CurrentCentenePolicy CP PMN.47

Clinical Policy: Rifaximin (Xifaxan)

Defines medical necessity, authorization, and renewal criteria for rifaximin (Xifaxan) for Centene lines of business (Commercial, HIM, Medicaid) for labeled and certain off-label uses.

Policy Summary

PayerCentene

PolicyRifaximin (Xifaxan) coverage

Policy CodePolicy CP PMN.47

Change TypeNo material changes

Effective DateNov 1, 2011

Next Review DateNov 24, 2024

Key ActionSubmit prior authorization with documentation that the patient meets indication-specific criteria, dosing limits, and required prior therapy or concurrent therapy (e.g., lactulose for HE).

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

3FDA-approved indications listed

12 moHE approval duration (commercial)

14 daysIBS-D approval duration

3 daysTD approval duration

200/550 mgTablet strengths

Coverage Criteria

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Initial Therapy

Covered when ALL of the following are met for each indication (separate groups below):

Hepatic Encephalopathy - Initial: 1) Diagnosis of hepatic encephalopathy (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 (rifaximin) is prescribed concurrently with lactulose unless contraindicated or clinically significant adverse effects are experienced; 5) Dose does not exceed 1,100 mg (2 tablets) per day.

Irritable Bowel Syndrome with Diarrhea - Initial: 1) Diagnosis of IBS-D; 2) Age ≥ 18 years; 3) Failure of an antispasmodic (e.g., dicyclomine) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced; 4) Dose does not exceed 1,650 mg (3 tablets) per day.

Travelers' Diarrhea - Initial: 1) Diagnosis of travelers' diarrhea (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; 4) Dose does not exceed 600 mg (3 tablets) per day; Note: Do not use in diarrhea with fever, bloody stool, or due to pathogens other than noninvasive E. coli.

Small Intestinal Bacterial Overgrowth (Off-label) - Initial: 1) Diagnosis of SIBO; 2) Age ≥ 12 years; 3) Dose does not exceed 1,650 mg (3 tablets) per day.

Continuation Therapy

Covered for continuation when the member meets indication-specific continuation criteria:

Hepatic Encephalopathy - Continued Therapy: 1) Member is currently receiving the medication via the Centene benefit or previously met initial approval criteria; 2) Member is responding positively to therapy; 3) Xifaxan is prescribed concurrently with lactulose unless contraindicated or clinically significant adverse effects are experienced; 4) If request is for a dose increase, new dose does not exceed 1,100 mg (2 tablets) per day.

Irritable Bowel Syndrome with Diarrhea - Continued Therapy: 1) Member is currently receiving the medication via the Centene benefit or previously met initial approval criteria; 2) Member is responding positively to therapy; 3) Member has not had ≥ three 14-day treatment courses that started within the last 6 months; 4) If request is for a dose increase, new dose does not exceed 1,650 mg (3 tablets) per day.

Travelers' Diarrhea - Continued Therapy: Re-authorization is not permitted; members must meet the initial approval criteria for new cases unrelated to the original medication request.

Hepatic Encephalopathy — coverage considerations

Coverage and authorization considerations referenced in the document include indication-specific dosing limits and guideline-based requirements.

Hepatic Encephalopathy (HE): Rifaximin covered when used to prevent overt HE recurrence as add-on therapy to lactulose per AASLD guideline; clinical trials had most patients on concurrent lactulose and no solid data support rifaximin alone.max 1,100 mg/day

Concurrent lactulose use is expected per guideline-based recommendation.

IBS-D and SIBO — coverage considerations

Indication-specific regimens and evidence summaries for IBS-D and SIBO.

IBS-D: Coverage for IBS-D references a dosing regimen of 550 mg PO three times daily for 14 days; maximum daily dose 1,650 mg/day.550 mg TID x14 days; max 1,650 mg/day

Regimen and limits cited in dosing table and guideline references.

SIBO: Multiple regimens noted for SIBO: 200 mg PO TID for 7 days, 550 mg PO BID for 14 days, and 550 mg PO TID for 7 days; higher-dose regimens (e.g., 1,200–1,600 mg/day) were studied with glucose breath test normalization as an outcome; maximum daily dose listed as 1,650 mg/day.up to 1,650 mg/day

Evidence includes dose-finding and randomized trials referenced in the appendix.

