Selenaza®

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

Composition:

Active substance: sodium selenite pentahydrate;

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

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

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group.

Mineral supplements. ATC code А12С Е02.

Pharmacological properties.

Pharmacodynamics.

Selenium is a cofactor of various enzymes in the human body and therefore belongs to essential trace elements. More than 25 selenium-containing proteins and protein subunits have been identified to date. Most 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.

Selenium-containing glutathione peroxidase and selenium protein P have been identified in humans. 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 affects the metabolism of leukotrienes, thromboxanes, and prostacyclins. In animals, type I iodothyronine-5’-deiodinase has been characterized as a selenium-dependent enzyme that converts thyroxine (T4) into triiodothyronine (T3), the active thyroid hormone.

Selenium deficiency manifests as reduced 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 nonspecific cells and body fluids. Selenium deficiency suppresses the activity of various hepatic enzymes. Selenium protects against the adverse effects of chemical factors.

Selenium deficiency may lead to the development of Keshan disease, endemic cardiomyopathy, and Kashin-Beck disease, an endemic osteoarthropathy associated with severe joint deformities. Clinical manifestations of selenium deficiency are also observed as a result of prolonged parenteral nutrition and unbalanced diets.

Pharmacokinetics.

In blood, most of the selenium entering the body is taken up by erythrocytes and enzymatically converted into hydrogen selenide. Hydrogen selenide acts as a central pool of selenium for both excretion and specific conversion 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 selenium protein P containing 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.

The total amount of selenium in the human body ranges from 4 mg to 20 mg. The human body excretes selenium via feces, kidneys, and the respiratory system (depending on the intake amount). Selenium is primarily excreted in the form of trimethylselenonium ions by the kidneys.

Selenium excretion occurs 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 faster in the liver, heart, and plasma than in joints, muscles, or bones. After intravenous administration of sodium selenite labeled with 75Se, 12% of the absorbed selenium is excreted within the first 24 hours. The next 40% is excreted with a biological half-life of 20 days. The half-life in the third phase is 115 days.

Following administration of 82 mcg of selenium as sodium selenite labeled with 75Se, 18% is excreted by the kidneys within the first 24 hours together with metabolized physiological selenium.

Clinical characteristics.

Indications.

Clinically proven selenium deficiency that cannot be compensated by consuming foods rich in selenium.

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

When preparing the infusion solution, ensure that the pH does not drop 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 (see "Incompatibilities"). Elemental selenium is insoluble in aqueous environments and therefore biologically unavailable.

Special precautions for use.

One vial containing 10 ml or 20 ml of injection solution contains 35.7 mg or 71.39 mg of sodium, respectively, which corresponds to 1.8% and 3.6% of the WHO recommended maximum daily intake of 2 g of sodium for adults.

Use during pregnancy or breastfeeding.

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 any negative effect on the course of pregnancy or on the fetus.

Breastfeeding period. Selenium passes into breast milk. However, doses used to correct selenium deficiency in the mother do not exert any negative effect on the breastfed infant.

Ability to influence reaction rate when driving or operating machinery.

No influence.

Dosage and Administration

The daily dose is 100–200 mcg of selenium (2–4 ml of injection solution). If necessary, this dose may be increased to 500 mcg of selenium (1 vial of 10 ml injection solution).

During treatment of severe conditions associated with selenium deficiency, such as systemic inflammatory response syndrome (SIRS)/sepsis, severe multiple trauma, traumatic brain injury, burns, acute pancreatitis, and acute myocardial infarction, normalization of selenium levels (serum selenium concentration — 80–120 ng/mL, whole blood selenium — 100–140 ng/mL) is possible only with high-dose selenium administration (up to 1000 mcg per day, temporarily up to 2000 mcg per day).

Administer intramuscularly or intravenously. To assess treatment efficacy, selenium levels in blood or serum should be monitored.

When the medicinal product is used in total parenteral nutrition, selenium intake should be ensured at a daily dose of 100 mcg. The duration of treatment with the drug as adjunctive therapy (100 mcg selenium per day) is prolonged and determined individually by the physician.

Patients with renal or hepatic impairment.

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

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.

There is no experience with the use of the medicinal product in children.

Overdose.

Symptoms of acute overdose include garlic odor of the breath, fatigue, nausea, diarrhea, and abdominal pain. Chronic overdose may affect nail and hair growth and may lead to peripheral polyneuropathy.

Treatment: forced diuresis or administration of high doses of vitamin C. Hemodialysis may be effective in cases of massive overdose (1000–10,000 times higher than the normal dose). The use of unithiol (dimercaptopropanol) is not recommended, as it potentiates the toxic effect of selenium.

Side effects

General disorders and administration site reactions.

Frequency unknown (cannot be estimated based on available data):

• Local pain after intramuscular injection;
• Hypersensitivity reactions.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after the medicine has been authorized is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy of the medicine via the Automated Information System for Pharmacovigilance at: http://aisf.dec.gov.ua.

Shelf life: 4 years.

After opening the vial, the solution must be used immediately. Any unused portion of the vial contents should be discarded.

Storage conditions:

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

Incompatibility:

For safety reasons, avoid using Selénaza® injection solution after mixing with infusion solutions if non-specific precipitates occur.

Packaging:

10 ml or 20 ml in a vial; 10 vials per cardboard box.

Prescription status:

Prescription only.

Manufacturer:

biosyn Arzneimittel GmbH, Germany.

Manufacturer's address and location of operations:

Schorndorfer Str. 32, 70734 Fellbach, Germany.