Pharmacy Prior Authorization Criteria

Xifaxan (rifaximin)

Indications for Prior Authorization

Xifaxan (rifaximin)

• For diagnosis of Travelers' Diarrhea
  200mg is indicated for the treatment of travelers' diarrhea (TD) caused by noninvasive strains of Escherichia coli in adults and pediatric patients 12 years of age and older.

  Limitations of use: Do not use in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli. [A]

• For diagnosis of Prophylaxis of Hepatic Encephalopathy Recurrence
  550 mg is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults. In the trials of Xifaxan for HE, 91% of patients were using lactulose concomitantly. Differences in the treatment effect of those patients not using lactulose concomitantly could not be assessed.

  Xifaxan has not been studied in patients with MELD (Model for End-Stage Liver Disease) score greater than 25, and only 8.6% of patients in the controlled trial had MELD scores over 19. There is increased systemic exposure in patients with more severe hepatic dysfunction.

• For diagnosis of Treatment of Hepatic Encephalopathy
  Used for the treatment of hepatic encephalopathy. [4, 5, 22]

• For diagnosis of Irritable Bowel Syndrome with Diarrhea
  550 mg is indicated for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.

• For diagnosis of Small Bowel Bacterial Overgrowth (SBBO)/Small Intestinal Bacterial Overgrowth (SIBO)
  Has been used for the treatment of small intestinal bacterial overgrowth. [7, 8, 10, 13]

Criteria

Xifaxan 200 mg tablets*

NOTE: *If patient meets criteria above, please approve at GPI-14.

Prior Authorization

Length of Approval: 1 Time only
For diagnosis of Travelers' Diarrhea (TD)

• Diagnosis of travelers' diarrhea (TD)
AND
• Disease is moderate to severe [D, 9]
AND
• One of the following:
• Trial and failure of one of the following: [2, 3, D, E]
• Zithromax (azithromycin)
• Cipro (ciprofloxacin)
• Levaquin (levofloxacin)
• Ofloxacin
OR
• Resistance, contraindication, or intolerance to all of the following antibiotics:
• Zithromax (azithromycin)
• Cipro (ciprofloxacin)
• Levaquin (levofloxacin)
• Ofloxacin

Xifaxan

Prior Authorization (Initial Authorization)

Length of Approval: 3 Months [C]
For diagnosis of Small Bowel Bacterial Overgrowth (SBBO)/Small Intestinal Bacterial Overgrowth (SIBO) (off-label)

• Diagnosis of Small Bowel Bacterial Overgrowth (SBBO)/Small Intestinal Bacterial Overgrowth (SIBO)
AND
• One of the following:
• Trial and failure of two of the following antibiotics: [5, 16-21]
• Neomycin
• Augmentin (amoxicillin/clavulanic acid)
• Cipro (ciprofloxacin)
• Bactrim (trimethoprim-sulfamethoxazole)
• Vibramycin (doxycycline) or Minocin (minocycline) or tetracycline
• Flagyl (metronidazole)
• Keflex (cephalexin)
OR
• Resistance, contraindication, or intolerance to all of the following antibiotics:
• Neomycin
• Augmentin (amoxicillin/clavulanic acid)
• Cipro (ciprofloxacin)
• Bactrim (trimethoprim-sulfamethoxazole)
• Vibramycin (doxycycline) or Minocin (minocycline) or tetracycline
• Flagyl (metronidazole)
• Keflex (cephalexin)

Xifaxan

Prior Authorization (Reauthorization)

Length of Approval: 3 Months [C]
For diagnosis of Small Bowel Bacterial Overgrowth (SBBO)/Small Intestinal Bacterial Overgrowth (SIBO) (off-label)

• Patient demonstrates positive clinical response to therapy (e.g., resolution of symptoms or relapse with Xifaxan discontinuation) [B]

Xifaxan 550 mg tablets*

NOTE: *If patient meets criteria above, please approve at GPI-14.

