METHODS AND COMPOSITIONS FOR IMPROVING KIDNEY FUNCTION IN PATIENTS WITH HEPATORENAL SYNDROME
The principles and embodiments of the present disclosure relate to methods for using terlipressin to treat a patient having impaired renal function associated with liver disease. A method of improving kidney function in an adult patient with hepatorenal syndrome with rapid reduction in kidney function may include determining the patient's acute-on-chronic liver failure (ACLF) grade and baseline serum creatinine level; obtaining a baseline oxygenation saturation (SpO 2 ) of the patient; administering a dose of terlipressin acetate to the patient by intravenous (IV) injection; and monitoring the patient's oxygenation saturation with pulse oximetry.
1 . A composition for improving kidney function in an adult patient with hepatorenal syndrome with rapid reduction in kidney function, the composition comprising terlipressin acetate having a formula of C 52 H 74 N 16 O 15 S 2 .(C 2 H 4 O 2 ) n , wherein n is 2.8.
2 . The composition of claim 1 , wherein the composition has a structure of:
3 . The composition of claim 1 , wherein the terlipressin acetate is in a dosage of 1 mg.
4 . The composition of claim 1 , further comprising glacial acetic acid or sodium hydroxide.
5 . A composition for improving kidney function in an adult patient with hepatorenal syndrome, the composition comprising terlipressin acetate having a formula of C 52 H 74 N 16 O 15 S 2 .(C 2 H 4 O 2 ) n , wherein n is 2.8, and wherein the composition comprises lyophilized powder in a single-dose vial for reconstitution.
6 . The composition of claim 5 , wherein the composition is preservative free.
7 . The composition of claim 5 , wherein the single-dose vial comprises 1 mg of terlipressin acetate.
8 . The composition of claim 7 , wherein the single-dose vial comprises 10.0 mg mannitol.
9 . A method for improve kidney function in an adult patient with hepatorenal syndrome with rapid reduction in kidney function, the method comprising: administering a composition comprising terlipressin acetate having a formula of C 52 H 74 N 16 O 15 S 2 .(C 2 H 4 O 2 ) n , wherein n is 2.8.
10 . The method of claim 9 , wherein the composition has a structure of:
11 . The method of claim 9 , wherein the terlipressin acetate is in a dosage of 1 mg.
12 . The method of claim 9 , wherein the composition further comprises glacial acetic acid and/or sodium hydroxide.
13 . The method of claim 9 , further comprising obtaining a baseline oxygen saturation (SpO 2 ) prior to administering the composition.
14 . The method of claim 13 , wherein the composition is not administered if the SpO 2 is <90%.
15 . The method of claim 14 , wherein the composition is administered if the SpO 2 improves to ≥90%.
16 . The method of claim 13 , further comprising continuously monitoring oxygen saturation during administration using continuous pulse oximetry.
17 . The method of claim 16 , wherein administration is discontinued if the SpO 2 decreases below 90%.
18 . The method of claim 9 , wherein a patient with a serum creatinine >5 mg/dL is unlikely to experience benefit.
19 . The method of claim 9 , wherein a patient with volume overload or with acute-on-chronic liver failure (ACLF) Grade 3 is at increased risk.
20 . The method of claim 9 , wherein following a 1 mg IV injection of terlipressin acetate to the adult patient, the median C max , AUC 24 h and C ave of terlipressin at steady state is 70.5 ng/mL, 123 ng×hr/mL and 14.2 ng/mL, respectively.
21 . A method for improving kidney function in an adult patient with hepatorenal syndrome with rapid reduction in kidney function, the method comprising:
administering intravenously every 6 hours a composition comprising terlipressin acetate having a formula of C 52 H 74 N 16 O 15 S 2 .(C 2 H 4 O 2 ) n , wherein n is 2.8.
22 . The method of claim 16 , wherein administering occurs from days 1 to 3.