CurrentmhnPolicy CP.PHAR.418

Clinical Policy: Dexrazoxane (Totect)

Policy governs medical necessity criteria, approved indications, dosing constraints, authorization durations, reauthorization rules, and coding implications for dexrazoxane (previously Totect) for commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyClinical Policy: Dexrazoxane (Totect)

Policy CodePolicy CP.PHAR.418

Change TypeAnnual review / revisions (2021-2025)

Effective Date03.19.19

Next Review Date

Key ActionProvider must submit documentation (office notes, labs or other clinical information) supporting that member meets all approval criteria.

POLICY UPDATE CHANGES

2Q 2025 annual review removed brand Totect from criteria as product discontinued and obsolete, clarified anthracycline-induced extravasation is off-label, removed Hodgkin lymphoma in adults > 60 years, and removed redirections to generic dexrazoxane.

2Q 2024 annual review added NCCN 2A indications (relapsed/refractory Ph-positive ALL, Hodgkin lymphoma in adults >60, neuroblastoma) and redirected to generic dexrazoxane.

2Q 2023 annual review updated FDA approved indication to mirror PI, clarified pediatric limitations, and added off-label use for soft tissue sarcoma per NCCN 2A.

2Q 2022 annual review added off-label pediatric uses per NCCN 2A and removed appendix with inconclusive thresholds; removed Zinecard; updated dosing section.

2Q 2021 annual review revised references for HIM line of business off-label use and updated section V dosing to include Totect for doxorubicin-induced cardiomyopathy.

2Primary covered indications (FDA)

12 monthsCardiomyopathy approval duration

Key pediatric anthracycline threshold

3 daysExtravasation approval duration

Coverage Summary

Dexrazoxane is a cytoprotective agent indicated to reduce the incidence and severity of doxorubicin-associated cardiomyopathy in women with metastatic breast cancer who have received a cumulative doxorubicin dose of ≥ 300 mg/m2 and will continue doxorubicin, and for the treatment of anthracycline extravasation. The policy incorporates FDA labeling (Dexrazoxane Prescribing Information) and NCCN-supported pediatric off-label indications and dosing constraints; pediatric NCCN-supported uses include select ALL, aggressive mature B-cell lymphomas, Hodgkin lymphoma, Wilms tumor, neuroblastoma, and soft tissue sarcoma with specific cumulative dose thresholds. Scope: this policy governs medical necessity criteria, approved indications, dosing constraints, authorization durations and reauthorization rules, and coding implications for dexrazoxane (commercial, HIM, Medicaid). Coverage stance: covered_with_criteria — approval requires documentation that the member meets the specified criteria including prescriber specialty, dose limits (e.g., dexrazoxane:doxorubicin ratio ≤ 10:1 unless guideline-supported), and diagnosis-specific thresholds.

Key Thresholds and Dosing Constraints

Cumulative doxorubicin dose (adults)≥ 300 mg/m2

Pediatric/other tumor thresholdsPh-negative or relapsed Ph-positive ALL: ≥ 250 mg/m2 (doxorubicin equivalent); Wilms tumor: ≥ 150 mg/m2; Soft tissue sarcoma: ≥ 250 mg/m2

Dose ratio (dexrazoxane:doxorubicin)Not to exceed 10:1 (e.g., dexrazoxane 500 mg/m2 for doxorubicin 50 mg/m2)

Anthracycline extravasation dosing max≤ 2000 mg/day on days 1 and 2; ≤ 1000 mg on day 3

Initial Therapy Criteria

Initial Approval Criteria

Provider must submit documentation supporting that member meets all approval criteria. Dexrazoxane is medically necessary when the following criteria are met:

A. Doxorubicin-Induced Cardiomyopathy (must meet all)

Prescribed to reduce the incidence or severity of cardiomyopathy associated with doxorubicin
Prescribed by or in consultation with an oncologist or hematologist
One of the following (a or b)
- a: Age ≥ 18 years; member has received a cumulative doxorubicin dose of ≥ 300 mg/m2Cumulative doxorubicin dose ≥ 300 mg/m2

