TERLIVAZ (terlipressin) for injection

TERLIVAZ (terlipressin) for injection

TERLIVAZ (terlipressin) for injection

TERLIVAZ contains terlipressin, a vasopressin receptor agonist. Terlipressin is a 12-amino acid peptide with the chemical name N-[N-(N-glycylglycyl)glycyl]-8-L-lysinevasopressin.

Molecular formula: C52H74N16O15S2 (as free base).

Average molecular weight: 1227.38 (as free base).

TERLIVAZ is supplied as a sterile, preservative-free, lyophilized, white-to off-white powder for intravenous administration. Each vial contains 0.85 mg terlipressin, equivalent to 1 mg terlipressin acetate, and 10.0 mg mannitol. Glacial acetic acid and/or sodium hydroxide may be added to adjust pH at the time of manufacture.

INDICATIONS AND USAGE

TERLIVAZ is indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function.

Limitation of Use: Patients with a serum creatinine > 5 mg/dL are unlikely to experience benefit.

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).

DOSAGE AND ADMINISTRATION

Important Considerations Prior to Initiating and During Therapy

Obtain baseline oxygen saturation (SpO2) prior to administering the first dose of TERLIVAZ. During treatment, monitor patient oxygen saturation using continuous pulse oximetry. Do not use TERLIVAZ treatment in patients experiencing hypoxia until hypoxia resolves.

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Assess Acute-on-Chronic Liver Failure (ACLF) Grade and volume status before initiating TERLIVAZ.

Recommended Dosage

Record last available serum creatinine (SCr) value prior to initiating treatment (baseline SCr). The recommended starting dosage is TERLIVAZ 0.85 mg every 6 hours by slow intravenous bolus injection (over 2 minutes) on Days 1 through 3. Adjust the dose on Day 4 based on changes from baseline SCr using the dosing chart

TERLIVAZ (terlipressin) for injection dosing chart

Preparation and Administration

Reconstitute each vial with 5 mL of 0.9% Sodium Chloride Injection to prepare a 0.85 mg/5 mL solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Administer TERLIVAZ through a peripheral or central line. A dedicated central line is not required. Flush the line after TERLIVAZ administration.

If not administered immediately, store TERLIVAZ at 2°C to 8°C (36°F to 46°F) for up to 48 hours. Do not freeze. The reconstituted solution does not need protection from light.

CONTRAINDICATIONS

TERLIVAZ is contraindicated in patients experiencing hypoxia or worsening respiratory symptoms.

TERLIVAZ is contraindicated in patients with ongoing coronary, peripheral or mesenteric ischemia.

WARNINGS AND PRECAUTIONS

Serious or Fatal Respiratory Failure: In the primary clinical trial, serious or fatal respiratory failure occurred in 14% of patients treated with TERLIVAZ compared to 5% of patients on placebo.

Obtain baseline oxygen saturation and do not initiate TERLIVAZ in hypoxic patients. Monitor patients for changes in respiratory status using continuous pulse oximetry and regular clinical assessments. Discontinue TERLIVAZ 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 TERLIVAZ 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: TERLIVAZ-related adverse reactions (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 TERLIVAZ may not outweigh its risks.

Ischemic Events: TERLIVAZ may cause cardiac, cerebrovascular, peripheral, or mesenteric ischemia. Avoid use of TERLIVAZ in patients with a history of severe cardiovascular conditions, cerebrovascular and ischemic disease. Discontinue TERLIVAZ in patients who experience signs or symptoms suggestive of ischemic adverse reactions.

Embryo-Fetal Toxicity: TERLIVAZ 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.

USE IN SPECIFIC POPULATIONS

Pregnancy: Based on findings from the published literature and on its mechanism of action, TERLIVAZ 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 TERLIVAZ is used during pregnancy, the patient should be informed of the potential risk to the fetus.

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 TERLIVAZ and any potential adverse effects on the breastfed child from TERLIVAZ or from the underlying maternal condition.

Pediatric Use:

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Safety and effectiveness of TERLIVAZ have not been established in pediatric patients.

Geriatric Use: Of the total number of patients in clinical studies treated with TERLIVAZ, 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.

OVERDOSAGE

Manifestations of TERLIVAZ overdose are expected to be similar to the adverse reactions described with therapeutic doses. In case of overdose, initiate close monitoring of vital signs, electrolytes, and potential ischemic events and initiate appropriate symptomatic treatment.

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