Enat 400

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ENAT 400 (ENAT 400)

Composition:

Active substance: 1 capsule contains vitamin E – 400 IU (D-alpha-tocopheryl acetate);

Excipients: soybean oil; gelatin capsule: gelatin, glycerin, purified water.

Pharmaceutical form. Soft capsules.

Main physicochemical properties: oval soft gelatin capsules filled with a clear light-yellow oily liquid.

Pharmacotherapeutic group.

Simple vitamin preparations. Tocopherol (vitamin E). ATC code A11HA03.

Pharmacological properties.

Pharmacodynamics.

Vitamin E is a fat-soluble vitamin with high antioxidant and radioprotective activity. It participates in heme and protein biosynthesis, cell proliferation, and other essential cellular metabolic processes. Vitamin E improves tissue oxygen uptake. It exhibits angioprotective effects by influencing vascular tone and permeability, as well as stimulating the formation of new capillaries.

The immunomodulatory effect of vitamin E is due to stimulation of T-cell and humoral immunity.

Tocopherol is essential for normal reproductive processes: fertilization, fetal development, and formation and functioning of the reproductive system.

Vitamin E deficiency leads to hypotonia and dystrophy of skeletal muscles and myocardium, increased capillary permeability and fragility, and degeneration of photoreceptors, which causes visual disturbances. It also results in reduced sexual function in men and menstrual cycle disorders, as well as increased susceptibility to miscarriages in women.

Vitamin E deficiency may lead to development of hemolytic jaundice in newborns, as well as malabsorption syndrome and steatorrhea.

Pharmacokinetics.

After absorption in the intestine, most of the tocopherol enters the lymph and blood, rapidly distributing throughout the body tissues, with predominant accumulation in the liver, muscles, and adipose tissue. The highest concentrations are observed in the adrenal glands, pituitary gland, sex glands, and myocardium. The majority of the drug is excreted from the body in urine, partially with bile.

Clinical characteristics.

Indications.

The medicinal product is used as part of combination therapy for the prevention of embryonal developmental disorders in the fetus, vegetative disorders, or as an adjunct in hormonal treatment of menstrual cycle disorders.

Atrophic processes in the mucous membranes of the respiratory and gastrointestinal tracts. Used as an adjunct in neurosensory hearing disorders.

Neurasthenia in conditions accompanied by exhaustion, muscular dystrophy, and muscle atrophy.

Degenerative and proliferative changes in joints and fibrous tissues of the spine and large joints; secondary muscle weakness and myopathy in chronic arthritis, muscle weakness due to frequent recurrences of discogenic blockades.

Used as an adjunct in certain endocrine disorders and as a therapeutic agent in combination with vitamin A in male infertility.

Nutritional disorders, malabsorption syndrome, alimentary anemia. Used as part of therapy for chronic hepatitis.

Used as an adjunct in the treatment of certain cases of periodontopathies.

Peyronie's disease (plastic induration of the penis), kraurosis of the vulva, scleroderma, eczema, balanitis.

Used as part of antioxidant therapy.

Contraindications.

Hypersensitivity to the active substance or to any component of the medicinal product; cardiosclerosis; acute phase of myocardial infarction; thyrotoxicosis; hypervitaminosis E; hypersensitivity to peanuts or soy.

Interaction with other medicinal products and other forms of interactions.

Iron increases the daily requirement for vitamin E. Vitamin E has been reported to increase the tendency to bleeding in patients with vitamin K deficiency or those taking anticoagulants; therefore, monitoring of prothrombin time and international normalized ratio (INR) is recommended to detect any changes in hemostasis. Adjustment of anticoagulant dosage may be necessary during and after vitamin E treatment.

Vitamin E may increase the risk of thrombosis in patients taking estrogens.

Vitamin E must not be used concomitantly with iron preparations, silver, alkaline agents (sodium bicarbonate, trisamin), or indirect-acting anticoagulants (dicoumarol, neodicoumarol).

Vitamin E enhances the effect of steroid and non-steroidal anti-inflammatory agents (sodium diclofenac, ibuprofen, prednisolone); reduces the toxic effects of cardiac glycosides (digoxin, digitoxin) and vitamins A and D.

Vitamin E and its metabolites exert antagonistic effects on vitamin K.

Vitamin E increases the efficacy of antiepileptic drugs in patients with epilepsy.

Cholestyramine, colestipol, and mineral oils reduce the absorption of vitamin E.

When high doses of vitamin E are taken, vitamin A stores in the body may decrease.

Special precautions for use.

The use of high doses of vitamin E may exacerbate hypoprothrombinemia caused by vitamin K deficiency; therefore, blood coagulation time should be monitored.

The drug should be used with caution in patients with atherosclerosis and an increased risk of thromboembolism.

