Tetrabenazine (Xenazine)

Coverage Summary

Coverage status: covered_with_criteria for chorea associated with Huntington disease (FDA‑approved) and for tardive dyskinesia (off‑label) when the policy's medical necessity criteria are met. Lines of business applicability: Commercial (approval duration up to 12 months or duration of request, whichever is less), Medicaid/HIM (approval duration 6 months).

Summary of scope: policy defines initial and continuation approval requirements (diagnosis, specialist prescriber or consultation, age > 18 years, required genetic testing and rating scale scores where applicable), dosing limits (including CYP2D6 testing to exceed certain thresholds), exclusions (concurrent VMAT2 inhibitors prohibited), and a generic redirection requirement for Xenazine brand requests.

Initial Approval Criteria - Chorea Associated with Huntington Disease (must meet all)

Covered when ALL of the following are met:

ALL of the following

Diagnosis of chorea associated with Huntington disease
Prescribed by or in consultation with a neurologist
Genetic testing: Targeted mutation analysis demonstrates a cytosine-adenine-guanine (CAG) trinucleotide expansion of ≥ 36 repeats in the huntingtin (HTT) geneHTT CAG ≥ 36
document genetic test results
Age > 18 years> 18 years
UHDRS chorea evidence: Evidence of chorea supported by a Unified Huntington Disease Rating Scale (UHDRS) score ranging from 1 to 4 on any one of chorea items 1 through 7UHDRS 1-4 on any one of items 1-7
see Appendix D
Concurrent VMAT2 exclusion: Tetrabenazine is not prescribed concurrently with deutetrabenazine (Austedo), Austedo XR, or valbenazine (Ingrezza)
concurrent VMAT2 inhibitors prohibited
Generic redirect: If request is for Xenazine (brand), member must use generic tetrabenazine unless contraindicated or clinically significant adverse effects are experienced
redirect to generic
Dose limits: Dose does not exceed 50 mg per day (100 mg per day if genotype testing confirms extensive or intermediate CYP2D6 metabolizer status)≤ 50 mg/day (≤ 100 mg/day if extensive/intermediate CYP2D6)
CYP2D6 testing required to exceed 50 mg/day

Initial Approval Criteria - Tardive Dyskinesia (off-label) (must meet all)

Covered when ALL of the following are met: (Off-label indication supported by the 2020 American Psychiatric Association Practice Guideline)

ALL of the following

Diagnosis of tardive dyskinesia (TD) secondary to treatment with a centrally acting dopamine receptor blocking agent (DRBA)
see Appendix G
Prescriber: Prescribed by or in consultation with a psychiatrist or neurologist
Age > 18 years> 18 years
AIMS evidence: Evidence of moderate to severe TD supported by an Abnormal Involuntary Movement Scale (AIMS) score of 3 or 4 on any one of items 1 through 9

Other diagnoses/indications

Coverage for other indications is governed by formulary and off-label policies:

ANY of the following

Formulary on PDL: For drugs on the formulary/PDL follow no coverage criteria policy for the relevant line of business: CP.CPA.190 (commercial), HIM.PA.33 (marketplace), CP PMN.255 (Medicaid)
Non-formulary: For drugs NOT on the formulary follow non-formulary policy: CP.CPA.190 (commercial), HIM.PA.103 (marketplace), CP PMN.16 (Medicaid)
Off-label policy: If use not listed under section III and criterion 1 does not apply, refer to off-label use policy: CP.CPA.09 (commercial), HIM.PA.154 (marketplace), CP PMN.53 (Medicaid)

Continuation Therapy Criteria

Continued Therapy

Continued therapy is permitted when the member meets continuation conditions:

ALL of the following

Member status
- Member is currently receiving medication via Centene benefit
- Member has previously met initial approval criteria
- Member is currently receiving medication and is enrolled in a state/product with continuity of care regulations (refer to state addendums)
Response evidence (must meet one)

Unapproved / Exclusions

Diagnoses/Indications Not Authorized

Not covered unless supported by off-label policies or sufficient evidence:

ALL of the following

Non-FDA indications not authorized: Non-FDA approved indications not addressed in this policy are not authorized unless sufficient documentation per off-label use policies is provided (CP.CPA.09 commercial, HIM.PA.154 marketplace, CP.PMN.53 Medicaid)

Explicit exclusion: requests will be denied if tetrabenazine is prescribed concurrently with deutetrabenazine (Austedo), Austedo XR, or valbenazine (Ingrezza).

