Centene zoledronic acid Coverage Update

Coverage Criteria

Initial Therapy - Osteoporosis

Initial approval for osteoporosis (treatment or prevention): covered when ALL of the following are met

Osteoporosis initial criteria: 1) Prescribed for treatment or prevention of postmenopausal osteoporosis (PMO) or glucocorticoid-induced osteoporosis (GIO); 2) Age >= 18 years or documentation of closed epiphyses on X‑ray; 3) Failure of a 12‑month trial of an oral bisphosphonate (see Appendix B; generic alendronate is preferred) at up to maximally indicated doses unless contraindicated or clinically significant adverse effects occur; 4) Dose does not exceed 5 mg; 5) If request is for brand Reclast, member must use zoledronic acid 5 mg/100 mL (generic Reclast) unless contraindicated or intolerant.

Initial Therapy - Paget Disease

Initial approval for Paget disease of bone: covered when ALL of the following are met

Paget disease criteria: 1) Diagnosis of Paget disease of bone; 2) Age >= 18 years or documentation of closed epiphyses on X‑ray; 3) If request is for brand Reclast, member must use zoledronic acid 5 mg/100 mL (generic Reclast) unless contraindicated or intolerant; 4) Dose does not exceed 5 mg.

Initial Therapy - Hypercalcemia of Malignancy

Hypercalcemia of malignancy: covered when ALL of the following are met

Hypercalcemia criteria: 1) Request is for zoledronic acid 4 mg/5 mL or 4 mg/100 mL (formerly Zometa); 2) Diagnosis of hypercalcemia of malignancy with albumin‑corrected calcium >= 12 mg/dL; 3) Prescribed by or in consultation with an oncologist; 4) Age >= 18 years or documentation of closed epiphyses on X‑ray; 5) Dose does not exceed 4 mg.

Initial Therapy - Multiple Myeloma or Solid Tumor

Multiple myeloma or solid tumor bone metastases: covered when ALL of the following are met

MM/solid tumor criteria: 1) Request is for zoledronic acid 4 mg/5 mL or 4 mg/100 mL (formerly Zometa); 2) Diagnosis of multiple myeloma with initiation/receipt of therapy for symptomatic disease OR diagnosis of bony metastasis from a solid tumor; 3) Prescribed by or in consultation with an oncologist; 4) Age >= 18 years or documentation of closed epiphyses on X‑ray; 5) Dose does not exceed 4 mg.

Off-label - Prostate/Breast Cancer Fracture Prevention

Off‑label: Prostate/Breast Cancer fracture prevention (covered when ALL are met)

Prostate/Breast cancer fracture prevention: 1) Diagnosis of prostate cancer receiving androgen deprivation therapy OR breast cancer receiving adjuvant endocrine therapy; 2) Age >= 18 years or documentation of closed epiphyses on X‑ray; 3) Prescribed by or in consultation with an oncologist; 4) If request is for brand Reclast, member must use zoledronic acid 5 mg/100 mL (generic Reclast) unless contraindicated or intolerant; 5) Dose does not exceed 4 mg; 6) Requested regimen must be FDA‑approved or recommended by NCCN OR dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence).

Off-label - Systemic Mastocytosis

Off‑label: Systemic mastocytosis (covered when ALL are met)

Systemic mastocytosis criteria: 1) Diagnosis of systemic mastocytosis; 2) Request is for zoledronic acid 4 mg/5 mL or 4 mg/100 mL (formerly Zometa); 3) Member has osteopenia or osteoporosis with bone pain; 4) Age >= 18 years or documentation of closed epiphyses on X‑ray; 5) Prescribed by or in consultation with an oncologist; 6) Requested dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence) OR requested dose does not exceed 4 mg.

Off-label - Histiocytic Neoplasms (LCH)

Off‑label: Langerhans cell histiocytosis (covered when ALL are met)

Langerhans cell histiocytosis criteria: 1) Diagnosis of Langerhans cell histiocytosis (LCH); 2) Request is for zoledronic acid 4 mg/5 mL or 4 mg/100 mL (formerly Zometa); 3) Member has multifocal bone disease or unifocal LCH with isolated bone disease; 4) Prescribed by or in consultation with an oncologist; 5) Age >= 18 years or documentation of closed epiphyses on X‑ray; 6) Requested dose does not exceed 4 mg OR dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence).