Traveler's Diarrhea — coverage considerations

Traveler's diarrhea (TD) dosing and coverage notes.

Travelers' Diarrhea (TD): Adults and children ≥ 12 years: 200 mg PO three times daily for 3 days (maximum 600 mg/day).200 mg TID x3 days; max 600 mg/day

Guidance and literature references (CDC and gastroenterology sources) cited.

Requests for use of rifaximin (Xifaxan) for non‑FDA approved indications that are not specifically addressed in this policy will not be authorized unless the provider submits sufficient supporting documentation of efficacy and safety in accordance with the applicable off‑label use policy (see CP.CPA.09 for commercial lines and HIM.PA.154 for health insurance marketplace).

Rifaximin (Xifaxan) is contraindicated in patients with a known history of hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any component of Xifaxan.

Uses of rifaximin for indications that are not FDA‑approved and are not addressed by this policy are considered not authorized without supporting off‑label documentation submitted per the plan’s off‑label use policies.

Off‑label criteria for Crohn’s disease were removed from the policy during the 4Q2020 annual review because use for Crohn’s disease is not supported by current treatment guidelines; the change and supporting references were documented in the policy history.

Initial Therapy Criteria

Initial therapy

Initial authorization requires meeting indication-specific criteria including age limits, prior therapy failure where specified, and dosing constraints.

Initial therapy - General: Provider must document diagnosis and that all indication-specific initial criteria (age, prior therapy trial/failure when required, and adherence to dosing limits) are met before initial approval is granted.

HE-specific initial requirements: Diagnosis of HE; age > 18 years; failure of lactulose monotherapy in past 30 days at maximally indicated doses unless contraindicated; Xifaxan prescribed concurrently with lactulose unless contraindicated; dose ≤ 1,100 mg/day.

IBS-D-specific initial requirements: Diagnosis of IBS-D; age ≥ 18 years; failure of an antispasmodic at up to maximally indicated doses unless contraindicated; dose ≤ 1,650 mg/day.

TD-specific initial requirements: Diagnosis of travelers' diarrhea; age ≥ 12 years; failure of azithromycin 1,000 mg single dose unless contraindicated; dose ≤ 600 mg/day; not for diarrhea with fever, bloody stool, or due to noninvasive E. coli exclusion conditions.

SIBO-specific initial requirements (off-label): Diagnosis of SIBO; age ≥ 12 years; dose ≤ 1,650 mg/day; approval duration limited per policy (up to 14 days).

Initial therapy regimens by indication

Initial therapy regimens vary by indication.

IBS-D initial therapy: 550 mg PO three times daily for 14 days (maximum 1,650 mg/day).550 mg TID x14 days

HE initial therapy: Regimen per dosing table with maximum 1,100 mg daily; typically used as add-on to lactulose per guidelines.max 1,100 mg/day

TD initial therapy: Adults and children ≥ 12 years: 200 mg PO three times daily for 3 days (maximum 600 mg/day).200 mg TID x3 days

SIBO initial therapy:

Continuation Therapy Criteria

Continuation criteria

Requirements for continuation mirror initial criteria and require evidence of benefit and adherence to dose limits.

Continuation - General: Continuation/renewal requires documentation that the member is responding positively to therapy and that dosing remains within indication-specific maximums; member should be currently receiving the medication via Centene benefit or have previously met initial approval criteria.

HE continuation specific: Currently receiving medication via Centene benefit or previously met initial approval criteria; responding positively to therapy; Xifaxan prescribed concurrently with lactulose unless contraindicated; dose ≤ 1,100 mg/day.

IBS-D continuation specific: Currently receiving medication via Centene benefit or previously met initial approval criteria; responding positively to therapy; member has not had ≥ three 14-day courses that started within the last 6 months; dose ≤ 1,650 mg/day.

SIBO continuation specific: Currently receiving medication via Centene benefit or previously met initial approval criteria; responding positively to therapy; dose ≤ 1,650 mg/day.

TD continuation specific: Re-authorization is not permitted for travelers' diarrhea; new cases must meet initial approval criteria.

Continuation therapy notes

Policy history and operational notes relevant to continuation authorizations.

