Methods of treating traveler's diarrhea and hepatic encephalopathy

• US 8,946,252 B2
• Filed: 10/18/2012
• Issued: 02/03/2015
• Est. Priority Date: 10/02/2008
• Status: Active Grant

• Current Assignee: Salix Pharmaceuticals Limited (Bausch Health Cos., Inc.)
• Original Assignee: Salix Pharmaceuticals Limited (Bausch Health Cos., Inc.)
• Inventors: Forbes, William, Bortey, Enoch
• Primary Examiner(s): Hui, San-Ming
• Assistant Examiner(s): Cruz, Kathrien
• Application Number:
  US13/654,978
• Publication Number:
  US 20130059875A1
• Time in Patent Office: 838 Days
• Field of Search: 514/279
• US Class Current: 514/279
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/7016 Disaccharides, e.g. lactose, lactulose lactobionic acid A61K31/7032
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: C07D 491/22 in which the condensed system contains four or more hetero rings
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Treatment of traveler'"'"'s diarrhea using in subjects having hepatic encephalopathy using gastrointestinal specific antibiotics is disclosed. One example of a gastrointestinal specific antibiotic is rifaximin.

Claims

1. A method of reducing the risk of overt hepatic encephalopathy (HE) recurrence in a subject comprising:

identifying a subject having Traveler'"'"'s Diarrhea (TD) that also has hepatic insufficiency;

determining if the subject'"'"'s Child-Pugh score is Child-Pugh Class C or if the subject'"'"'s model end stage liver disease (MELD) score is 25 or greater; and

administering between 1000 and 1200 mg of rifaximin daily and cautiously to the subject if his or her Child-Pugh score is Child-Pugh Class C or if his or her MELD score is 25 or greater.

2. The method of claim 1, wherein the hepatic insufficiency is hepatic encephalopathy.

3. The method of claim 1, wherein the subject is administered 1100 mg of rifaximin.

4. The method of claim 3, wherein the subject is administered 550 mg of rifaximin BID.

5. The method of claim 1, wherein the subject is a human.

6. The method of claim 1, wherein the rifaximin comprises tablets for oral administration comprising one or more of colloidal silicon dioxide, disodium edetate, glycerol palmitostearate, hypromellose, microcrystalline cellulose, propylene glycol, red iron oxide, sodium starch glycolate, talc, or titanium dioxide.

7. The method of claim 1, wherein the clearance rate of rifaximin is decreased in a population of subjects with hepatic insufficiency as compared to a population of subjects without hepatic insufficiency.

8. The method of claim 1, wherein the elimination rate of rifaximin is decreased in subjects with hepatic insufficiency as compared to subjects without hepatic insufficiency.

9. The method of claim 1, wherein the systemic exposure to rifaximin is increased in a population of subjects with hepatic insufficiency as compared to a population of subjects without hepatic insufficiency.

10. The method of claim 1, wherein the serum level of rifaximin is increased in a population of subjects with hepatic insufficiency as compared to a population of subjects without hepatic insufficiency.

11. The method of claim 1, comprising administering 1100 mg of rifaximin per day to a patient for more than 28 days.

12. The method of claim 11, comprising administering rifaximin to the subject for 6 months or longer.

13. The method of claim 12, comprising administering rifaximin to the subject for 1 year or longer.

26. The method of claim 1, further comprising selecting for treatment if his or her Child-Pugh score is Child-Pugh Class C or if his or her MELD score is 25 or greater.

14. A method to reduce the risk of overt hepatic encephalopathy (HE) recurrence in a subject suffering from Traveler'"'"'s Diarrhea (TD), comprising:

identifying a subject that has had overt HE and also TD;

determining the severity of the subject'"'"'s HE;

administering between 1000 and 1200 mg of rifaximin daily and cautiously for TD to the subject if the HE is severe.

15. The method of claim 14, wherein the subject is administered 1100 mg of rifaximin.

16. The method of claim 15, wherein the subject is administered 550 mg of rifaximin BID.

17. The method of claim 14, wherein the subject is a human.

18. The method of claim 14, wherein the rifaximin comprises tablets for oral administration comprising one or more of colloidal silicon dioxide, disodium edetate, glycerol palmitostearate, hypromellose, microcrystalline cellulose, propylene glycol, red iron oxide, sodium starch glycolate, talc, or titanium dioxide.

19. The method of claim 14, wherein the clearance rate of rifaximin is decreased in a population of subjects with hepatic insufficiency as compared to a population of subjects without hepatic insufficiency.

20. The method of claim 14, wherein the elimination rate of rifaximin is decreased in subjects with hepatic insufficiency as compared to subjects without hepatic insufficiency.

21. The method of claim 14, wherein the systemic exposure to rifaximin is increased in a population of subjects with hepatic insufficiency as compared to a population of subjects without hepatic insufficiency.

22. The method of claim 14, wherein the serum level of rifaximin is increased in a population of subjects with hepatic insufficiency as compared to a population of subjects without hepatic insufficiency.

23. The method of claim 14, comprising administering 1100 mg of rifaximin per day to a patient for more than 28 days.

24. The method of claim 23, comprising administering rifaximin to the subject for 6 months or longer.

25. The method of claim 24, comprising administering rifaximin to the subject for 1 year or longer.

27. The method of claim 14, further comprising selecting for treatment if his or her Child-Pugh score is Child-Pugh Class C or if his or her MELD score is 25 or greater.