Selenious Acid

1 INDICATIONS AND USAGE 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. Selenious Acid Injection is a trace element 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.

2 DOSAGE AND ADMINISTRATION • Pharmacy Bulk Package : Not for direct intravenous infusion . ( 2.1 ) • See full prescribing information for information on preparation, administration, and general dosing considerations. ( 2.1 , 2.2, 2.3 , 2.4 , 2.5 ) Recommended Dosage ( 2.5 ) • Selenious Acid Injection provides 60 mcg/mL of selenium. • Individualize the dosage based upon the patient’s clinical condition, nutritional requirements, and the contribution of oral or enteral selenium intake. The following dosages are general recommendations intended for most patients. However, based upon clinical requirements, some patients may require a higher dosage: o Adults : 60 mcg/day Pediatric Patients 7 kg and above : 2 mcg/kg/day (up to 60 mcg/day) o Pediatric Patients less than 7 kg : 2 to 4 mcg/kg/day • Monitor selenium concentrations during treatment. 2.1 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 [see Warnings and Precautions ( 5.2 )]. 2.2 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. 2.3 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. 2.4 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 [see Dosage and Administration ( 2.5 )]. 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. 2.5 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 Population Recommended Dosage Adults 60 mcg/day Pediatric Patients 7 kg and above 2 mcg/kg/day (up to 60 mcg/day) Pediatric Patients less than 7 kg 2 to 4 mcg/kg/day • Monitor selenium concentrations during treatment. Selenium concentrations may vary depending on the assay used and the laboratory reference range.

6 ADVERSE REACTIONS 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 [see Warnings and Precautions ( 5.1 )] • Vein damage and thrombosis [see Warnings and Precautions ( 5.2 )] • Aluminum toxicity [see Warnings and Precautions ( 5.3 )] 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

12.3 Pharmacokinetics Distribution In humans 85% of intravenous administered 75 Se-sodium selenite was protein-bound within 4 to 6 hours and 95% by 24 hours. Elimination Selenium is primarily eliminated in urine.