2.1  Important Administration Information

Selenious Acid Injection is supplied as a pharmacy bulk package or single-dose vial for admixing use only. It is not for direct intravenous infusion. Prior to administration, Selenious Acid Injectionmust 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 inparenteral 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 America Regent. If it is deemed advisable to introduce additives to the parenteral nutrition container, use aseptic technique.
• Inspect the final parenteral nutrition containing Selenious Acid Injection to ensure that:
  • Precipitates have not formed during mixing or addition of additives. 
  • 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 of the accumulation of yellowish droplets. 
• Discard if any precipitates are observed.

Stability and Storage

• Single-dose vial (2 mL): Discard unused portion.
• 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 content.
• 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 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

• There are two dosage strengths for Selenious Acid Injection: 6 mcg/mL and 60 mcg/mL of selenium. 

• Selenious Acid Injection in a concentration of 6 mcg/mL is recommended for use in pediatric patients, particularly those weighing 7 kg or less.

• 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.

5.1  Pulmonary Embolism due to Pulmonary Vascular Precipitates

Pulmonary vascular precipitates causing pulmonary vascular emboli and pulmonary distress have been reported in patients receiving parenteral nutrition. The cause of precipitate formation has not been determined in all cases; however, in some fatal cases, pulmonary emboli occurred as a result of calcium phosphate precipitates. Precipitation has occurred following passage through an in-line filter; in vivo precipitate formation may also have occurred. If signs of pulmonary distress occur, stop the parenteral nutrition infusion and initiate a medical evaluation. In addition to inspection of the solution [see Dosage and Administration (2.2, 2.3)], the infusion set and catheter should also periodically be checked for precipitates.

5.2  Vein Damage and Thrombosis

Selenious Acid Injection has a low pH and must be prepared and used as an admixture in parenteral nutrition solutions. It is not for direct intravenous infusion.

In addition, consider the osmolarity of the final parenteral nutrition solution in determining peripheral versus central administration. Solutions with an osmolarity of 900 mOsmol/L or greater must be infused through a central catheter [see Dosage and Administration (2.1)]. The infusion of hypertonic nutrient injections into a peripheral vein may result in vein irritation, vein damage, and/or thrombosis. The primary complication of peripheral access is venous thrombophlebitis, which manifests as pain, erythema, tenderness or a palpable cord. Remove the catheter as soon as possible, if thrombophlebitis develops.

5.3  Aluminum Toxicity

Selenious Acid Injection contains aluminum that may be toxic.

Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Preterm infants are particularly at risk for aluminum toxicity because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which also contain aluminum.

Patients with impaired kidney function, including preterm neonates, who receive greater than 4 to 5 mcg/kg/day of parenteral aluminum can accumulate aluminum to levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Exposure to aluminum from Selenious Acid Injection is not more than 0.6 mcg/kg/day. When prescribing Selenious Acid Injection for use in parenteral nutrition containing other small volume parenteral products, the total daily patient exposure to aluminum from the admixture should be considered and maintained at no more than 5 mcg/kg/day [see Use in Specific Populations (8.4)].

5.4  Monitoring and Laboratory Tests

Monitor selenium concentrations, fluid and electrolyte status, serum osmolarity, blood glucose, liver and kidney function, blood count and coagulation parameters during treatment [see Dosage and Administration (2.5)]. 

8.1  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. n the U.S. 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

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.

8.2  Lactation

Risk Summary

Selenium is present in human milk. Administration of the approved recommended dose of Selenious Acid Injection in parenteral nutrition is not expected to cause harm to a breastfed infant. There is no information on the effects of selenious acid on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Selenious Acid Injection and any potential adverse effects on the breastfed infant from Selenious Acid Injection or from the underlying maternal condition.

8.4  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 [see Dosage and Administration (2.5)].

Because of immature renal function, preterm infants receiving prolonged parenteral nutrition treatment with Selenious Acid Injection may be at higher risk of aluminum toxicity [see Warnings and Precautions (5.3)].

8.5  Geriatric Use

Reported clinical experience with intravenous selenious acid has not identified a difference in selenium requirements between elderly and younger patients. In general, dose selection should be individualized based on the patient’s clinical condition, nutritional requirements, and additional nutritional intake provided orally or enterally to the patient.

12.1 Mechanism of Action

Selenious acid is converted in vivo to hydrogen selenide via glutathione-involved electron reductions. Hydrogen selenide acts as a selenium pool to form selenoproteins which include, but are not limited to, glutathione peroxidase, iodothyronine deiodinase, peroxidase and thioredoxins.

12.2 Pharmacodynamics

Selenious acid exposure-response relationships and the time course of pharmacodynamic responses is unknown. 

12.3 Pharmacokinetics

Distribution

In humans 85% of intravenous administered 75Se-sodium selenite was protein-bound within 4 to 6 hours and 95% by 24 hours.

Elimination 

Selenium is primarily eliminated in urine.