Prior Authorization (Initial Authorization)

Length of Approval: 2 Weeks [1, I]
For diagnosis of Irritable Bowel Syndrome with Diarrhea (IBS-D)

• Diagnosis of irritable bowel syndrome with diarrhea (IBS-D) [F]
AND
• Patient is 18 years of age or older [L]
AND
• Trial and failure, contraindication, or intolerance to a Tricyclic Antidepressant (e.g., amitriptyline)

Xifaxan 550 mg tablets*

NOTE: *If patient meets criteria above, please approve at GPI-14.

Prior Authorization (Reauthorization)

Length of Approval: 2 Weeks [1, I]
For diagnosis of Irritable Bowel Syndrome with Diarrhea (IBS-D)

• Symptoms of Irritable Bowel Syndrome continue to persist [G, H]
AND
• Patient demonstrates positive clinical response to therapy as evidenced by both of the following: [1]
• Improvement in abdominal pain
• Reduction in the Bristol Stool Scale
AND
• Trial and failure, contraindication, or intolerance to a Tricyclic Antidepressant (e.g., amitriptyline)

Xifaxan 550 mg tablets*

NOTE: *If patient meets criteria above, please approve at GPI-14.

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Prophylaxis of Hepatic Encephalopathy (HE) Recurrence

• Used for prophylaxis of hepatic encephalopathy (HE) recurrence
AND
• Patient is 18 years of age or older [L]
AND
• One of the following: [J, 22]
• Both of the following:
• Used as add-on therapy to lactulose
AND
• Patient is unable to achieve an optimal clinical response with lactulose monotherapy
OR
• History of contraindication or intolerance to lactulose

Xifaxan 550 mg tablets*

NOTE: *If patient meets criteria above, please approve at GPI-14.

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Prophylaxis of Hepatic Encephalopathy (HE) Recurrence

• Patient demonstrates positive clinical response to therapy [M, 27, 28]

Xifaxan

Prior Authorization

Length of Approval: 12 Month(s)
For diagnosis of Treatment of Hepatic Encephalopathy (Off-Label)

• Used for the treatment of hepatic encephalopathy (HE) [5, K]
AND
• Patient is 18 years of age or older [L]
AND
• One of the following: [22, K]
• Both of the following:
• Used as add-on therapy to lactulose
AND
• Patient is unable to achieve an optimal clinical response with lactulose monotherapy
OR
• History of contraindication or intolerance to lactulose

P & T Revisions

2024-06-18, 2023-10-17, 2023-06-19, 2022-09-19, 2022-09-19, 2022-07-01, 2021-09-28, 2021-05-10, 2020-05-07