Continuation therapy notes: Policy history documents template changes to continuation and approval durations; continued therapy requires meeting the stated clinical criteria in the policy and providing evidence of benefit. Specific administrative changes to approval durations have been applied over time (see policy history).

See full policy for historical approval-duration details and state-specific addendums.

Provider Actions and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required. Requests must include documentation that the patient meets the specific initial or continuation criteria for the requested indication and dosing regimen. Prior authorization decisions will reflect indication-specific dosing limits (see dosing: HE max 1,100 mg/day; IBS-D and SIBO high-dose up to 1,650 mg/day; TD max 600 mg/day). Requests exceeding maximum indicated daily doses or with documented hypersensitivity to rifaximin or rifamycin agents may be denied.

Indication-specific dose limits: HE ≤ 1,100 mg/day; IBS-D ≤ 1,650 mg/day; SIBO (when used high-dose for IBS) ≤ 1,650 mg/day; TD ≤ 600 mg/day.

Documentation Required

Provider must submit supporting clinical documentation (e.g., office chart notes, lab results, prescriptions) demonstrating the member meets all approval criteria for the requested indication and dosing. Documentation should explicitly support the clinical indication and the concomitant therapies when required (for example, documented IBS for SIBO high‑dose use; evidence of concurrent lactulose for hepatic encephalopathy).

Examples of acceptable documentation: office notes, diagnostic test results (e.g., glucose breath test for SIBO), medication history showing prior therapies, lactulose use for HE.

Denial Risk

Non‑FDA Indications Risk Denial

Non‑FDA approved indications that are not addressed in this policy are not authorized unless there is sufficient documentation of efficacy and safety per the applicable off‑label use policies. Requests for off‑label uses without adequate supporting evidence may be denied.

Off‑label policies: CP.CPA.09 (commercial), HIM.PA.154 (marketplace).

Step Therapy

Step Therapy / Prior Failures

Step therapy requirements and prior failures must be documented where specified: for hepatic encephalopathy (HE), failure of lactulose monotherapy at up to maximally indicated doses within the past 30 days is required unless lactulose is contraindicated or not tolerated; for IBS‑D, documented trial and failure of an antispasmodic (e.g., dicyclomine) at maximally indicated doses is required unless contraindicated; for traveler’s diarrhea, failure of azithromycin 1,000 mg single dose is required unless contraindicated.

HE: trial/failure of lactulose monotherapy (unless contraindicated) in past 30 days.
IBS‑D: trial/failure of an antispasmodic at maximally indicated doses.
TD: trial/failure of azithromycin 1,000 mg single dose.

Note

Concurrent Lactulose Requirement (HE)

For hepatic encephalopathy, rifaximin is recommended as add‑on therapy to lactulose per clinical guidelines; concurrent lactulose use should be documented unless there is a contraindication or clinically significant adverse effect preventing its use.

If lactulose is contraindicated or not tolerated, document reason (e.g., adverse effects).
Clinical trial data: most HE trial patients used lactulose concomitantly; lack of lactulose may affect assessment of treatment effect.

Step Therapy Requirements

Indication	Required prior trial/failure or contraindication	Notes / dosing limits
Irritable Bowel Syndrome with Diarrhea (IBS-D)	Trial and inadequate response to an antispasmodic (e.g., dicyclomine) at up to maximally indicated doses, unless contraindicated or adverse effects	Typical initial regimen: 550 mg PO TID for 14 days; dose must not exceed 1,650 mg (3 tablets) per day. Approval duration: 14 days.
Travelers' Diarrhea (TD)	Failure of azithromycin 1,000 mg as a single dose, unless contraindicated or adverse effects	Dosing: 200 mg PO TID for 3 days (maximum 600 mg/day). Age ≥ 12 years. Approval duration: 3 days. Not for diarrhea with fever, bloody stool, or non‑E. coli pathogens.
Small Intestinal Bacterial Overgrowth (SIBO) — off‑label	No first‑line failure specified in policy; authorization reflects indication‑specific criteria per policy (off‑label may be considered with documentation)	Regimens noted include 200 mg PO TID for 7 days, 550 mg PO BID for 14 days, or 550 mg PO TID for 7 days; maximum daily dose not to exceed 1,650 mg/day.

