U.S. Food and Drug Administration (FDA)-Approved Indications

To reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors

Limitations of Use: The safety and efficacy of Pedmark have not been established when administered following cisplatin infusions longer than 6 hours. Pedmark may not reduce the risk of ototoxicity when administered following longer cisplatin infusions, because irreversible ototoxicity may have already occurred.

Sodium thiosulfate is available as Pedmark (Fennec Pharmaceuticals, Inc.) and interacts directly with cisplatin to form an inactive platinum species. Additionally, sodium thiosulfate can enter cells through the sodium sulfate cotransporter 2 and cause intracellular effects such as the increase in antioxidant glutathione levels and inhibition of intracellular oxidative stress. Both of these mechanisms may contribute to the ability of sodium thiosulfate to reduce the risk of ototoxicity (Fennec Pharmaceuticals, 2022).

Per the prescribing information, sodium thiosulfate (Pedmark) carries the following warnings and precautions:

Per the prescribing information, sodium thiosulfate (Pedmark) carries the following adverse reactions:

On September 20, 2022, the U.S. Food and Drug Administration (FDA) approved sodium thiosulfate (Pedmark) to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month and older with localized, non-metastatic solid tumors. The FDA approval was based on supporting data evaluating efficacy in two multicenter open-label, randomized controlled trials in pediatric patients undergoing treatment with cisplatin-based chemotherapy for cancer: SIOPEL 6 and COAG ACCL0431 (FDA, 2022).

The SIOPEL 6 study enrolled 114 patients with standard risk hepatoblastoma receiving 6 cycles of perioperative cisplatin-based chemotherapy. Patient randomization occurred 1:1 to receive 6 cycles of perioperative cisplatin-based chemotherapy without (cisplatin alone arm) (n=53) or with Pedmark (Pedmark + cisplatin arm) (n=61). Pedmark was dosed by body weight and administered intravenously over 15 minutes, beginning 6 hours after completion of each cisplatin infusion. Pedmark doses were as follows: 10 g/m

for patients weighing < 5kg; 15 g/m

for patients weighing 5 kg to 10 kg; and 20 g/m

for patients weighing > 10 kg.. The primary efficacy measure was the percentage of patients with Brock Grade ≥ 1 hearing loss, assessed using pure tone audiometry after study treatment or at an age of at least 3.5 years, whichever was later. The incidence of hearing loss was lower in the Pedmark and cisplatin arm (39%) compared with the cisplatin arm (68%); unadjusted relative risk 0.58 (95% Confidence Interval [CI]: 0.40, 0.83) (FDA, 2022; Fennec Pharmaceuticals, 2022).

The COG ACCL0431 study enrolled 125 pediatric patients with solid tumors receiving a chemotherapy regimen including cumulative cisplatin doses of 200 mg/m

or higher, with individual cisplatin doses to be infused over 6 hours or less. Patient randomization occurred 1:1 to receive cisplatin-based chemotherapy with (n=61) or without Pedmark (n=64). Efficacy evaluation was in a subset of 77 patients with localized, non-metastatic solid tumors. The primary efficacy measure was hearing loss according to American Speech-Language-Hearing Association (ASHA) criteria, assessed at baseline and 4-weeks after the final course of cisplatin. The incidence of hearing loss was lower in the sodium thiosulfate and cisplatin arm (44%) compared with the cisplatin alone arm (58%); unadjusted relative risk 0.75 (95% CI: 0.48, 1.18) (FDA, 2022; Fennec Pharmaceuticals, 2022).

: Requires Precertification:

Precertification of sodium thiosulfate (Pedmark) is required of all Aetna participating providers and members in applicable plan designs. For precertification of sodium thiosulfate (Pedmark), call (866) 752-7021 (commercial), or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see

For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

Criteria for Initial Approval

Aetna considers sodium thiosulfate (Pedmark) medically necessary to reduce the risk of ototoxicity in pediatric members 1 month of age and older when

of the following criteria are met:

Aetna considers all other indications as experimental and investigational.

Continuation of Therapy

Aetna considers continuation of sodium thiosulfate (Pedmark) therapy medically necessary for all members (including new members) requesting authorization who meet all initial authorization criteria.

Dosage and Administration

Sodium thiosulfate is supplied as Pedmark 12.5 grams/100 mL in a single-dose vial injection for intravenous use.

The recommended dose of Pedmark is based on surface area according to actual body weight and is as follows:

Pedmark is administered via intravenous infusion over 15 minutes starting 6 hours after completion of cisplatin infusion. For multiday cisplatin regimens, Pedmark is administered 6 hours after each cisplatin infusion but at least 10 hours before the next cisplatin infusion. Pedmark should not be started if less than 10 hours before starting the next cisplatin infusion.

Pedmark is not substitutable with other sodium thiosulfate products which are approved for other toxicities.

Source: Fennec Pharmaceuticals, 2022