Terlipressin

Overview

Terlipressin is a man-made version of the hormone vasopressin that tightens blood vessels. In the U.S. it is sold as Terlivaz, approved in 2022 as a hospital IV drug to improve kidney function in adults with hepatorenal syndrome, a fast kidney failure that can happen with severe liver disease. It carries a boxed warning because it can cause serious or fatal breathing failure.

How it works

Established: terlipressin activates vasopressin receptors, with about twice the selectivity for V1 (blood-vessel) receptors as for V2 receptors ¹. It works partly on its own and partly as a prodrug: tissue enzymes cut off its three glycines to release the active hormone lysine-vasopressin ¹. In hepatorenal syndrome it is thought to improve kidney blood flow by lowering pressure in the liver's portal veins and raising blood pressure and effective blood volume ¹. After one dose, mean arterial pressure rose by up to about 16 mmHg and heart rate fell by about 11 beats per minute ¹.

What research shows

• CONFIRM (phase 3 double-blind RCT, n=300 adults with cirrhosis and HRS type 1, terlipressin plus albumin vs placebo plus albumin): the published paper reported verified HRS reversal in 32% vs 17% (P=0.006) ⁴; the FDA label's analysis gives 29.1% vs 15.8% (P=0.012) ¹.
• CONFIRM: by day 90, 51% on terlipressin and 45% on placebo had died, and deaths from respiratory disorders were 11% vs 2% ⁴. The trial was funded by Mallinckrodt ⁴.
• CONFIRM subgroup with systemic inflammation (SIRS): HRS reversal 33.3% vs 6.3% in the label's analysis ¹.
• Verified reversal without HRS coming back by day 30 was not significantly different (24.1% vs 15.8% in the label; 26% vs 17% in the paper) ¹⁴.
• A 2022 EU safety review, triggered by CONFIRM, found respiratory failure in 11% of terlipressin patients and sepsis in 7% vs none on placebo, and added new restrictions ⁵.

Doses studied in people

Doses shown are from the FDA label and the CONFIRM trial only; they are reported, not recommended. Terlivaz is a hospital-only IV drug.

Read this first: these are the amounts given to participants in published studies or written on official prescribing labels, reported for reference. They are not recommendations. Trial doses were chosen for specific patients under medical supervision, and a dose that is safe in one person can be harmful in another.

Safety

• Boxed warning: serious or fatal respiratory failure. People with fluid overload or grade 3 acute-on-chronic liver failure (ACLF) are at higher risk; it should not be started if blood oxygen is low (e.g. SpO2 below 90%) ¹.
• In CONFIRM, serious or fatal respiratory failure occurred in 14% on terlipressin vs 5% on placebo ¹.
• Most common side effects (label, terlipressin vs placebo): belly pain 19.5% vs 6.1%, nausea 16.0% vs 10.1%, respiratory failure 15.5% vs 7.1%, diarrhea 13.0% vs 7.1%, shortness of breath 12.5% vs 5.1% ¹.
• It narrows blood vessels and can cause heart, brain, limb or gut ischemia; it is contraindicated with ongoing coronary, peripheral or mesenteric ischemia ¹. Skin necrosis, gangrene, low sodium and headache have been reported after marketing ¹.
• Side effects may make a person ineligible for a liver transplant; for those with very high transplant priority (MELD 35 or more) benefits may not outweigh risks ¹. People with creatinine above 5 mg/dL are unlikely to benefit ¹.
• It can cause uterine contractions and may harm a fetus ¹. The EU review also flagged sepsis as a new risk ⁵.

Report side effects of any drug or product to the FDA through MedWatch. For a possible poisoning in the US, call Poison Control at 1-800-222-1222.

Legal status

FDA

FDA-approved as Terlivaz (Mallinckrodt, NDA 022231) on September 14, 2022 to improve kidney function in adults with hepatorenal syndrome with rapid loss of kidney function ¹². Label last revised June 2026 ²³.

Compounding

No compounding-specific FDA action for terlipressin was found in the sources reviewed; it is an FDA-approved prescription drug.

Sports (WADA)

Not named on the WADA 2026 Prohibited List; check with your anti-doping body. The S5 class (diuretics and masking agents, prohibited at all times) names the related drug desmopressin plus other substances with a similar chemical structure or similar biological effect(s), and lists local felypressin in dental anaesthesia among its exceptions ⁹.

Other

Prescription-only, given in hospital. Authorised nationally in EU countries (brands include Glypressin and Variquel); after a 2022 EMA review, EU use should be avoided in people with serum creatinine of 5 mg/dL or more or with ACLF grade 3 and/or MELD 39 or more unless benefits outweigh risks, and continuous infusion may be considered instead of bolus doses ⁵.

Rules change often. See Legal status of peptides for how these categories work.

History

Terlipressin was approved and used in Europe for many years before it reached the U.S. ⁷; in the EU it is authorised through national procedures rather than a central EU licence ⁵. Mallinckrodt sought U.S. approval for hepatorenal syndrome type 1. An FDA advisory committee voted to recommend it in July 2020, but FDA issued a complete response letter in September 2020 asking for more risk-benefit information ⁷. A second complete response letter in February 2022 cited only an uninspected packaging facility ⁸. FDA approved Terlivaz on September 14, 2022 as a new molecular entity with priority review and orphan status ², making it the only FDA-approved drug for hepatorenal syndrome at the time ⁷. A June 2026 label update clarified a secondary-endpoint definition and noted Mallinckrodt is now part of Keenova Therapeutics ³.

Common questions

Related compounds

Sources

1. Terlivaz (terlipressin) for injection Prescribing Information, revised 06/2026 (FDA) FDA label
2. Drugs@FDA: NDA 022231 Terlivaz (original approval 09/14/2022; supplement 4 approved 06/10/2026) Regulatory
3. FDA supplement approval letter, NDA 022231/S-004 (June 2026) Regulatory
4. Wong F et al. Terlipressin plus albumin for the treatment of type 1 hepatorenal syndrome (CONFIRM). N Engl J Med 2021;384(9):818-828 (PMID 33657294) Journal
5. EMA: Terlipressin-containing medicinal products, Article 31 referral (2022) Regulatory
6. PubChem: Terlipressin (CID 72081) – formula, molecular weight, CAS 14636-12-5, sequence notation Gly-Gly-Gly-Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Lys-Gly-NH2 (4-9 disulfide) Database
7. BioSpace: Mallinckrodt's Terlivaz becomes first FDA-approved drug for hepatorenal syndrome (Sept 16, 2022) Regulatory
8. Mallinckrodt press release: regulatory update on terlipressin (complete response letter, Feb 22, 2022, via BioSpace) Regulatory
9. WADA 2026 Prohibited List, full text (official WADA file as hosted by Asia Rugby) Regulatory