ModifiedmhnPolicy CP.PMN.299

Xanomeline/Trospium Chloride (Cobenfy) coverage

Clinical coverage and prior authorization criteria for Cobenfy (xanomeline/trospium chloride) for treatment of schizophrenia in adults for members of the payer lines of business listed.

Policy Summary

Payermhn

PolicyXanomeline/Trospium Chloride (Cobenfy) coverage

Policy CodePolicy CP.PMN.299

Change TypeMaterial updates: IL step therapy bypass addedAR step therapy note revised

Effective DateJan 1, 2025

Next Review DateN/A

Key ActionSubmit prior authorization with supporting clinical documentation showing diagnosis, age ≥18, prescriber specialty, step therapy history or applicable exception, and dose within limits.

SourceLink

POLICY UPDATE CHANGES

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

Removed 'applies to HIM request only' for Arkansas in Appendix D per AR HB 1276.

≥18minimum age for coverage

250 mg/60 mgmax daily dose

12 monthsapproval duration

18+document chunks

50/20,100/20,125/30

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Coverage Criteria

Initial Therapy — Covered when ALL of the following are met

Covered when ALL of the following are met:

Initial Schizophrenia criteria

Diagnosis of schizophrenia.
Age ≥ 18 years.
Prescribed by or in consultation with a psychiatrist or mental health specialist (see Appendix E).
Appendix E defines mental health specialists to include clinical psychologists, psychiatric mental health nurse practitioners, psychiatric physician assistants, and therapists/counselors.
Step therapy or exception (one required)
- Request is for treatment of a member in a State with limitations on step therapy in certain mental health settings (see Appendix D).
- Failure of a ≥ 4-week trial of one of the following generic atypical antipsychotics at up to maximally indicated doses unless clinically significant adverse effects are experienced or all are contraindicated: risperidone, quetiapine, olanzapine, ziprasidone.
- Member has diabetes mellitus or body mass index (BMI) > 30.
Aripiprazole requirement (one required)
- Request is for treatment of a member in a State with limitations on step therapy in certain mental health settings (see Appendix D).
- Failure of a ≥ 4-week trial of aripiprazole at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced.
Dose does not exceed both of the following: (a) 250 mg/60 mg per day; and (b) 2 capsules per day.dose <= 250 mg/60 mg per day and <= 2 capsules/day
For Illinois HIM requests the step therapy requirements do not apply as of 1/1/2026 per IL HB 5395.

Continuation Therapy — Covered when ALL of the following are met

Covered when ALL of the following are met:

Continued Schizophrenia criteria

Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Cobenfy for schizophrenia and has received this medication for at least 30 days.>= 30 days current therapy
Member is responding positively to therapy.
If request is for a dose increase, new dose does not exceed both of the following: (a) 250 mg/60 mg per day; and (b) 2 capsules per day.dose <= 250 mg/60 mg per day and <= 2 capsules/day

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized for coverage unless the provider submits sufficient documentation of efficacy and safety in accordance with the payer's off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), or CP.PMN.53 (Medicaid), or unless coverage is supported by the applicable evidence of coverage documents.

Coverage determinations under this clinical policy are intended as a medical necessity guide and do not constitute a contract or guarantee of payment. Decisions and benefit administration remain subject to all terms, conditions, exclusions, and limitations of the member's coverage documents (for example, evidence of coverage, certificate of coverage, policy or contract of insurance), as well as applicable state and federal laws and Health Plan administrative policies.

Use of Cobenfy for non‑FDA approved indications without the required off‑label documentation or justification per the referenced off‑label use policies is considered not authorized and may be denied.

Coding and Product Information

NDC / product codesNDC

NDC	Not specified in this part of the document

inv-07: Maximum daily dose — 250 mg/60 mg per day

Maximum daily dose (combined)250 mg/60 mg per day

Max capsules/day2 capsules per day (policy limit)

Titration start regimenInitiate 50 mg/20 mg PO BID for 2 days, then 100 mg/20 mg PO BID for ≥5 days; may increase to 125 mg/30 mg PO BID based on tolerability

Geriatric considerationInitiate at 50 mg/20 mg PO BID; consider slower titration

Provider Actions and Administrative Requirements

Prior Authorization

Prior authorization required for Cobenfy

Prior authorization is required for Cobenfy. Requests must meet the policy's initial or continued therapy criteria, including diagnosis of schizophrenia, age ≥ 18 years, prescriber specialty/consultation requirements, applicable step-therapy or exception conditions, and dose limits (not to exceed 250 mg/60 mg per day and 2 capsules per day). Approval duration is 12 months.

