Terlipressin Acetate (Monograph)
Brand name: Terlivaz
Drug class: Pituitary
Warning
- Serious or Fatal Respiratory Failure
-
Terlipressin may cause serious or fatal respiratory failure. Patients with volume overload or with acute-on-chronic liver failure (ACLF) grade 3 are at increased risk. Assess oxygenation saturation (e.g., SpO2) before initiating terlipressin.
-
Do not initiate terlipressin in patients experiencing hypoxia (e.g., SpO2 <90%) until oxygenation levels improve. Monitor patients for hypoxia using continuous pulse oximetry during treatment and discontinue terlipressin if SpO2 decreases below 90%.
Introduction
Synthetic vasopressin analogue.
Uses for Terlipressin Acetate
Hepatorenal Syndrome
Improvement of kidney function in adults with hepatorenal syndrome (HRS) with rapid reduction in kidney function.
Limitations of use: patients with a Scr >5 mg/dL unlikely to experience benefit.
Generally, standard of care for HRS involves administration of albumin and vasoconstrictors. Terlipressin and norepinephrine are recommended in patients with cirrhosis and HRS-acute kidney injury (AKI; previously termed HRS-1) without high grade of acute-on-chronic liver failure (ACLF) or major cardiopulmonary or vascular disease. The American Association for the Study of Liver Disease states that terlipressin is the preferred vasoconstrictor for HRS-AKI.
Terlipressin Acetate Dosage and Administration
General
Pretreatment Screening
-
Obtain baseline oxygen saturation (SpO2) prior to administering the first dose of terlipressin. Do not use terlipressin in patients experiencing hypoxia until hypoxia resolves.
-
Assess acute-on-chronic liver failure (ACLF) grade and volume status before initiating terlipressin treatment.
-
Record the last available serum creatinine value on Day 1 prior to initiating terlipressin treatment.
Patient Monitoring
-
Monitor oxygen saturation using continuous pulse oximetry.
Administration
IV Administration
Administered by slow IV bolus injection (over 2 minutes). Administer through a peripheral or central line; dedicated central line not required. Flush the line after administration.
Reconstitution
Reconstitute each vial with 5 mL of 0.9% sodium chloride injection to prepare a 0.85 mg/5 mL solution.
Dosage
Dosage of terlipressin acetate is expressed in terms of terlipressin. Each 1 mg of terlipressin acetate is equivalent to terlipressin 0.85 mg.
Adults
Hepatorenal Syndrome
IV
Recommended starting dosage of terlipressin is 0.85 mg (1 vial) every 6 hours by slow IV bolus injection (over 2 minutes) on days 1 through 3. Adjust dose on day 4 based on changes from baseline Scr (the last available Scr before initiating treatment):
-
If Scr has decreased by ≥30% from baseline: continue terlipressin 0.85 mg (1 vial) every 6 hours. Continue until 24 hours after the patient achieves a second consecutive Scr value of ≤1.5 mg/dL at least 2 hours apart or for a maximum of 14 days.
-
If Scr has decreased by <30% from baseline: increase terlipressin dose to 1.7 mg (2 vials) every 6 hours. Continue until 24 hours after the patient achieves a second consecutive Scr value of ≤1.5 mg/dL at least 2 hours apart or for a maximum of 14 days.
-
If Scr is at or above baseline value: discontinue terlipressin.
Special Populations
Hepatic Impairment
No dosage adjustment required.
Renal Impairment
No specific dosage recommendation at this time.
Geriatric Patients
No specific dosage recommendation at this time.
Cautions for Terlipressin Acetate
Contraindications
-
Patients experiencing hypoxia or worsening respiratory symptoms.
-
Patients with ongoing coronary, peripheral, or mesenteric ischemia.
Warnings/Precautions
Warnings
Serious or Fatal Respiratory Failure
Serious or fatal respiratory failure occurred in 14% of patients treated with terlipressin compared to 5% of patients on placebo (see Boxed Warning).
Obtain baseline oxygen saturation (e.g., SpO2) and do not initiate in hypoxic patients (e.g., SpO2 <90%) until oxygenation levels improve. Monitor for changes in respiratory status using continuous pulse oximetry and regular clinical assessments. Discontinue terlipressin in patients experiencing hypoxia (e.g., SpO2 <90%) or increased respiratory symptoms.
Patients with fluid overload may be at increased risk of respiratory failure. Manage intravascular volume overload by reducing or discontinuing the administration of albumin and/or other fluids and judicious use of diuretics. Temporarily interrupt, reduce, or discontinue terlipressin until volume status improves.
