Sodium thiosulfate is known to be substantially excreted by the kidney, and the risk of adverse reactions of sodium thiosulfate may be greater in patients with impaired renal function. Because cisplatin chemotherapy is associated with renal toxicity, renal function should be monitored and caution applied with close monitoring of electrolytes if the glomerular filtration rate (GFR) falls below 60 mL/min/1.73 m².

There are no or limited amount of data from the use of sodium thiosulfate in pregnant women. Animal studies are insufficient with respect to reproductive toxicity with intravenous infusion of sodium thiosulfate. As a precautionary measure, it is preferable to avoid the use of sodium thiosulfate during pregnancy.

It is unknown whether sodium thiosulfate/metabolites are excreted in human milk. A risk to newborns/infants cannot be excluded. As a precautionary measure, it is preferable to avoid the use of sodium thiosulfate during breast-feeding.

Fertility

There are no clinical data available on the effects of sodium thiosulfate on fertility. There is insufficient information from animal studies to assess the effects of intravenous infusion of sodium thiosulfate on fertility.

Sodium thiosulfate has no or negligible influence on the ability to drive and use machines.

Prevention of ototoxicity induced by cisplatin chemotherapy

Summary of the safety profile

The most serious adverse reaction is hypersensitivity, observed at a frequency of ≥1 case per 10 patients (11%).

The most commonly reported adverse reactions with a frequency of ≥1 case per 10 patients are vomiting (44%), nausea (23%), hypernatraemia (19%), hypophosphataemia (18%) and hypokalaemia (21%).

Tabulated list of adverse reactions

The table presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level) and frequency. Frequencies have been evaluated according to the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Adverse reactions:

Description of selected adverse reactions

Nausea and vomiting

Administration of sodium thiosulfate is associated with a high incidence of nausea and vomiting. This nausea and vomiting tends to stop soon after the sodium thiosulfate infusion has finished.

Hypernatraemia

A 12.8 g/m² dose delivers a sodium load of 162 mmol/m², a 9.6 g/m² dose delivers a sodium load of 121 mmol/m² and a 6.4 g/m² dose delivers a sodium load of 81 mmol/m². In clinical studies doses of sodium thiosulfate equivalent to these resulted in a small, transient increase in serum sodium levels, independent of age, body surface area, body weight, total daily sodium thiosulfate dose or cisplatin cycle. Sodium levels return to baseline by 18 hours or 24 hours after administration.

Electrolyte imbalance

Hypophosphataemia and hypokalaemia are very common following sodium thiosulfate treatment. Electrolyte balance and blood pressure should be monitored carefully.

Treatment of acute cyanide poisoning

There have been no controlled clinical trials conducted to systematically assess the adverse events profile of sodium thiosulfate.

The medical literature has reported the following adverse events in association with sodium thiosulfate administration. These adverse events were not reported in the context of controlled trials or with consistent monitoring and reporting methodologies for adverse events. Therefore, frequency of occurrence of these adverse events cannot be assessed.

^*Description of selected adverse reactions

Nausea and vomiting

In humans, rapid administration of concentrated solutions or solutions not freshly prepared, and administration of large doses of sodium thiosulfate have been associated with a higher incidence of nausea and vomiting. However, administration of 0.045 g sodium thiosulfate per kilogram up to a maximum of 15 g in a 10-15% solution over 10-15 minutes was associated with nausea and vomiting in 7 of 26 patients without concomitant cyanide intoxication.

Prolonged bleeding time

In a series of 11 human subjects, a single intravenous infusion of 50 mL of 50% sodium thiosulfate was associated with increases in clotting time 1-3 days after administration. However, no significant changes were observed in other hematological parameters.