Continuation (Re-authorization) Criteria

For members currently receiving dexrazoxane

A. Doxorubicin-Induced Cardiomyopathy (must meet all)

Member meets one of the following (a or b): currently receiving medication via Centene benefit or previously met initial approval criteria; or member is currently receiving medication and is enrolled in a state and product with continuity of care regulations
Refer to state addendums CC.PHARM.03A and CC.PHARM.03B
Member continues to receive doxorubicin
Member is responding positively to therapy
Request meets one of the following (a or b): dose does not exceed 10 times the dose of doxorubicin OR dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit evidence)

Diagnoses / Indications NOT Authorized

Diagnoses/Indications NOT authorized

Coverage not authorized for

Non-FDA approved indications which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety per off-label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53)

Applicable Codes

HCPCS - Injectable dexrazoxaneHCPCSCovered

J1190

Injection, dexrazoxane hydrochloride, per 250 mg.

Provider Actions

Documentation Required

Support clinical criteria

Provider must submit documentation (office notes, labs or other clinical information) supporting that member meets all approval criteria.

Prior Authorization

Prescriber specialty requirement

Prescriptions must be by or in consultation with an oncologist or hematologist for doxorubicin-induced cardiomyopathy and by or in consultation with an oncologist for extravasation.

Clinical Evidence & References

Evidence and guideline sources referenced in the policy include the Dexrazoxane Prescribing Information (Hikma Pharmaceuticals USA, Inc; January 2025), NCCN guidance citing multiple pediatric tumor guideline versions (2024–2025) for off-label pediatric indications and dosing thresholds, and the ASCO 2008 Clinical Practice Guideline Update on use of chemotherapy and radiation therapy protectants. The policy explicitly states it incorporates FDA labeling and NCCN-supported pediatric indications into coverage criteria.

Background

Background and scope: Dexrazoxane is a cytoprotective agent used primarily to protect the heart from anthracycline (doxorubicin) cardiotoxicity and to treat anthracycline extravasation. Therapeutic role: administered intravenously prior to doxorubicin (given as an IV infusion over 15 minutes and within 30 minutes before doxorubicin) at a standard ratio of 10:1 dexrazoxane to doxorubicin for cardioprotection; extravasation dosing follows a separate short-duration regimen. Prior branded product Totect has been discontinued and the policy now references generic dexrazoxane availability (single-dose 500 mg vial). Pediatric off-label uses: NCCN-supported pediatric indications (e.g., selected ALL protocols, aggressive mature B-cell lymphoma, Hodgkin lymphoma, Wilms tumor, neuroblastoma, soft tissue sarcoma) are incorporated with specified cumulative anthracycline thresholds (for example, pediatric ALL and relapsed/refractory Ph-positive or Ph-negative ALL situations with anticipated cumulative anthracycline dose ≥ 250 mg/m2, Wilms tumor threshold ≥ 150 mg/m2, soft tissue sarcoma threshold ≥ 250 mg/m2). Definitions/glossary: ALL = acute lymphoblastic leukemia; FDA = Food and Drug Administration. The policy sets approval durations (cardiomyopathy: up to 12 months or duration of doxorubicin therapy; extravasation: 3 days) and enforces dose limits for extravasation (≤ 2000 mg/day on days 1–2 and ≤ 1000 mg on day 3).

Revision History

05.21annual_review

2Q 2021 annual review revised references for HIM line of business off-label use and updated dosing section to include Totect for doxorubicin‑induced cardiomyopathy.

05.22annual_review

2Q 2022 annual review added off-label pediatric uses per NCCN 2A (Ph‑negative ALL, aggressive mature B‑cell lymphomas, Hodgkin lymphoma, Wilms Tumor), removed appendix with inconclusive thresholds, removed Zinecard, and updated dosing section.

05.23annual_review

2Q 2023 annual review updated FDA approved indication to mirror the prescribing information, clarified pediatric limitations for Ph‑negative ALL and Hodgkin lymphoma, and added off‑label use for soft tissue sarcoma per NCCN 2A.