G. Histiocytic Neoplasms — Langerhans Cell Histiocytosis (off-label)

Langerhans Cell Histiocytosis (off‑label) - Covered when ALL of the following are met

LCH off-label coverage: 1) Request is for zoledronic acid 4 mg/5 mL or 4 mg/100 mL; 2) Diagnosis of Langerhans cell histiocytosis; 3) Member has multifocal bone disease or unifocal LCH with isolated bone disease; 4) Prescribed by or in consultation with an oncologist; 5) Patient is >= 18 years or documentation of closed epiphyses on X‑ray; 6) Dose does not exceed 4 mg; 7) Prescribed regimen must be FDA‑approved or recommended by NCCN OR dose is supported by practice guidelines/peer‑reviewed literature with supporting evidence from the prescriber.

Off‑label; prescriber must submit supporting evidence.

Continued Therapy — Osteoporosis and Paget Disease

Continued Therapy — Osteoporosis and Paget Disease of Bone (must meet ALL):

Continued therapy osteoporosis/Paget: a) Member is currently receiving medication via the Centene benefit or has previously met initial approval criteria; b) Member is responding positively to therapy; c) Continuity of care applies where state/product regulations require;

Approval duration: osteoporosis treatment and Paget disease: 12 months (one infusion).

Continued Therapy — Oncology

Continued Therapy — Oncology‑Related Indications (must meet ALL):

Oncology continued therapy: 1) Member is currently receiving medication via Centene benefit or documentation supports current receipt for a covered indication and member has received medication for at least 30 days; 2) Member is responding positively to therapy; 3) If request is for a dose increase, new dose must be supported by practice guidelines or peer‑reviewed literature (prescriber must submit evidence) OR new dose does not exceed 4 mg; 4) Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval durations vary by oncology indication (e.g., hypercalcemia: 1 week; prostate cancer: 12 months (one infusion); breast cancer: 12 months (two infusions); other indications: 12 months every 3 weeks).

Other diagnoses/indications routing

Other diagnoses/indications (procedural routing):

Other diagnoses/indications: 1) If the drug has recently (within the last 6 months) undergone a label change (new indication, age expansion, or dosing regimen) not yet reflected in this policy, refer to the specified line‑of‑business policies; 2) For drugs not on the formulary/PDL or for non‑formulary requests, refer to the non‑formulary/no coverage criteria policies for the relevant line of business; 3) If the requested use is not listed in this policy and criterion 1 does not apply, refer to the off‑label use policy for the relevant line of business.

References: CP.CPA.190, HIM.PA.103, CP PMN.16, HIM.PA.33, CP.CPA.09, HIM.PA.154, CP.PMN.53.

Notable coverage criteria and changes

Policy-level coverage stance and notable criteria changes

Oncology indications: Frequency/duration for prostate and breast cancer fracture prevention updated: prostate cancer once yearly; breast cancer twice yearly (1Q 2021 update).

Refer to policy revision history.

Osteoporosis: For osteoporosis, failure of generic alendronate is preferred prior to zoledronic acid use (1Q 2024 update).

Refer to policy revision history.

Paget disease: Initial requirement to fail an oral bisphosphonate for Paget disease was removed (1Q 2024 update).

Refer to policy revision history.

Product distinctions: Distinction between Zometa and Reclast was removed after Zometa became obsolete; restrictions preventing combined use were removed (1Q 2023 update).

The policy notes a specific limitation of use: the safety and efficacy of zoledronic acid for treatment of hypercalcemia associated with hyperparathyroidism or other non‑tumor‑related conditions have not been established. Requests for zoledronic acid to manage non‑tumor‑related hypercalcemia should be evaluated against this limitation and are not supported by the evidence cited in this clinical policy.

Requests for non‑FDA approved (off‑label) indications that are not explicitly addressed in this policy will only be considered when the prescriber submits sufficient documentation demonstrating efficacy and safety in accordance with the applicable off‑label use policies (e.g., CP.CPA.09 for commercial, HIM.PA.154 for Health Insurance Marketplace, CP.PMN.53 for Medicaid) or other evidence of coverage documents.

When state Medicaid coverage provisions conflict with the coverage statements in this clinical policy, the state Medicaid coverage provisions take precedence. Providers should consult the applicable state Medicaid manual for any specific coverage rules that supersede this policy for Medicaid members.

Non‑FDA approved indications for which there is insufficient supporting evidence are considered not authorized (not medically necessary) under this policy. Such requests must meet the documentation standards set out in the referenced off‑label use policies to be considered for coverage.