Particular caution is required in patients predisposed to the development of creatinuria, increased creatine kinase activity, elevated serum cholesterol levels, thrombophlebitis, pulmonary artery embolism, and thrombosis.

Rarely, creatinuria, increased creatine kinase activity, elevated cholesterol concentration, thrombophlebitis, pulmonary artery embolism, and thrombosis may occur in predisposed patients. In patients with bullous epidermolysis, white hair may grow in areas affected by alopecia.

When using the drug, it is necessary to strictly follow the dosage and duration of treatment prescribed by a physician to prevent overdose and the development of vitamin E hypervitaminosis.

The medicinal product contains soybean oil. Patients with allergy to peanuts or soy should not use this medicinal product.

Use during pregnancy or breastfeeding.

The drug may be used under medical supervision at recommended doses during pregnancy or breastfeeding.

The drug partially crosses the placental barrier; vitamin E enters the fetal body, where its concentration amounts to 20–30% of the vitamin E concentration in maternal plasma.

Vitamin E passes into breast milk.

Ability to affect reaction speed when driving or operating machinery.

When using the drug, adverse reactions such as visual disturbances and dizziness may occur. In such cases, patients should refrain from driving or operating machinery.

Dosage and Administration

Vitamin E should be taken orally after meals. The dose should be individually adjusted depending on the type of disease, course of illness, and patient's condition. To achieve the prescribed dose, the drug should be used in the appropriate dosage. The capsule should be swallowed whole with plenty of water.

Dosage for adults:

• In menstrual cycle disorders (as an adjunct to ongoing hormonal therapy): 300–400 IU every other day, repeated 5 times consecutively, starting from day 17 of the cycle.

• In menstrual cycle disorders in young girls, prior to initiation of hormonal therapy: 100 IU 1–2 times daily for 2–3 months.

• For prevention of embryonic developmental disorders: 100–200 IU once daily during the first trimester of pregnancy.

• In rheumatological diseases: 100–300 IU daily for several weeks.

• Neurasthenia in conditions accompanied by exhaustion: 100 IU daily.

• In muscular dystrophies: 100 IU 1–2 times daily for 30–60 days; repeat course after 2–3 months.

• In vascular diseases: 100 IU daily.

• In endocrine disorders: 300–500 IU daily.

• In nutritional anemia: 300 IU daily for 10 days.

• In chronic active hepatitis: 300 IU daily for a prolonged period.

• In periodontopathies: 200–300 IU daily.

• In penile plastic induration: 300–400 IU daily for several weeks, then as prescribed by the physician.

• In other dermatological diseases: 100–200 IU (or more) daily; dosage and duration of treatment determined by the physician.

• As part of antioxidant therapy: 200–400 IU 1–2 times daily.

• In other cases, dosage and duration of treatment are determined by the physician.

For adults, the average single dose is 100 IU, the maximum single dose is 400 IU; the average daily dose is 200 IU, the maximum daily dose is 1000 IU.

Children.

The drug is contraindicated in children under 12 years of age.

Overdose.

Symptoms. When high doses of vitamin E are taken (400–800 IU daily for a prolonged period), possible symptoms include visual disturbances, diarrhea, dizziness, headache, nausea or abdominal cramps, extreme fatigue or weakness.

Very high doses (over 800 IU for a prolonged period) may provoke bleeding in patients with vitamin K deficiency; they may disrupt thyroid hormone metabolism and increase the risk of thrombophlebitis and thromboembolism in susceptible patients. Increased creatine kinase activity, elevated serum cholesterol and triglyceride levels, and increased urinary excretion of estrogens and androgens may occur.

Treatment. Management of overdose consists of eliminating vitamin E from the body and providing symptomatic therapy.

Adverse reactions.

When the recommended doses are followed, adverse effects generally do not occur.

The table below summarizes data on adverse effects of tocopherol, categorized according to MedDRA terminology, with frequencies specified as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), and frequency not known (cannot be estimated from available data).

* When using high doses from 400 IU to 800 IU per day over a prolonged period.

The product contains soybean oil, which may cause allergic reactions.

Reporting of suspected adverse reactions. Reporting of suspected adverse reactions after registration of the medicinal product is an important procedure. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are requested to report all suspected adverse reactions to the State Expert Center of the Ministry of Health of Ukraine.

Shelf life. 5 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 ºC.

Keep out of reach and sight of children.

Packaging.

10 capsules in a blister; 3 blisters in a cardboard box.

Prescription status. Over-the-counter.

Manufacturer.

Mega Lifesciences Public Company Limited.

Manufacturer's address and location of its business operations.

Plant 2, 515/1 Moo 4, Soi 8, Bangpoo Industrial Estate, Pattana 3 Road, Phraeksa, Mueang, Samutprakarn 10280, Thailand.