ModifiedCentenePolicy CP.PHAR.92

Clinical Policy: Tetrabenazine (Xenazine)

Defines medical necessity, prior authorization, and continuation criteria for tetrabenazine (Xenazine) for Huntington disease chorea and off-label tardive dyskinesia for Centene-affiliated health plans and affected lines of business.

Policy Summary

PayerCentene

PolicyTetrabenazine (Xenazine) coverage

Policy CodePolicy CP.PHAR.92

Change TypeConcurrent use exclusion addedapproval durations revisedgeneric redirection reinforced

Effective DateDec 1, 2011

Next Review DateN/A

Key ActionSubmit prior authorization with documentation showing member meets indication-specific criteria and redirect to generic tetrabenazine unless contraindicated.

SourceLink

POLICY UPDATE CHANGES

Added Ingrezza Sprinkle to the concurrent use exclusion and revised initial approval durations from 6 to 12 months for Medicaid/HIM; added ICHRA line of business.

Per prior guidance, require redirection for both initial and continuation of therapy to generic tetrabenazine.

Updated Appendix definitions per DSM-5-TR and updated references.

2indications with criteria

12 monthsstandard approval duration

≥18minimum age

50 / 200 mgdose limits (Huntington/TD)

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Coverage Criteria

Initial Therapy — Huntington disease chorea

Covered when ALL of the following are met for Chorea Associated with Huntington Disease:

Huntington chorea initial therapy criteria: 1) Diagnosis of chorea associated with Huntington disease; 2) Prescribed by or in consultation with a neurologist; 3) Age ≥ 18 years; 4) Targeted mutation analysis demonstrates a CAG trinucleotide expansion of ≥ 36 repeats in the HTT gene; 5) Evidence of chorea is supported by a UHDRS score of 1–4 on any one of chorea items 1–7; 6) If request is for Xenazine, member must use generic tetrabenazine unless contraindicated or clinically significant adverse effects are experienced; 7) Tetrabenazine is not prescribed concurrently with deutetrabenazine (Austedo/Austedo XR) or valbenazine (Ingrezza/Ingrezza Sprinkle); 8) Dose does not exceed 50 mg per day (100 mg per day if genotype testing confirms extensive or intermediate CYP2D6 metabolizer status).see node text

Dose exception for CYP2D6 extensive/intermediate metabolizers noted

Initial Therapy — Tardive Dyskinesia

Covered when ALL of the following are met for Tardive Dyskinesia (off‑label):

Tardive dyskinesia initial therapy criteria: 1) Diagnosis of tardive dyskinesia secondary to treatment with a centrally acting dopamine receptor blocking agent; 2) Prescribed by or in consultation with a psychiatrist or neurologist; 3) Age ≥ 18 years; 4) Evidence of moderate to severe TD is supported by an AIMS score of 3 or 4 on any one of items 1–9; 5) If request is for Xenazine, member must use generic tetrabenazine unless contraindicated or clinically significant adverse effects are experienced; 6) Tetrabenazine is not prescribed concurrently with deutetrabenazine (Austedo/Austedo XR) or valbenazine (Ingrezza/Ingrezza Sprinkle); 7) Dose does not exceed 200 mg per day.AIMS 3–4 on any one item

Off‑label use allowed per criteria

Continuation Therapy

Covered when ALL of the following are met for Continued Therapy (all indications):

Continued therapy criteria: 1) Member currently receiving medication via Centene benefit or previously met initial approval criteria (or continuity of care applies); 2) Member is responding positively to therapy: for Huntington disease, reduction since baseline in any UHDRS chorea item 1–7; for TD, reduction since baseline in any AIMS item 1–9; 3) If request is for Xenazine, member must use generic tetrabenazine unless contraindicated or clinically significant adverse effects are experienced; 4) Tetrabenazine is not prescribed concurrently with deutetrabenazine (Austedo/Austedo XR) or valbenazine (Ingrezza/Ingrezza Sprinkle); 5) If request is for a dose increase, new dose does not exceed indication‑specific maximums (Huntington: 50 mg/day or 100 mg/day with CYP2D6 genotype exception; TD: 200 mg/day).documented symptomatic improvement vs baseline

Approval durations as specified

Dosing and monitoring

Covered when ALL of the following are met (dosing and monitoring expectations):

Huntington chorea dosing initiation: Start 12.5 mg PO QD for week 1, then 12.5 mg PO BID for week 2, then increase by 12.5 mg weekly to tolerated dose that reduces chorea; doses ≥37.5 mg and up to 50 mg/day should be given in 3 divided doses. Maximum dose 50 mg/day (max single dose 25 mg). Extensive or intermediate CYP2D6 metabolizers: up to 100 mg/day (max single dose 37.5 mg).max 50 mg/day (100 mg/day with CYP2D6 exception)

Follow genotype‑based dosing limits and division of doses

Tardive dyskinesia (off-label) dosing: Typical dosing range 25–75 mg/day in divided doses; initiate 25–50 mg/day and increase by 12.5 mg/week to a maximum of 150–200 mg/day; retitrate after interruptions >5 days. Test CYP2D6 metabolizer status before doses >50 mg/day; do not exceed 50 mg/day in poor metabolizers.max 150–200 mg/day (TD off‑label)

CYP2D6 testing required prior to high dosing

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: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), or CP.PMN.53 (Medicaid/ICHRA), or unless the indication is covered by the member's evidence of coverage document.

