Videin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT VIDEYIN (VIDEYIN)

Composition:

Active substance: cholecalciferol;

1 capsule contains 500 mcg of cholecalciferol (vitamin D3 — 20,000 IU);

Excipients: α-tocopheryl acetate, medium-chain triglycerides;

capsule shell: gelatin, glycerin.

Pharmaceutical form. Soft capsules.

Main physicochemical properties: soft gelatin capsules, oval-shaped, with a seam, light yellow in color, filled with a colorless or slightly yellowish oily liquid.

Pharmacotherapeutic group. Vitamins. Preparations of vitamin D and its analogs. Cholecalciferol. ATC code A11CC05.

Pharmacological Properties

Pharmacodynamics

Cholecalciferol (vitamin D3) is synthesized in the skin from 7-dehydrocholesterol under the influence of ultraviolet radiation and is converted into its biologically active form (1,25-dihydroxycholecalciferol) in two hydroxylation steps: first in the liver (at position 25), then in kidney tissues (at position 1). Together with parathyroid hormone and calcitonin, 1,25-dihydroxycholecalciferol plays a significant role in regulating calcium and phosphate balance. In its biologically active form, vitamin D3 stimulates intestinal absorption of calcium, calcium penetration into osteoid, and calcium release from bone tissue. In the small intestine, it promotes both rapid and delayed calcium absorption. In addition, passive and active phosphate transport is enhanced. In the kidneys, it inhibits calcium and phosphate excretion by stimulating tubular reabsorption. The biologically active form of cholecalciferol directly suppresses parathyroid hormone production in the parathyroid glands. Parathyroid hormone secretion is further suppressed due to increased intestinal calcium absorption induced by biologically active vitamin D3.

The so-called vitamin D3, considering its formation, physiological regulation, and mechanism of action, can be regarded as a precursor of a steroid hormone. Cholecalciferol, in addition to endogenous synthesis in the skin, can enter the body through diet or as a medicinal product. The latter route may lead to overdose and intoxication, as it does not inhibit the physiological production of vitamin D, such as skin synthesis.

Natural occurrence and requirement fulfillment

The recommended daily intake of vitamin D for adults is 20 mcg, equivalent to 800 IU. Healthy adults can meet their vitamin D requirements through endogenous synthesis provided there is sufficient sunlight exposure. Dietary intake of vitamin D is of secondary importance but may be crucial under certain conditions (climate, lifestyle).

Foods particularly rich in vitamin D include cod liver oil and fatty fish, although small amounts are also present in meat, eggs, egg yolks, milk, dairy products, and avocado.

Symptoms of vitamin D deficiency

Signs of vitamin D deficiency may occur, for example, in premature newborns, infants exclusively breastfed for more than 6 months without calcium supplementation, or children on a strict vegetarian diet. Rare vitamin D deficiency in adults may result from inadequate dietary intake, lack of sufficient ultraviolet exposure, impaired absorption and digestion, liver cirrhosis, or renal insufficiency.

In vitamin D deficiency, skeletal calcification does not occur (leading to rickets) or bone decalcification occurs (leading to osteomalacia). Deficiency of calcium and/or vitamin D causes reversible elevation of parathyroid hormone secretion. This secondary hyperparathyroidism increases bone tissue metabolism, potentially leading to bone fragility and fractures.

Pharmacokinetics

Vitamin D, in the amounts present in food, is almost completely absorbed from the diet. It is absorbed together with dietary lipids and bile acids; therefore, administering vitamin D during the main meal of the day may enhance its absorption.

Distribution and biotransformation

Metabolic conversion of cholecalciferol occurs in the liver via microsomal hydroxylase, forming 25-hydroxycholecalciferol (25(OH)D3). This is then converted in the kidneys into 1,25-dihydroxycholecalciferol, the biologically active form.

