PEDMARK

The pharmacokinetics (PK) of thiosulfate was assessed in pediatric patients. At the recommended dosage, the mean (±SD) maximum concentration (C max ) was 13 ± 1.2 mM. The C max of thiosulfate increased proportionally to dose over the range of 4 g/m 2 to 20 g/m 2 . No accumulation of thiosulfate is expected following administration of PEDMARK on two consecutive days.

DistributionSodium thiosulfate does not bind to human plasma proteins. Sodium thiosulfate is an inorganic salt and thiosulfate ani...

The efficacy of PEDMARK in reducing the risk of cisplatin-associated ototoxicity was evaluated in two multicenter studies: SIOPEL 6 and COG ACCL0431. SIOPEL 6 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 PEDMARK (PEDMARK + cisplatin arm). Patients received PEDMARK at a dose based on bod...

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Warnings and Precautions (5.1) ] Hypernatremia and Hypokalemia [see Warnings and Precautions (5.2) ] Nausea and Vomiting [see Warnings and Precautions (5.3) ] Most common adverse reactions (≥ 25% with difference between arms of >5% compared to cisplatin alone) in SIOPEL 6 are vomiting, nausea, decreased hemoglobin, and hypernatremia. ( 6 ) Most common adverse reaction (≥25% with ...

PEDMARK is contraindicated in patients with history of a severe hypersensitivity to sodium thiosulfate or any of its components [see Warnings and Precautions (5.1) ] . History of severe hypersensitivity to sodium thiosulfate or any components. ( 4 )

Hypersensitivity : Immediately discontinue PEDMARK and institute appropriate care. Administer premedications before each subsequent dose. PEDMARK may contain sodium sulfite; patients with sulfite sensitivity may have hypersensitivity reactions. ( 5.1 ) Hypernatremia and Hypokalemia : PEDMARK is not indicated for use in pediatric patients less than 1 month of age. Monitor serum sodium and potassium at baseline and as clinically indicated. Withhold PEDMARK in patients with serum sodium greater tha...