Is terlipressin FDA-approved, and what does the research show?

What is terlipressin?

Terlipressin is a man-made peptide built on vasopressin, a hormone the body makes to narrow blood vessels and hold water in the kidneys ¹, ². The label calls it "a synthetic vasopressin analogue," a chain of 12 amino acids ¹. An analog is a molecule altered from the original. Terlipressin swaps one amino acid in vasopressin for another and adds three glycine units at one end ⁵. Tissue enzymes clip those units off in the body, releasing lysine-vasopressin, its active metabolite; the label calls terlipressin a prodrug that also acts on its own ¹.

Vasopressin itself is a different molecule with its own page. Terlivaz is a powder in a single-dose vial, dissolved for injection into a vein ¹. Mallinckrodt Pharmaceuticals Ireland holds the approval, and FDA granted the drug orphan designation, its status for rare diseases, in 2004 ³, ⁵.

Is terlipressin FDA-approved?

Yes. Terlipressin is approved by FDA as the prescription medicine Terlivaz, with initial U.S. approval in 2022 ¹. FDA's Drugs@FDA record shows Mallinckrodt's new drug application, NDA 022231, approved on September 14, 2022, as a new molecular entity, a drug FDA had not approved before in any form, with marketing status "Prescription" ³. The label's indication is "to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function" ¹. It adds one limitation: "Patients with a serum creatinine > 5 mg/dL are unlikely to experience benefit" ¹.

Hepatorenal syndrome is kidney failure that develops in people with cirrhosis, the scarring of the liver from long-term damage, and ascites, fluid collecting in the abdomen ¹, ⁶. FDA's reviewers called its rapidly worsening type 1 form "a rare and serious disease associated with significant morbidity and mortality," and the syndrome's "only definitive treatment" a liver transplant ⁵. Serum creatinine is the blood measure of kidney function the label uses ¹. In the trial, "rapid reduction in kidney function" meant creatinine rising on a path to doubling within two weeks ¹, ⁸. Before Terlivaz, FDA's reviewers wrote, there were "no FDA-approved treatments" for the syndrome ⁵.

The approval took thirteen years, from the application's filing in May 2009 to September 2022 ⁴. FDA sent a complete response letter, its notice that it would not approve the application as submitted, that November ⁹. The letter said the trial "failed to show durability of effect" and that the company would "need to conduct at least one additional adequate and well-controlled study" ⁹. After a third placebo-controlled trial, CONFIRM, described below, FDA sent a second letter on September 11, 2020 ⁹, ⁵. It agreed the trial met its primary endpoint, the main result it was built to measure, but wrote that the higher rate of respiratory failure on terlipressin "raise[s] concern that the risks of terlipressin may outweigh its benefits" ⁹.

FDA's advisory committee, a panel of outside experts, had split on the drug: on July 15, 2020, eight members voted that it should be approved and seven voted no ⁵. FDA then suggested "a more narrowly defined population," and later agreed the company's proposed population "appeared reasonable," which became the label's limits on who should receive it ⁵. A third letter, in February 2022, concerned a manufacturing facility, and approval followed in September 2022 once that was resolved ⁹, ⁵.

It is prescription-only, so the route to it is a clinician's prescription ³. The label requires oxygen saturation measured before the first dose and continuous pulse oximetry, a sensor that reads oxygen through the skin, throughout treatment ¹. The label was last revised in June 2026 ¹.

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How does terlipressin work?

Terlipressin is a vasoconstrictor, a drug that narrows blood vessels ¹. It binds vasopressin receptors, with "twice the selectivity for vasopressin V1 receptors versus V2 receptors" ¹. V1 receptors sit on the muscle of blood-vessel walls and narrow the vessels, and V2 receptors tell the kidney to hold water ². So terlipressin leans toward the blood-vessel effect of vasopressin rather than the water-retaining one ¹, ².

The label says it "is thought to increase renal blood flow in patients with hepatorenal syndrome by reducing portal hypertension and blood circulation in portal vessels and increasing effective arterial volume and mean arterial pressure" ¹. Portal hypertension ¹ is high pressure in the vein that carries blood from the gut through the scarred liver. Mean arterial pressure ¹ is the average pressure in the arteries. In patients with the syndrome, a single dose raised blood pressure and slowed the heart within 5 minutes, and the effects lasted at least 6 hours ¹. The estimated maximum rise in mean arterial pressure was 16.2 mmHg, and the maximum fall in heart rate 10.6 beats a minute ¹.

