ModifiedmhnPolicy CP.PHAR.291

Paliperidone long-acting injectable products

Coverage and prior authorization criteria for paliperidone long-acting injectable formulations (Invega Hafyera, Invega Sustenna, Invega Trinza, Erzofri) for adult members with schizophrenia or schizoaffective disorder under Centene-affiliated plans.

Policy Summary

Payermhn

PolicyPaliperidone long-acting injectable products

Policy CodePolicy CP.PHAR.291

Change TypeAdded product (Erzofri)HCPCS and approval duration updates

Effective DateDec 1, 2016

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results, or other clinical information) demonstrating the member meets all approval criteria and include referenced HCPCS codes when requesting coverage.

SourceLink

POLICY UPDATE CHANGES

Added newly approved Erzofri to the policy.

Added HCPCS code J2428 for Erzofri and J2427 for Invega Hafyera or Trinza; removed misc J- or C- miscellaneous codes.

Revised approval duration for commercial line of business to 6 months or to the member's renewal date.

Added newly approved Invega Hafyera to the policy.

4brands/formulations covered

≥18minimum age (years)

6 monthscommercial approval duration

Dementia-related psychosis

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J2426,J2427,J2428HCPCS codes

Coverage Criteria

inv-01: Initial Therapy — Schizophrenia

Covered when ALL of the following are met:

Schizophrenia initial therapy: 1) Diagnosis of schizophrenia; 2) Prescribed by or in consultation with a psychiatrist; 3) Age >= 18 years; 4) Member meets one of: (a) requested product was initiated in an inpatient setting during a recent (within 60 days) hospital admission, OR (b) history of non-adherence to oral antipsychotic therapy and one of the following based on requested product: (i) If Invega Trinza requested: adequate treatment established with Invega Sustenna or Erzofri for at least the last 4 months; (ii) If Invega Sustenna or Erzofri requested: (1) established tolerability with oral paliperidone or oral risperidone and (2) no known hypersensitivity to paliperidone or risperidone; (iii) If Invega Hafyera requested: (1) adequate treatment with Invega Sustenna or Erzofri for at least the last 4 months, OR (2) adequate treatment with Invega Trinza for at least one three-month cycle; 5) Dose does not exceed product-specific maximums: Invega Hafyera 1,560 mg every 6 months; Invega Sustenna 234 mg per month; Invega Trinza 819 mg every 3 months; Erzofri 351 mg first dose then 234 mg per month.

inv-02: Initial Therapy — Schizoaffective Disorder

Covered when ALL of the following are met:

Schizoaffective disorder initial therapy: 1) Diagnosis of schizoaffective disorder; 2) Request is for Invega Sustenna or Erzofri; 3) Prescribed by or in consultation with a psychiatrist; 4) Age >= 18 years; 5) Member meets one of: (a) history of non-adherence to oral antipsychotic therapy and has established tolerability to oral risperidone (preferred) or oral paliperidone; OR (b) therapy was initiated in an inpatient setting during a recent (within 60 days) hospital admission; 6) Dose does not exceed product-specific maximums: Invega Sustenna 234 mg/month; Erzofri 351 mg first dose then 234 mg/month.

inv-03: Continuation Therapy

Continued coverage when ALL of the following are met:

Continuation therapy: 1) Member is currently receiving medication via the Centene benefit or documentation supports that the member has received Invega Hafyera, Invega Sustenna, Invega Trinza, or Erzofri for at least 30 days OR therapy was initiated in an inpatient setting within the last 60 days; 2) Member is responding positively to therapy; 3) If the request is for a dose increase, the new dose does not exceed product-specific maximums: Invega Hafyera 1,560 mg every 6 months; Invega Sustenna or Erzofri 234 mg per month; Invega Trinza 819 mg every 3 months.

inv-04: Product-specific initiation and continuation criteria

Covered when criteria specific to product initiation and prior product use are met

Invega Hafyera initiation: Use only after Invega Sustenna has been established as adequate treatment for at least 4 months OR after Invega Trinza has been established as adequate treatment for at least one three-month cycle. The recommended initial Hafyera dose is based on the previous Sustenna or Trinza dose and is initiated when the next Sustenna/Trinza dose would have been scheduled (examples: last Sustenna 156 mg -> Hafyera 1,092 mg; last Sustenna 234 mg -> Hafyera 1,560 mg; last Trinza 546 mg -> Hafyera 1,092 mg).duration requirements specified

