Coverage Policy Manual
Policy #: 2023009
Category: Pharmacy
Initiated: March 2023
Last Review: February 2025
  Sodium Thiosulfate (e.g., Pedmark)
Description:
Sodium thiosulfate (e.g., Pedmark), a unique formulation of sodium thiosulfate, is the first FDA-approved treatment indicated to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors. Generic sodium thiosulfate (available since the 1930s) is indicated for acute cyanide toxicity and may also be used off-label for use as renal protection during hyperthermic intraperitoneal chemotherapy with cisplatin at the time of interval debulking surgery for stage III ovarian cancer. Prior to the approval of sodium thiosulfate (e.g., Pedmark), generic sodium thiosulfate was also used off-label to reduce the risk of ototoxicity associated with cisplatin in pediatric patients. Cisplatin-induced ototoxicity is caused by irreversible damage to hair cells in the cochlea hypothesized to be due to a combination of reactive oxygen species production and direct alkylation of DNA leading to cell death. Sodium thiosulfate interacts directly with cisplatin to produce an inactive platinum species.  
 
Regulatory Status
 
Sodium thiosulfate (e.g., Pedmark) was approved by the U.S. Food and Drug Administration (FDA) on September 20th, 2022, to reduce the risk of ototoxicity associated with cisplatin in pediatric individuals 1 month of age and older with localized, non-metastatic solid tumors.
 
Coding
 
See CPT/HCPCS Code section below.
 
Policy/
Coverage:
This policy does not apply to the on- or off-label use of the generically available sodium thiosulfate product.
 
The Step Therapy Medication Act is applicable to fully insured (Arkansas Blue Cross, Health Advantage, and Exchange) and specified governmental (ASE/PSE and ASP) health plans. The law is not applicable to FEP or self-insured ERISA groups (including but not limited to Walmart or other Blue Advantage groups). Initial approval for exigent request is 28 days. Otherwise, initial approval for standard review is up to 1 year.
   
For members of plans that utilize an oncology benefits management program, Prior Approval is required for this service when rendered for oncologic indications and is managed through the oncology benefits management program.
 
Effective February 21, 2024
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
Sodium thiosulfate meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
1. Individual is 1 month of age to less than 18 years of age (FDA, 2022); AND
2. Individual has a diagnosis of localized, non-metastatic solid tumor (FDA, 2022); AND
3. Individual is receiving a cisplatin-based regimen (FDA, 2022); AND
4. Individual has a baseline serum sodium less than 145 mmol/L (Brock, 2018); AND
5. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for up to 1 year:
 
1. Individual has met the criteria for initial approval; AND
2. Individual is continuing to receive a cisplatin-based regimen (FDA, 2022); AND
3. Individual does not have serum sodium less than 145 mmol/L (FDA 2022); AND
4. Must be dosed according to FDA label.
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended dose of sodium thiosulfate is based on body surface area according to actual body weight as summarized below and given after each cycle of cisplatin. Refer to FDA label for timing and administration of sodium thiosulfate in relation to cisplatin dose.
 
    • Less than 5 kg dose is 10g/square meters
    • 5-10 kg dose is 15g/square meters
    • Greater than 10 kg dose is 20g/square meters
 
Sodium thiosulfate is available as a 12.5 g/100 mL solution for intravenous injection.
  
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Sodium thiosulfate, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, sodium thiosulfate, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective November 2023  to February 20, 2024
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
Sodium thiosulfate meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
1. Individual is > 1 month of age but < 18 years of age (FDA, 2022); AND
2. Individual has a diagnosis of localized, non-metastatic solid tumor (FDA, 2022); AND
3. Individual is receiving a cisplatin-based regimen (FDA, 2022); AND
4. Individual has a baseline serum sodium <145 mmol/L (Brock, 2018); AND
5. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for up to 1 year:
 
1. Individual has met the criteria for initial approval.
2. Is continuing to receive a cisplatin-based regimen (FDA, 2022)
3. Individual does not have serum sodium <145 mmol/L (FDA 2022);
4. Is dosed according to FDA label
 
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended dose of sodium thiosulfate is based on body surface area according to actual body weight as summarized below and given after each cycle of cisplatin. Refer to FDA label for timing and administration of sodium thiosulfate in relation to cisplatin dose.
 
    • Less than 5 kg dose is 10g/square meters
    • 5-10 kg dose is 15g/square meters
    • Greater than 10 kg dose is 20g/square meters
 
Sodium thiosulfate is available as a 12.5 g/100 mL solution for intravenous injection.
  
