Selenium is an essential nonmetallic element which is chemically related to sulfur. Selenium, which is nutritionally essential for humans, is a constituent of more than two dozen selenoproteins that play critical roles in reproduction, thyroid hormone metabolism, DNA synthesis, and protection from oxidative damage and infection. Foods which contain significant amounts of selenium include meat, poultry, grains, and seafood. Selenium concentrations are relatively high in many of the soils of the United States, especially the western states. Although selenium deficiency is rare in the United States, selenium deficiency has been linked to diseases such as Keshan disease, a juvenile cardiomyopathy due to very low dietary selenium intake, and Kashin-Beck disease, an endemic osteoarthritis. Low selenium body concentrations are also associated with prematurity, acute illness, and prolonged parenteral nutrition (PN) therapy. Symptoms of selenium deficiency include muscle weakness, myalgia, myositis, increased erythrocyte fragility, pancreatic degeneration, macrocytosis, and pseudoalbinism. While some data suggested that selenium may protect against overall cancer risk, follow-up data of sufficent quality are needed, especially for prostate cancer prevention. Selenium is available for oral use (elemental selenium) in dietary supplements, or as an injection (selenious acid) that is used mostly to supplement patients on parenteral nutrition. Recommended daily allowances (RDA) for selenium have been defined.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Selenium supplements may administered without regard to meals.
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Selenium injection must be diluted and used as an admixture in parenteral nutrition solutions; do not administer by direct IV infusion.
-Follow proper admixing sequence as related to parenteral nutrition.
-Single-use vial: Contains no bacteriostat; discard unused portion.
-Pharmacy bulk vial:
--Penetrate vial closure only 1 time with a suitable transfer device.
-Use vial contents immediately for admixture or within 4 hours after the container closure has been penetrated if stored at room temperature. Discard any remaining drug.
-Storage: After mixing in parenteral nutrition solutions, admixtures are stable for 24 hours under refrigeration; after removal from refrigeration, use solution promptly and complete the infusion within 24 hours. Discard any remaining admixture.
At recommended daily dosages, selenium supplementation usually has no adverse effects. However, selenium toxicity may result in alopecia, chronic dermatitis, diarrhea, excessive fatigue, fingernail weakening, drug-induced body odor (garlic-like odor in the sweat or breath), irritability, metallic taste, nausea, and vomiting. Thrombocytopenia and moderate hepatorenal dysfunction could also be seen with toxicity.
Selenium injection contains no more than 2,500 mcg/L of aluminum. However, aluminum toxicity may occur with prolonged administration in high-risk patients, including those with renal impairment and premature neonates. Premature neonates are at particular risk for aluminum toxicity because of immature renal function, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Patients with renal impairment, who receive parenteral aluminum at rates more than 4 to 5 mcg/kg/day, may develop aluminum toxicity (central nervous system and bone toxicity). Tissue loading may occur at lower administration rates.
Pulmonary embolism due to pulmonary vascular precipitates, vein damage, and venous thrombo-phlebitis have been reported with the use of selenium injection. 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. Remove the catheter as soon as possible, if thrombophlebitis develops.
In animal models, selenium has been shown to improve glucose metabolism. However, a randomized clinical trial indicates that selenium 200 mcg/day may be associated with an increased risk for developing type 2 diabetes mellitus (HR 1.55, 95% CI, 1.03 to 2.33). The results of this trial were derived from a secondary analysis of the Nutritional Prevention of Cancer (NPC) trial designed to determine the effects of selenium supplementation on preventing nonmelanoma skin cancer. In this trial, 1,202 patients randomized to selenium (n = 600) or placebo (n = 602) and followed for an average of 7.7 years self-reported a diagnosis of diabetes mellitus. The patients were primarily non-Hispanic white (98.4%), had a mean age of 63 years, and lived in areas of the U.S. with low rates of selenium consumption. Although the diagnosis of diabetes was confirmed by medical record review in 92% of the patients reporting a positive diagnosis, the results of this trial should be validated using a broader patient population and a more objective mechanism for diagnosing diabetes.
Selenium injection contains no more than 2,500 mcg/L of aluminum. However, aluminum toxicity may occur with prolonged administration in high-risk patients, including those with renal impairment or renal disease and premature neonates. Premature neonates are at particular risk for aluminum toxicity because of immature renal function, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Patients with renal impairment, who receive parenteral aluminum at rates more than 4 to 5 mcg/kg/day, may develop aluminum toxicity (central nervous system and bone toxicity). Tissue loading may occur at lower administration rates.
Administration of the recommended dose of selenium injection or use of oral selenium within the recommended dietary daily intakes for a pregnant female is not expected to cause major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with selenium injection. The use of selenium in excess of the recommended dietary allowance during normal pregnancy should be avoided unless, in the judgment of the physician, potential benefits in a specific, unique case outweigh the significant hazards involved.
Selenium is present in human milk as a natural component, and dietary supplementation is usually compatible with breast-feeding. Administration of the recommended dose of selenium injection or use of oral selenium within the recommended daily dietary intake for lactating women is not expected to cause harm to a breastfed infant.
Selenium injection must be diluted and used as an admixture in parenteral nutrition solutions; do not administer by direct IV infusion. Hypertonic solutions (osmolarity of 900 mOsm/L or greater) should be infused through a central catheter. Infusion of hypertonic nutrient solutions through a peripheral vein may result in vein irritation/damage, thrombophlebitis, and/or thrombosis. Remove the IV catheter as soon as possible if thrombophlebitis occurs.