Dose conversion table provided in policy

Invega Trinza initiation: Use only after Invega Sustenna has been established as adequate treatment for at least 4 months. Initiate Trinza when the next 1-month paliperidone palmitate dose is scheduled using the 3.5-fold higher dose equivalents (78 mg -> 273 mg; 117 mg -> 410 mg; 156 mg -> 546 mg; 234 mg -> 819 mg). After the initial dose, administer every 3 months (may be administered up to 7 days around schedule).4 months of Sustenna

Dose conversion table provided in policy

This policy does not authorize coverage for non‑FDA approved indications unless there is sufficient documentation of efficacy and safety per the payer’s off‑label use policies (CP.CPA.09 for commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid) or other evidence of coverage documents. In addition, dementia‑related psychosis is explicitly excluded from coverage under this policy.

Use of paliperidone long‑acting injectables is contraindicated in patients with a known hypersensitivity to paliperidone, risperidone, or any excipients. Requests for therapy in patients with documented hypersensitivity to these agents or their components should be denied.

These agents carry a boxed warning noting an increased risk of death in elderly patients with dementia‑related psychosis treated with antipsychotic drugs. Because of this boxed warning, use of paliperidone long‑acting injectables for dementia‑related psychosis is not authorized by this policy.

Treatment of dementia‑related psychosis with antipsychotics is contraindicated by the boxed warning implications in this policy. Providers should not initiate paliperidone long‑acting injectable therapy for the indication of dementia‑related psychosis, and requests for such use may be denied.

Initial Therapy Criteria (per product/indication)

inv-26: Initial Therapy Criteria

Initial authorization criteria per indication and product:

Schizophrenia — initial authorization: 1) Diagnosis of schizophrenia; 2) Prescribed by or in consultation with a psychiatrist; 3) Age >= 18 years; 4) Member meets one of: inpatient initiation within 60 days OR history of non-adherence to oral antipsychotics plus product-specific prior tolerability/stabilization requirements (see product rules); 5) Dose within product-specific maximums.

Schizoaffective disorder — initial authorization: 1) Diagnosis of schizoaffective disorder; 2) Request limited to Invega Sustenna or Erzofri; 3) Prescribed by or in consultation with a psychiatrist; 4) Age >= 18 years; 5) Member meets one of: history of non-adherence with established tolerability to oral risperidone (preferred) or paliperidone, OR inpatient initiation within 60 days; 6) Dose within product-specific maximums (Sustenna 234 mg/month; Erzofri 351 mg first dose then 234 mg/month).

inv-27: Initial therapy requirements

Product-specific initiation and sequencing requirements (initial dosing regimens and conversions):

Continuation / Renewal Criteria

inv-03: Continuation Therapy

Continued coverage is allowed when ALL of the following are met:

Continuation/renewal requirements: 1) Member is currently receiving the product via the Centene benefit or has received the medication for >=30 days, OR therapy was initiated inpatient within the last 60 days; 2) Member is responding positively to therapy; 3) Dose increases must not exceed product-specific maximums (Hafyera 1,560 mg/6 months; Sustenna or Erzofri 234 mg/month; Trinza 819 mg/3 months).

inv-29: Maintenance dosing

Maintenance dosing and maximums differ by product and indication:

Invega Sustenna maintenance: Maintenance dosing 39-234 mg IM monthly for schizophrenia (78-234 mg for schizoaffective), administered 5 weeks after first injection; maximum 234 mg/month.

Invega Trinza maintenance:

Provider Actions and Billing Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for paliperidone long-acting injectable products (Invega Hafyera, Invega Sustenna, Invega Trinza, Erzofri). Providers must submit supporting clinical documentation (e.g., office chart notes, hospital records, lab results) demonstrating that the member meets all approval criteria in the policy.

