The U.S. Food and Drug Administration (FDA) approved Terlivaz® (terlipressin – Mallinckrodt Pharmaceuticals) injection on Sept. 14, 2022. It will be used for hospitalized adult patients whose kidney function is failing rapidly due to hepatorenal syndrome (HRS), an acute complication of late-stage liver disease. Its recommended dosing is one vial (0.85mg) given over two minutes as an intravenous (IV) bolus injection once every six hours for three days. Depending on the patient’s serum creatinine (SCr) level, treatment then can stop, continue at the same rate or be doubled until two consecutive SCr readings are seen at 1.5mg/dL or lower, separated by two hours or more, within two weeks or the date of discharge from the hospital. Labeling for Terlivaz carries a boxed warning about the possibility of respiratory failure, so it should not be used for patients who have low amounts of oxygen in their blood. Release to the U.S. market is planned for within a few weeks. A cost estimate is not yet available. Terlivaz will be available in hospitals and clinics; Accredo will not have access. Prescribing information is here.
At a Glance
- Brand (Generic) Name: Terlivaz (terlipressin)
- Manufacturer: Mallinckrodt Pharmaceuticals
- Date Approved: Sept. 14, 2022
- Indication: to improve kidney function for adults who have HRS with rapid reduction in kidney function
- Dosage Forms Available: single-dose 0.85mg vials for reconstitution and IV bolus injection
- Launch Date: in the coming weeks
- Estimated Annual Cost: Pricing information is not yet available.
- Associated with advanced liver disease, HRS with rapid loss of kidney function is believed to affect up to 40,000 U.S. patients, every year; including about 10% of those who have cirrhosis with ascites (abnormal accumulation of fluid in the abdomen). If not treated, patients who develop it live an average of only around two weeks.
- One measure of kidney function is SCr. The normal range for men is 0.74mg/dL to 1.35 mg/dL. For women, it is 0.59mg/dL to 1.04 mg/dL.
- Terlivaz helps to reduce the pressure in blood vessels of the liver, allowing improved blood flow in the kidneys.
- In the decisive clinical trial, HRS reversed for 29% of patients given Terlivaz, compared to 16% of those receiving placebo injections. Reversal included both no need for dialysis and a SCr level of 1.5mg/dL or lower for two consecutive times, separated by at least two hours, after two weeks of treatment.
- Among actively treated study patients, 14% had severe cases of or died from respiratory failure and therapy was stopped for 12% as a result of adverse events.
- The most common side effects were abdominal pain, nausea, diarrhea and/or trouble with breathing.
- A surgical procedure may relieve the swelling associated with the condition, but the only cure for HRS is a liver transplant. Some patients may need kidney transplants, as well, if kidney function has deteriorated beyond recovery.
- Although terlipressin currently is recommended therapy for HRS with rapid kidney failure in practice guidelines from the American College of Gastroenterology (ACG) and the American Association for the Study of Liver Diseases, it was not FDA approved until now. It has been used in Europe and other parts of the world for three decades, however.