XIFAXAN, Rifaximin Form

Rifaximin (Xifaxan®) is a rifamycin antibacterial. FDA Approved Indication(s) Xifaxan is indicated for the: • Treatment of travelers’ diarrhea (TD) caused by noninvasive strains of Escherichia coli in adult and pediatric patients 12 years of age and older • Reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults • Treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults Limitation(s) of use in TD: Do not use in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli.
Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Xifaxan is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Hepatic Encephalopathy (must meet all):

1. Diagnosis of HE;
   2. Age ≥ 18 years;
   3. Failure of lactulose monotherapy in the past 30 days at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
   4. Xifaxan is prescribed concurrently with lactulose, unless contraindicated or clinically significant adverse effects are experienced;
2. Dose does not exceed 1,100 mg (2 tablets) per day. Approval duration:
   HIM/Medicaid – 6 months
   Commercial – 12 months or duration of request, whichever is less B. Irritable Bowel Syndrome with Diarrhea (must meet all):

3. Diagnosis of IBS-D;

   2. Age ≥ 18 years; Page 1 of 9

   CLINICAL POLICY Rifaximin

4. Failure of an anti-diarrheal agent (e.g., loperamide) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
5. Failure of an antispasmodic (e.g., dicyclomine) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
6. Dose does not exceed 1,650 mg (3 tablets) per day. Approval duration: 14 days
   C. Travelers’ Diarrhea (must meet all):
7. Diagnosis of TD;
   2. Age ≥ 12 years;
   3. Failure of azithromycin 1,000 mg as a single dose, unless contraindicated or clinically significant adverse effects are experienced;
8. Dose does not exceed 600 mg (3 tablets) per day.
   Approval duration: 3 days D. Small Intestinal Bacterial Overgrowth (off-label) (must meet all):
   1. Diagnosis of small intestinal bacterial overgrowth (SIBO);
   2. Age ≥ 12 years;
   3. Dose does not exceed 1,650 mg (3 tablets) per day.
      Approval duration: Up to 14 days E. Other diagnoses/indications (must meet 1 or 2):
9. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
10. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    II. Continued Therapy A. Hepatic Encephalopathy (must meet all):

11. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; Page 2 of 9

    CLINICAL POLICY Rifaximin b. Member is receiving benefit from the referenced states for the applicable product and regulation (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

12. Xifaxan is prescribed concurrently with lactulose, unless contraindicated or clinically significant adverse effects are experienced;
    3. Member is responding positively to therapy;
    4. If request is for a dose increase, new dose does not exceed 1,100 mg (2 tablets) per day. Approval duration:
       HIM/Medicaid – 12 months
       Commercial – 12 months or duration of request, whichever is less B. Irritable Bowel Syndrome with Diarrhea (must meet all):
13. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is receiving benefit from the referenced states for the applicable product and regulation (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
14. Member has not had ≥ three 14-day treatment courses that started within the last 6 months;
15. Member is responding positively to therapy;
    4. If request is for a dose increase, new dose does not exceed 1,650 mg (3 tablets) per day. Approval duration: 14 days C. Travelers’ Diarrhea
16. Re-authorization is not permitted. Members must meet the initial approval criteria. Review initial approval criteria for new cases of travelers’ diarrhea unrelated to original medication request. Approval duration: Not applicable D. Small Intestinal Bacterial Overgrowth (off-label) (must meet all):
17. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is receiving benefit from the referenced states for the applicable product and regulation (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

18. Member is responding positively to therapy;

    3. If request is for a dose increase, new dose does not exceed 1,650 mg (3 tablets) per day. Approval duration: Up to 14 days Page 3 of 9

    CLINICAL POLICY Rifaximin E. Other diagnoses/indications (must meet 1 or 2):

19. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

20. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration
    HE: hepatic encephalopathy
    IBS-D: irritable bowel syndrome with diarrhea SIBO: small intestinal bacterial overgrowth
    TD: travelers’ diarrhea
    Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose* 500 mg/day PO is FDA-approved dosage; however, doses up to 1,200 mg/day PO are used off-label; 2 g PO when given as single dose azithromycin (Zithromax®) TD 1,000 mg PO single dose Page 4 of 9

    CLINICAL POLICY Rifaximin Drug Name Dosing Regimen lactulose (Enulose®) dicyclomine (Bentyl®) hyoscyamine (Levsin, Levbid) loperamide (Imodium A-D) diphenoxylate/atropine (Lomotil) HE 30 to 45 mL, containing 20 g to 30 g of lactulose), PO TID-QID; may be adjusted every day or two to produce 2 or 3 soft stools daily IBS-D 20 mg PO QID IBS-D Levsin: 0.125 – 0.25 mg PO Q 4h Levbid: 0.375 – 0.75 mg PO Q 12h IBS-D 2 to 4 mg PO up to QID IBS-D Initially, 5 mg (2 tablets) PO QID; Discontinue after 10 days if clinical improvement is not observed Dose Limit/ Maximum Dose Specific maximum dosage information is not available 160 mg/day 1.5 mg/day 16 mg/day 20 mg/day (of diphenoxylate) Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Maximum dose of the drug, not indication specific
    Appendix C: Contraindications/Boxed Warnings • Contraindication(s): history of hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any of the components of Xifaxan • Boxed warning(s): none reported Appendix C: General Information • Per the 2014 hepatic encephalopathy practice guidelines by the American Association for the Study of Liver Diseases, rifaximin is recommended as an add-on to lactulose to prevent overt HE recurrence. No solid data support the use of rifaximin alone. In the clinical trials for approval of Xifaxan for HE, 91% of the patients were using lactulose concomitantly. Differences in the treatment effect of those patients not using lactulose concomitantly could not be assessed. • Xifaxan 550 mg 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 1,200 mg/day or 1,600 mg/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 1,600 mg/day had normalized GBT, compared to 58% of patients on 1,200 mg/day (P < 0.05, OR 1.82, 95% CI 1.09–8.01). V. Dosage and Administration
    Indication HE IBS-D Dosing Regimen 550 mg PO BID 550 mg PO TID for 14 days Maximum Dose 1,100 mg daily 1,650 mg daily Page 5 of 9

    CLINICAL POLICY Rifaximin Indication TD SIBO Dosing Regimen Adults and children ≥ 12 years of age: 200 mg PO TID for 3 days 200 mg PO TID for 7 days Or 550 mg PO BID for 14 days 550 mg PO TID for 7 days may be considered in patients with SIBO and IBS Maximum Dose 600 mg daily 1,650 mg daily VI. Product Availability
    Tablets: 200 mg, 550 mg VII.