Note

Prior authorization overview

This document includes administrative history and statements about the provider–health plan relationship but does not spell out specific prior authorization codes in the cited sections. Review the policy for created/revision dates and administrative notes.

Step Therapy

Step therapy and exceptions

Background

Cobenfy is the proprietary combination of xanomeline (a muscarinic agonist) and trospium chloride (a muscarinic antagonist) developed for the treatment of schizophrenia in adults. It is a first‑in‑class agent with a unique mechanism of action, which prompted a prescriber restriction requiring prescribing by or in consultation with a psychiatrist or other mental health specialist (see Appendix E). Dosing guidance in the policy references initiation and titration schedules and specifies a maximum daily dose of 250 mg/60 mg and a limit of 2 capsules per day for schizophrenia; full administration details are in the Dosage and Administration section.

Definitions and Contraindications

inv-17: Cobenfy — drug components (xanomeline + trospium chloride)

Brand nameCobenfy

Active componentsXanomeline (muscarinic agonist)

Active components (second)Trospium chloride (muscarinic antagonist)

inv-18: Key contraindications — urinary retention, hepatic impairment, gastric retention, hypersensitivity, etc.

Urinary retentionContraindication: urinary retention

Hepatic impairmentContraindication: moderate or severe hepatic impairment

Gastric retention

Prescriber and Treatment Modalities

Prescriber restriction

Prescriber restriction:

Prescriber restriction: Cobenfy must be prescribed by or in consultation with a psychiatrist or mental health specialist as defined in Appendix E to ensure appropriate use given first-in-class status.

Appendix E defines mental health specialists to include clinical psychologists, psychiatric mental health nurse practitioners, psychiatric physician assistants, and therapists or counselors.

Policy Summary

Payermhn

PolicyXanomeline/Trospium Chloride (Cobenfy) coverage

Policy CodePolicy CP.PMN.299

Change TypeMaterial updates: IL step therapy bypass addedAR step therapy note revised

Effective DateJan 1, 2025

Next Review DateN/A

Key ActionSubmit prior authorization with supporting clinical documentation showing diagnosis, age ≥18, prescriber specialty, step therapy history or applicable exception, and dose within limits.

SourceLink

On This Page

Step therapy is required unless an exception applies: the member must have failed a ≥4-week trial of one listed generic atypical antipsychotic (risperidone, quetiapine, olanzapine, ziprasidone) and a ≥4-week trial of aripiprazole, unless contraindicated or adverse effects are experienced; exceptions include diabetes or BMI >30 or state-specific prohibitions.

Failure defined as ≥4-week trial at up to maximally indicated doses unless clinically significant adverse effects or contraindications are present.
State-specific exceptions listed in Appendix D; Illinois HIM bypass applies per IL HB 5395.

Note

Step therapy administrative notes

Administrative notes record a step therapy bypass for Illinois HIM requests effective 1/1/2026 (IL HB 5395) and removal of the 'HIM request only' qualifier for Arkansas in Appendix D per AR HB 1276.

IL HIM bypass for step therapy added per IL HB 5395.
Appendix D for Arkansas revised to remove HIM-only qualifier per AR HB 1276.

Documentation Required

Required documentation for authorization

Providers must submit supporting clinical documentation (such as office chart notes, laboratory results, or other clinical information) that the member meets all approval criteria when requesting authorization.

Documentation should demonstrate diagnosis, duration of therapy (for continuation), response to therapy, and any step-therapy trials or exceptions relied upon.

Note

Provider responsibilities and policy ownership

Providers are bound by the policy's terms when submitting services or claims; the policy is the property of the Health Plan and unauthorized copying, use, or distribution is prohibited.

By submitting claims or providing services, providers agree to be bound by the policy terms either via contract or by provision of services to members.

Denial Risk

Documentation and indication-based denials

Requests that do not include documentation showing the member meets all approval criteria (diagnosis, age, prescriber type, step therapy or exceptions, dosing limits, etc.) may be denied.

Non‑FDA uses without appropriate off‑label policy justification may be considered not authorized and denied.

Denial Risk

Coverage alignment required

Coverage determinations are subject to the health plan's terms, conditions, exclusions, and limitations; a request not aligned with the member's evidence of coverage or applicable state/federal requirements may be denied.

The policy is a guide to medical necessity and does not guarantee payment; contractual and regulatory requirements govern coverage decisions.

Contraindication: gastric retention

HypersensitivityHistory of hypersensitivity to Cobenfy or trospium chloride

GlaucomaContraindication: untreated narrow‑angle glaucoma