Prior Auth Protocol

FDA Approved Indications:

Treatment of patients > 12 years of age with traveler's diarrhea caused by noninvasive strains of Escherichia coli.
Reduction in risk of overt hepatic encephalopathy (HE) recurrence in patients ≥ 18 years of age
Treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults

Health Net Approved Indications and Usage Guidelines:

Traveler's Diarrhea

Patient is 18 years or older with traveler's diarrhea and failure or clinically significant adverse effects to ciprofloxacin

OR

Patient is 12-17 years of age with traveler's diarrhea

Hepatic Encephalopathy

Treatment or prophylaxis of hepatic encephalopathy and failure or clinically significant adverse effects to lactulose

Small Intestinal Bacterial Overgrowth

Patient has small intestinal bacterial overgrowth

Crohn's Disease

Patient has Crohn's Disease and failure or clinically significant adverse reaction to metronidazole or ciprofloxacin

IBS-D (Irritable Bowel Syndrome with Diarrhea)

Patient has irritable bowel syndrome with diarrhea

AND

Failure of or clinically significant adverse effects to two of the following:

Bulk forming agent (e.g., psyllium)
Anti-diarrhea agent (e.g., bismuth subsalicylate, loperamide)
Antispasmodic agent (e.g., diphenoxylate-atropine, dicyclomine, hyoscyamine, hyoscyamine/atropine/scopolamine/phenobarbital)

Coverage is Not Authorized For:

Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.

General Information:

Xifaxan should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli.
Xifaxan should be discontinued if diarrhea persists or worsens following 24-48 hours of therapy. An alternative antibiotic should be considered.
Xifaxan is not suitable for treating systemic bacterial infections because less than 0.4% of the drug is absorbed after oral administration.
Further investigation is warranted to determine efficacy in diverticulitis and inflammatory bowel disease.
There is not enough evidence available to support the use of Xifaxan for C. Difficile infections. C. Diff is not recognized as a valid off-label indication for Xifaxan in either Micromedex or Clinical Pharmacology. One study of 20 patients and one case series of 8 patients are available looking at Xifaxan for this indication, but there is not enough data presented to support approval.
Xifaxan should not be used as a second course of therapy for the same incident of travelers` diarrhea secondary to concerns of resistance.
The FDA approval for IBS-D was based on data from three clinical studies of more than 3,000 patients. Results of TARGET 1 and 2 showed patients treated with Xifaxan 550 mg achieved relief of the FDA composite endpoint (stool consistency and abdominal pain) versus placebo. TARGET 3 showed that patients who responded to treatment with Xifaxan 550 mg but experienced recurrent symptoms responded to repeat treatment in the FDA composite endpoint versus placebo. Xifaxan is not FDA approved indicated for irritable bowel syndrome with constipation( IBS-C). Xifaxan should not be initiated in patients with constipation.
Xifaxan 550mg TID dosing regimens may be appropriate in the treatment of SIBO for patients with documented IBS. A trial by Scarpellini, et al. (2007) compared 80 adult patients with SIBO randomized to either 1200mg/day or 1600mg/day of Xifaxan for 7 days. 78.75% of the patient group had IBS. Using glucose breath test (GBT) normalization as an indicator for improved SIBO, 80% of patients on 1600mg/day had normalized GBT, compared to 58% of patients on 1200mg/day (P < 0.05, OR 1.82, 95% CI 1.098.01).

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Cipro^R(ciprofloxacin)	Traveler's diarrhea 750 mg PO BID or 1 - 3 days Infectious diarrhea, >/= 18 yrs 500 mg to 750 mg PO BID for 3 - 7 days	Traveler's diarrhea 6 tablets Infectious diarrhea, >/= 18 yrs 14 tablets
Various brands (neomycin)	Hepatic Encephalopathy 4 gm-12 gm PO QD	12 gm/day
Various brands (lactulose)	Hepatic Encephalopathy 30-45 ml PO TID-QID	This field intentionally left blank
dicyclomine (Bentyl^R)	IBS-D: Adults: 80mg/day PO divided QID then increase to 160 mg/day. If efficacy not achieved in 2 weeks, therapy should be discontinued	160 mg/day
hyoscyamine (Levsin^R, Levbid^R, Hyosyne, Anaspaz)	IBS-D: Adults: Levsin: 0.125 - 0.25 mg PO Q 4h Levbid: 0.375 - 0.75 mg PO Q 12h	1.5 mg/day
hyoscyamine, atropine, scopolamine, phenobarbital (Donnatal^R, Phenogytro)	IBS-D: Adults: Donnatal: 1-2 tablets or 5-10 ml of elixir PO TID-QID Donnatal Extentabs: 1 tablet PO Q 12h; may increase to 1 tablet PO Q 8h if needed	2 tablets or 10 mL per day
Loperamide (Imodium^R)	IBS-D: Adults: 4 mg PO followed by 2mg after each unformed stool until diarrhea is resolved; then individualize dose. Administer optimal daily dose (4-8 mg) as single or divided doses.	If no clinical improvement after treatment with 20 mg/day for at least 10 days, symptoms are unlikely to be controlled by further use.
Diphenoxylate/atropine (Lomotil^R)	IBS-D: Initial dose 5 mg PO QID. Individualize dose.	If no clinical improvement after treatment with 20 mg/day for at least 10 days, symptoms are unlikely to be controlled by further use.

