Terlipressin Adverse Events: What the Label and Studies Report

Terlipressin is a prescription medicine that is administered by specialists in a clinical setting. It is given in hospital wards, infusion areas and critical care units where blood pressure, oxygenation, fluid balance, urine output and skin perfusion can be observed during and after administration. Because of that setting, every practical question about whether terlipressin is appropriate, how it is given, how long it is continued and what to do about a symptom is a question for the prescribing clinician and the treating specialist team, not something a reader resolves independently. This page is for educational purposes only and is not medical advice; consult a licensed physician or the prescribing specialist about any individual situation.

The approved indication in the United States concerns adults with hepatorenal syndrome accompanied by a rapid reduction in kidney function. Uses outside an approved indication, including vasopressor use in septic shock, are investigational and are described here only as they appear in published research. Nothing below should be read as encouragement of any use beyond what a prescriber decides.

Boxed warning on the approved label

The United States label for the approved terlipressin product carries a boxed warning for serious or fatal respiratory failure. The boxed warning is the strongest safety statement a product label can carry, and in this case it directs prescribers to assess oxygenation before administration and to monitor for respiratory symptoms, with attention to patients who already have respiratory compromise or volume overload. The label also describes situations in which the manufacturer states terlipressin should not be initiated or should be discontinued. The full labeling text is maintained by the United States Food and Drug Administration and by the product manufacturer, and interpretation of it for a specific patient sits with the treating specialist team.

The respiratory signal that anchors the boxed warning was visible in the pivotal placebo controlled trial. In that phase 3 randomised trial of terlipressin plus albumin versus placebo plus albumin in adults with type 1 hepatorenal syndrome, researchers reported that respiratory failure occurred more frequently in the terlipressin group and that deaths within 90 days attributed to respiratory disorders were more common with terlipressin than with placebo (PMID 33657294).

Serious Adverse Reactions: What Studies Report

Respiratory events

The pivotal trial described above is the main controlled source for the respiratory signal, and the study reported respiratory failure among the serious adverse events that occurred more often in patients assigned to terlipressin plus albumin than in those assigned to placebo plus albumin (PMID 33657294). Review articles covering pharmacologic therapy for hepatorenal syndrome with acute kidney injury have since discussed respiratory adverse events as a central consideration when terlipressin is selected and monitored (PMID 37625864), and a more recent review of hepatorenal syndrome management described how clinicians weigh that signal alongside kidney outcomes in current practice (PMID 41123991).

Because terlipressin for hepatorenal syndrome is given together with intravenous albumin, the volume load contributed by albumin has also been examined. A 2025 analysis in the hepatology literature reviewed albumin infusion in hepatorenal syndrome with acute kidney injury and argued that recent consensus positions on albumin volume deserve reconsideration, a question that intersects directly with pulmonary oedema and respiratory risk (PMID 40250764). A pharmacist focused review of albumin use in cirrhosis discussed similar practical points about albumin dosing decisions, monitoring and avoidance of fluid overload in this population (PMID 37013893).

Ischemic events affecting skin, digits and abdominal organs

Terlipressin is a vasoconstrictor, and the published safety literature is dominated by reports of reduced perfusion to peripheral and splanchnic tissue. A 2021 case report in a clinical case reports journal described foot ischemia that developed during terlipressin treatment (PMID 33489226). A 2020 case report in a case reports journal described ischaemic skin necrosis attributed to terlipressin (PMID 31948983). Case reports describe single patients and cannot establish how often an event occurs, but they document that the event has been observed and reported.

Local tissue injury at or around an infusion site is a related concern for vasoconstrictor drugs generally. A 2023 focused update in the pharmacotherapy literature reviewed management of noncytotoxic extravasation injuries and discussed peripheral administration of vasopressors, including monitoring approaches and treatment strategies when extravasation occurs (PMID 36938775). The pivotal hepatorenal syndrome trial also recorded ischemic adverse events among patients treated with terlipressin (PMID 33657294).

Electrolyte and neurologic events

Hyponatremia has been described with terlipressin, reflecting its activity at vasopressin receptors. A 2010 report in a gastroenterology journal described a terlipressin associated hyponatremic seizure, linking a rapid fall in serum sodium during treatment to a neurologic event (PMID 20302535). Serum sodium monitoring during treatment is discussed in reviews of vasoconstrictor therapy for kidney dysfunction in cirrhosis (PMID 29023314).

