Thiosulfate Drug Information

Sodium Thiosulfate Injection is indicated for sequential use with sodium nitrite for the treatment of acute cyanide poisoning that is judged to be serious or life-threatening. When the diagnosis of cyanide poisoning is uncertain, the potential risks associated with Sodium Thiosulfate Injection should be carefully weighed against the potential benefits, especially if the patient is not in extremis. Sodium Thiosulfate Injection, an antidote, is indicated for sequential use with sodium nitrite for treatment of acute cyanide poisoning that is judged to be serious or life-threatening.

Use with caution if the diagnosis of cyanide poisoning is uncertain.

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. Cardiovascular system: hypotension Central nervous system: headache, disorientation Gastrointestinal system: nausea, vomiting Hematological : prolonged bleeding time Body as a Whole: salty taste in mouth, warm sensation over body 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 0.1 g sodium thiosulfate per pound 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.

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. Most common adverse reactions are: Hypotension, headache, disorientation To report SUSPECTED ADVERSE REACTIONS, contact Hope Pharmaceuticals at 1-800-755-9595 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Formal drug interaction studies have not been conducted with Sodium Thiosulfate Injection.

Pregnancy Risk Summary There are no available data on Sodium Thiosulfate Injection use in pregnant women to establish a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the pregnant woman and fetus associated with untreated cyanide poisoning (see Clinical Considerations ). Therefore, if a pregnant woman has known or suspected cyanide poisoning, Sodium Thiosulfate Injection for sequential use with sodium nitrite is recommended . In published animal studies, no evidence of embryotoxicity or malformations was reported when sodium thiosulfate was administered during organogenesis to pregnant mice, rats, hamsters, or rats at 0.2 to 0.9 times the human daily dose of 12.5 g for cyanide poisoning. The studies did not test doses that were comparable to the human dose for cyanide poisoning (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Cyanide readily crosses the placenta.

Cyanide poisoning is a medical emergency in pregnancy, which can be fatal for the pregnant woman and fetus if left untreated. Life-sustaining therapy should not be withheld due to pregnancy. Data Animal Data: No malformations or evidence of embryo-fetal toxicity were noted when pregnant mice, rats, hamsters, or rabbits were administered oral doses of sodium thiosulfate of up to 550, 400, 400, or 580 mg/kg, respectively during organogenesis (0.2, 0.3, 0.26, and 0.9 times the human dose of 12.5 g/60 kg person for cyanide poisoning based on body surface area). Published studies suggest that treatment with sodium thiosulfate ameliorates the teratogenic effects of maternal cyanide poisoning in hamsters.

Pediatric Use There are case reports in the medical literature of sodium nitrite in conjunction with sodium thiosulfate being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of sodium thiosulfate in the pediatric population. As for adult patients, dosing recommendations for pediatric patients have been based on theoretical calculations of antidote detoxifying potential, extrapolation from animal experiments, and a small number of human case reports.

There is limited information about the effects of large doses of sodium thiosulfate in humans. Oral administration of 3 g sodium thiosulfate per day for 1-2 weeks in humans resulted in reductions in room air arterial oxygen saturation to as low as 75%, which was due to a rightward shift in the oxygen hemoglobin dissociation curve. The subjects returned to baseline oxygen saturations 1 week after discontinuation of sodium thiosulfate.

A single intravenous administration of 20 mL of 10% sodium thiosulfate reportedly did not change oxygen saturations.