Selenium 10 Micrograms/Ml Solution For Infusion
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
SELENIUM 10 micrograms/ml solution for infusion
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each vial of 10 ml solution contains 219 micrograms of sodium selenite, equivalent to 100 micrograms of selenium.
Each ml of solution contains 21.9 micrograms of sodium selenite, equivalent to 10 micrograms of selenium.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Solution for infusion. (Infusion)
Clear colourless solution. pH 8.0 - 9.5
Osmolarity = 20 mOsm/l
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Prevention of selenium deficiency in patients receiving parenteral nutrition. Treatment of proven selenium deficiency that cannot be cured by nutrition alone.
4.2 Posology and method of administration
Posology 1 ml of solution contains 10 micrograms of selenium.
The dose must be adapted individually according to selenium deficiency and selenium status.
For monitoring of therapy the selenium concentration in whole blood or serum should be determined. The whole blood level should be between 120 and 160 micrograms selenium/litre, the concentration of selenium in serum should not exceed 130 micrograms/l.
The recommended posology is:
- Adults:
o Supplementation to total parenteral nutrition: 60 to 100 micrograms daily.
o Other situation with proven selenium deficiency: 100 micrograms up to a maximum of 400 micrograms daily for a short-term until normalization of laboratory monitoring values.
- Paediatric population:
o Infants: 2 micrograms/kg/day and infants with low birth weight: 2 to 3 micrograms/kg/day.
o Children: 2 micrograms/kg/day, up to a maximum of 30 micrograms daily.
Method of administration Intravenous administration:
SELENIUM 10 micrograms/ml solution for infusion must be administered after dilution in solution for parenteral nutrition, after stability has been validated, or in isotonic solution (such as sodium chloride 0.9% or glucose 5%) with a slow infusion rate.
4.3 Contraindications
This product must not be administrated in case of selenium poisoning or hypersensitivity to selenium containing products.
4.4 Special warnings and precautions for use
Special warnings:
The product must not be injected straight, but diluted in a solution for infusion (see section 4.2).
Precautions for use:
Serum selenium levels must be controlled regularly.
In case of complex parenteral nutrition and if mixing of medicines is necessary, caution is required in order to avoid incompatibilities.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
4.6 Fertility, Pregnancy and lactation
Pregnancy
There are no or limited amount of data from the use of selenium in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The use of selenium may be considered during pregnancy, if necessary.
Lactation
Selenium is excreted in human milk, but at therapeutic doses of selenium no effects on the breastfed newborns/infants are anticipated. Selenium can be used during breast-feeding.
Fertility
Selenium did not impair male fertility in rats. The effects of selenium on female fertility in rodents were observed at high doses (See section 5.3).
4.7 Effects on ability to drive and use machines
Not relevant.
4.8 Undesirable effects
Administrated doses in parenteral nutrition are low, and signs of toxicity are not found for the recommended intakes.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme - Website: www.mhra.gov.uk/yellowcard.
4.9 Overdose
Symptoms of acute overdose are: garlicky breath, tiredness, nausea and vomiting, diarrhoea and abdominal pain. In case of chronic overdose, effects on skin and phaneres with changes in the nail and hair growth as well as peripheral polyneuropathies have been observed.
In case of overdose, the treatment must be interrupted, and a symptomatic treatment should be given if necessary. In case of acute overdose, gastric lavage and forced diuresis are possible. There is no known specific antidote.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Mineral supplements. ATC code: A12CE02
Selenium is an essential trace element. Up to 20 selenoproteins have been identified in rodents. In human, selenium compounds are glutathione peroxidase and a selenium protein P found in the plasma. In both these proteins, selenium is protein-bound and is present in the form of the amino acid selenocysteine. Other selenium-dependent enzymes are the thioredoxine-reductase and the 5'-deiodinase that catalyses the conversion from tetraiodothyronine (T4) to the active thyroid hormone triiodothyronine (T3).
