HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use
`SELENIOUS ACID INJECTION safely and effectively. See full
`prescribing information for SELENIOUS ACID INJECTION.
`
`SELENIOUS ACID INJECTION, for intravenous use
`Initial U.S. Approval: 2019
`
`--------1NDICATIONS AND USAGE-----(cid:173)
`is
`Selenious Acid Injection a trace element indicated in adult and
`(PN)
`pediatric patients as a source of selenium for parenteral nutrition
`when oral or enteral nutrition is not possible, insufficient, or
`contraindicated. ( 1 )
`
`------uOSAGE 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)
`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
`o 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.
`
`-----.iDOSAGEFORMSANDSTRENGTHS----(cid:173)
`Selenious Acid Injection, USP: 600 mcg/10 ml (60 mcg/mL) of
`(3)
`selenium as a Pharmacy Bulk Package vial.
`
`--------\.ONTRAINDICATIONS-----(cid:173)
`(4)
`None.
`
`------11WARNINGS 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 Thrombosis: Solutions with osmolarity of 900
`mOsm/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, 2.4)
`
`-------.ADVERSE REACTIONS------(cid:173)
`No selenium-related adverse reactions in patients receiving
`intravenously administered PN solutions containing selenious acid
`(6)
`within the recommended dosage range.
`
`To report SUSPECTED ADVERSE REACTIONS, contact American
`or FDA at 1
`Regent INC. at 1-800-734-9236
`-800-FDA-1088 or
`www.fda.gov/medwatch.
`
`See 17 for PATIENT COUNSELING INFORMATION.
`
`Revised: 04/2019
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`1
`2
`
`INDICATIONS AND USAGE
`DOSAGE AND ADMINISTRATION
`2.1 Important Administration Information
`2.2 Preparation and Administration Instructions
`2.3 Preparation Instructions for Admixing Using a Parenteral
`Nutrition (PN) Container
`2.4 Dosing Considerations
`2.5 Recommended Dosage in Adults and Pediatric Patients
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS
`5 WARNINGS AND PRECAUTIONS
`5.1 Pulmonary Embolism due to Pulmonary Vascular Precipitates
`5.2 Vein Damage and Thrombosis
`5.3 Aluminum Toxicity
`5.4 Monitoring and Laboratory Tests
`
`6 ADVERSE REACTIONS
`8 USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`8.2 Lactation
`8.4 Pediatric Use
`8.5 Geriatric Use
`10 OVERDOSAGE
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`16 HOW SUPPLIED/STORAGE AND HANDLING
`17 PATIENT COUNSELING INFORMATION
`
`*Sections or subsections omitted from the full prescribing information
`are not listed.
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`FULL PRESCRIBING INFORMATION
`
`1 INDICATIONS AND USAGE
`
`Selenious Acid Injection is indicated in adult and pediatric patients as a source of selenium for
`parenteral nutrition (PN) when oral or enteral nutrition is not possible, insufficient, or contraindicated.
`DOSAGE AND ADMINISTRATION
`
`2
`
`2.1
`
`Important Administration Information
`is
`supplied as a pharmacy bulk package for admixing use only. It is not for
`Selenious Acid Injection
`direct intravenous infusion. Prior to administration, Selenious Acid Injection must be transferred to a
`separate PN container, prepared and used as an admixture in PN solutions.
`
`The final PN 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 mOsm/L or greater must be infused through a central venous catheter [see
`Warnings and Precautions (5.2)].
`
`2.2
`
`Preparation and Administration Instructions
`
`is
`• Selenious Acid Injection not for direct intravenous infusion. Prior to administration, Selenious
`Acid Injection must be prepared and used as an admixture in PN 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 PN solution containing Selenious Acid Injection for particulate
`matter before admixing, after admixing, and prior to administration. The solution should be
`clear and there should be no precipitates. A slight yellow color does not alter the quality and
`efficacy of this product.
`
`2.3
`
`Preparation Instructions for Admixing Using a Parenteral Nutrition (PN) Container
`
`•
`
`Inspect Selenious Acid Injection Bulk Pharmacy Package for particulate matter.
`
`• Transfer Selenious Acid Injection to the PN solution following the admixture of amino acids,
`dextrose, lipid (if added), and electrolytes solutions.
`
`• Because additives may be incompatible, evaluate all additions to the PN container for
`compatibility and stability of the resulting preparation. Consult with pharmacist, if available.
`Questions about compatibility may be directed to American Regent. If it is deemed advisable to
`introduce additives to the PN container, use aseptic technique.
`
`•
`
`Inspect the final PN solution containing Selenious Acid Injection to ensure that:
`
`o Precipitates have not formed during mixing or addition of additives.
`
`o The emulsion has not separated, if lipids have been added. Separation of the emulsion
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`can be visibly identified by a yellowish streaking or the accumulation of yellowish
`droplets in the admixed emulsion.
