Boric acid

UPDATE (Jan. 8, 2024): FDA is aware that some providers, including hospital or health-system pharmacies, may be preparing other STS products for patient use in place of Pedmark, including diluting STS products approved for other uses to match Pedmark’s strength. FDA reminds health care providers that as stated in Pedmark’s prescribing information, Pedmark is not substitutable with other sodium thiosulfate products. Such substitutions, pose potential health risks including: Potassium chloride exposure which, at high doses, can lead to increased risk of acute cardiac events and other serious adverse reactions. Potassium chloride is not present in Pedmark. Overexposure to boric acid (a boron compound), can cause health risks including headache, hypothermia, restlessness, weariness, renal injury, dermatitis, alopecia, anorexia and indigestion. Although Pedmark also contains boric acid, it is at a lower concentration than other STS products. Overexposure to sodium nitrite, which can lead to health risks including methemoglobinemia. Sodium nitrite is copackaged with sodium thiosulfate as a separate vial in some products; it is not present in Pedmark. On September 20, 2022, the Food and Drug Administration approved sodium thiosulfate (Pedmark, Fennec Pharmaceuticals Inc.) to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month and older with localized, non-metastatic solid tumors. Efficacy was evaluated in two multicenter open-label, randomized controlled trials in pediatric patients undergoing treatment with cisplatin-based chemotherapy for cancer: SIOPEL 6 (NCT00652132) and COG ACCL0431 (NCT00716976). SIOPEL 6 enrolled 114 patients with standard risk hepatoblastoma undergoing 6 cycles of perioperative cisplatin-based chemotherapy. Patients were randomized (1:1) to receive cisplatin-based chemotherapy with or without sodium thiosulfate administered at various doses of 10 g/m2, 15 g/m2, or 20 g/m2 based on actual body weight. The primary outcome was the percentage of patients with Brock Grade ≥1 hearing loss, assessed using pure tone audiometry after treatment or at an age of at least 3.5 years, whichever was later. The incidence of hearing loss was lower in the sodium thiosulfate and cisplatin arm (39%) compared with the cisplatin alone arm (68%); unadjusted relative risk 0.58 (95% CI: 0.40, 0.83). COG ACCL0431 enrolled 125 pediatric patients with solid tumors undergoing a chemotherapy regimen including cumulative cisplatin doses 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 with or without sodium thiosulfate. Efficacy was evaluated in a subset of 77 patients with localized, non-metastatic solid tumors. The primary outcome 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). The most common adverse reactions in the two trials (≥25% with difference between arms of >5% compared to cisplatin alone) were vomiting, nausea, decreased hemoglobin, hypernatremia, and hypokalemia. The recommended sodium thiosulfate dose is based on surface area according to actual body weight. Sodium thiosulfate is administered as an intravenous infusion over 15 minutes following cisplatin infusions that are 1 to 6 hours in duration. View full prescribing information for Pedmark. This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The application also was granted Orphan Drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.  Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov. For information on the COVID-19 pandemic, see the following resources: FDA: Coronavirus Disease 2019 (COVID-19) NCI: Coronavirus: What People With Cancer Should Know CDC: Coronavirus (COVID-19) Follow the Oncology Center of Excellence on Twitter @FDAOncology