ModifiedmhnPolicy CP.PMN.224

Clinical Policy: Tenapanor (Ibsrela, Xphozah)

Defines medical necessity and prior authorization criteria for tenapanor products Ibsrela (for IBS-C) and Xphozah (for hyperphosphatemia in adults on dialysis) for Centene-affiliated health plans; affects prescribers and prior authorization reviewers for HIM and Medicaid lines of business.

Policy Summary

Payermhn

PolicyClinical Policy: Tenapanor (Ibsrela, Xphozah)

Policy CodePolicy CP.PMN.224

Change TypeMulti-item revision (added Xphozahredirectionsstrength removalstep therapy bypass)

Effective DateMar 1, 2020

Next Review DateN/A

Key ActionSubmit prior authorization with clinical documentation showing the member meets the listed initial or continuation therapy criteria.

SourceLink

POLICY UPDATE CHANGES

Xphozah (tenapanor for hyperphosphatemia in dialysis patients) was added to the policy.

Redirection to generic lubiprostone was added to the policy.

Removed Xphozah 10 mg strength due to product discontinuation.

For IBS-C added redirection to Linzess and Trulance for HIM line of business and applied similar redirections from initial to continuation therapy requests.

Added step therapy bypass for Illinois HIM per IL HB 5395.

2FDA-approved indications

12Approval duration (months)

100 mg/dayMax dose Ibsrela

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60 mg/dayMax dose Xphozah

multipleAnnual reviews

Coverage Criteria

Initial Therapy — Irritable Bowel Syndrome with Constipation

Covered when ALL of the following are met

IBS-C Initial: Request is for Ibsrela; diagnosis of irritable bowel syndrome with constipation (IBS-C); age ≥ 18 years; failure of one bulk-forming laxative (e.g., psyllium, methylcellulose, calcium polycarbophil) unless clinically significant adverse effects or contraindications; failure of generic lubiprostone unless contraindicated or intolerant; failure of linaclotide (Linzess) unless contraindicated or intolerant; failure of plecanatide (Trulance) unless contraindicated or intolerant; dose does not exceed 100 mg (2 tablets) per day.

For Illinois HIM requests, step therapy requirements do not apply as of 1/1/2026 per IL HB 5395.

Initial Therapy — Hyperphosphatemia (CKD on dialysis)

Covered when ALL of the following are met

Hyperphosphatemia Initial: Request is for Xphozah; diagnosis of hyperphosphatemia associated with chronic kidney disease (CKD); member is on dialysis; prescribed by or in consultation with a nephrologist; age ≥ 18 years; member meets one of the following: (a) failure (e.g., serum phosphorus > 5.5 mg/dL) of a 4-week trial of calcium acetate at up to maximally indicated doses unless contraindicated or intolerant; (b) hypercalcemia with corrected total serum calcium > 10.2 mg/dL within prior 30 days; (c) plasma PTH < 150 pg/mL on two consecutive measurements within the past 180 days; or (d) history of severe vascular and/or soft-tissue calcifications; failure (e.g., serum phosphorus > 5.5 mg/dL) of a 4-week trial of a non-calcium phosphate binder at up to maximally indicated doses unless contraindicated or intolerant; Xphozah is prescribed as add-on therapy to phosphate binder therapy; dose does not exceed 60 mg per day (2 tablets).serum phosphorus > 5.5 mg/dL used as an example failure criterion

Prior authorization may be required for non-calcium phosphate binders; For Illinois HIM requests, step therapy requirements do not apply as of 1/1/2026 per IL HB 5395.

Continuation Therapy — Irritable Bowel Syndrome with Constipation

Covered when ALL of the following are met

IBS-C Continued: Request is for Ibsrela; member is currently receiving medication via Centene benefit or previously met initial approval criteria or is in a continuity of care situation; member is responding positively to therapy; continued documentation of prior step therapy failures as per initial criteria unless contraindicated or intolerant (bulk-forming laxative, generic lubiprostone, linaclotide, plecanatide); if request is for a dose increase, new dose does not exceed 100 mg (2 tablets) per day.

Approval duration: 12 months. For Illinois HIM requests, step therapy requirements do not apply as of 1/1/2026 per IL HB 5395.

Continuation Therapy — Hyperphosphatemia

Covered when ALL of the following are met

Hyperphosphatemia Continued: Request is for Xphozah; member is currently receiving medication via Centene benefit or previously met initial approval criteria or is in a continuity of care situation; member is responding positively to therapy (e.g., reduction in serum phosphorus from pretreatment level or maintenance of serum phosphorus level ≤ 5.5 mg/dL); Xphozah is prescribed as add-on therapy to phosphate binder therapy; if request is for a dose increase, new dose does not exceed 60 mg per day (2 tablets).serum phosphorus ≤ 5.5 mg/dL as a response target

Approval duration: 12 months.

