.
Splanchnic vasoconstriction
Redirects blood from the gut circulation, raising pressure to the kidney in hepatorenal syndrome.
Prodrug
Converted to lysine-vasopressin; the label models both in 69 patients.
Fluid and oxygen
Volume overload raises the risk of the boxed-warning respiratory failure, so oxygenation is checked first and monitored continuously (label).
Published Research
The studies behind terlipressin, read from their PubMed abstracts: hepatorenal syndrome trials and a Cochrane review, variceal bleeding, and septic shock.
The trial it was approved on, including the harm
In 300 adults with type 1 hepatorenal syndrome, verified HRS reversal was 32% on terlipressin against 17% on placebo; 90-day deaths were 51% against 45%, and respiratory deaths 11% against 2%.
Against noradrenaline
In hepatorenal-type acute kidney injury in acute-on-chronic liver failure, noradrenaline predicted non-response (OR 3.05) and higher mortality (HR 2.08) compared with terlipressin, which gave earlier and higher response; adverse events were more frequent on terlipressin (23.3% against 8.3%) but reversible.
Against midodrine and octreotide
In hepatorenal syndrome, kidney function recovered in 70.4% on terlipressin plus albumin against 28.6% on midodrine and octreotide plus albumin (P = 0.01).
Cochrane: against other vasoactive drugs
Across 10 trials (474 participants), terlipressin did not differ from other vasoactive drugs on mortality (RR 0.96) and may help reverse hepatorenal syndrome (RR 0.79), with very low quality evidence.
In refractory septic shock
In 130 patients with refractory septic shock, 22.7% on terlipressin against 9.4% on placebo met the catecholamine-sparing primary outcome; 28-day mortality was 60.6% against 64.1% and digital ischaemia 28.8% against 27.4%.
Infusion rather than boluses
Continuous intravenous infusion was better tolerated than boluses in type 1 hepatorenal syndrome, and the mean daily effective dose was lower (2.23 against 3.51 mg/day, p < 0.05).
Variceal bleeding: against somatostatin
Success was 80% on terlipressin and 84% on somatostatin, with similar rebleeding (30% against 28.4%) and six-week mortality; side effects were more frequent on terlipressin (38.8% against 23.5%).
Variceal bleeding: two days against five
Two days of terlipressin with ceftriaxone was non-inferior to five for 5-day rebleeding (2.1% against 3.8%), with shorter hospital stays.
Dosing Data
Terlivaz is given intravenously every six hours, with the dose decided on day 4 by the change in creatinine.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the Terlivaz prescribing information (DailyMed set 3a35b86c, version 7, effective June 19, 2026) and the trials above.
Contraindications & Cautions
From the label.
Legal Status
An approved hospital drug.
Frequently Asked Questions
?What is terlipressin for?
Improving kidney function in adults with hepatorenal syndrome, the kidney failure that follows advanced liver disease.
?How is it given?
Intravenously, 0.85 mg every six hours, with a creatinine check on day 4 to decide whether to continue.
?What is the boxed warning?
Serious or fatal respiratory failure. Oxygen saturation must be checked before the first dose and monitored throughout, and it must not be started in a hypoxic patient.
?Does it work in septic shock?
In a randomised trial it cut the need for high-dose catecholamines at six hours but did not significantly change mortality.
?How is the dose adjusted?
0.85 mg every six hours for three days, then by day 4 creatinine: continue, double to 1.7 mg, or stop, for at most 14 days (label).
?Does it improve survival?
Not in CONFIRM, where 90-day mortality was 51% on terlipressin against 45% on placebo, and a Cochrane review found no mortality difference against other vasoactive drugs.
?Is it used for variceal bleeding?
Not on the US label, but trials found it about as effective as somatostatin, and two days as good as five for preventing early rebleeding.
References
- [fda-pi] Terlivaz (terlipressin) prescribing information, boxed warning and sections 1, 2 and 12.3 (DailyMed SPL version 7, effective June 19, 2026; read October 1, 2026).
- [pubmed] Wong F, et al. "Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome." N Engl J Med, 2021;384(9):818-828. PMID: 33657294.
- [pubmed] Arora V, et al. "Terlipressin Is Superior to Noradrenaline in the Management of Acute Kidney Injury in Acute on Chronic Liver Failure." Hepatology, 2020;71(2):600-610. PMID: 30076614.
- [pubmed] Cavallin M, et al. "Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial." Hepatology, 2015;62(2):567-74. PMID: 25644760.
- [pubmed] Israelsen M, et al. "Terlipressin versus other vasoactive drugs for hepatorenal syndrome." Cochrane Database Syst Rev, 2017;9(9):CD011532. PMID: 28953318.
- [pubmed] Tongyoo S, et al. "Adjunctive terlipressin versus placebo in the treatment of refractory septic shock: a randomized, placebo-controlled trial." Crit Care, 2025;29(1):443. PMID: 41121365.
- [pubmed] Cavallin M, et al. "Terlipressin given by continuous intravenous infusion versus intravenous boluses in the treatment of hepatorenal syndrome: A randomized controlled study." Hepatology, 2016;63(3):983-92. PMID: 26659927.
- [pubmed] Feu F, et al. "Double-blind randomized controlled trial comparing terlipressin and somatostatin for acute variceal hemorrhage. Variceal Bleeding Study Group." Gastroenterology, 1996;111(5):1291-9. PMID: 8898643.
- [pubmed] Lo GH, et al. "A Noninferiority Trial Comparing 2 Days vs 5 Days of Terlipressin and Ceftriaxone in Terms of 5-Day Rebleeding for Patients With Acute Gastroesophageal Variceal Hemorrhage." Am J Gastroenterol, 2024;119(9):1821-1830. PMID: 38526204.
- [news-release] Mallinckrodt plc. "Mallinckrodt Receives U.S. FDA Approval for Terlivaz® (terlipressin) for injection for the Treatment of Hepatorenal Syndrome (HRS)." September 14, 2022.
Sources & Citations
Studies were read from their PubMed records (October 6, 2026); the label and Drugs@FDA are listed below with their read dates.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.