Selenaza®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SELENASE® (SELENASE®)

Composition:

Active ingredient: sodium selenite pentahydrate;

1 ml of solution contains sodium selenite pentahydrate equivalent to 50 mcg of selenium;

Excipients: sodium chloride, diluted hydrochloric acid, water for injections.

Pharmaceutical form. Oral solution.

Main physicochemical properties: clear, colorless solution without visible particles.

Pharmacotherapeutic group.
Mineral supplements. ATC code A12CE02.

Pharmacological Properties

Pharmacodynamics

Selenium is a cofactor in various enzymes in the human body and therefore belongs to the essential trace elements. To date, more than 25 selenium-containing proteins and protein subunits have been identified. Most of the clinical and biochemical effects of selenium can be explained by their activity. However, not all effects of selenium are exclusively attributable to the action of various enzymes.

In humans, selenium-containing glutathione peroxidase and selenoprotein P have been identified. Glutathione peroxidase is part of the antioxidant defense mechanism in mammalian cells. As a component of glutathione peroxidase, selenium may slow lipid peroxidation and thus prevent cell membrane damage caused by it. Glutathione peroxidase influences the metabolism of leukotrienes, thromboxanes, and prostacyclins. In animals, iodothyronine-5’-deiodinase type I has been characterized as a selenium-containing enzyme that converts thyroxine (T4) into triiodothyronine (T3), the active thyroid hormone.

Selenium deficiency manifests as reduced levels of selenium in blood or serum, as well as decreased activity of glutathione peroxidase in blood, plasma, or platelets. The pathophysiological significance of selenium-dependent reactions has been demonstrated in studies of selenium deficiency in humans and animals: selenium deficiency activates and inhibits immunobiological mechanisms, particularly the response of non-specific cells and body fluids. Selenium deficiency negatively affects the activity of various hepatic enzymes. Selenium deficiency potentiates the harmful effects of chemical factors on the liver and the toxicity of heavy metals such as mercury and cadmium.

Keshan disease, an endemic cardiomyopathy, and Kashin-Beck disease, an endemic osteoarthropathy associated with severe joint deformities, develop as a result of selenium deficiency in humans. Clinical manifestations of selenium deficiency are also observed following prolonged parenteral nutrition and unbalanced diets.

Pharmacokinetics

The conversion of sodium selenite into proteins occurs in several stages. In the blood, most of the administered selenium is taken up by erythrocytes and enzymatically converted into hydrogen selenide. Hydrogen selenide acts as a central selenium pool for both excretion and specific integration of selenium into selenoproteins. Reduced selenium binds to plasma proteins, which transport it to the liver and other organs. Secondary plasma transport from the liver to target tissues producing glutathione peroxidase via synthesis occurs through selenoprotein P, which contains selenocysteine. The further metabolic pathway of selenoprotein synthesis has so far been studied only in prokaryotes. During the metabolic process, selenocysteine is specifically incorporated into the peptide chains of glutathione peroxidase.

All excess hydrogen selenide is metabolized via methylselenol and dimethylselenide into trimethylselenonium ions, the main excretion product.

After oral administration, selenium is predominantly absorbed from the small intestine. The absorption of sodium selenite in the intestine is not regulated by homeostatic mechanisms. Depending on the concentration of sodium selenite and the presence of related impurities, absorption typically ranges from 44–89%, and sometimes exceeds 90%. The amino acid cysteine enhances the absorption of sodium selenite.

The total amount of selenium present in the human body is 4–20 mg. Selenium is excreted from the human body via feces, urine, and exhaled air, depending on the administered amount. Selenium is primarily excreted by the kidneys in the form of trimethylselenonium ions. Excretion depends on the selenium status.

After intravenous or oral administration, selenium elimination occurs in three phases. Following oral administration of 10 μg as [75Se]sodium selenite, 14–20% of the absorbed selenium is excreted by the kidneys within the first two weeks, while excretion via the lungs and skin is negligible. Selenium retention in the body decreases in three phases, with half-lives of 0.7–1.2 days in phase 1, 7–11 days in phase 2, and 96–144 days in phase 3. Selenium concentration decreases more rapidly in the liver, heart, and plasma than in joints, muscles, or bones. From an intravenous dose of [75Se]sodium selenite, 12% is excreted within the first 24 hours. The next 40% is eliminated with a biological half-life of 20 days. The half-life in the third phase is 115 days.

Excretion after oral and intravenous administration of a physiological dose of [74Se]sodium selenite was directly compared: after administration of 82 μg selenium as sodium selenite, 18% of the intravenous dose and 12% of the oral dose were excreted by the kidneys within the first 24 hours along with metabolized physiological selenium. After this phase, the elimination process following oral or intravenous administration is approximately the same. In healthy volunteers, excretion of orally and parenterally administered sodium selenite was comparable.

