Terlipressin (Monograph)

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

Medically reviewed by Drugs.com on Feb 26, 2023. Written by ASHP.

Introduction

Synthetic vasopressin analogue.

Uses for Terlipressin

Hepatorenal Syndrome

Improvement of kidney function in adults with hepatorenal syndrome (HRS) with rapid reduction in kidney function.

Limitations of use: patients with a S_cr >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 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 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 S_cr (the last available S_cr before initiating treatment):

• If S_cr 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 S_cr value of ≤1.5 mg/dL at least 2 hours apart or for a maximum of 14 days.

• If S_cr 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 S_cr value of ≤1.5 mg/dL at least 2 hours apart or for a maximum of 14 days.

• If S_cr 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

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.

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 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, Cl_cr, 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. (See Cautions.)

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.

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