sodium thiosulfate + mannitol

Sodium thiosulfate and mannitol is a combination therapy primarily investigated for reducing ototoxicity (hearing loss) in patients receiving cisplatin chemotherapy. This combination works through complementary mechanisms: sodium thiosulfate protects cells in the inner ear from cisplatin damage, while mannitol helps sodium thiosulfate enter the inner ear more effectively, potentially increasing its protective efficacy[4][5][9]. The timing of administration is crucial for this combination therapy. Typically, sodium thiosulfate and mannitol are administered 4-8 hours following cisplatin chemotherapy to avoid interfering with cisplatin's anticancer effects while still providing otoprotection[4][5][9]. ## Mechanisms of Action Sodium thiosulfate functions as an otoprotectant by binding to free platinum from cisplatin, thereby reducing its toxicity to the inner ear cells. It also has antioxidant properties that may contribute to its protective effects[8][9]. Mannitol, an osmotic diuretic, increases the permeability of the blood labyrinth barrier (BLB), which allows sodium thiosulfate to more effectively enter the inner ear. This enhanced delivery potentially increases the otoprotective efficacy of sodium thiosulfate[2][9]. ## Clinical Development The combination is currently being investigated in clinical trials. A randomized phase II clinical trial is evaluating the efficacy of sodium thiosulfate and mannitol in reducing hearing impairment caused by cisplatin chemotherapy. The trial includes a 2-year pilot feasibility study with 24 patients (12 in each arm) to assess treatment outcomes, adverse events, logistics of treatment delivery, and recruitment rates[4][5]. ## Individual Components ### Sodium Thiosulfate Sodium thiosulfate has been approved for treating certain rare medical conditions including cyanide poisoning, calciphylaxis, and cisplatin toxicity. The FDA has recently approved a pediatric formula of intravenous sodium thiosulfate for otoprotection[8][9]. ### Mannitol Mannitol is an osmotic diuretic used to treat acute kidney failure, reduce intracranial pressure, reduce intraocular pressure, and promote urinary excretion of toxic substances. It's administered intravenously and works by hindering water reabsorption in the kidneys and drawing water from cells into extracellular spaces[1][6][7]. The combination of these two medications represents a promising approach to prevent cisplatin-induced hearing loss, a significant side effect that affects 50-70% of children treated with this chemotherapy agent[9].