Indication	Step therapy / prerequisite	Concurrent therapy expectation
Hepatic Encephalopathy (HE)	Initial authorization requires meeting HE-specific criteria including prior trial/response to lactulose monotherapy in the past 30 days at up to maximally indicated doses unless contraindicated (see initial criteria).	Rifaximin is recommended as add‑on therapy to lactulose per AASLD guidelines; clinical trials had most patients on concomitant lactulose (≈91%). Concurrent lactulose is expected unless contraindicated. Maximum dose: 1,100 mg/day.
Other indications (IBS‑D, TD, SIBO)	See indication‑specific step requirements (e.g., antispasmodic failure for IBS‑D; azithromycin single dose failure for TD).	Concurrent lactulose requirement applies specifically to HE; not required for IBS‑D, TD, or SIBO per policy.

Definitions

Hepatic encephalopathy — definition / key term

Hepatic encephalopathy (HE) — termHE = hepatic encephalopathy (condition for which rifaximin is used to prevent overt HE recurrence)

ContextRifaximin is recommended as add‑on therapy to lactulose to prevent overt HE recurrence (AASLD guideline); most clinical trial patients used lactulose concomitantly.

Age/approvalIndication (reduction in risk of overt HE recurrence) is an FDA‑approved adult indication for Xifaxan.

Irritable bowel syndrome with diarrhea (IBS‑D) — definition / key term

IBS‑D — termIBS‑D = irritable bowel syndrome with diarrhea

Approved useXifaxan is FDA‑approved for treatment of IBS‑D in adults with a recommended regimen of 550 mg PO TID for 14 days (maximum 1,650 mg/day).

Prior therapy requirementInitial approval requires trial and failure of an antispasmodic at maximally indicated doses unless contraindicated.

Small intestinal bacterial overgrowth (SIBO) — definition / key term

SIBO — termSIBO = small intestinal bacterial overgrowth

Treatment contextSIBO is an off‑label indication in this policy; various rifaximin regimens are described (e.g., 200 mg PO TID for 7 days; 550 mg PO BID for 14 days; 550 mg PO TID for 7 days).

Dose considerationsHigher‑dose regimens (e.g., 1,200–1,600 mg/day) were evaluated in trials and policy notes that 550 mg TID regimens may be appropriate for patients with documented IBS and SIBO; policy maximum listed as 1,650 mg/day.

Traveler's diarrhea (TD) — definition / key term

Traveler's diarrhea (TD) — termTD = travelers' diarrhea (caused by noninvasive E. coli in patients ≥12 years)

Limitation of useDo not use rifaximin for TD with fever, bloody stool, or due to pathogens other than Escherichia coli.

Typical regimenRecommended dosing: 200 mg PO TID for 3 days (maximum 600 mg/day) in adults and patients ≥12 years.

HE — Hepatic encephalopathy — clinical role / note

HE — clinical useRifaximin is used to prevent overt HE recurrence, typically as add‑on therapy to lactulose per guideline recommendations.

Trial data contextIn HE clinical trials, 91% of patients were using lactulose concomitantly; there are no strong data supporting rifaximin monotherapy for HE.

Authorization implicationPolicy expects Xifaxan to be prescribed concurrently with lactulose for HE unless contraindicated or intolerant.

SIBO — Small Intestinal Bacterial Overgrowth — treatment note

SIBO — clinical noteSmall Intestinal Bacterial Overgrowth is treated with various rifaximin regimens; some trials evaluated higher doses (e.g., 1,200–1,600 mg/day) with glucose breath test normalization as an outcome.

Regimen examplesExamples include 200 mg PO TID for 7 days, 550 mg PO BID for 14 days, and 550 mg PO TID for 7 days; 550 mg TID has been used in patients with documented IBS and SIBO.

Policy statusSIBO is considered off‑label in the policy but may be authorized up to 14 days when criteria are met.

OpenPayer

Clinical Policy: Rifaximin (Xifaxan)

Coverage Criteria

Initial Therapy Criteria

Continuation Therapy Criteria

Provider Actions and Documentation

Dose Limits and Coding

Step Therapy Requirements

Quantity and Maximums

Definitions

Background

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