Concurrent use with other VMAT2 inhibitor formulations listed as excluded is prohibited. The policy history notes the addition of the Austedo XR formulation previously and, per the 2Q 2026 update, Ingrezza Sprinkle was added to the concurrent use exclusion, making co‑prescription of those formulations with tetrabenazine disallowed.

Tetrabenazine is contraindicated in patients who are actively suicidal or have untreated or undertreated depression, in those with hepatic impairment, and in patients taking monoamine oxidase inhibitors (MAOIs) or reserpine. Concomitant use with deutetrabenazine or valbenazine is also listed among contraindications. These conditions should preclude authorization per the policy.

The policy requires formulary redirection to generic tetrabenazine for both initiation and continuation of therapy. Per prior guidance and repeated policy updates, requests for brand Xenazine should be redirected to generic tetrabenazine unless the member has a documented contraindication or intolerance to the generic formulation; failure to use the generic may result in coverage redirection or denial under plan formulary management.

Coding and Diagnostic Criteria

Diagnosis CodesICD-10

G24.01

Tardive dyskinesia

UHDRS / AIMS score thresholds

UHDRS chorea threshold (Huntington disease)UHDRS chorea items rated 1–4 on any one of chorea items 1–7 (supports presence/severity of chorea)

AIMS threshold (Tardive dyskinesia)AIMS score of 3 or 4 on any one of items 1–9 (supports moderate to severe TD)

Use of clinician-rated scalesUHDRS motor chorea subscore and AIMS are referenced as assessment tools to document baseline severity and response to therapy

HTT CAG repeat threshold

HTT CAG repeat thresholdCAG trinucleotide expansion ≥ 36 repeats in the HTT gene

Test required for Huntington indicationTargeted mutation analysis demonstrating the HTT CAG expansion is a required criterion for coverage

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation (office chart notes, lab results, or other clinical information) supporting that the member meets all approval criteria.

Applicable for initial and continuation requests
See policy criteria for diagnosis-specific requirements (UHDRS for Huntington chorea; AIMS for tardive dyskinesia)

Prior Authorization

Prior Authorization Durations and Metabolic Testing

Initial approval durations: for Medicaid and Health Insurance Marketplace (HIM/ICHRA) lines of business, initial approvals are 12 months (revised from 6 months). Metabolic/CYP2D6 testing: test for CYP2D6 metabolizer status before doses > 50 mg/day; dosing adjustments and maximum doses depend on metabolizer status.

Initial approval duration: 12 months for Medicaid/HIM/ICHRA (per 2Q 2026 review)
Test CYP2D6 prior to doses > 50 mg/day; do not exceed 50 mg/day in poor metabolizers
Dose limits: Huntington chorea max 50 mg/day (100 mg/day if extensive/intermediate CYP2D6); TD dosing up to 150–200 mg/day per policy dosing section

Background

Tetrabenazine is a vesicular monoamine transporter 2 (VMAT2) inhibitor indicated for the treatment of chorea associated with Huntington disease and is also used off‑label for tardive dyskinesia secondary to dopamine receptor blocking agents. Clinical assessment tools referenced in the policy include the UHDRS chorea subscore for Huntington disease and the AIMS for tardive dyskinesia to document baseline severity and response to therapy.

Definitions

Tetrabenazine (Xenazine) — VMAT2 inhibitor

Drug class and brandTetrabenazine (Xenazine) — vesicular monoamine transporter 2 (VMAT2) inhibitor

FDA-approved indicationApproved for treatment of chorea associated with Huntington's disease

Typical initiation regimen (Huntington chorea)Start 12.5 mg PO QD for first week, then 12.5 mg PO BID week 2, increase by 12.5 mg weekly to tolerated dose

UHDRS / AIMS definitions

UHDRS definitionUHDRS motor chorea subscore rates seven body regions on a 0–4 scale to evaluate chorea severity; used for Huntington disease assessment

AIMS definitionAIMS is a clinician-rated 12-item assessment; items 1–10 rated 0–4 with items 1–7 assessing dyskinesia by body region and item 8 using highest score of items 1–7