For the treatment and prevention of selenium deficiency in patients receiving parenteral nutrition (PN):
Intravenous dosage:
Adults: 60 to 100 mcg elemental selenium IV per day. Higher doses (i.e., up to 400 mcg/day) may be needed in patients who are critically ill, septic, or have severe burns.
Children and Adolescents: 2 mcg elemental selenium/kg/day IV (Max: 100 mcg/day). Higher doses may be needed in patients who are critically ill, septic, or have severe burns.
Infants: 2 to 4 mcg elemental selenium/kg/day IV. Higher doses may be needed in patients who are critically ill, septic, or have severe burns.
Neonates: 2 to 4 mcg elemental selenium/kg/day IV. 64532] Higher doses may be needed in patients who are critically ill, septic, or have severe burns.
For nutritional supplementation to provide the recommended dietary allowance (RDA) of selenium in healthy individuals:
Oral dosage:
Adults: 55 mcg PO per day.
Pregnant females: 60 mcg PO per day.
Lactating females: 70 mcg PO per day.
Adolescents 14 to 17 years: 55 mcg PO per day.
Children and Adolescents 9 to 13 years: 40 mcg PO per day.
Children 4 to 8 years: 30 mcg PO per day.
Children 1 to 3 years: 20 mcg PO per day.
Infants 7 to 12 months: 20 mcg PO per day is the Adequate Intake (AI). No RDA is established.
Infants 1 to 6 months: 15 mcg PO per day is the Adequate Intake (AI). No RDA is established.
Neonates: 15 mcg PO per day is the Adequate Intake (AI). No RDA is established.
Maximum Dosage Limits:
The following are recommended tolerable intake upper limits (UL) for oral dietary intake and the usual upper limit of daily dosing for parenteral nutrition (PN) supplementation.
-Adults
400 mcg/day PO; 60 mcg/day IV per FDA-approved labeling; however, higher doses (i.e., 100 to 400 mcg/day) have been used off-label.
-Geriatric
400 mcg/day PO; 60 mcg/day IV per FDA-approved labeling; however, higher doses (i.e., 100 to 400 mcg/day) have been used off-label.
-Adolescents
14 to 17 years: 400 mcg/day PO; 2 mcg/kg/day IV (Max: 60 mcg/day IV per FDA-approved labeling; however, higher doses (i.e., 100 mcg/day) have been used off-label).
13 years: 280 mcg/day PO; 2 mcg/kg/day IV (Max: 60 mcg/day IV per FDA-approved labeling; however, higher doses (i.e., 100 mcg/day) have been used off-label).
-Children
9 to 12 years: 280 mcg/day PO; 2 mcg/kg/day IV (Max: 60 mcg/day IV per FDA-approved labeling; however, higher doses (i.e., 100 mcg/day) have been used off-label).
4 to 8 years: 150 mcg/day PO; 2 mcg/kg/day IV (Max: 60 mcg/day IV per FDA-approved labeling; however, higher doses (i.e., 100 mcg/day) have been used off-label).
1 to 3 years: 90 mcg/day PO; 2 mcg/kg/day IV.
-Infants
7 to 12 months: 60 mcg/day PO; 4 mcg/kg/day IV.
1 to 6 months: 45 mcg/day PO; 4 mcg/kg/day IV.
-Neonates
45 mcg/day PO; 4 mcg/kg/day IV.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available.
Patients with Renal Impairment Dosing
Dosage reductions may be necessary, but specific guidelines for dosage adjustments in renal impairment are not available. Selenium is primarily excreted via the renal route.
*non-FDA-approved indication
Baloxavir Marboxil: (Major) Do not administer baloxavir with selenium. Polyvalent cations, such as selenium, can chelate with baloxavir, reducing its absorption.
Dimercaprol: (Major) Avoid concomitant use of dimercaprol and products containing selenium. Dimercaprol forms toxic-chelates with selenium which increases the risk for nephrotoxicity and other adverse effects.
Eltrombopag: (Major) Eltrombopag chelates polyvalent cations (e.g., selenium) in foods, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag 2 hours before or 4 hours after any oral products containing selenium.
Trientine: (Major) In general, oral mineral supplements should not be given since they may block the oral absorption of trientine. However, iron deficiency may develop, especially in children and menstruating or pregnant women, or as a result of the low copper diet recommended for Wilson's disease. If necessary, iron may be given in short courses, but since iron and trientine each inhibit oral absorption of the other, 2 hours should elapse between administration of trientine and iron doses.
Selenium functions as a cofactor for the enzyme glutathione peroxidase, a major intracellular antioxidant. Glutathione peroxidase utilizes glutathione as a proton donor to catalyze the reduction of hydrogen peroxide and organic hydroperoxides to nontoxic products, thereby protecting cells from peroxide-induced damage. The tissue peroxidase lowering actions of selenium are similar to those of vitamin E.
Selenium is administered orally in dietary supplements or intravenously as a component of parenteral nutrition solutions. Once in the systemic circulation, the highest concentrations of selenium are found in the kidney, followed by the liver, muscle, and skin. Muscle contains almost 50% of the total body selenium. Other storage sites include erythrocytes, spleen, heart, nails, tooth enamel, testes, and sperm. Total body content of selenium varies with the relative amount found in the soil, and the subsequent concentration of selenium into the food supply. Excretion occurs primarily in the urine with a minor amount excreted in the feces.
-Route-Specific Pharmacokinetics
Oral Route
Following oral administration, selenium is rapidly absorbed from the gastrointestinal tract.
Intravenous Route
Specific pharmacokinetic data are not available; selenium is often found in intravenous trace elements solutions that contain multiple minerals essential for parenteral nutrition.