Selenious Acid Drug Information

Selenious Acid Injection is indicated in adult and pediatric patients as a source of selenium for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated.

Important Administration Information Selenious Acid Injection is supplied as a pharmacy bulk package for admixing use only. It is not for direct intravenous infusion. Prior to administration, Selenious Acid Injection must be transferred to a separate parenteral nutrition container, prepared and used as an admixture in parenteral nutrition solutions.

The Pharmacy Bulk Package vial of Selenious Acid Injection is intended for dispensing of single doses to multiple patients in a pharmacy admixture program. The final parenteral nutrition solution is for intravenous infusion into a central or peripheral vein. The choice of a central or peripheral venous route should depend on the osmolarity of the final infusate.

Solutions with osmolarity of 900 mOsmol/L or greater must be infused through a central venous catheter.

Preparation and Administration Instructions • Selenious Acid Injection is not for direct intravenous infusion. Prior to administration, Selenious Acid Injection must be prepared and used as an admixture in parenteral nutrition solutions. • Selenious Acid Injection is to be prepared only in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area). The key factor in the preparation is careful aseptic technique to avoid inadvertent touch contamination during mixing of solutions and addition of other nutrients. • Visually inspect the prepared parenteral nutrition solution containing Selenious Acid Injection for particulate matter before admixing, after admixing, and prior to administration.

Preparation Instructions for Admixing Using a Parenteral Nutrition Container • Inspect Selenious Acid Injection vials for particulate matter. • Transfer Selenious Acid Injection to the parenteral nutrition solution following the admixture of amino acids, dextrose, lipid (if added), and electrolytes solutions. • Because additives may be incompatible, evaluate all additions to the parenteral nutrition container for compatibility and stability of the resulting preparation. Consult with pharmacist, if available. Questions about compatibility may be directed to Gland Pharma.

If it is deemed advisable to introduce additives to the parenteral nutrition container, use aseptic technique. • Inspect the final parenteral nutrition solution containing Selenious Acid Injection to ensure that: o Precipitates have not formed during mixing or addition of additives. o The admixed emulsion has not separated, if a lipid emulsion has been added. Separation of the admixed emulsion can be visibly identified by a yellowish streaking or the accumulation of yellowish droplets. • Discard if any precipitates are observed. Stability and Storage • Pharmacy Bulk Package vial (10 mL): Penetrate vial closure only one time with a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents.Use Selenious Acid Injection for admixing promptly once the sterile transfer set has been inserted into the Pharmacy Bulk Package container or not more than 4 hours at room temperature (25ºC/77ºF) after the container closure has been penetrated.

Discard any remaining drug. • Use parenteral nutrition solutions containing Selenious Acid Injection promptly after mixing. Any storage of the admixture should be under refrigeration from 2°C to 8°C (36°F to 46°F) and limited to a period of time no longer than 9 days. After removal from refrigeration, use promptly and complete the infusion within 24 hours.

Discard any remaining admixture. • Protect the admixed parenteral nutrition solution from light.

Dosing Considerations •

The dosage of the final parenteral nutrition solution containing Selenious Acid Injection must be based on the concentrations of all components in the solution and the recommended daily nutritional requirements. Consult the prescribing information of all added components to determine the recommended nutritional requirements for dextrose, amino acids and lipid emulsion, as applicable. • Prior to administration of parenteral nutrition solution containing Selenious Acid Injection, correct severe fluid, electrolyte and acid-base disorders.

Recommended Dosage and Monitoring in Adults and Pediatric Patients • The dosage strength for Selenious Acid Injection: 60 mcg/mL of selenium. • The dosage of Selenious Acid Injection should be individualized based on the patient’s clinical condition, nutritional requirements, and the contribution of oral or enteral selenium intake. • The dosages in Table 1 are general recommendations intended for most patients. However, based on clinical requirements, some patients may require a higher dosage. Table 1: Recommended Dosage of Selenious Acid Injection for Adults and Pediatric Patients by Estimated Weight • Monitor selenium concentrations during treatment.

Selenium concentrations may vary depending on the assay used and the laboratory reference range.

• No selenium-related adverse reactions have been reported in clinical studies or postmarketing reports in patients receiving intravenously administered parenteral nutrition solutions containing selenious acid within the recommended dosage range. The following adverse reactions associated with use of other components of parenteral nutrition solutions were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:
• Pulmonary embolism due to pulmonary vascular precipitates
• Vein damage and thrombosis
• Aluminum toxicity No selenium-related adverse reactions in patients receiving intravenously administered parenteral nutrition solutions containing selenious acid within the recommended dosage range. To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma Limited at 609-250-7990 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Pregnancy Risk Summary Administration of the recommended dose of Selenious Acid Injection in parenteral nutrition is not expected to cause major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with intravenous selenious acid. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Clinical Considerations Disease-associated Maternal and/or Embryo-Fetal Risk Deficiency of trace elements, including selenium, is associated with adverse pregnancy and fetal outcomes.

Pregnant women have an increased metabolic demand for trace elements, including selenium. Parenteral nutrition with selenium should be considered if a pregnant woman’s nutritional requirements cannot be fulfilled by oral or enteral intake.

Pediatric Use Selenious Acid Injection is approved for use in the pediatric population, including neonates, as a source of selenium for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated. Safety and dosing recommendations in pediatric patients are based on clinical experience. Because of immature renal function, preterm infants receiving prolonged parenteral nutrition treatment with Selenious Acid Injection may be at higher risk of aluminum toxicity.

There are no known cases of overdosage with intravenous selenious acid in parenteral nutrition. Overdosage has been reported with oral selenium. Available selenium concentrations in these subjects have been reported using various assays and laboratory-based reference ranges over a period of time.

Interpret results in the context of current reported ranges. For oral selenium, the Tolerable Upper Limit (UL) is 400 mcg/day and the No Observed Adverse Effect Level (NOAEL) is 800 mcg/day. The estimated oral bioavailability of selenium is approximately 70%.

Acute Oral Toxicity Effects Serious adverse events and deaths have been reported with acute oral toxicity, however, there is no clear correlation between the amount ingested, signs and symptoms of toxicity, or selenium blood concentrations. With severe toxicity, the most common presenting symptoms within a few hours post-ingestion of oral doses greater than 1 gram/day of selenium are gastrointestinal (nausea, vomiting, diarrhea, and abdominal pain), altered mental status, and “garlic” breath odor. Death from circulatory collapse has been reported after oral ingestion of 5 to 10 grams of selenium.

Selenium serum or blood concentrations in fatal cases have been reported in the range of 190 mcg/dL to 3,800 mcg/dL. Mild to moderate intoxication (myalgia, muscle spasms, and irritability) has been reported in patients with selenium serum or blood concentrations in the range of 41 to 750 mcg/dL. Other signs include gastrointestinal disturbances, skin rash, garlic breath, fatigue, irritability, and nervous system abnormalities including paresthesia and ataxia.

Selenium serum or blood concentrations in patients in China exposed through oral (non-dietary) supplementation were in the range of 32 to 150 mcg/dL. Management There is no known antidote for acute selenium toxicity. Management of selenium overdosage is supportive care based on presenting signs and symptoms.