Warnings and precautions described in labeling and reviews

• Respiratory compromise and fluid overload. Labeling for the approved product directs assessment of oxygenation before and during treatment, and the trial data behind that direction reported respiratory failure more often with terlipressin than placebo (PMID 33657294).
• Ischemic complications. Published case reports document foot ischemia (PMID 33489226) and ischaemic skin necrosis (PMID 31948983) during terlipressin treatment.
• Infusion site and extravasation injury. The vasopressor extravasation literature describes tissue injury risk and management strategies when vasoconstrictors are infused peripherally (PMID 36938775).
• Electrolyte shifts. A case report described hyponatremia severe enough to be associated with seizure during terlipressin treatment (PMID 20302535).
• Co-administered albumin. Reviews of albumin use in hepatorenal syndrome with acute kidney injury have examined volume related harm and the evidence behind albumin strategies (PMID 40250764).

Common Adverse Reactions: What Studies Report

In the placebo controlled hepatorenal syndrome trial, researchers reported that abdominal pain, nausea and diarrhoea were among the adverse events occurring more frequently in patients who received terlipressin plus albumin than in those who received placebo plus albumin (PMID 33657294). Gastrointestinal symptoms are consistent with splanchnic vasoconstriction, which is the mechanism by which the drug is thought to act in portal hypertension. Reviews of current pharmacologic therapy for hepatorenal syndrome with acute kidney injury have summarised this adverse event profile alongside efficacy data when comparing terlipressin with alternative vasoconstrictor regimens (PMID 37625864).

Adverse Events in Septic Shock Research: What Studies Report

Use of terlipressin as a vasopressor in septic shock is investigational rather than an approved indication, and it is summarised here only to describe what the research literature reported. A 2019 systematic review and meta-analysis compared terlipressin with norepinephrine in septic shock and examined mortality as well as adverse events including peripheral ischemia (PMID 31920672). A 2023 systematic review and network meta-analysis of vasopressors in septic shock assessed efficacy and safety across agents, placing terlipressin within a wider comparison of vasoactive drugs (PMID 37548686). Meta-analyses pool heterogeneous trials with differing populations and protocols, so their adverse event estimates carry wide uncertainty.

Reported events grouped by body system

Population context

The population studied in hepatorenal syndrome trials carries advanced liver disease, circulatory dysfunction and frequent infection, which complicates attribution of any single event to the drug. A 2017 review of renal dysfunction in cirrhosis described the physiology that places these patients at risk and the monitoring considerations that follow (PMID 29023314). A 2026 review of hepatorenal syndrome treatment in the current era summarised how clinicians select candidates and follow them during vasoconstrictor therapy (PMID 41123991). Those reviews describe decisions that are made by the treating specialist team at the bedside.

Limitations of this evidence

1. Case reports such as those describing foot ischemia (PMID 33489226) and skin necrosis (PMID 31948983) document occurrence, not frequency.
2. Trial adverse event counts reflect one protocol in one population, as in the hepatorenal syndrome trial that reported respiratory failure imbalance (PMID 33657294).
3. Meta-analyses in septic shock pool trials with varied designs, and their safety conclusions are correspondingly uncertain (PMID 37548686).
4. Approved labeling is updated over time, so the current label held by the prescriber is the authoritative safety document.

Where questions belong

Any new breathlessness, chest discomfort, abdominal pain, colour change in fingers or toes, pain at an infusion site, confusion or seizure activity during or after treatment is a matter to raise immediately with the treating specialist team. Questions about whether terlipressin is appropriate, whether it should continue, and how its risks compare with alternatives belong with the prescribing clinician. This page does not provide dosing, administration or preparation information, and it does not evaluate individual suitability.

References

• Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome (The New England Journal of Medicine, 2021)
• Terlipressin-induced foot ischemia (Clinical Case Reports, 2021)
• Terlipressin-induced ischaemic skin necrosis (BMJ Case Reports, 2020)
• Terlipressin-induced hyponatremic seizure (Scandinavian Journal of Gastroenterology, 2010)
• Management of noncytotoxic extravasation injuries: A focused update on medications, treatment strategies, and peripheral administration of vasopressors and hypertonic saline (Pharmacotherapy, 2023)
• Current Pharmacologic Therapies for Hepatorenal Syndrome-Acute Kidney Injury (Clinical Gastroenterology and Hepatology, 2023)
• Treating Hepatorenal Syndrome in the Current Era (Journal of the American Society of Nephrology, 2026)
• Albumin infusion in hepatorenal syndrome-acute kidney injury: New evidence challenges recent consensus (Journal of Hepatology, 2025)
• Expert perspectives for the pharmacist on facilitating and improving the use of albumin in cirrhosis (American Journal of Health-System Pharmacy, 2023)
• Renal dysfunction and cirrhosis (Current Opinion in Critical Care, 2017)
• Terlipressin Versus Norepinephrine for Septic Shock: A Systematic Review and Meta-Analysis (Frontiers in Pharmacology, 2019)
• The Efficacy and Safety of Vasopressors for Septic Shock Patients: A Systematic Review and Network Meta-Analysis (Shock, 2023)