Policy Summary

Payermhn

PolicyClinical Policy: Dexrazoxane (Totect)

Policy CodePolicy CP.PHAR.418

Change TypeAnnual review / revisions (2021-2025)

Effective Date03.19.19

Next Review Date

Key ActionProvider must submit documentation (office notes, labs or other clinical information) supporting that member meets all approval criteria.

On This Page

i: Pediatric acute lymphoblastic leukemia (ALL) and one of the following (1 or 2); pediatric aggressive mature B-cell lymphomas; pediatric Hodgkin lymphoma; Wilms Tumor with planned cumulative doxorubicin ≥ 150 mg/m2; neuroblastoma; soft tissue sarcoma with planned cumulative doxorubicin ≥ 250 mg/m2See pediatric thresholds: ≥250 mg/m2 for certain ALL and sarcoma; ≥150 mg/m2 for Wilms
Includes Ph-negative ALL per DFCI protocols with anticipated cumulative anthracycline dose ≥ 250 mg/m2 or relapsed/refractory Ph-positive ALL in combination regimens as specified by NCCN/COG

Will be used concurrently with doxorubicin

Request must meet one of the following (a or b)

a: Dose does not exceed 10 times the dose of doxorubicin (example: dexrazoxane 500 mg/m2 for doxorubicin 50 mg/m2) given with each doxorubicin doseDexrazoxane: Doxorubicin ratio not to exceed 10:1
b: Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

Prescribed regimen must be FDA-approved or recommended by NCCN

Approval duration: 12 months or duration of doxorubicin therapy, whichever is less

Documentation Required

Support clinical criteria

Provider must submit documentation (office notes, labs or other clinical information) supporting that the member meets all approval criteria.

See provider documentation requirements

Prior Authorization

Prescriber specialty requirement

Prescriptions must be written by or in consultation with an oncologist or hematologist for doxorubicin-induced cardiomyopathy, and by or in consultation with an oncologist for anthracycline-induced extravasation.

Dexrazoxane: Doxorubicin ratio not to exceed 10:1 or guideline-supported

Prescribed regimen must be FDA-approved or recommended by NCCN

Approval duration: 12 months or duration of doxorubicin therapy, whichever is less

B. Anthracycline-Induced Extravasation (off-label): Re-authorization is not permitted. Member must meet the initial approval criteria.

Approval duration: Not applicable

C. Other diagnoses/indications (must meet 1 or 2): If drug recently (within last 6 months) had a label change not reflected in this policy, follow referenced formulary/no-coverage or non-formulary policies; if requested use not listed under section III and criterion 1 does not apply, refer to off-label use policy for relevant line of business

Prior Authorization

Re-authorization restriction for extravasation

Re-authorization is not permitted for anthracycline-induced extravasation; approval is limited to meeting the initial approval criteria.

Initial approval only; re-authorization not allowed

Prior Authorization

Dose justification for off-label uses

If the requested dexrazoxane dose exceeds a 10:1 ratio relative to doxorubicin or is for an off-label indication, the prescriber must submit supporting practice guideline(s) or peer-reviewed literature to justify the dosing.

Submit relevant practice guidelines or peer-reviewed literature as evidence

Prior Authorization

Dose justification for off-label uses

If dose exceeds a 10:1 ratio relative to doxorubicin or if used for an off-label indication, prescriber must submit supporting practice guidelines or peer-reviewed literature to justify the dose.

Submit guideline or peer‑reviewed literature evidence

Prior Authorization

Re-authorization restriction for extravasation

Re-authorization is not permitted for anthracycline-induced extravasation; member must meet the initial approval criteria for coverage.

Billing Rule

HCPCS billing

J1190
Use J1190 for claims reporting (per 250 mg)

05.24annual_review

2Q 2024 annual review added redirection to generic dexrazoxane and added NCCN 2A indications including relapsed/refractory Ph‑positive ALL, Hodgkin lymphoma in adults > 60 years, and neuroblastoma.

05.25annual_reviewLatest

2Q 2025 annual review removed brand Totect from criteria as discontinued/obsolete, clarified anthracycline‑induced extravasation is off‑label, removed Hodgkin lymphoma in adults > 60 years per NCCN, and removed redirections to generic dexrazoxane. (MATERIAL CHANGE)