This concurrent VMAT2 inhibitor exclusion applies to initial and continuation requests and is reiterated in the provider actions requiring documentation and noting denial risk for concurrent therapy.

Applicable Codes

Relevant ICD-10 diagnosis codes mentionedICD-10

G24.01

Tardive dyskinesia

Formulary / policy references (administrative)mixed

CP.CPA.190	No coverage criteria policy - commercial
HIM.PA.33	No coverage criteria policy - marketplace
CP PMN.255	No coverage criteria policy - Medicaid
HIM.PA.103	Non-formulary policy - marketplace
CP PMN.16	Non-formulary policy - Medicaid
CP.CPA.09	Off-label use policy - commercial
HIM.PA.154	Off-label use policy - marketplace
CP PMN.53	Off-label use policy - Medicaid

Provider Actions / Prior Authorization

Prior Authorization

Prior authorization required

Requests for tetrabenazine require prior authorization. Requests must meet the policy's listed initial or continuation criteria (diagnosis, prescriber specialty, age, rating scale or genetic evidence, dosing limits, and exclusions) and include supporting documentation to demonstrate the criteria are met.

Documentation Required

Submit supporting documentation

Submit supporting clinical documentation with the request, including office/chart notes, relevant laboratory results, genetic testing showing HTT CAG repeat count when applicable, and rating scale scores (UHDRS for Huntington disease chorea or AIMS for tardive dyskinesia) to demonstrate the member meets approval criteria.

Office/chart notes
Laboratory results

Clinical Evidence & Indications

Evidence summary: The FDA‑approved indication for tetrabenazine (Xenazine) is for the treatment of chorea associated with Huntington disease.

Although use for tardive dyskinesia (TD) is off‑label, the APA 2020 Practice Guideline recommends treatment of moderate to severe or disabling TD with reversible VMAT2 inhibitors, which includes tetrabenazine, providing guideline support for the off‑label TD indication.

Background

Background and mechanism: Tetrabenazine is a vesicular monoamine transporter 2 (VMAT2) inhibitor used for movement disorders.

Indications: FDA‑approved for chorea associated with Huntington disease; also addressed for tardive dyskinesia (off‑label) with guideline support.

Boxed warnings/contraindications summary: boxed warning for depression and suicidality; contraindications/precautions include active suicidal ideation or untreated/undertreated depression, hepatic impairment, and concurrent use of deutetrabenazine or valbenazine or MAOIs/ reserpine.

Dosing overview: Huntington disease typical titration to a maximum of 50 mg/day (up to 100 mg/day if CYP2D6 genotype confirms extensive or intermediate metabolizer status); TD dosing range typically 25–75 mg/day with titration up to 150–200 mg/day; test CYP2D6 status before doses > 50 mg/day.

Operational change: policy includes an operational preference to redirect brand Xenazine requests to generic tetrabenazine for both initial and continuation therapy.

Definitions:

• UHDRS — Unified Huntington Disease Rating Scale; chorea subscore items 1–7 rated 0–4 used to support chorea severity.

• AIMS — Abnormal Involuntary Movement Scale; items 1–9 used to assess tardive dyskinesia severity (items scored 0–4).

• HTT CAG repeats — cytosine‑adenine‑guanine (CAG) trinucleotide repeat count in the huntingtin gene; policy requires ≥ 36 repeats to support Huntington disease diagnosis.

Revision History

2Q 2021added

Added off-label indication of tardive dyskinesia supported by APA 2020 Practice Guideline (2Q 2021). Detail: Commercial line of business added and references revised for HIM line of business.

09.27.21revised

Revised approval duration for Commercial line of business to 12 months or duration of request, whichever is less (09.27.21). Detail: Approval duration updated for commercial members.

05.20.22 / 08.22clarified

Added redirection for both initial and continuation therapy to require redirection to generic tetrabenazine (05.20.22 / 08.22). Detail: Operational change to prefer generic product.