Subject: Xifaxan 550 mg PA 681-A P04-2026

Drug

XIFAXON  (rifaximin)

Policy:

Indications

FDA-approved Indications

Hepatic Encephalopathy

Xifaxan is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults.

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

Irritable Bowel Syndrome with Diarrhea

Xifaxan is indicated for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.

Compendial Uses

Small intestinal bacterial overgrowth (SIBO)³

Coverage Criteria

Hepatic Encephalopathy (HE)

Authorization may be granted when the requested drug is being prescribed to reduce the risk of overt hepatic encephalopathy (HE) recurrence when the following criteria is met:

·        The requested drug is being used as add-on therapy to lactulose.

Irritable Bowel Syndrome with Diarrhea (IBS-D)

Authorization may be granted when the requested drug is being prescribed for the treatment of irritable bowel syndrome with diarrhea (IBS-D) when ONE of the following criteria is met:

·        The patient has NOT previously received treatment with the requested drug for IBS-D.

·        The patient has previously received treatment with the requested drug for IBS-D and ALL of the following criteria are met:

§  The patient is experiencing a recurrence of symptoms.

§  The patient has received fewer than three 14-day courses of treatment with the requested drug for the treatment of IBS-D.

Small Intestinal Bacterial Overgrowth (SIBO)

Authorization may be granted when the requested drug is being prescribed for the treatment of small intestinal bacterial overgrowth (SIBO) when ONE of the following criteria is met:

·        The patient’s diagnosis has been confirmed by ONE of the following: quantitative culture of upper gut aspirate, breath testing (e.g., lactulose hydrogen or glucose hydrogen breath test).

·        The patient is experiencing a recurrence of SIBO after completion of a successful course of the requested drug.

Duration of Approval (DOA)

·        681-A:

§  Hepatic Encephalopathy (HE): DOA: 12 months

§  Irritable Bowel Syndrome with Diarrhea (IBS-D): DOA: 14 days

§  Small Intestinal Bacterial Overgrowth (SIBO): DOA: 14 days

Place of Service:

Outpatient

The above policy is based on the following references:

1.      Xifaxan [package insert]. Bridgewater, NJ: Salix Pharmaceuticals, Inc.; October 2023.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

August 20, 2026