Other Indications / Off-label

Other/Off-label uses

Other Indications: If the drug has undergone a recent label change (within the last 6 months) not yet reflected in this policy, follow the appropriate formulary/no-coverage or non-formulary policy for the line of business; if the requested use is not listed under section III and no recent label change applies, refer to the off-label use policy for the relevant line of business (HIM.PA.154 for marketplace; CP.PMN.53 for Medicaid).

See referenced policies HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16, HIM.PA.154, CP.PMN.53 as applicable.

Coverage adjustments and redirections — Policy changes and redirections for lines of business

Policy changes and redirections for lines of business

Redirection and line-of-business rules: For IBS-C, the HIM line of business redirects to linaclotide (Linzess) and plecanatide (Trulance) per adapted redirections; step therapy bypass is available for Illinois HIM per IL HB 5395; Xphozah 10 mg strength has been removed from product availability due to discontinuation.

Specific initial and continuation therapy criteria remain as stated in Sections I and II; see appendices and revision history for timing of changes.

Non-FDA approved indications that are not specifically addressed by this policy are not authorized unless the provider submits sufficient clinical documentation demonstrating efficacy and safety in accordance with the applicable off‑label use policies. See HIM.PA.154 for health insurance marketplace requests and CP.PMN.53 for Medicaid when relying on off‑label evidence or coverage documents.

This policy does not apply to California Exchange Plans. Requests for members covered under California Exchange Plans must be reviewed using HIM.PA.174 rather than this policy.

Use of tenapanor products for non‑FDA approved indications is not authorized under this policy unless the request is supported by sufficient documentation of efficacy and safety per the off‑label use policies referenced in this document (see HIM.PA.154 and CP.PMN.53). Providers must provide clinical evidence consistent with those off‑label guidance documents to be considered for authorization.

Within the provided policy excerpt there are no explicit statements

Coding and Clinical Thresholds

Product strengths (NDC-level details expected elsewhere)NDC

50 mg	Ibsrela tablet strength
20 mg, 30 mg	Xphozah tablet strengths

No explicit codes in excerptmixed

N/A	No explicit procedure, diagnosis, or NDC codes present in this document extract

inv-13: Serum phosphorus control — Maintenance of serum phosphorus level ≤ 5.5 mg/dL

Serum phosphorus maintenance targetMaintenance of serum phosphorus level ≤ 5.5 mg/dL for continued therapy response

Context in criteriaUsed as an objective response target for continuation of Xphozah in patients on dialysis (e.g., maintenance ≤ 5.5 mg/dL)

Approval duration linked to targetApproval duration for continuation when maintenance achieved: 12 months

inv-14: Hyperphosphatemia failure threshold — Serum phosphorus > 5.5 mg/dL after trial of phosphate binder

Failure threshold definitionSerum phosphorus > 5.5 mg/dL after a 4-week trial of a phosphate binder (calcium acetate or non-calcium binder) constitutes treatment failure

Provider Actions and Requirements

Prior Authorization
Prior Authorization Required
Prior authorization is required. Requests must include documentation demonstrating that the member meets all applicable initial or continuation therapy criteria. Approval duration is specified in the criteria (typically 12 months).
Prior authorization required for Ibsrela and Xphozah when approval criteria are met
Approval duration: 12 months (where specified in criteria)

Prior Authorization
Prior Authorization and Redirection
This policy implements redirections and step therapy rules for the HIM line of business. Prior authorization requirements and redirection rules vary by line of business; for California Exchange Plans, requests should be reviewed using HIM.PA.174.
HIM line of business includes redirection for IBS-C to Linzess (linaclotide) and Trulance (plecanatide)
California Exchange Plans: review using HIM.PA.174

Background

Tenapanor is a sodium/hydrogen exchanger 3 (NHE3) inhibitor marketed as Ibsrela for adults with irritable bowel syndrome with constipation (IBS‑C) and as Xphozah to reduce serum phosphorus in adults with chronic kidney disease on dialysis. Typical dosing described in the policy is Ibsrela 50 mg PO twice daily (maximum 100 mg/day) for IBS‑C and Xphozah 30 mg PO twice daily (maximum 60 mg/day) for hyperphosphatemia when used as add‑on therapy to phosphate binders. Contraindications and safety considerations noted in the referenced prescribing information include pediatric age limits and risk of gastrointestinal obstruction.