References

1. Xifaxan prescribing information. Salix Pharmaceuticals, Inc. Bridgewater, NJ. October 2020.
2. DuPont HL, Jiang Z-D, 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.
3. Riddle MS, Connor BA, Beeching NJ, et al. Guidelines for the prevention and treatment of travelers’ diarrhea: a graded expert panel report. J Travel Med. 2017;24(suppl 1):S63-S80.
4. Williams R, James OFW, Warnes TW, Morgan MY. Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study. Eur J Gastroenterol Hepatol. 2000;12(2):203-8.
5. DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically. Accessed June 10, 2019.
6. Guerrant R, Van Gilder T, Steiner T, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis. 2001;32:331-50.
7. Singh V, Toskes P. Small Bowel Bacterial Overgrowth: Presentation, Diagnosis, and Treatment. Curr Treat Options Gastroenterol. 2004;7:19-28.
8. Lauritano E, Gabrielli M, Lupascu A, et al. Rifaximin Dose-Finding Study for the Treatment of Small Intestinal Bacterial Overgrowth. Aliment Pharmacol Ther. 2005;22:31-35.
9. Connors BA. Travelers’ diarrhea: CDC Health Information for International Travel. Centers for Disease Control and Prevention; 2020. Available at: https://wwwnc.cdc.gov/travel/yellowbook/2018/the-pre-travel-consultation/travelers-diarrhea. Accessed June 22, 2022.
10. Scarpellini E, Gabrielli M, Lauritano CE, et al. High dosage rifaximin for the treatment of Small Intestinal Bacterial Overgrowth. Aliment Pharmacol Ther. 2007; 25(7):781.
11. Diemert D.J. Prevention and Self-Treatment of Traveler's Diarrhea. Clin Microbiol Rev. 2006;19(3):583-594.
12. Pimental M, Lembo A, Chey W.D., et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation (TARGET I and II). New Engl J Med. 2011; 364: 22-32.
13. Boltin D, Perets T.T., Shporn E., et al. Rifaximin for small intestinal bacterial overgrowth in patients without irritable bowel syndrome. Ann Clin Microbiol Antimicrob. 2014;13:49.
14. Schoenfeld P, Pimentel M, Chang L., et al. Safety and tolerability of Rifaximin for the treatment of irritable bowel syndrome without constipation: a pooled analysis of randomized, double-blind, placebo-controlled trials. Aliment Pharmacol Ther. 2014;39:1161-1168.
15. Drossman, D., 2016. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features, and Rome IV. Gastroenterology, 150(6), pp.1262-1279.e2.
16. Pimentel M, Chang C, Chua KS, et al. Antibiotic treatment of constipation-predominant irritable bowel syndrome. Dig Dis Sci 2014;59:1278.
17. Walters B, Vanner SJ. Detection of bacterial overgrowth in IBS using thelactulose H2 breath test: Comparison with the 14C-d-xylose and healthy controls. Am J Gastroenterol. 2005;1566-1570.
18. Attar A, Flourie B, Rambaud JC, et al. Antibiotic efficacy in small intestinal bacterial overgrowth-related chronic diarrhea: a crossover, randomized trial. Gastroenterology. 1999;117:794-797.
19. Tahan S, Melli LC, Mello CS, et al. Effectiveness of trimethoprim-sulfamethoxazole and metronidazole in the treatment of small intestinal bacterial overgrowth in children living in a slum. J Pediatr Gastroenterol Nutr 2013;57:316.
20. Lewis SJ, Potts LF, Malhotra R, et al. Small bowel bacterial overgrowth in subjects living in residential care homes. Age Ageing. 1999;28:181-185.
21. Miazga A, Osinski M, Cichy W and Zaba R. Current views on the etiopathogenesis, clinical manifestation, diagnostics, treatment and correlation with other nosological entities of SIBO. Advances in Medical Sciences. 2015(60):118-124.
22. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic Encephalopathy in Chronic Liver Disease: 2014 Practice Guideline by AASLD and EASL. Hepatology 2014;60:715.
23. Weinberg, D., Smalley, W., Heidelbaugh, J. and Sultan, S., 2014. American Gastroenterological Association Institute Guideline on the Pharmacological Management of Irritable Bowel Syndrome. Gastroenterology, 147(5), pp.1146-1148.
24. Karuppiah S, Pomianowski K. Rifaximin (Xifaxan) for Irritable Bowel Syndrome. Am Fam Physician. 2017 Feb 15;95(4):258-259.
25. Ford AC, Moayyedi P, Chey WD, Harris LA, Lacy BE, Saito YA, Quigley EMM; ACG Task Force on Management of Irritable Bowel Syndrome. American College of Gastroenterology Monograph on Management of Irritable Bowel Syndrome. Am J Gastroenterol. 2018 Jun;113(Suppl 2):1-18.
26. Scarpellini E, Giorgio V, Gabrielli M, Filoni S, Vitale G, Tortora A, Ojetti V, Gigante G, Fundarò C, Gasbarrini A. Rifaximin treatment for small intestinal bacterial overgrowth in children with irritable bowel syndrome. Eur Rev Med Pharmacol Sci. 2013 May;17(10):1314-20.
27. Bass, N., Mullen, K., Sanyal, A., Poordad, F., Neff, G., & Leevy, C. et al. (2010). Rifaximin Treatment in Hepatic Encephalopathy. New England Journal Of Medicine, 362(12), 1071-1081.
28. Kimer, N., Krag, A., Møller, S., Bendtsen, F., & Gluud, L. (2014). Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Alimentary Pharmacology &Amp; Therapeutics, 40(2), 123-132.

