CurrentmhnPolicy CP.PHAR.371

Triamcinolone ER Injection (Zilretta)

Medical necessity and prior authorization criteria for Zilretta (triamcinolone ER) intra‑articular injection for osteoarthritis of the knee and related coverage guidance for Centene-affiliated health plans.

Policy Summary

Payermhn

PolicyTriamcinolone ER Injection (Zilretta)

Policy CodePolicy CP.PHAR.371

Change TypeNo material change

Effective DateMar 1, 2024

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis (imaging), specialist involvement, age ≥18, required NSAID and intra‑articular steroid trials, and dose ≤32 mg; do not request retreatment of a knee previously treated with Zilretta.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

32 mgDose (mg)

one dose per knee lifetimeReuse

≥18Min age

3 monthsApproval length

J3304HCPCS

Coverage Criteria

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inv-01: Initial Therapy — Osteoarthritis of the Knee — Covered when ALL of the following are met

Covered when ALL of the following are met:

Diagnosis of osteoarthritis of the knee supported by imaging (e.g., X-ray, MRI);

imaging required

Prescriber: Prescribed by or in consultation with a rheumatologist, orthopedist, or sports medicine physician;

specialist involvement required

Prior intra-articular steroid trial: Trial of at least one other intra-articular glucocorticoid injection for the knee to be treated with a documented positive, but inadequate response (e.g., inadequate pain relief, frequent need of rescue medications, inability to increase activity, or steroid-induced hyperglycemia);

documented positive but inadequate response required

No prior Zilretta to same knee: Member is not receiving re-treatment of knee(s) previously treated with Zilretta;

repeat administration to same knee not permitted

Dose limit: Dose does not exceed 32 mg as a single intra-articular injection into the knee;<=32 mg

single intra-articular injection per knee

inv-03: Other Indications / Off‑label guidance — For other indications

For other indications:

Label change or off-label handling: If the drug has undergone a label change within the last 6 months that is not yet reflected in this policy, follow the applicable formulary/no-coverage or non-formulary policies for the relevant line of business;6 months

refer to listed policies (see CP.CPA.190, HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16)

Off-label use: If the requested use (diagnosis, age, dosing) is not listed under section III and criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business (e.g., CP.CPA.09, HIM.PA.154, CP.PMN.53);

refer to off-label use policy

inv-04: Coverage criteria (dosing and retreatment) — Covered when ALL of the following are met

Covered when ALL of the following are met

Dose and administration: Single intra-articular injection of 32 mg (5 mL) per knee (extended-release formulation);32 mg (5 mL) single dose

product provided as a single-dose vial for reconstitution

Retreatment restriction: Member is not receiving re-treatment of knee(s) previously treated with Zilretta;one dose per knee lifetime

requirement added/clarified in 1Q 2025 review

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider supplies sufficient clinical documentation demonstrating efficacy and safety consistent with the applicable off‑label use policies (see CP.CPA.09 for commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid).

Retreatment of knee(s) previously treated with Zilretta is restricted. The policy was updated in the 1Q 2025 annual review to add a requirement that members must not be receiving re‑treatment of any knee previously treated with Zilretta; approval duration was clarified as one dose per knee lifetime.

Repeat administration of Zilretta to the same knee is considered not authorized / not permitted. Clinical safety data from a repeat‑administration study showed higher rates of arthralgia and treatment‑emergent adverse events with a second injection, and the FDA label indicates that available data are insufficient to characterize the safety of repeat dosing; therefore re‑authorization for the same knee is not permitted.

No explicit additional 'not medically necessary' statements beyond the repeat‑administration restriction are present in this portion of the document.

Continuation / Retreatment Criteria

inv-26: Continuation Therapy Restrictions — Continuation / repeat dosing considerations

Continuation / repeat dosing considerations

No repeat for same knee: Re-authorization is not permitted; Zilretta is not indicated for repeat administration in the same knee due to insufficient safety data on repeat dosing (higher rates of arthralgia and other AEs reported with second injections).

see Spitzer study and FDA label safety language; for an untreated knee, initial criteria must be met

inv-27: Retreatment — Continuation / retreatment rules

Continuation / retreatment rules

Retreatment prohibition: Member is not receiving re-treatment of knee(s) previously treated with Zilretta; retreatment of the same knee is restricted (one dose per knee lifetime).one dose per knee lifetime

added and clarified in 1Q 2025 annual review

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Zilretta (triamcinolone acetonide extended‑release) prior to administration. Requests must document the diagnosis and show that all applicable approval criteria are met. Providers should obtain prior authorization when submitting claims for J3304 (injection, triamcinolone acetonide, preservative‑free, extended‑release, microsphere formulation, 1 mg) or other related codes.

Prior authorization required for Zilretta (Triamcinolone ER).
Reference HCPCS code J3304 when applicable.

Denial Risk

Documentation and Denial Risk

Provider must submit supporting documentation such as office chart notes, imaging reports, laboratory results, consultation notes, and records of prior treatments demonstrating the member meets the policy criteria (including specialist involvement, age, medication trials, and dosing limits). Requests lacking sufficient documentation or clinical information to demonstrate that criteria are met may be denied.

