Terlipressin
Brand name: Terlivaz
Drug class: Pituitary
Chemical name: (2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]acetyl]amino]-3-sulfanylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]-N-[(2S)-4-amino-1-[[(2R)-1-[(2S)-2-[[(2S)-6-amino-1-[(2-amino-2-oxoethyl)amino]-1-oxohexan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-sulfanylpropan-2-yl]amino]-1,4-dioxobutan-2-yl]pentanediamide
Molecular formula: C52H76N16O15S2
Warning
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
Terlipressin acetate is a synthetic vasopressin analogue.
Uses for Terlipressin
Terlipressin acetate has the following uses:
Terlipressin is indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function.
Limitations of use: patients with a serum creatinine >5 mg/dL are unlikely to experience benefit.
Terlipressin Dosage and Administration
General
Terlipressin acetate is available in the following dosage form(s) and strength(s):
For injection: terlipressin 0.85 mg (1 vial) as a lyophilized powder in a single-dose vial for reconstitution.
Dosage
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Adults
Dosage and Administration
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Prior to initial dosing, assess patients for acute-on-chronic liver failure (ACLF) Grade 3 and obtain patient baseline oxygenation level. Monitor patient oxygen saturation with pulse oximetry.
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Reconstitute each vial with 5 mL of 0.9% sodium chloride injection to prepare a 0.85 mg/5 mL solution.
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Administer terlipressin by slow intravenous bolus injection (over 2 minutes) through a peripheral or central line. A dedicated central line is not required. Flush the IV line after administration.
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Recommended Dosage Regimen:
• Days 1 to 3: Administer terlipressin 0.85 mg (1 vial) intravenously every 6 hours.
• Day 4: Assess serum creatinine (SCr) versus baseline.
• If SCr has decreased by at least 30% from baseline, continue terlipressin 0.85 mg (1 vial) intravenously every 6 hours.
• If SCr has decreased by less than 30% from baseline, dose may be increased to terlipressin 1.7 mg (2 vials) intravenously every 6 hours.
• If SCr is at or above baseline value, discontinue terlipressin acetate.
• Continue terlipressin acetate until 24 hours after two consecutive SCr ≤1.5 mg/dL values at least 2 hours apart or a maximum of 14 days.
• See full prescribing information for instructions on preparation and administration.
Cautions for Terlipressin
Contraindications
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Patients experiencing hypoxia or worsening respiratory symptoms.
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Patients with ongoing coronary, peripheral, or mesenteric ischemia.
Warnings/Precautions
Serious or Fatal Respiratory Failure
In the primary clinical trial, serious or fatal respiratory failure occurred in 14% of patients treated with terlipressin compared to 5% of patients on placebo.
Obtain baseline oxygen saturation and do not initiate terlipressin in hypoxic patients. Monitor patients for changes in respiratory status using continuous pulse oximetry and regular clinical assessments. Discontinue terlipressin in patients experiencing hypoxia 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 treatment until patient volume status improves.
Avoid use in patients with ACLF Grade 3 because they are at significant risk for respiratory failure.
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., MELD ≥ 35), the benefits of terlipressin may not outweigh its risks.
Ischemic Events
Terlipressin may cause cardiac, cerebrovascular, peripheral, or mesenteric ischemia. Avoid use of terlipressin in patients with a history of severe cardiovascular conditions, cerebrovascular and ischemic disease. Discontinue terlipressin in patients who experience signs or symptoms suggestive of ischemic adverse reactions.
Embryo-fetal Toxicity
Terlipressin 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
Based on findings from the published literature and on its mechanism of action, terlipressin may cause fetal harm when administered to a pregnant woman. In small, published studies, administration of a single intravenous dose of terlipressin to pregnant women during the first trimester induced uterine contractions and endometrial ischemia. The limited published data are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. If terlipressin is used during pregnancy, the patient should be informed of the potential risk to the fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
In published reproductive toxicity animal studies, administration of terlipressin to pregnant guinea pigs at doses lower than the maximum recommended human dose of 4 mg/day caused a marked decrease in blood flow to the uterus and placenta. In rabbits, terlipressin is both embryotoxic and teratogenic (increased resorptions, increased implantation loss, fetal anomalies and fetal deformities).
Lactation
There are no data on the presence of terlipressin in human or animal milk, the effects on the breastfed infant, or the effect on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for terlipressin and any potential adverse effects on the breastfed child from the drug or underlying maternal condition.
Pediatric Use
Safety and effectiveness of terlipressin acetate have not been established in pediatric patients.
Geriatric Use
Of the total number of patients in clinical studies treated with terlipressin acetate, 55 (16%) were ≥65 years of age. No overall differences in safety or effectiveness were 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.
Common Adverse Effects
The most common adverse reactions (≥10%) include abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea.
Drug Interactions
Specific Drugs
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Please see product labeling for drug interaction information.
Actions
Mechanism of Action
Terlipressin is a synthetic vasopressin analogue with twice the selectivity for vasopressin V1 receptors versus V2 receptors. Terlipressin acts as both a prodrug for lysine-vasopressin, as well as having pharmacologic activity on its own. Terlipressin 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 (MAP).
Advice to Patients
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Inform female patients of reproductive potential that terlipressin may cause fetal harm and to inform their prescriber of a known or suspected pregnancy.
Additional Information
AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
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 Drug Information. © Copyright 2023, Selected Revisions September 28, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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