Methods of treating hepatic encephalopathy
View Patent ↗The application describes treatment of hepatic encephalopathy using gastrointestinal specific antibiotics. One example of a gastrointestinal specific antibiotic is rifaximin.
1. A method of decreasing a subject's risk of a hepatic encephalopathy (HE) breakthrough episode comprising administering rifaximin daily for a period of about 12 months or longer to a subject suffering from HE, thereby decreasing the subject's risk of an HE breakthrough episode, wherein a breakthrough episode is defined as an increase of the Conn score to Grade ≧2 or an increase in Conn score of 1 and asterixis grade of 1 for subjects having a baseline Conn score of 0.
2. The method of claim 1 , wherein the risk of the episode for subjects having a last HE episode equal to, or greater than, 90 days prior to the administration of rifaximin is reduced by about 58%.
3. The method of claim 1 , wherein the risk of the episode for subjects having a last HE episode equal to, or greater than, 90 days prior to the administration of rifaximin is reduced by between about 30% to 70%.
4. The method of claim 1 , wherein the risk of the episode for subjects having a last HE episode greater than 90 days prior to the administration of rifaximin is decreased by between about 60%.
5. The method of claim 1 , wherein the risk of the episode for subjects having a last HE episode greater than 90 days prior to the administration of rifaximin is decreased by between about 2% to 80%.
6. The method of claim 1 , wherein the risk of the episode for subjects having two or fewer HE episodes in the six months prior to the administration of rifaximin is reduced by about 56%.
7. The method of claim 1 , wherein the risk of the episode for subjects having 2 or fewer HE episodes in the six months prior to administration of rifaximin is reduced by between about 20% to 70%.
8. The method of claim 1 , wherein the risk of the episode for subjects having greater than two HE episodes in the six months prior to administration of rifaximin is reduced by about 63%.
9. The method of claim 1 , wherein the risk of the episode for subjects having greater than two HE episodes in the six months prior to the administration of rifaximin is reduced by between about 30% to about 80%.
10. The method of claim 1 , wherein administering rifaximin daily comprises administering 550 mg of rifaximin to the subject two times per day (BID).
11. The method of claim 1 , wherein administering rifaximin daily comprises administering 275 mg of rifaximin to the subject four times per day.
12. The method of claim 1 , wherein administering rifaximin daily comprises administering 275 mg of rifaximin to the subject as two dosage forms two times per day.
13. The method of claim 1 , wherein rifaximin is administered to the subject for two to three years.
14. The method of claim 1 , wherein rifaximin is administered daily to the subject until the subject's death.
15. The method of claim 1 , further comprising administering lactulose.
16. The method of claim 1 , further comprising administering one or more of align, alinia, pentasa, cholestyramine, sandostatin, vancomycin, lactose, amitiza, flagyl, zegerid, prevacid, or miralax.
17. The method of claim 1 , wherein administration of rifaximin results in an increase in time to a first HE-related hospitalization of the subject.
18. The method of claim 1 , wherein administration of rifaximin results in an increase in the time to development of spontaneous bacterial peritonitis (SBP) in the subject.
19. The method of claim 1 , wherein administration of rifaximin results in a decrease in blood ammonia concentration from baseline in the subject.
20. The method of claim 19 , wherein the decrease in blood ammonia concentration from baseline to 170 days is about 6 μg/dL.
21. The method of claim 1 , wherein administration of rifaximin results in an increase in critical flicker frequency values from baseline in the subject.
22. The method of claim 1 , wherein administration of rifaximin results in a decrease in daily lactulose consumption from baseline over time in the subject.
23. The method of claim 22 , wherein the decrease in daily lactulose consumption is from between about 7 doses of lactulose to about 2 doses of lactulose.
24. The method of claim 1 , wherein administration of rifaximin results in a change from baseline in Chronic Liver Disease Questionnaire (CLDQ) scores over time in the subject.
25. The method of claim 1 , wherein administration of rifaximin results in a change from baseline in Epworth Sleepiness Scale scores over time in the subject.
26. The method of claim 1 , wherein subjects having a MELD level of between about 1 to 24 respond to administration of rifaximin.
27. The method of claim 1 , wherein subjects having a MELD level less than or equal to ten respond to administration of rifaximin.
28. The method of claim 1 , wherein subjects having a MELD level between 11 and 18 respond to administration of rifaximin.
29. The method of claim 1 , wherein subjects having a MELD level between 19 and 24 respond to administration of rifaximin.