Terlipressin itself has a half-life, the time for half the drug to leave the blood, of 0.9 hours, and the lysine-vasopressin it releases has one of 3.0 hours ¹. The label describes this mechanism in patients with hepatorenal syndrome, for an approved drug ¹.

What does the research show?

The evidence is at the top tier, FDA approval, resting on one randomized, placebo-controlled trial after FDA found three earlier trials insufficient ¹, ⁹, ⁵. FDA's 2009 letter said the first trial "appeared to show a modest reduction in serum creatinine, but the study failed to show durability of effect" ⁹. A third trial, REVERSE, "was not successful on its prespecified primary endpoint," FDA wrote in 2015 ⁵. The fourth, CONFIRM, is the trial the label describes ¹.

Studied in people against placebo: CONFIRM, published March 4, 2021, was a multicenter, double-blind trial, so neither patients nor clinicians knew who received the drug ⁷, ¹. It ran at 60 sites, 55 in the United States and 5 in Canada, from July 2016 to July 2019, funded by Mallinckrodt ⁶, ⁸. It enrolled 300 adults with cirrhosis, ascites and type 1 hepatorenal syndrome, the rapidly worsening form ⁷, ¹. They were randomized 2 to 1, 199 to terlipressin and 101 to placebo, for up to 14 days ⁷. Albumin, a blood protein given by infusion to expand the circulation, was "strongly recommended" in both groups ⁷.

Entry required a serum creatinine of at least 2.25 mg/dL and no sustained improvement after diuretics, water-removing drugs, were stopped and albumin given ¹. People with a creatinine above 7.0 mg/dL, shock, sepsis or uncontrolled infection were excluded ¹.

The primary endpoint was "verified reversal of HRS," the syndrome's initials: two serum creatinine readings of 1.5 mg/dL or less at least 2 hours apart ⁷. Patients also had to survive without renal replacement therapy, a machine doing the kidneys' work, such as dialysis, for at least 10 days after treatment ended ⁷. In the paper's count it was reached by 63 of 199 (32 percent) on terlipressin and 17 of 101 (17 percent) on placebo, P = 0.006 ⁷. In FDA's count, in the label and its trial snapshot, it was 58 (29.1 percent) against 16 (15.8 percent), P = 0.012 ¹, ⁶. The paper counts the 10 days from the end of treatment, the label from the reversal itself; the sources cited here do not say whether that explains the difference ⁷, ¹.

Of the secondary endpoints, any creatinine of 1.5 mg/dL or less in the first 14 days was reached by 78 (39 percent) against 18 (18 percent) ⁷. Reversal without renal replacement therapy by day 30 was reached by 68 (34 percent) against 17 (17 percent) ⁷. Among patients with systemic inflammatory response syndrome, a body-wide inflammatory state, HRS reversal was 31 of 84 (37 percent) against 3 of 48 (6 percent) ⁷. Verified reversal without recurrence by day 30 was 52 (26 percent) against 17 (17 percent), P = 0.08, not significant ⁷.

Survival did not improve. At day 90, 101 patients (51 percent) on terlipressin had died, against 45 (45 percent) on placebo ⁷. Liver transplants by day 90 were done in 46 (23 percent) on terlipressin and 29 (29 percent) on placebo ⁷. FDA's reviewers wrote that the trial "did not suggest a mortality benefit" and found "a trend in improvement" in survival free of dialysis ⁵. The authors concluded that terlipressin "was more effective than placebo in improving renal function but was associated with serious adverse events, including respiratory failure" ⁷.

After the 2020 letter, the company reanalyzed the trial in a "Mitigated Population" ⁵. It excluded patients with acute-on-chronic liver failure grade 3, meaning three or more failing organ systems ⁵. It also excluded a creatinine of 5 mg/dL or more and a transplant listing with a MELD score of 35 or more ⁵. MELD, the Model for End-Stage Liver Disease score, marks at 35 the sickest patients waiting for a liver ⁵. That left 132 on terlipressin and 71 on placebo ⁵.

In them, verified reversal was 36 against 18 percent, serious or fatal respiratory failure 10 against 7 percent, and death by day 90 46.2 against 45.1 percent ⁵. FDA called these analyses "post-hoc," done after the trial on subgroups, and accepted them for the narrower population rather than requiring another trial ⁵.

No trial for weight, performance or wellness is reported in the label, the trial or FDA's review; the label's healthy-subject data are pharmacokinetic only ⁷, ¹, ⁵. The label says safety and effectiveness "have not been established in pediatric patients," that carcinogenicity studies "have not been performed," and that no animal fertility studies have been done ¹.

What are the side effects?

