Terlipressin, a synthetic vasopressin analog, has been approved by the US Food and Drug Administration (FDA) as the first therapeutic option for patients with type 1 hepatorenal syndrome with rapidly worsening kidney function. An injectable formulation, it will be available as a lyophilized powder in a single-dose vial (0.85 mg) for reconstitution.

Efficacy of terlipressin has been demonstrated in the phase III CONFIRM trial published last year in March in the New England Journal of Medicine, in which the improvement in renal function was more with terlipressin than placebo (N Engl J Med. 2021 Mar 4;384(9):818-828).

Dose and administration

• Days 1-3: 0.85 mg (1 vial) IV every 6 hours
• Day 4: Test for serum creatinine and compare it with baseline value
• Continue treatment until 24 hours after two consecutive serum creatinine values of  ≤1.5 mg/dL values at least 2 hours apart or 14 days (maximum).

Note: If serum creatinine is 30% less than baseline levels, dose may be increased to 1.7mg (2 vials) every 6 hours. Stop the drug if serum creatinine rises above the baseline level.

Side effects: Abdominal pain, nausea, diarrhea, dyspnea and respiratory failure

Contraindication: Hypoxic patients (SpO2 <90%) and those experiencing coronary, peripheral, or mesenteric ischemia

 Warning and precautions

• Avoid administration of the drug in patients with serum creatinine levels ≥5 mg/dL because of apparent lack of benefit.
• Assess the patient for hypoxia with pulse oximeter before initiating treatment as terlipressin increases risk of respiratory failure, which may be potentially life-threatening. Discontinue if SpO2 falls below 90%.
• Remain alert about the likelihood of ischemic events.
• Possible teratogenicity
• Side effects may render a patient ineligible for hepatic transplantation

Sources

1. US FDA press release, Sept. 14, 2022.
2. TERLIVAZ prescribing information, https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022231s000lbl.pdf.