Acceptable documentation: office chart notes, lab results, imaging (X‑ray/MRI), consultation notes.
Insufficient documentation or unmet criteria may result in denial.

Documentation Required

Imaging Requirement

Imaging evidence (e.g., X‑ray or MRI) supporting the diagnosis of knee osteoarthritis is required as part of the prior authorization submission. The diagnosis must be supported by the imaging study to meet initial approval criteria.

Imaging (X‑ray, MRI) required to confirm osteoarthritis of the knee.

Billing Rule

Coding Implications

Providers should reference current professional coding guidance when submitting claims. Codes listed in this policy are informational only; inclusion or exclusion of any code does not guarantee coverage. Verify the correct HCPCS/CPT/ICD‑10 codes and modifiers prior to claim submission.

Codes in this policy are informational only; verify up‑to‑date coding guidance before claim submission.
Informatory HCPCS code referenced for Zilretta: J3304 (triamcinolone acetonide, extended‑release, 1 mg).

Step Therapy

Step Therapy / State‑Specific

Step therapy/state‑specific rules: general step therapy requirements apply (e.g., failure of a 4‑week trial of a prescription‑strength oral NSAID or topical NSAID when applicable, and trial of ≥1 other intra‑articular glucocorticoid with inadequate response). For Illinois HIM requests, the step therapy requirements do not apply per IL HB 5395 effective 01/01/2026; an administrative step therapy bypass for Illinois HIM has been added.

Requires failure of ≥4‑week trial of an oral prescription‑strength NSAID (or topical NSAID if ≥75 years or unable to take oral NSAIDs) unless contraindicated.
Trial of at least one other intra‑articular glucocorticoid with documented inadequate response is required.
Illinois HIM: step therapy requirements do not apply per IL HB 5395 (effective 01/01/2026).

Step	Requirement
1	Must document a trial and inadequate response or intolerance to a ≥4‑week course of an oral prescription‑strength NSAID at continuous therapeutic dosing (or a topical NSAID if member is ≥75 years or unable to take oral NSAIDs).

Step	Requirement
2	Document trial of at least one other intra‑articular glucocorticoid injection for the knee to be treated with a documented positive but inadequate response (e.g., inadequate pain relief, frequent need for rescue medications, inability to increase activity, or steroid‑induced hyperglycemia).

State-specific note	Effect on step therapy
Illinois (IL)	Step therapy requirements do not apply for Illinois HIM requests per IL HB 5395 (step therapy bypass added).

Site of Care

Note

Administer as a single intra‑articular injection (32 mg/5 mL)

Administer Zilretta as a single intra‑articular injection into the knee using the single‑dose 32 mg/5 mL vial formulation; document administration details in the medical record.

Product supplied as a single‑dose vial for reconstitution: 32 mg/5 mL.
Record site of injection, dose, and procedural setting in the chart.

Note

Administered as an intra‑articular injection in an appropriate setting

Zilretta must be administered via intra‑articular injection in an appropriate procedural setting (e.g., office or other suitable setting); document the setting and procedure in the clinical record.

Ensure documentation includes the procedural setting and any applicable sedation/sterile technique notes.
Billing should reflect the appropriate site-of-care and procedure codes per payer guidance.

Definitions

inv-20: Zilretta — Extended‑release synthetic corticosteroid formulation of triamcinolone acetonide

DescriptionExtended‑release synthetic corticosteroid formulation of triamcinolone acetonide (Zilretta).

MechanismExtended‑release microsphere technology for sustained intra‑articular delivery over ~12 weeks.

ClassIntra‑articular corticosteroid, extended‑release formulation

inv-21: Clinical outcome measures — ADP, WOMAC, KOOS QoL mentioned in trials

Primary efficacy measureAverage Daily Pain (ADP) — primary endpoint in pivotal trial

Other patient‑reported outcomesWOMAC (Western Ontario and McMaster Universities Osteoarthritis Index)

Quality of life subscaleKOOS QoL (Knee injury and Osteoarthritis Outcome Score — Quality of Life)

inv-22: Product formulation — Injectable suspension of microspheres in single-dose vial (32 mg/5 mL)

FormulationInjectable suspension of microspheres in a single‑dose vial for reconstitution

Vial content32 mg per vial in 5 mL

PresentationSingle‑dose vial (reconstitute prior to intra‑articular injection)

inv-23: Approved dosing — Dose of 32 mg (5 mL) as single intra-articular injection per affected knee

Approved dose per affected knee32 mg (5 mL) administered as a single intra‑articular extended‑release injection

Dosing frequencySingle injection per knee; repeat administration to the same knee is not permitted

Maximum per administration32 mg (single dose)

OpenPayer

Triamcinolone ER Injection (Zilretta)

Coverage Criteria

Initial Therapy Criteria

Continuation / Retreatment Criteria

Provider Actions and Requirements

Coding

Step Therapy

Quantity Limits

Site of Care

Definitions

Background