Respiratory failure leads, and FDA put it in a boxed warning. The label opens: "TERLIVAZ may cause serious or fatal respiratory failure. Patients with volume overload or with ACLF Grade 3 are at increased risk" ¹. Respiratory failure ¹ means the lungs can no longer keep enough oxygen in the blood, and volume overload ¹ is too much fluid in the circulation. ACLF is the label's abbreviation for acute-on-chronic liver failure ¹.

In CONFIRM, "serious or fatal respiratory failure occurred in 14% of patients treated with TERLIVAZ compared to 5% of patients on placebo" ¹. In the paper's count, death within 90 days from respiratory disorders occurred in 22 patients (11 percent) on terlipressin and 2 (2 percent) on placebo ⁷. FDA's reviewers counted 17 of 28 serious respiratory-failure events on terlipressin as fatal, 61 percent, against 1 of 5 on placebo ⁵.

The boxed warning directs clinicians to assess oxygen saturation before starting and not to start in patients with hypoxia, low blood oxygen, "until oxygenation levels improve" ¹. It calls for monitoring "using continuous pulse oximetry" and for stopping the drug if saturation falls below 90 percent ¹. The label says to "avoid use in patients with ACLF Grade 3 because they are at significant risk for respiratory failure" ¹. It warns that fluid overload raises the risk, and FDA's reviewers thought the albumin given for the syndrome "may have contributed" to the respiratory failure seen ¹, ⁵.

The label's adverse reactions come from CONFIRM's safety population, the 200 who received terlipressin and the 99 who received placebo ¹. Abdominal pain was reported by 19.5 percent against 6.1 on placebo, nausea by 16.0 against 10.1, and respiratory failure of any severity by 15.5 against 7.1 ¹. Diarrhea was reported by 13.0 against 7.1, and dyspnea, shortness of breath, by 12.5 against 5.1 ¹. Fluid overload was 8.5 against 3.0 percent, and pleural effusion, fluid around the lungs, 5.5 against none ¹. Sepsis, infection in the blood, was 5.5 against 1.0, and bradycardia, a slow heart rate, 5.0 against none ¹.

Ischemia-related events, tissue starved of blood, were 4.5 against none ¹. Treatment was stopped for adverse events in 12.0 percent (24 of 200) against 5.1 percent (5 of 99) ¹. The leading reasons were respiratory failure, abdominal pain, and intestinal ischemia or obstruction, a blocked bowel ¹. Worldwide post-marketing reports add headache, hyponatremia, low blood sodium, skin necrosis, the death of skin tissue, and gangrene ¹.

The label contraindicates terlipressin "in patients experiencing hypoxia or worsening respiratory symptoms" and "in patients with ongoing coronary, peripheral, or mesenteric ischemia" ¹. Coronary ischemia ¹ starves the heart of blood, peripheral ischemia ¹ the limbs, and mesenteric ischemia ¹ the bowel. The label warns that it "may cause cardiac, cerebrovascular, peripheral, or mesenteric ischemia," and says to avoid it "in patients with a history of severe cardiovascular conditions, cerebrovascular and ischemic disease" ¹. It warns that terlipressin-related reactions "may make a patient ineligible for liver transplantation, if listed," and that for patients with a MELD score of 35 or more "the benefits of TERLIVAZ may not outweigh its risks" ¹.

On pregnancy, the label says terlipressin "may cause fetal harm" and "induces uterine contractions and endometrial ischemia in both humans and animals" ¹. Of patients in the clinical studies, 55 (16 percent) were 65 or older, with no overall differences in safety or effectiveness observed ¹. There are no data on its presence in human milk ¹.

In sport

Terlipressin is not named on WADA's 2026 Prohibited List, and neither is vasopressin ¹⁰. WADA, the World Anti-Doping Agency, does name desmopressin, another vasopressin analog with its own page, in section S5 among diuretics and masking agents, prohibited at all times ¹⁰. S5 also covers "other substances with a similar chemical structure or similar biological effect(s)"; the list does not say whether that reaches terlipressin ¹⁰. The list also carries a method rule on injections ¹⁰. M2.2 prohibits "Intravenous infusions and/or injections of more than a total of 100 mL per 12-hour period except for those legitimately received in the course of hospital treatments, surgical procedures or clinical diagnostic investigations" ¹⁰.

What JumpstartMD offers

JumpstartMD does not prescribe terlipressin. Our peptide library covers it so you have the facts on its FDA status and the evidence, current as of November 10, 2026.

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Compounded medications are not FDA-approved, and FDA does not review their safety, effectiveness, or quality before they are marketed. A licensed clinician decides after an evaluation whether a peptide is appropriate for you, and not every patient will qualify.