SEACALPHYX Solution for injection Ref.[27833] Active ingredients: Thiosulfate

Use with Other Cyanide Antidotes

Caution should be exercised when administering cyanide antidotes, other than sodium nitrite, simultaneously with sodium thiosulfate pentahydrate injection as the safety of co-administration has not been established. If a decision is made to administer another cyanide antidote, other than sodium nitrite, with sodium thiosulfate pentahydrate injection, these drugs should not be administered concurrently in the same IV line.

Sulfites

Sodium thiosulfate drug product may contain trace impurities of sodium sulfite. The presence of a trace amount of sulfites in this product should not deter administration of the drug for treatment of emergency situations, even if the patient is sulfite-sensitive.

Special Populations

Pregnant Women

Teratogenic Effects: Pregnancy Category C.

There are no adequate and well-controlled studies in pregnant women. Sodium thiosulfate pentahydrate injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

There are no reported epidemiological studies of congenital anomalies in infants born to women treated with sodium thiosulfate during pregnancy. In animal studies, there are no teratogenic effects in offspring of hamsters treated during pregnancy with sodium thiosulfate in doses similar to those given intravenously to treat cyanide poisoning in humans. Other studies suggest that treatment with sodium thiosulfate ameliorates the teratogenic effects of maternal cyanide poisoning in hamsters. In other studies, sodium thiosulfate was not embryotoxic or teratogenic in mice, rats, hamsters, or rabbits at maternal doses of up to 550, 400, 400 and 580 mg/kg/day, respectively.

Nursing Women

It is not known whether sodium thiosulfate is excreted in human milk. Because sodium thiosulfate pentahydrate injection may be administered in life-threatening situations, breast-feeding is not a contraindication to its use. Because many drugs are excreted in human milk, caution should be exercised following sodium thiosulfate pentahydrate injection administration to a nursing woman. There are no data to determine when breastfeeding may be safely restarted following administration of sodium thiosulfate.

Pediatrics (<18 years of age)

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.

Geriatrics (>65 years of age)

Sodium thiosulfate is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Decreased Renal Function

Sodium thiosulfate is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.

Monitoring and Laboratory Tests

Patients should be monitored for at least 24-48 hours after sodium thiosulfate pentahydrate injection administration for adequacy of oxygenation and perfusion and for recurrent signs and symptoms of cyanide toxicity. When possible, hemoglobin/hematocrit should be obtained when treatment is initiated. Measurements of oxygen saturation using standard pulse oximetry and calculated oxygen saturation values based on measured PO₂ are unreliable in the presence of methemoglobinemia.

Adverse Drug Reaction Overview

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.

Formal drug interaction studies have not been conducted with sodium thiosulfate pentahydrate injection.