Avoid use in patients with acute-on-chronic liver failure (ACLF) grade 3 because they are at significant risk for respiratory failure.
Other Warnings and Precautions
Ineligibility for Liver Transplant
Terlipressin-related adverse reactions (e.g., respiratory failure, ischemia) may make a patient ineligible for liver transplantation, if listed. For patients with high prioritization for liver transplantation (e.g., Model for End-Stage Liver Disease [MELD] ≥35), the benefits of terlipressin may not outweigh its risks.
Ischemic Events
May cause cardiac, cerebrovascular, peripheral, or mesenteric ischemia. Avoid use in patients with a history of severe cardiovascular conditions, cerebrovascular and ischemic disease. Discontinue in patients who experience signs or symptoms suggestive of ischemic adverse reactions.
Embryo-fetal Toxicity
May cause fetal harm when administered to a pregnant woman based on the mechanism of action and data from published literature. Terlipressin induces uterine contractions and endometrial ischemia in both humans and animals. If this drug is used during pregnancy, the patient should be apprised of the potential risk to the fetus.
Specific Populations
Pregnancy
May cause fetal harm. In small, published studies, administration during first trimester induced uterine contractions and endometrial ischemia. Limited data are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. If used during pregnancy, inform patient of potential risk to fetus.
In animal studies, administration to pregnant guinea pigs caused marked decrease in blood flow to the uterus and placenta. In rabbits, terlipressin is both embryotoxic and teratogenic.
Lactation
No data on presence in human or animal milk, effects on breast-fed infant, or effect on milk production. Consider developmental and health benefits of breastfeeding along with mother’s clinical need for terlipressin and any potential adverse effects on breast-fed child from the drug or underlying maternal condition.
Pediatric Use
Safety and effectiveness not established.
Geriatric Use
In clinical studies, 55 patients treated with terlipressin (16%) were ≥65 years of age. No overall differences in safety or effectiveness observed between these subjects and younger subjects; other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Hepatic Impairment
No dose adjustment is required in patients with hepatic impairment.
Renal Impairment
No information on use in patients with varying degrees of renal dysfunction.
Common Adverse Effects
The most common adverse reactions (≥10%) include abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea.
Drug Interactions
Based on in vitro studies, likely not an inhibitor or inducer of any of the CYP enzymes evaluated. Likely not an inhibitor or substrate of human adenosine triphosphate-binding cassette (ABC) and solute carrier (SLC) transporters. No significant drug-drug interactions anticipated.
Due to the ubiquitous nature of the tissue peptidases that metabolize the terlipressin parent compound and its active metabolize, metabolism is likely not affected by other disease states or drugs.
Terlipressin Acetate Pharmacokinetics
Elimination
Metabolism
Metabolized by various tissue peptidases to pharmacologically active metabolite lysine-vasopressin. Lysine-vasopressin is metabolized by various tissue peptidase-mediated routes. Not metabolized in blood or plasma.
Elimination Route
<1% of terlipressin and <0.1% of lysine-vasopressin excreted in urine in healthy subjects.
Half-life
0.9 hours for terlipressin; 3.0 hours for lysine-vasopressin.
Special Populations
Clearance of terlipressin and lysine-vasopressin appears to be unaffected by gender, age, Clcr, Child-Pugh score, serum alkaline phosphatase, ALT, AST, and total bilirubin.
Stability
Storage
Parenteral
Lyophilized powder
Store terlipressin vials at 2–8°C in the carton to protect from light. If reconstituted solution is not administered immediately, store at 2–8°C for up to 48 hours. Do not freeze. Reconstituted solution does not need protection from light.
Actions
-
Synthetic vasopressin analogue with twice the selectivity for vasopressin V1 receptors versus V2 receptors.
-
Acts as a prodrug for lysine-vasopressin; terlipressin also has pharmacologic activity on its own.
-
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 (MAP).
Advice to Patients
-
Inform female patients of reproductive potential that terlipressin may cause fetal harm and to inform their prescriber of a known or suspected pregnancy.
-
Advise women to inform clinicians if they are or plan to breast-feed.
-
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
-
Advise patients of other important precautionary information.
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Parenteral |
For injection, for IV use |
0.85 mg (of terlipressin) |
Terlivaz |
Mallinckrodt Hospital Products |
AHFS DI Essentials™. © Copyright 2025, Selected Revisions December 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
Reload page with references included
More about terlipressin
- Check interactions
- Compare alternatives
- Side effects
- Dosage information
- During pregnancy
- Drug class: antidiuretic hormones
- En español