General Information

Terlivaz (terlipressin) is a vasopressin receptor agonist. 

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

Terlivaz is supplied as an injection for intravenous administration. Terlivaz can cause serious or fatal respiratory failure. 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. Assess Acute-on-Chronic Liver Failure (ACLF) Grade and volume status before initiating Terlivaz.

Recommended Dosage Regimen:

Days 1 to 3 administer Terlivaz 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 Terlivaz 0.85 mg (1 vial) intravenously every 6 hours.
• If SCr has decreased by less than 30% from baseline, dose may be increased to Terlivaz 1.7 mg (2 vials) intravenously every 6 hours.

Mechanism of Action

Terlivaz (terlipressin) is a vasopressin receptor agonist 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.

Side Effects

Adverse effects associated with the use of Terlivaz may include, but are not limited to, the following:

• abdominal pain
• nausea
• respiratory failure
• diarrhea
• dyspnea

The Terlivaz drug label comes with the following Black Box Warning: Terlivaz may cause serious or fatal respiratory failure. Patients with volume overload or with ACLF Grade 3 are at increased risk. Assess oxygenation saturation (e.g., SpO2) before initiating Terlivaz. Do not initiate Terlivaz in patients experiencing hypoxia (e.g., SpO2 <90%) until oxygenation levels improve. Monitor patients for hypoxia using continuous pulse oximetry during treatment and discontinue Terlivaz if SpO2 decreases below 90%.

Clinical Trial Results

The FDA approval was based, in part, on results from the Phase 3 CONFIRM trial, the largest-ever prospective study (n=300) conducted to assess the safety and efficacy of terlipressin in patients with HRS type 1 (HRS-1) in the U.S. and Canada. Patients in the study were critically ill, as indicated by assessments of their liver and kidney function at the start of the trial. 

The study met its primary endpoint of Verified HRS Reversal (VHRSR), which is defined as renal function improvement, avoidance of dialysis and short-term survival. 29.1 percent (58/199) of patients administered terlipressin plus albumin achieved Verified HRS Reversal versus 15.8 percent (16/101) on placebo plus albumin. In order to achieve Verified HRS Reversal, patients had to have two consecutive SCr values ≤1.5 mg/dL, at least two hours apart by day 14 or hospital discharge and be alive without intervening renal replacement therapy (RRT) for at least 10 days following discharge or treatment.