PA required prior to service; include clinical justification and documentation
Acceptable documentation: office notes, hospital discharge summaries, medication administration records, and relevant labs

Billing Rule

Prior Authorization and HCPCS Coding

Include applicable HCPCS codes on the PA request and on claims to assist processing. Providers should reference the most current professional coding guidance prior to claim submission.

Coding and HCPCS

Document header (no codes listed in this part)mixed

No codes listed

HCPCS codes — paliperidone injectable (J2426)HCPCS

J2426

Injection, paliperidone palmitate extended release (Invega Sustenna), 1 mg.

HCPCS codes — paliperidone injectable (J2427)HCPCS

J2427

Injection, paliperidone palmitate extended release (Invega Hafyera, or Invega Trinza), 1 mg.

HCPCS codes — paliperidone injectable (J2428)HCPCS

J2428

Injection, paliperidone palmitate extended release (Erzofri), 1 mg.

Dose limits — product maximums

Invega Hafyera maximum1,560 mg every 6 months

Invega Trinza maximum819 mg every 3 months

Invega Sustenna maximum234 mg per month

Erzofri maximum351 mg for first dose, then 234 mg per month thereafter

Quantity Limits and Maximum Doses

Invega Hafyera

Maximum dose1,560 mg every 6 months

Initiation noteHafyera is used only after established treatment with Invega Sustenna (≥4 months) or Invega Trinza (≥1 three‑month cycle).

Available strengths1,092 mg and 1,560 mg extended‑release injectable suspensions

Invega Sustenna

Typical monthly limit234 mg per month (maximum)

Initiation regimenInitial: 234 mg IM on day 1 and 156 mg on day 8 (deltoid); maintenance 39–234 mg monthly starting 5 weeks after first injection.

Available strengths

Step Therapy / Prior Treatment Requirements

Requirement	Details
Prior adequate treatment or established tolerability depending on requested product
If Invega Trinza requested: adequate treatment established with Invega Sustenna or Erzofri for at least the last 4 months
If Invega Sustenna or Erzofri requested: established tolerability with oral paliperidone or oral risperidone AND no known hypersensitivity to paliperidone or risperidone
If Invega Hafyera requested: adequate treatment established with Invega Sustenna or Erzofri for ≥4 months OR with Invega Trinza for at least one three‑month cycle
Requested dose must not exceed product maximums (Hafyera 1,560 mg/6 months; Sustenna 234 mg/month; Trinza 819 mg/3 months; Erzofri 351 mg first dose then 234 mg/month)

Product	Step requirement before approval
Invega Hafyera
Use only after Invega Sustenna has been established as adequate treatment for at least 4 months OR after Invega Trinza has been established as adequate treatment for at least one three‑month cycle; initial Hafyera dose is based on prior Sustenna or Trinza dose and initiated when the next Sustenna/Trinza dose would be scheduled
Invega Trinza
Use only after Invega Sustenna has been established as adequate treatment for at least 4 months; initiate Trinza when the next 1‑month paliperidone palmitate dose is scheduled using 3.5‑fold higher dose equivalents (e.g., last Sustenna 78→Trinza 273 mg; 117→410 mg; 156→546 mg; 234→819 mg); then administer every 3 months

Definitions and Product Names

Product definitions & indications

Product definitionsBrand‑name long‑acting injectable formulations of paliperidone (Invega Hafyera, Invega Sustenna, Invega Trinza, Erzofri) used to treat schizophrenia; some products also indicated for schizoaffective disorder.

Hafyera indicationSchizophrenia in adults after adequate treatment with monthly paliperidone (e.g., Sustenna) for ≥4 months or every‑3‑month paliperidone (Trinza) for ≥1 cycle.

Sustenna and Erzofri indicationsTreatment of schizophrenia in adults; treatment of schizoaffective disorder in adults (monotherapy or adjunct) for Sustenna and Erzofri.

Trinza indicationTreatment of schizophrenia in patients after adequate treatment with Invega Sustenna for at least four months.