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End Notes

1. Antibiotic treatment should be avoided in diarrhea caused by enterohemorrhagic E. coli. [6]
2. The main goals in the treatment of SBBO are 1) treatment of underlying small intestinal abnormality, when possible; 2) concentration on long-term antibiotic therapy when surgical management is not feasible; 3) adjunctive treatment of dysmotility, such as a prokinetic agent; and 4) nutritional support, particularly in patients with weight loss or vitamin deficiency. [7]
3. In most patients, a single course of treatment (10 days) markedly improves symptoms, and patients may remain free of symptoms for months. In others, symptoms recur quickly, and acceptable results can only be obtained with cyclic treatment (1 of every 4 weeks). In still others, continuous treatment may be needed for 1 to 2 months. If the antimicrobial agent is effective, a resolution or marked diminution of symptoms will be notable within several days of initiating therapy. Diarrhea and steatorrhea will decrease, and cobalamin malabsorption will be corrected. [7]
4. According to the Centers for Disease Control and Prevention's Yellow Book, antibiotics may be used to treat cases of moderate to severe travelers’ diarrhea. Fluoroquinolones including, but not limited to, ciprofloxacin and levofloxacin, are considered first line agents in the treatment of Traveler's Diarrhea (TD). Azithromycin is also considered a first line agent for treatment of TD and is especially efficacious in the pediatric population. The overall usefulness of Rifaximin for empiric self-treatment remains to be determined as Rifaximin has only been shown to be efficacious in patients with noninvasive strains of E. coli. [9]
5. Levofloxacin, ofloxacin and ciprofloxacin have all been shown to be highly effective in the treatment and prevention of Travelers' Diarrhea and should be considered first-line therapy options for this indication. [11]
6. In the TARGET I, II and III pivotal trials, Irritable Bowel Syndrome was diagnosed using the ROME II diagnostic criteria. According to the ROME-II criteria, an IBS-D diagnosis requires at least 12 consecutive weeks in the previous 12 months of abdominal discomfort or pain that has two out of the three following features: relieved with defecation; and/or onset associated with a change in frequency of stool; and/or onset associated with a change in appearance of stool [12, 14]
7. In the TARGET III pivotal trial, a total of 636 responders (59%) required retreatment. The median time to recurrence for patients who experienced initial response was 10 weeks (range from 6 to 24 weeks) [14]
8. According to the ROME-IV criteria, recurrent signs and symptoms of IBS-D include the following: a return of abdominal pain or mushy/watery stool consistency for at least 3 weeks during a 4-week follow-up period. [15]
9. The recommended dose of Xifaxan for IBS-D is one 550 mg tablet taken orally three times a day for 14 days. [1]
10. The American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) recommend rifaximin as an effective add-on therapy to lactulose for prevention of over hepatic encephalopathy with strength of recommendation 1A. No solid data support the use of rifaximin alone. [22]
11. Rifaximin has been used for the treatment of HE in a number of trials comparing it with placebo, other antibiotics, nonabsorable disaccharides, and in dose-ranging studies. These trials showed effect of rifaximin that was equivalent or superior to the compared agents with good tolerability. No solid data support the use of rifaximin alone. [22]
12. A minimum age requirement that aligns with the prescribing information was added for prophylaxis and treatment of hepatic encephalopathy and IBS-D to prevent misuse of Xifaxan in pediatrics. The same age requirement was not added for traveler’s diarrhea or SBBO/SIBO due to the patient population (e.g., pediatrics) that Xifaxan was studied in. [1, 8, 10, 13, 26]
13. The risk of a breakthrough episode of hepatic encephalopathy (HE) in patients who recently had history of recurrent overt HE was reduced while taking Xifaxan. Additionally, patients on Xifaxan achieved full resolution of HE, so there is benefit with long-term use of Xifaxan for the prophylaxis of HE. [27, 28]

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Revision History

• 2024-06-18: 2024 Annual Review.
• 2023-10-17: Program update to standard reauthorization language. No changes to clinical intent.
• 2023-06-19: 2023 Annual Review.
• 2022-09-19: Program Update.
• 2022-09-19: Program Update.
• 2022-07-01: 2022 UM Annual Review.
• 2021-09-28: 2021 UM Annual Review.
• 2021-05-10: 2021 UM Annual Review.
• 2020-05-07: 2020 UM Annual Review.

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