Clinical Guideline ​ Guideline Number: PG022, Ver. 1

Xifaxan (rifaximin)

Disclaimer Clinical guidelines are developed and adopted to establish evidence-based clinical criteria for utilization management decisions. Oscar may delegate utilization management decisions of certain services to third-party delegates who may develop and adopt their own clinical criteria.

The clinical guidelines are applicable to all commercial plans. Services are subject to the terms, conditions, limitations of a member’s plan contracts, state laws, and federal laws. Please reference the member’s plan contracts (e.g., Certificate/Evidence of Coverage, Summary/Schedule of Benefits) or contact Oscar at 855-672-2755 to confirm coverage and benefit conditions.

Summary Xifaxan (Rifaximin) is an intestinal antibiotic that comes in two different formulation strengths - 200 mg tablets and 550 mg tablets. It works by inhibiting bacterial and mycobacterial RNA synthesis. It is FDA indicated for use in hepatic encephalopathy, irritable bowel syndrome with diarrhea, and traveler’s diarrhea. The 200 mg formulation is used for treatment of traveler’s diarrhea and the 550 mg formulation is used for treatment of hepatic encephalopathy and irritable bowel syndrome with diarrhea.

The most common potential adverse reactions associated with drug administration are gastrointestinally related (i.e. abdominal pain, nausea, ascites).

Definitions “Hepatic encephalopathy” is a reversible impairment of neuropsychiatric function associated with ​ impaired hepatic function.

“Irritable bowel syndrome” is a chronic functional disorder of the gastrointestinal tract characterized by ​ chronic abdominal pain and altered bowel habits in the absence of an organic disease.

“Small Intestinal Bacterial Overgrowth (SIBO)” is a condition in which the small bowel is colonized by ​ excessive aerobic and anaerobic microbes that are normally present in the colon.

“Traveler’s diarrhea” is diarrhea that develops in individuals from resource-rich settings during or within ​ 10 days of returning from travel to resource-limited countries or regions.

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Hepatic Encephalopathy: Medical Necessity Criteria for Initial Authorization Oscar covers Xifaxan (rifaximin) 550 mg when ALL of the following criteria are met: 1. Member is age 18 years or older; and ​ 2. Member has a diagnosis of hepatic encephalopathy; and ​ 3. Member has documented trial and failure, intolerance to, or contraindication to lactulose

If the above prior authorization criteria are met, the requested medication will be approved for 12 months. ​

Medical Necessity Criteria for Reauthorization: 1. Authorization may be granted for continuation of therapy when all criteria for initial authorization are met

If the above prior authorization criteria is met, the requested medication will be approved for 12 months. ​

Irritable Bowel Syndrome with diarrhea: Medical Necessity Criteria for Initial Authorization Oscar covers Xifaxan (rifaximin) 550 mg when ALL of the following criteria are met: 1. Age 18 years or older; and ​ 2. Member has a diagnosis of irritable bowel syndrome with diarrhea; and ​ 3. Member has documented trial and failure, intolerance to, or contraindication to TWO of the ​ ​ following: a. Antispasmodic agents (such as dicyclomine, hyoscyamine) b. Antidiarrheal agents (such as loperamide) c. Tricyclic antidepressants (such as amitriptyline, nortriptyline, imipramine)

If the above prior authorization criteria are met, the requested medication will be approved for 14 days.

Medical Necessity Criteria for Reauthorization: Oscar covers Xifaxan (rifaximin) 550 mg when ALL of the following criteria are met: 1. Member is age 18 years or older; and ​ 2. Member has a diagnosis of irritable bowel syndrome with diarrhea; and ​ 3. Member is experiencing a recurrence of symptoms; and ​ 4. Member has not received more than 3 total treatment cycles of 14 days each in the last 365 days.

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If the above prior authorization criteria are met, the requested medication will be approved for 14 days at at time (up to 3 total treatment cycles per year). ​

Small Intestinal Bacterial Overgrowth (SIBO): Medical Necessity Criteria for Initial Authorization Oscar covers Xifaxan (rifaximin) 550 mg when ALL of the following criteria are met: 1. Member is age 18 years or older; and ​ 2. Prescribing physician is a gastroenterologist specialist or is being prescribed in consultation with a gastroenterologist 3. Member has a diagnosis of small intestinal bacterial overgrowth; and ​ 4. Member has documented trial and failure, intolerance to, or contraindication to ONE of the ​ ​ following: a. Amoxicillin / Clavulanic Acid b. Ciprofloxacin c. Metronidazole d. Sulfamethoxazole / Trimethoprim e. Doxycycline

If the above prior authorization criteria are met, the requested medication will be approved for 14 days.

Medical Necessity Criteria for Reauthorization: Oscar covers Xifaxan (rifaximin) 550 mg when ALL of the following criteria are met: 1. Member is age 18 years or older; and ​ 2. Member has a diagnosis of small intestinal bacterial overgrowth; and ​ 3. Member is experiencing a recurrence of symptoms; and ​ 4. Member has not received more than 2 total treatment cycles of 14 days each in the last 90 days.

If the above prior authorization criteria are met, the requested medication will be approved for 14 days at at time (up to 2 total treatment cycles).

Travelers’ Diarrhea: Medical Necessity Criteria for Initial Authorization Oscar covers Xifaxan (rifaximin) 200 mg when ALL of the following criteria are met: ​ ​ 1. Member is age 12 years or older and ​ 2. Member has a diagnosis of travelers’ diarrhea; and ​ 3. Member has documented trial and failure, intolerance to, or contraindication to ONE of the ​ ​ following: a. Azithromycin b. Ciprofloxacin c. Levofloxacin

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d. Ofloxacin

If the above prior authorization criteria are met, the requested medication will be approved for 1 month.

Experimental or Investigational / Not Medically Necessary Xifaxan for any other indication is not covered by Oscar as it is considered experimental, investigational, ​ ​ or unproven.

References 1. American College of Gastroenterology Task Force on Irritable Bowel Syndrome, Brandt LJ, Chey WD, et al. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol 2009; 104 Suppl 1:S1. 2. Bajaj JS, Barrett AC, Bortey E, et al. Prolonged remission from hepatic encephalopathy with rifaximin: results of a placebo crossover analysis. Aliment Pharmacol Ther 2015; 41:39. 3. Quigley EM, Abu-Shanab A. Small intestinal bacterial overgrowth. Infect Dis Clin North Am 2010; 24:943. 4. Sanyal A, Younossi ZM, Bass NM, et al. Randomised clinical trial: rifaximin improves health-related quality of life in cirrhotic patients with hepatic encephalopathy - a double-blind placebo-controlled study. Aliment Pharmacol Ther 2011; 34:853. 5. Shah SC, Day LW, Somsouk M, Sewell JL. Meta-analysis: antibiotic therapy for small intestinal bacterial overgrowth. Aliment Pharmacol Ther 2013; 38:925. 6. Steffen R, Sack DA, Riopel L, et al. Therapy of travelers' diarrhea with rifaximin on various continents. Am J Gastroenterol 2003; 98:1073.

Clinical Guideline Revision / History Information

Original Date: 08/06/2020 Reviewed/Revised:

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