Contraindication — known hypersensitivity

Definition

Background

Paliperidone is an atypical (second‑generation) antipsychotic available in multiple long‑acting injectable formulations (brand examples include Invega Hafyera, Invega Sustenna, Invega Trinza, and Erzofri). These products are indicated for the treatment of schizophrenia in adults, and certain formulations (Invega Sustenna and Erzofri) are also indicated for schizoaffective disorder per their labels. Specific formulations have labeled requirements for prior stabilization or established tolerability on shorter‑interval paliperidone products before conversion to longer‑interval formulations; dosing schedules, administration sites (deltoid or gluteal), and maximum product‑specific doses are provided in the policy.

Site of Care / Administration

Note

Administration site — deltoid or gluteal per product; initial doses deltoid

Administer intramuscularly in the deltoid or gluteal muscle per product-specific instructions; initial Sustenna and Erzofri doses are given in the deltoid.

Invega Sustenna initial injections (day 1 and day 8) are both administered in the deltoid; maintenance may be deltoid or gluteal
Erzofri initial 351 mg IM on day 1 is administered in the deltoid; maintenance may be deltoid or gluteal

Revision History

2025-04-11annual_reviewLatest

3Q 2025 annual review: no significant clinical changes; references reviewed and updated.

2025-02-13coding_update

Added HCPCS code J2428 for Erzofri and removed miscellaneous codes J3590 and C9399A.

2024-08-08product_addition

Policy Summary

Payermhn

PolicyPaliperidone long-acting injectable products

Policy CodePolicy CP.PHAR.291

Change TypeAdded product (Erzofri)HCPCS and approval duration updates

Effective DateDec 1, 2016

Next Review Date

SourceLink

On This Page

Invega Sustenna initiation: Initial regimen: 234 mg IM on day 1 and 156 mg IM on day 8 (both deltoid). Maintenance: 39-234 mg IM monthly (schizophrenia) administered 5 weeks after the first injection; schizoaffective maintenance 78-234 mg monthly. Maximum 234 mg per month.per product dosing limits

Initial and maintenance regimens specified

Erzofri initiation: Initial: 351 mg IM on day 1 in the deltoid. Maintenance: 39-234 mg IM monthly (recommended 117 mg) administered 4 weeks after the first injection; some patients may benefit from longer or higher monthly doses within available strengths. Maximum: 351 mg for the first dose, then 234 mg per month thereafter.per product dosing limits

Some patients may benefit from longer or higher monthly doses within available strengths

Invega Sustenna dosing: Initial: 234 mg IM on day 1 and 156 mg IM on day 8 (deltoid). Maintenance: 39-234 mg IM monthly (schizophrenia) administered 5 weeks after first injection; schizoaffective maintenance 78-234 mg monthly. Maximum 234 mg/month.

Invega Trinza sequencing and dosing: Trinza may be used only after Invega Sustenna has been established as adequate treatment for at least 4 months. Initiate Trinza when next 1-month dose is scheduled using 3.5-fold equivalents (78->273 mg; 117->410 mg; 156->546 mg; 234->819 mg). Then administer every 3 months.

Invega Hafyera sequencing and dosing: Hafyera may be used only after Invega Sustenna established >=4 months OR after Invega Trinza established for at least one 3-month cycle. Initial Hafyera dose is based on prior Sustenna or Trinza dose and started when next Sustenna/Trinza dose would be due (examples: Sustenna 156->Hafyera 1,092 mg; 234->1,560 mg; Trinza 546->Hafyera 1,092 mg).

Erzofri dosing: Initial: 351 mg IM on day 1 (deltoid). Maintenance: 39-234 mg IM monthly (recommended 117 mg) starting 4 weeks after first injection; maximum 351 mg first dose then 234 mg/month thereafter.

After initiation, administer IM every 3 months; maximum 819 mg every 3 months.

Invega Hafyera maintenance: Maximum dose 1,560 mg every 6 months; initiation and maintenance dosing based on prior Sustenna/Trinza dosing conversion rules.

Erzofri maintenance: After the initial 351 mg dose, maintenance 39-234 mg IM monthly (recommended 117 mg); maximum 234 mg/month after the first dose.

List HCPCS codes on prior authorization and claims when applicable
Reference the most up-to-date coding guidance before submitting claims

Documentation Required

Coding and Documentation Guidance

Providers should document applicable dosing, prior tolerability, sequencing, and hypersensitivity status in the clinical record and include this information with the PA to avoid denial.