The selenium-containing glutathionperoxidase is a part of the anti-oxidative protection system of the mammal cell. In case of sufficient quantities of reduced glutathione, the glutathionperoxidase converts a variety of hydroperoxides into relevant alcohols. In cellular or sub-cellular in vitro models, it has been observed that the integrity of cellular or sub-cellular membranes depends on the intactness of the glutathionperoxidase system. Synergetic effect with vitamin E in various cell fractions is postulated but has not been conclusively proven. Selenium as a part of the glutathionperoxidase can reduce the lipidperoxide rate and the resulting membrane damage.
The patho-physiological relevance of selenium-dependent reactions has been demonstrated by observations in selenium deficiency humans and animals. The selenium-containing glutathionperoxidase affects the leucotriene, thromboxane and prostacyclin metabolism. Selenium deficiency inhibits reactions of the immune system, especially the non-specific, cell-bound and humoral reactions. Selenium deficiency affects the activity of a few liver enzymes. Selenium deficiency potentiates oxidatively or chemically induced liver damage and toxicity of heavy metals such as quicksilver and cadmium.
Deficiency of selenium has been associated with an endemic form of cardiomyopathy, Keshan disease. It has also been associated with Kaschin-Beck disease, an endemic osteoarthropathy which causes a severe deformity of the joints.
Clinically manifested selenium deficiency has also been seen to be a result of longterm parenteral nutrition and unbalanced diets. Cardiomyopathies and myopathies are observed most frequently.
5.2 Pharmacokinetic properties
In the blood, selenite is mainly absorbed by erythrocytes and enzymatically reduced to hydrogen selenide. Hydrogen selenide serves as the central selenium pool for excretion and for specific incorporation in selenoproteins. In this reduced form, selenium is bound to plasma proteins present in the liver and other organs. The plasmatic secondary transport from the liver to the glutathionperoxidase-synthesing target tissues takes place in the form of selenocystein (selenoprotein P). The further metabolic process of the selenoprotein biosynthesis is currently known only in prokaryotes. Selenocystein is then specifically incorporated into the peptide chains of the glutathionperoxidase.
Excess of hydrogen selenide is transformed into methylated metabolites (methyl selenol, dimethylselenide and trimethylselenonium ion) prior to being excreted into urine and/or exhaled.
The total quantity of selenium in the human body is between 3 mg and 20 mg. In human, selenium is excreted in feces, urine or lung, depending on the administered dosage. Selenium is primarily renally excreted in the form of trimethylselenonium ion. The excretion depends on the selenium status.
The selenium excretion after the intravenous or oral intake takes place in three phases with a terminal half-life of 65 to 116 days.
5.3 Preclinical safety data
Sodium selenite is highly toxic and kills laboratory animals in single doses of 1 to 3mg/kg of body weight.
Selenium did not impair male fertility in rats. The effects of selenium on female fertility, reproduction and offspring observed in rodents were observed at high doses that were related to maternal toxicity. There was no evidence of teratogenicity in monkeys.
In various in vitro studies, mutagenic as well as anti-mutagenic effects of sodium selenite were seen. In vivo, a mutagenic and carcinogenic potential could be seen in case of extremely high doses, which is not the case for therapeutic doses.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Water for injection.
6.2 Incompatibilities
Selenium is generally incompatible with high concentration of ascorbic acid (reduction of selenite to elemental selenium which is not soluble and unavailable as a nutritional source of selenium).
SELENIUM 10 micrograms/ml solution for infusion can not be mixed with medicines other than sodium chloride 0.9%, glucose 5%, solution for parenteral nutrition or solution of trace elements.
6.3 Shelf life
3 years.
After opening/reconstitution/dilution, the product must be used immediately
6.4 Special precautions for storage
There are no special storage conditions.
6.5
Nature and contents of container
10 ml solution in a type I glass vial with a type I elastomer (bromobutyl) stopper fitted with an aluminium cover and crimped.
Pack of 10 vials.
6.6 Special precautions for disposal
No special requirements for disposal.
7 MARKETING AUTHORISATION HOLDER
Laboratoire Aguettant 1, rue Alexander Fleming 69007 Lyon France
8 MARKETING AUTHORISATION NUMBER(S)
PL 14434/0030
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
28/10/2013
10 DATE OF REVISION OF THE TEXT
07/01/2014