COMPOSITIONS FOR IMPROVING KIDNEY FUNCTION IN PATIENTS WITH HEPATORENAL SYNDROME
The principles and embodiments of the present disclosure relate to a composition for improving kidney function in an adult patient with hepatorenal syndrome with rapid reduction in kidney function. The composition includes terlipressin acetate having a formula of C 52 H 74 N 16 O 15 S 2 ·(C 2 H 4 O 2 ) n , where n is 2.8.
1 . A method for improving kidney function in an adult patient with hepatorenal syndrome with rapid reduction in kidney function, the method comprising:
reconstituting a lyophilized composition comprising terlipressin acetate and glacial acetic acid in sodium chloride, wherein the terlipressin acetate has a formula of C 52 H 74 N 16 O 15 S 2 ·(C 2 H 4 O 2 ) n , and wherein n is theoretically 2.8;
obtaining a baseline oxygen saturation (SpO 2 ) prior to administering the composition;
assessing an ACLF Grade of the patient prior to administering;
administering the composition only if the baseline SpO 2 is >90% and the patient is ACLF Grade <3;
administering the reconstituted composition by slow intravenous (IV) bolus injection over 2 minutes;
monitoring an SpO 2 level at least 3 times a day during administration using pulse oximetry; and
discontinuing administration if the SpO 2 level decreases below 90%.
2 . The method of claim 1 , wherein the SpO 2 level is monitored at least 4 times a day during administration.
3 . The method of claim 1 , wherein the SpO 2 level is monitored at least 5 times a day during administration.
4 . The method of claim 1 , wherein the SpO 2 level is monitored at least 6 times a day during administration.
5 . The method of claim 1 , wherein the SpO 2 level is monitored continuously during administration.
6 . The method of claim 1 , wherein the administering is through a peripheral or central line.
7 . The method of claim 1 , further comprising assessing the serum creatinine (SCr) of the patient or recording the last available SCr as a baseline SCr before administering, wherein the composition is not administered if the patient has a baseline SCr>5 mg/dl.
8 . The method of claim 1 , wherein a total dose of terlipressin acetate administered to the adult patient per day is 3.1 mg.
9 . The method of claim 1 , wherein the administering occurs every 6 hours for at least 3 days.
10 . The method of claim 1 , wherein administering occurs after storing the reconstituted solution at 2° C. to 8° C. for less than 48 hours.
11 . A method for improving kidney function in an adult patient with hepatorenal syndrome with rapid reduction in kidney function, the method comprising:
obtaining a baseline oxygen saturation (SpO 2 ) of the adult patient;
assessing an ACLF Grade of the adult patient prior to administering;
administering intravenously by bolus injection 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 theoretically 2.8; and
monitoring an SpO 2 level of the adult patient at least 3 times a day during administration of the composition,
wherein the composition is not administered, or the administration is discontinued if the SpO 2 is below 90% or the adult patient is ACLF Grade 3.
12 . The method of claim 11 , wherein the SpO 2 level is monitored at least 4 times a day during administration.
13 . The method of claim 11 , wherein the SpO 2 level is monitored at least 5 times a day during administration.
14 . The method of claim 11 , wherein the SpO 2 level is monitored at least 6 times a day during administration.
15 . The method of claim 11 , wherein the SpO 2 level is monitored continuously during administration.
16 . The method of claim 11 , wherein the administering occurs from days 1 to 3.
17 . The method of claim 11 , further comprising assessing the serum creatinine of the adult patient before administering, wherein the composition is not administered if the adult patient has a serum creatinine >5 mg/dl.
18 . The method of claim 11 , wherein following a 1 mg IV injection of terlipressin acetate to the adult patient, the median C max , AUC 24h and C ave of terlipressin at steady state is 70.5 ng/ml, 123 ng×hr/ml and 14.2 ng/ml, respectively.
19 . A method for improving kidney function in an adult patient with hepatorenal syndrome with rapid reduction in kidney function, the method comprising:
assessing an ACLF Grade of the patient before administering;
administering intravenously by bolus injection 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; and,
wherein the composition is not administered if the patient is ACLF Grade 3.
20 . The method of claim 19 , further comprising assessing a serum creatinine of the adult patient before administering, wherein the composition is not administered if the adult patient has a serum creatinine >5 mg/dl.
21 . The method of claim 20 , further comprising:
obtaining a baseline oxygen saturation (SpO 2 ) of the patient prior to administering the composition; and
continuously monitoring the SpO 2 of the patient during administration of the composition,
wherein the composition is not administered, or the administration is discontinued if the SpO 2 is below 90%.