SELENIUM: 142 Adverse Event Reports & Safety Profile

Selenious Acid Injection, USP is a sterile, non-pyrogenic, clear, colorless solution intended for use as a trace element and additive to intravenous solutions for parenteral nutrition.

Each

600 mcg/10 mL Pharmacy Bulk Package vial contains 10 mL of selenious acid solution.

Each

6 mcg/mL single-dose vial contains 2 mL of selenious acid solution. None of the presentations contain preservatives. Each mL of the 60 mcg/mL strength contains 60 mcg of selenium present as 98 mcg of selenious acid, nitric acid for pH adjustment (1.8 to 2.4), and water for injection q.s. Each mL of the 6 mcg/mL strength contains 6 mcg of selenium present as 9.8 mcg of selenious acid, nitric acid for pH adjustment (1.8 to 2.4), and water for injection q.s.

Selenious Acid Injection

60 mcg/mL contains no more than 2,500 mcg/L of aluminum and has a calculated osmolarity of 16 mOsmol/L.

Selenious Acid Injection

6 mcg/mL contains no more than 900 mcg/L of aluminum and has a calculated osmolarity of 13 mOsmol/L. Selenious acid has a molecular weight of 128.97 g/mol and a formula of H 2 SeO 3 . The structural formula is: Structure

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

Injectionis 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. ( 1 )

AND ADMINISTRATION

• Pharmacy Bulk Package or Single-Dose Vial: 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 )

Recommended

Dosage ( 2.5)

• Selenious Acid Injection provides 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.
• 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: ○ 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.

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 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 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 <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.5 )]</span> . 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 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.

CONTRAINDICATIONS Selenium Injection should not be given undiluted by direct injection into a peripheral vein because of the potential for infusion phlebitis.

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. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact American Regent Inc. at 1-800-734-9236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

AND PRECAUTIONS

• Pulmonary Embolism due to Pulmonary Vascular Precipitates: If signs of pulmonary distress occur, stop the infusion and initiate a medical evaluation. ( 5.1 )
• Vein Damage and Thrombosi s: Solutions with osmolarity of 900 mOsmol/L or more must be infused through a central venous catheter. ( 2.1 , 5.2 )
• Aluminum Toxicity : Increased risk in patients with renal impairment, including preterm infants. ( 5.3 , 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 throughout treatment. ( 5.4 , 2.5 )

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 <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.2, 2.3 )]</span>, 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 <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.1 )]</span>. 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 <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.4 )]</span>.

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 <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.5 )]</span>.

PRECAUTIONS As selenium is eliminated in urine and feces, selenium supplements may be adjusted, reduced or omitted in renal dysfunction and/or gastrointestinal malfunction. In patients receiving blood transfusions, contribution from such transfusions should also be considered. Frequent selenium plasma level determinations are suggested as a guideline. In animals, selenium has been reported to enhance the action of Vitamin E and decrease the toxicity of mercury, cadmium and arsenic.

Selenium metallicum 200CK (**contains 0.443 mg of the active ingredient per pellet)

Yellow Fulvic Acid Peptide,Ferrous Ion,Active Calcium Ion,Magnesium Ion