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Xifaxan	Traveler's Diarrhea Adults and children > 12 years of age: 200 mg PO TID for 3 days Hepatic Encephalopathy 550 mg PO BID SIBO 200 mg PO TID for 7 days or 550 mg PO BID for 14 days SIBO with IBS 550 mg PO TID for 7 days Crohn's Disease 200 mg PO TID or 800 mg PO BID IBS-D 550 mg PO TID	Traveler's Diarrhea 9 tablets/month Hepatic Encephalopathy Length of benefit SIBO 200 mg PO TID for 7 days or 550 mg PO BID for 14 days SIBO with IBS 550 mg for 7 days Crohn's Disease 12 weeks IBS-D 550 mg PO TID for 14 Days Patients who experience recurrence can be retreated up to two times with the same regimen.

Product Availability:

Tablet: 200 mg, 550 mg

References:

1. Xifaxan [Prescribing Information]. Salix Pharmaceuticals, Inc., May 2015.

2. Adachi JA, Ericsson CD, Jiang Z, et al. Azithromycin found to be comparable to levofloxacin for the treatment of US travelers with acute diarrhea acquired in Mexico. Clin Infect Dis. 2003; 37:1165-71.

3. Gomi H, Jiang Z, Adachi JA, et al. In vitro antimicrobial susceptibility testing of bacterial enteropathogens causing travelers diarrhea in four geographic regions. Antimicrob Agents Ch. 2001; 45(1):212-16.

4. DuPont HL, Jiang Z, Ericsson CD, et al. Rifaximin versus ciprofloxacin for the treatment of travelers` diarrhea: a randomized, double-blind clinical trial. Clin Infect Dis. 2001; 33:1807-15.

5. CDC Travelers` Health Website. Available at: http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-2-the-pre-travel-consultation/travelers-diarrhea. Accessed July 7, 2015.

6. Mas A, Rodes J, Sunyer L, et al. Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial. J Hepatol. 2003;38:51-58.

7. Pedretti G, Calzetti C, Missale G, Fiaccodori F. Rifaximin versus neomycin on hyperammonemia in chronic portal systemic encephalopathy of cirrhotics. A double-blind, randomized trial. Ital J Gastroenterol. 1991;23(4):175-178.

8. Lauritano EC, Gabrielli M, Lupascu A, et al. Xifaxan Dose-Find Study for the Treatment of Small Intestinal Bacterial Overgrowth. Aliment Pharmacol Ther. 2005 Jul 1;22(1):31-35.

9. Cuoco L, Salvagnini M. Small intestine bacterial overgrowth in irritable bowel syndrome: a retrospective study with rifaximin. Min Gastroentero Dietol. 2006;52(1):89-95.

10. Taylor DN, Bourgeois AL, Ericsson CD, et al. A randomized, double-blind, multicenter study of rifaximin compared with placebo and with ciprofloxacin in the treatment of travelers` diarrhea. Am J Trop Med & Hygiene. 2006;74(6):1060-1066.

11. Paik YH, Lee KS, Han KH, et al. Comparison of rifaximin and lactulose for the treatment of hepatic encephalopathy: a prospective randomized study. Yonsei Med J. 2005;46(3):399-407.

12. Shafran I, Johnson LK. An open-label evaluation of rifaximin in the treatment of active Crohn`s disease. Curr Med Res Opin 2005;21:1165-9.

13. Prantera C, Lochs H, Campieri M, Scribano ML, Sturniolo GC, et al. Antibiotic treatment of Crohn`s disease: results of a multicentre, double blind, randomized, placebo-controlled trial with rifaximin. Aliment Pharmacol Ther. 2006: 23:1117-25.

14. Lauritano EC, Gabrielli M, Scarpedellini E, Lupascu A, Novi M, et al. Small intestinal bacterial overgrowth recurrence after antibiotic therapy. Am J Gastroenterol 2008;103:2031-2035.

15. Sanford Guide to Antimicrobial Therapy, 2011, p. 15,18, 99.

16. Clinical Pharmacology website. Available at: http://clinicalpharmacology-ip.com/. Accessed June 12, 2015.

17. Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364:22-32.

18. Tack J. Antibiotic therapy for the irritable bowel syndrome. N Engl J Med. 2011;364:81-82.

19. Scarpellini E, Gabrielli M, Lauritano CE, et al. High dosage rifaximin for the treatment of small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2007;1;25(7):781-786.