Definitions

inv-25: NHE3 — Sodium/hydrogen exchanger 3, the pharmacologic target of tenapanor

DefinitionNHE3 = sodium/hydrogen exchanger 3, the pharmacologic target of tenapanor

RelevanceTarget referenced in abbreviations and clinical description for Ibsrela/Xphozah formulations

Source placementListed in the policy description and Appendix A abbreviation key

inv-26: Bulk-forming laxative — Examples include psyllium (Metamucil), methylcellulose (Citrucel), and calcium polycarbophil (FiberCon)

ExamplesPsyllium (Metamucil), methylcellulose (Citrucel), calcium polycarbophil (FiberCon)

Role in step therapyFailure of one bulk-forming laxative (e.g., these agents) is required before Ibsrela for IBS-C unless contraindicated or intolerant

Policy Summary

Payermhn

PolicyClinical Policy: Tenapanor (Ibsrela, Xphozah)

Policy CodePolicy CP.PMN.224

Change TypeMulti-item revision (added Xphozahredirectionsstrength removalstep therapy bypass)

Effective DateMar 1, 2020

Next Review DateN/A

Key ActionSubmit prior authorization with clinical documentation showing the member meets the listed initial or continuation therapy criteria.

SourceLink

On This Page

Applicable trials

Failure example applies to 4-week trials of calcium acetate at maximally indicated doses or a non-calcium phosphate binder (e.g., lanthanum, sevelamer)

Use in initial approval logicOne of the failure criteria used to justify initiation of Xphozah as add-on therapy in dialysis patients

inv-15: Annual review notes — Multiple annual review entries from 1Q 2022 through 1Q 2026

Review timelineAnnual review entries recorded from 1Q 2022 through 1Q 2024 with updates noted; overall log documents multiple reviews from 1Q 2022 through 1Q 2026

Notable 1Q2022 change1Q 2022 annual review added redirection to generic lubiprostone (SDC), references reviewed and updated

RT4 additionRT4 entry: added Xphozah to the policy (noted in 10.26.23 / P&T 12.23)

Template and clarification notesTemplate/clarification changes and reference updates documented across annual reviews

Step Therapy
Step Therapy Requirements
Step therapy is required for IBS-C prior to approval of Ibsrela unless exceptions apply. Members must have trialed and failed specified therapies or have contraindications or clinically significant adverse effects to those agents.
IBS-C initial therapy step requirements include failure of one bulk-forming laxative (e.g., psyllium, methylcellulose, calcium polycarbophil)
Failure of generic lubiprostone (Amitiza), linaclotide (Linzess), and plecanatide (Trulance) is required unless contraindicated or clinically significant adverse effects are experienced
Dose limit for Ibsrela: does not exceed 100 mg (2 tablets) per day

Step Therapy
Step Therapy and Statutory Bypass (Illinois HIM)
For Illinois HIM requests, step therapy requirements do not apply as of 1/1/2026 per IL HB 5395; a statutory bypass has been added for Illinois HIM.
IL HIM step therapy bypass effective 1/1/2026 per IL HB 5395
HIM redirections remain applicable to other jurisdictions/lines of business as specified

Documentation Required
Required Documentation and Provider Responsibility
Provider must submit supporting documentation (e.g., office chart notes, lab results, consultation notes) that the member has met all approval criteria. Failure to submit required documentation may result in denial or delay of the request.
Acceptable documentation: office chart notes, recent labs (e.g., serum phosphorus, corrected calcium, PTH where relevant), prior medication trials and dates, documentation of contraindications or adverse effects
Failure to provide adequate documentation may result in denial or processing delays

Note
Provider Responsibility and Documentation
Providers remain responsible for medical judgment and for maintaining complete clinical documentation. This policy is a guide to coverage decisions and does not guarantee payment.
Providers must ensure documentation supports clinical necessity and meets plan criteria
Policy does not replace clinical judgment or plan contract terms

Appendix referenceExamples and dosing details provided in Appendix B: Therapeutic Alternatives

inv-27: Sources — Ibsrela/Xphozah prescribing information and guideline references

Primary sourcesIbsrela and Xphozah prescribing information (Ardelyx) as listed in references

Guideline referencesAGA and ACG clinical practice guidelines and KDIGO guideline for CKD-MBD cited in policy references

Appendix and prescribing info accessFull prescribing information links and guideline citations are provided in References sections VII and appendices