Terlivaz Drug Information

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.

Important Considerations Prior to Initiating and During Therapy Obtain baseline oxygen saturation (SpO 2 ) 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.

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). Adjust the dose on Day 4 based on changes from baseline SCr using the dosing chart (Figure 1). Figure 1: Dosing Chart a Baseline SCr is the last available serum creatinine before initiating treatment.

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.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of TERLIVAZ cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of TERLIVAZ was evaluated in the CONFIRM trial. The most common adverse reactions that led to TERLIVAZ discontinuation were respiratory failure, abdominal pain, and intestinal ischemia/obstruction.

Table 1 lists adverse reactions that occurred more commonly on TERLIVAZ than on placebo, and in at least 4% of patients treated with TERLIVAZ in the CONFIRM trial. The most commonly observed adverse reactions in TERLIVAZ-treated patients (≥10%) were abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to terlipressin exposure.

Pregnancy Risk Summary 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. 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 respectively.

Data Animal Data 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).

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

TERLIVAZ is contraindicated in patients experiencing hypoxia or worsening respiratory symptoms. TERLIVAZ is contraindicated in patients with ongoing coronary, peripheral, or mesenteric ischemia.

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.