`
`o Discard if any precipitates are observed.
`Stability and Storage
`
`• 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 (25°C/77°F) after the container closure has been penetrated. Discard any
`remaining drug.
`
`• Use PN solution containing Selenious Acid Injection promptly after mixing. Any storage of the
`C
`admixture should be under refrigeration from 2°
`to 8°C (36°F to 46°F) and limited to a brief
`period of time, no longer than 24 hours. After removal from refrigeration, use promptly and
`complete the infusion within 24 hours. Discard any remaining admixture.
`
`• Protect the PN solution from light during storage.
`
`2.4 Dosing Considerations
`
`• The dosage of the final PN 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 PN solution containing Selenious Acid Injection, correct severe fluid,
`electrolyte and acid-base disorders.
`
`2.5 Recommended Dosage in Adults and Pediatric Patients
`
`• Selenious Acid Injection provides 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 the following table are general recommendations intended for most patients.
`However, based on clinical requirements, some patients may require a higher dosage.
`
`Po ulation
`Adults
`
`Pediatric Patients less than 7 k
`
`• Monitor selenium concentrations during treatment. Selenium concentrations may vary
`depending on the assay used and the laboratory reference range. The lower end of the range
`is
`reported in healthy adults 7 to 10 mcg/dL.
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`3 DOSAGE FORMS AND STRENGTHS
`
`Selenious Acid Injection, USP: 600 mcg/10ml (60 mcg/mL) of selenium as a clear, colorless solution
`in a 10 ml Pharmacy Bulk Package vial.
`
`4 CONTRAINDICATIONS
`
`None.
`
`5 WARNINGS AND PRECAUTIONS
`
`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 PN. 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 PN
`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 PN
`solutions. It is not for direct intravenous infusion.
`
`In addition, consider the osmolarity of the final PN solution in determining peripheral versus central
`administration. Solutions with an osmolarity of 900 mOsm/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 PN containing other small volume parenteral products,
`the total daily patient exposure to aluminum from the admixture should be considered and maintained
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`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)].
`
`6 ADVERSE REACTIONS
`
`No selenium-related adverse reactions have been reported in clinical studies or postmarketing reports
`in patients receiving intravenously administered PN solutions containing selenious acid within the
`recommended dosage range.
`
`The following adverse reactions associated with use of other components of PN 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)1
`• Aluminum toxicity [see Warnings and Precautions (5.3)]
`
`8. USE IN SPECIFIC POPULATIONS
`
`8.1 Pregnancy
`
`Risk Summary
`Administration of the recommended dose of Selenious Acid Injection in PN 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 PN 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
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`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 PN 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 PN 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.
`
`10 OVERDOSAGE
`
`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.
`is
`For oral selenium, the Tolerable Upper Limit (UL) 400 mcg/day and the No Observed Adverse
`is
`is
`Effect Level (NOAEL) 800 mcg/day. The estimated oral bioavailability of selenium
`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 3800 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.
`
`Chronic Selenosis
`
`Chronic daily exposure to selenium from dietary sources (0.003 to 0.007 grams/day) or oral
`supplements (0.0016 to 0.25 grams/day) may result in alopecia and nail brittleness. Other signs
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`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.
`
`11 DESCRIPTION
`
`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 PN.
`s
`Each ml contains 60 mcg selenium present as 98 mcg of elenious acid and Water for Injection q.s.
`The pH range is 1.8 to 2.4; pH may be adjusted with Nitric Acid. Each Pharmacy Bulk Package vial
`contains 10 ml of selenious acid solution and does not contain preservatives.
`c
`Selenious Acid Injection, USP ontains no more than 2,500 mcg/l of aluminum and has a calculated
`osmolarity of 108.8 mOsmol/L.
`
`Selenious acid has a molecular weight of 128.97 g/mol and a formula of H2SeQ3.
`
`12 CLINICAL PHARMACOLOGY
`
`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
`
`v
`In humans 85% of intra enous administered 75Se was protein-bound within 4 to 6 hours and 95% by
`24 hours.
`
`Elimination
`
`Selenium is primarily eliminated in urine.
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
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`Selenious Acid Injection, USP is a clear, colorless solution available as 600 mcg/10ml (60 mcg/ml)
`of selenium in a 10 ml Pharmacy Bulk Package vial.
`
`Carton of 25 vials (NOC 0517-6560-25)
`
`Store at 20°c to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]
`
`For storage of admixed solution, see Dosage and Administration (2.3).
`
`17 PATIENT COUNSELING INFORMATION
`
`Inform patients, caregivers or home healthcare providers of the following risks of Selenious Acid
`Injection:
`
`• 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)]
`
`AMERICAN
`REGENT, INC.
`SHIRLEY:, NY 11967
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