Clinical characteristics.

Indications.

Selenium deficiency that cannot be compensated by dietary sources of selenium.

Contraindications.

Hypersensitivity to sodium selenite pentahydrate or to any of the excipients.

Selenosis.

Interaction with other medicinal products and other forms of interaction.

Selenaza® oral solution must not be taken together with reducing agents (e.g., vitamin C), as this may lead to the formation of a precipitate of elemental selenium (see section "Incompatibilities").

Elemental selenium is insoluble in aqueous media and therefore biologically unavailable. Selenaza® oral solution and ascorbic acid may be administered orally, provided there is a 4-hour interval between administrations.

Special precautions for use

One 2 ml ampoule contains less than 1 mmol (23 mg) of sodium, i.e. practically sodium-free.

One 10 ml vial contains 35.70 mg of sodium chloride, corresponding to 1.8% of the WHO recommended maximum daily intake of 2 g of sodium for adults.

Use during pregnancy or breast-feeding.

Pregnancy. There are no data on the use of the medicinal product Selenaza® in pregnant women. Limited published animal studies indicate some toxicity to reproductive function when administered at doses toxic to the maternal organism.

When used in confirmed selenium deficiency, sodium selenite is not expected to have a negative effect on pregnancy or the fetus.

Breast-feeding period. Selenium passes into breast milk. Doses used to correct selenium deficiency in the mother are not expected to have a negative effect on the breastfed infant.

Ability to influence reaction rate while driving or operating machinery.

No effect.

Dosage and Administration

The daily dose for adults is 100–200 mcg of selenium (corresponding to 1–2 ampoules of 2 ml volume). If necessary, the dose may be increased up to 500 mcg of selenium (corresponding to 5 ampoules of 2 ml or 1 vial of 10 ml of the medicinal product Celenaza®, oral solution).

Administration method.

Detach the single-dose ampoule (2 ml) from the strip and open the ampoule containing the oral solution by twisting off its top part. Squeeze the entire content of the ampoule into the mouth.

When using the 10 ml vial:

Fig. 1 Fig. 2 Fig. 3

Figure 1. Open the vial immediately before use. To open the vial, turn the cap clockwise while pressing it down onto the vial. This will cause the inner blade of the cap to cut through the seal.

Figure 2. Then, turn the cap counterclockwise.

Figure 3. Squeeze the entire content of the vial into the mouth.

Before swallowing, the solution should be held in the oral cavity for approximately 30–60 seconds.

To monitor treatment efficacy, selenium levels in blood or serum should be determined.

Treatment with Celenaza®, oral solution, at the maintenance dose (100 mcg selenium per day — equivalent to 1 ampoule) may be prolonged or even continuous.

Dosage in children.

There is no experience with the use of the drug in children.

Dosage in patients with renal or hepatic impairment.

There are no scientific data regarding the need for dose adjustment in patients with renal or hepatic impairment.

Children

The medicinal product must not be used in children.

Overdose

Symptoms of acute overdose include garlic-like breath odor, fatigue, nausea, diarrhea, and abdominal pain. Prolonged use of doses exceeding the recommended amounts may affect nail and hair growth and may lead to peripheral polyneuropathy.

Treatment: gastric lavage, forced diuresis, or administration of high doses of vitamin C. In cases of severe overdose (1000–10000 times higher than the usual dose), attempts should be made to remove selenium via dialysis. Dimercaprol is not recommended, as it may potentiate the toxic effects of selenium.

Side effects.

To date, no side effects have been reported with the use of Selenium®, oral solution, according to the instructions for medical use.

Possible hypersensitivity reactions.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after the medicine has been authorized is of great importance. It allows ongoing monitoring of the benefit-risk balance of the medicine. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: http://aisf.dec.gov.ua.

Shelf life.

Ampoules — 3 years.

Vials — 2.5 years.

After opening the ampoule or vial, the solution should be used immediately. Any unused portion of the medicinal product should be discarded.

Storage conditions.

Store at a temperature not exceeding 25 °C, in a place inaccessible to children.

Incompatibility. When preparing the oral solution by adding the medicinal product Selenium®, oral solution, ensure that the pH value does not fall below 7.0 and that the solution is not mixed with reducing agents (e.g., vitamin C), as this may lead to precipitation of elemental selenium.

Packaging. 2 ml of solution in an ampoule; 20 ampoules per cardboard box.

10 ml of solution in a vial; 10 vials per cardboard box.

Prescription status. Prescription only.

Manufacturer. biosyn Arzneimittel GmbH, Germany / biosyn Arzneimittel GmbH, Germany.

Manufacturer's address and location of operations.

Schorndorfer Str. 32, 70734 Fellbach, Germany / Schorndorfer Str. 32, 70734 Fellbach, Germany.