Document established tolerability to oral paliperidone or risperidone when required
Document absence of known hypersensitivity to paliperidone, risperidone, or excipients
Include dosing history and dates showing adequate trial durations when applicable

Step Therapy

Tolerability / Prior Product Requirements

Certain products require prior tolerability or prior product use before authorization. Ensure the member's medication history demonstrates these requirements and include supporting notes.

Invega Sustenna or Erzofri requests: show established tolerability with oral paliperidone or oral risperidone
Invega Trinza requests: show adequate treatment established with Invega Sustenna or Erzofri for at least 4 months
Invega Hafyera requests: show either ≥4 months of adequate treatment with Invega Sustenna/Erzofri or at least one 3‑month cycle of Invega Trinza

Step Therapy

Product Sequencing Requirement

Product sequencing is required for Invega Hafyera: it is authorized only after Invega Sustenna has been established as adequate treatment for at least four months or after Invega Trinza has been established as adequate treatment for at least one three-month cycle. Include dates and dosing that demonstrate this sequencing.

Hafyera initiation must align with last Sustenna/Trinza dose schedule and documented treatment duration
Follow dosing conversion guidance (e.g., last Sustenna dose 156 mg → Hafyera 1,092 mg; 234 mg → 1,560 mg; last Trinza 546 mg → Hafyera 1,092 mg)

Billing Rule

Coding / Documentation Guidance — HCPCS Codes

Providers should include the applicable HCPCS codes on claims and the PA request to reduce processing delays. The following HCPCS codes are referenced in this policy for informational purposes.

J2426 — Injection, paliperidone palmitate extended release (Invega Sustenna), 1 mg
J2427 — Injection, paliperidone palmitate extended release (Invega Hafyera or Invega Trinza), 1 mg
J2428 — Injection, paliperidone palmitate extended release (Erzofri), 1 mg

39, 78, 117, 156, and 234 mg extended‑release injectable suspensions

Invega Trinza

Maximum dose819 mg every 3 months

Initiation requirementUse only after ≥4 months of Invega Sustenna; initiate Trinza when next 1‑month dose is scheduled using 3.5‑fold equivalent doses.

Available strengths273, 410, 546, and 819 mg extended‑release injectable suspensions

Erzofri

Initial dose351 mg IM on day 1 (deltoid)

Maintenance dosing39–234 mg IM monthly starting 4 weeks after first injection (recommended 117 mg monthly)

Maximum dosing plan351 mg first dose, then maximum 234 mg per month thereafter

Paliperidone long‑acting injectables — consolidated maximums

Invega HafyeraMaximum 1,560 mg every 6 months; initiation requires prior Sustenna (≥4 months) or Trinza (≥1 three‑month cycle)

Invega TrinzaMaximum 819 mg every 3 months; initiate after ≥4 months of Invega Sustenna using 3.5‑fold conversion

Invega SustennaMaximum 234 mg per month; initial 234 mg day 1 and 156 mg day 8 then maintenance 39–234 mg monthly

Erzofri351 mg initial dose then maintenance 39–234 mg monthly (recommended 117 mg); maximum 234 mg/month after first dose

Known hypersensitivity to paliperidone, risperidone, or to any excipients.

Policy impactRequests for products in patients with this hypersensitivity are contraindicated and may be denied.

Relevant appendixSee Appendix C: Contraindications in policy document.

Boxed warning — dementia‑related psychosis

Boxed warning statementIncreased risk of death in elderly patients with dementia‑related psychosis treated with antipsychotic drugs.

Coverage implicationUse for dementia‑related psychosis is not authorized under this policy (explicit exclusion).

Clinical cautionAntipsychotic treatment in elderly patients with dementia‑related psychosis is associated with increased mortality risk.

RT4 entry added newly approved Erzofri to the policy.

2024-05-09policy_revision

3Q 2024 annual review revised commercial approval duration to 6 months or to the member's renewal date and updated HCPCS code description for J2426.

2023-04-11policy_update

3Q 2023 annual review applied template changes to continued therapy section and added HCPCS code J2427 for Invega Hafyera or Invega Trinza.

2021-09-23product_addition

RT4 entry added newly approved Invega Hafyera to the policy.