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Sodium thiosulfate for any indication or circumstance not described above, including metastatic cancer, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, sodium thiosulfate, for any indication or circumstance not described above, including metastatic cancer, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective March 2023 - November 2023
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
Sodium thiosulfate (e.g., Pedmark) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
    1. Individual is > 1 month of age but < 18 years of age (FDA, 2022); AND
    2. Individual has a diagnosis of localized, non-metastatic solid tumor (FDA, 2022); AND
    3. Individual is receiving a cisplatin-based regimen (FDA, 2022); AND
    4. Individual has a baseline serum sodium <145 mmol/L (Brock, 2018); AND
    5. Must be dosed in accordance with the FDA label.
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended dose of sodium thiosulfate (e.g., Pedmark) is based on body surface area according to actual body weight as summarized below and given after each cycle of cisplatin. Refer to FDA label for timing and administration of Pedmark in relation to cisplatin dose.
 
    • Less than 5 kg dose is 10g/square meters
    • 5-10 kg dose is 15g/square meters
    • Greater than 10 kg dose is 20g/square meters
 
Sodium thiosulfate (e.g., Pedmark) is available as a 12.5 g/100 mL solution for intravenous injection.
  
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Sodium thiosulfate (e.g., Pedmark) for any indication or circumstance not described above, including metastatic cancer, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, sodium thiosulfate (e.g., Pedmark), for any indication or circumstance not described above, including metastatic cancer, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Rationale:
The efficacy of sodium thiosulfate (e.g., Pedmark) in reducing the risk of cisplatin-associated ototoxicity was evaluated in two multicenter studies: SIOPEL 6 and COG ACCL0431.
 
SIOPEL 6 (NCT00652132) was a multicenter, randomized, controlled, open-label study. Eligible patients were between 1 month and 18 years of age and were receiving cisplatin-based chemotherapy for standard-risk hepatoblastoma. Patients were randomized 1:1 to receive 6 cycles of perioperative cisplatin-based chemotherapy without (cisplatin alone arm) or with sodium thiosulfate (e.g., Pedmark) (Pedmark + cisplatin arm). The major efficacy outcome measure was hearing loss defined as a Brock Grade ≥1; hearing was assessed using pure tone audiometry after study treatment or at an age of at least 3.5 years, whichever was later.
 
A total of 114 patients were randomized, 61 patients to the Pedmark + cisplatin arm and 53 patients to the cisplatin alone arm. The median age was 1.1 years (range: 1.2 months to 8.2 years).
 
The incidence of hearing loss was lower in the Pedmark + cisplatin arm (39%) compared with the cisplatin alone arm (68%).
COG ACCL0431 (NCT00716976) was a multicenter, randomized, controlled, open-label study. Eligible patients were between 1 and 18 years of age and were receiving a chemotherapy regimen that included a cumulative cisplatin dose of 200 mg/m2 or higher, with individual cisplatin doses to be infused over 6 hours or less. Patients were randomized 1:1 to receive cisplatin-based chemotherapy without (cisplatin alone arm) or with sodium thiosulfate (e.g., Pedmark) (Pedmark + cisplatin arm). The major efficacy outcome measure was hearing loss assessed by American Speech-Language-Hearing Association (ASHA) criteria; hearing was assessed at baseline and 4 weeks after the final course of cisplatin.
 
A total of 125 pediatric patients were randomized, 61 patients to the Pedmark + cisplatin arm and 64 patients to the cisplatin alone arm. The efficacy was evaluated in patients with localized disease in the ITT population (n = 77). The median age was 8 years (range: 1 to 18).
 
The incidence of hearing loss was lower in the Pedmark + cisplatin arm (44%) compared with the cisplatin alone arm (58%).
In the clinical practice guidelines for the prevention of cisplatin-induced ototoxicity in children and adolescents with cancer published in the Lancet Child Adolescent Health in 2020, “the panel made a strong recommendation [for administration of sodium thiosulfate] in non-metastatic hepatoblastoma, a weak recommendation for administration in other non-metastatic cancers, and a weak recommendation against its routine use in metastatic cancers” (Freyer, 2020).
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2024. No new literature was identified that would prompt a change in the coverage statement.
 
2025 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2025. No new literature was identified that would prompt a change in the coverage statement.
CPT/HCPCS:
C9399Unclassified drugs or biologicals
J0208Injection, sodium thiosulfate, 100 mg
J3490Unclassified drugs
References: Brock, P.R. et al.(2018) Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss. N Engl J Med. 2018 Jun 21;378(25):2376-2385. doi: 10.1056/NEJMoa1801109. PMID: 29924955; PMCID: PMC6117111.

Freyer, D.R. et al.(2017) Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017 Jan;18(1):63-74. doi: 10.1016/S1470-2045(16)30625-8. Epub 2016 Dec 1. Erratum in: Lancet Oncol. 2017 Jun;18(6):e301. PMID: 27914822; PMCID: PMC5520988.

Freyer, D.R. et al.(2020) Prevention of cisplatin-induced ototoxicity in children and adolescents with cancer: a clinical practice guideline. Lancet Ahild Adolesc Health. 2020 February; 4(2): 141-150. doi: 10.1016/S2352-4642(19)30336-0.

U.S. Food and Drug Administration (FDA).(2022) 2022 Pedmark. Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212937s000lbl.pdf. Accessed March 6, 2023.
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2025 American Medical Association.