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The FDA , the first drug for treating patients with hepatorenal syndrome (HRS).

A synthetic vasopressin analog, terlipressin is an injectable drug indicated for patients with HRS experiencing rapid deterioration of kidney function (type 1 HRS). The disease affects patients with advanced liver disease, most commonly those with advanced cirrhosis and ascites, and has a poor prognosis without liver transplantation.

Support for the approval came in part from the trial, a North American phase III study that randomized 300 patients with HRS and a rapid reduction in kidney function to either 0.85-mg terlipressin (n=199) or placebo (n=101), given via injection every 6 hours for up to 14 days.

CONFIRM met its primary endpoint, showing that terlipressin led to verified HRS reversal by day 14 or hospital discharge in a significantly higher proportion of patients (29% vs 16%). Reversal was defined as two consecutive serum creatinine values of 1.5 mg/dL or less measured at least 2 hours apart.

FDA advised that patients with serum creatinine levels of 5 mg/dL or greater are unlikely to benefit and should not receive the drug.

A serious and sometimes fatal side effect of the treatment, respiratory failure, was a sticking point when FDA advisors reviewed the drug back in 2020. At that time, the Cardiovascular and Renal Drugs Advisory Committee voted 8-7 in favor of recommending approval, with nephrologists on the panel in large part voting against the drug.

Terlipressin has had a long road to approval, after it was declined by the FDA in 2009 on the basis of two trials that missed their primary endpoints.

Low oxygen blood levels are a for terlipressin, the agency noted, and patients receiving the drug should be monitored with a pulse oximeter for respiratory problems. Terlipressin can also cause ischemic events, which may necessitate dose interruptions or discontinuation.

In its of the approval, drugmaker Mallinckrodt Pharmaceuticals noted that terlipressin is recommended for HRS in guidelines from both the and , and that the synthetic vasopressin analog has been approved outside the U.S. for more than 3 decades.

Common adverse events with terlipressin and placebo, respectively, included abdominal pain (19.5% vs 6.1%), nausea (16% vs 10.1%), respiratory failure (15.5% vs 7.1%), diarrhea (13% vs 7.1%), and dyspnea (12.5% vs 5.1%).

Other safety concerns noted by the FDA included potential for fetal harm and that certain side effects of the drug could prevent patients from going on to liver transplantation.

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