The inclusion or exclusion of procedure or billing codes in this clinical policy does not by itself guarantee coverage or payment. Coverage decisions remain subject to the member’s plan terms, conditions, exclusions, and limitations; providers should reference current professional coding guidance and the member’s evidence of coverage when submitting claims.

Product Strengths, Formulations and Codes

Product strengths and formulationsNDC | product

4 mg/5 mL	Zoledronic acid (Zometa) single-use vial concentrate strength
4 mg/100 mL	Zoledronic acid (Zometa) ready-to-infuse solution strength
5 mg/100 mL	Zoledronic acid (Reclast) ready-to-infuse solution strength

HCPCS codes referencedHCPCS

J3489

Injection, zoledronic acid

inv-20: Maximum oncology dose — 4 mg single infusion (may retreat after minimum 7 days)

Maximum oncology single infusion4 mg IV as a single-use infusion (may retreat after a minimum of 7 days)

Applicable indicationsHypercalcemia of malignancy; multiple myeloma; solid tumor bone metastases; select off-label oncology uses per criteria

Dose limit for retreatment intervalMay re-treat with 4 mg after at least 7 days; typical oncology dosing intervals for metastatic disease are every 3–4 weeks

inv-21: Reclast annual dose — 5 mg IV once yearly (treatment); 5 mg IV once every 2 years (prevention)

Reclast treatment dosing5 mg IV once yearly (treatment)

Reclast prevention dosing

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for zoledronic acid. Providers must obtain prior authorization per the Health Plan's medical necessity criteria before submitting claims.

Prior authorization required for zoledronic acid
Approval durations vary by indication (e.g., Commercial typically 6 months; Osteoporosis treatment 12 months; see policy for other indications)
Coding reference: HCPCS J3489 (Injection, zoledronic acid)

Note

Non‑FDA Indications — Evidence Requirement

Requests for indications that are not FDA-approved and not addressed in this policy will not be authorized unless the prescriber submits sufficient documentation supporting efficacy and safety in accordance with the Health Plan's off‑label use policies.

For commercial members follow CP.CPA.09; for Health Insurance Marketplace follow HIM.PA.154; for Medicaid follow CP.PMN.53 (or equivalent Health Plan off‑label use policies)
Prescriber must submit practice guidelines or peer‑reviewed literature supporting the requested off‑label dose/regimen

Background

Zoledronic acid is a nitrogen‑containing bisphosphonate available in formulations marketed as Reclast (commonly supplied as a 5 mg/100 mL ready‑to‑infuse solution for osteoporosis and Paget disease) and previously as Zometa formulations (4 mg strengths used for oncology indications such as hypercalcemia of malignancy and bone metastases). The agent is indicated for treatment and prevention of osteoporosis, treatment of Paget disease of bone, management of hypercalcemia of malignancy, and treatment of skeletal complications from multiple myeloma or solid tumor metastases; off‑label oncology uses may be considered when supported by guidelines or peer‑reviewed literature.

Definitions and Abbreviations

inv-36: Reclast vs Zometa — Reclast refers to zoledronic acid indicated for osteoporosis and Paget disease (5 mg dosing); Zometa refers to zoledronic acid formulation for oncology

Reclast (osteoporosis/Paget)Zoledronic acid formulation indicated for osteoporosis and Paget disease; typical Reclast ready-to-infuse strength is 5 mg/100 mL

Zometa (oncology)Zoledronic acid formulation formerly used for oncology indications (hypercalcemia of malignancy, bone metastases) with 4 mg strengths

Policy distinctionPolicy notes historical distinction: Reclast used for 5 mg dosing, Zometa referenced for 4 mg oncology dosing (Zometa later became obsolete)

inv-37: BMD — Bone mineral density (abbreviation listed in Appendix A).

AbbreviationBMD = bone mineral density

Location in policy

Revision History

2025-02-25annual_reviewLatest

1Q 2025 annual review: added redirection of brand Reclast requests to generic; clarified initial oncology requests (other than prostate and breast cancer) specify zoledronic acid 4 mg/5 mL or 4 mg/100 mL (formerly Zometa).

2024-02-24annual_review

1Q 2024 annual review: clarified that failure of generic alendronate is preferred for osteoporosis and removed the initial oral bisphosphonate failure requirement and Appendix B listing for Paget disease.

2023-11-02

OpenPayer

Zoledronic Acid (Reclast/Zometa) coverage

Coverage Criteria

Product Strengths, Formulations and Codes

Provider Actions & Requirements

Background

Definitions and Abbreviations

Revision History