After a single oral dose of cholecalciferol, peak serum concentration of 25(OH)D3—the main storage form—is reached approximately one week later. Subsequently, 25(OH)D3 is slowly eliminated, with an apparent half-life in serum of approximately 50 days. After administration of high doses of vitamin D, serum concentrations of 25-hydroxycholecalciferol may remain elevated for several months. Hypercalcemia caused by overdose may persist for several weeks (see section "Overdose").

Elimination

Metabolites bound to specific α-globulin circulating in the blood are primarily excreted via bile and feces.

Special patient groups

In individuals with impaired kidney function, metabolic clearance rate is reduced by 57% compared to healthy volunteers.

In cases of malabsorption, absorption of vitamin D3 is decreased and elimination is increased. Obese individuals show a reduced ability to maintain vitamin D3 levels upon sun exposure and may require higher oral doses of vitamin D3 to correct deficiency.

Clinical characteristics.

Indications.

• For the treatment of clinically confirmed vitamin D deficiency in adults.
• For the prevention of vitamin D deficiency in patients at high risk.
• As an adjunct to specific osteoporosis therapy in patients with vitamin D deficiency or at high risk of vitamin D deficiency.

Contraindications.

• Hypersensitivity to the components of the medicinal product.
• Hypercalcemia.
• Hypercalciuria.
• Hypervitaminosis D.
• Pseudohypoparathyroidism (the requirement for vitamin D may be lower than during periods of normal vitamin sensitivity, with a risk of prolonged overdose).
• Nephrolithiasis (urinary stone disease).
• Renal insufficiency.
• Sarcoidosis.
• Tuberculosis.
• Additional intake of vitamin D (may lead to overdose).

Interaction with other medicinal products and other forms of interaction.

Concomitant use of anticonvulsants (such as phenytoin and phenobarbital) or barbiturates (as well as other drugs inducing liver enzymes) may lead to reduced effect of vitamin D3 due to metabolic inactivation.

Rifampicin may reduce the efficacy of cholecalciferol due to induction of liver enzymes.

Isoniazid may reduce the efficacy of cholecalciferol by inhibiting the metabolic activation of cholecalciferol.

Ion-exchange resins, laxatives, orlistat may reduce the absorption of vitamin D in the gastrointestinal tract.

The cytotoxic agent actinomycin and imidazole antifungal agents reduce the activity of vitamin D3 by inhibiting the conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol by renal enzymes, resulting in reduced activity of 25-hydroxyvitamin D-1-hydroxylase.

Glucocorticoids increase the metabolism of vitamin D, which may lead to reduced efficacy of vitamin D.

Simultaneous administration of benzothiadiazine derivatives (thiazide diuretics) increases the risk of hypercalcemia due to reduced renal excretion of calcium. Therefore, monitoring of plasma and urinary calcium levels is necessary.

The use of the medicinal product Videin, 20000 IU, in combination with metabolites or analogs of vitamin D should be avoided. Concurrent administration of vitamin D3 with metabolites or analogs of vitamin D is possible only exceptionally and only with monitoring of serum calcium levels (increases the risk of toxic effects).

Oral intake of vitamin D together with cardiac glycosides may enhance the efficacy and toxicity of digoxin due to increased calcium levels (risk of cardiac arrhythmias). In such patients, regular ECG monitoring and measurement of plasma and urinary calcium levels are required, as well as determination of digoxin or digitoxin concentration, if possible.

Concomitant use of the drug with antacids containing aluminum or magnesium may provoke toxic effects of aluminum on bone and hypermagnesemia in patients with renal insufficiency.

Ketoconazole may reduce the biosynthesis and catabolism of 1,25(OH)2-cholecalciferol.

Concomitant use with medicinal products containing high doses of calcium and phosphorus increases the risk of hyperphosphatemia.

Vitamin D may antagonize medicinal products used in the treatment of hypercalcemia, such as calcitonin, etidronate, and pamidronate.

Special precautions for use

Videin, 20000 IU, is not recommended for individuals who have a tendency to form calcium-containing kidney stones.

Videin, 20000 IU, should be administered with particular caution to patients with impaired renal function during treatment with benzothiadiazine derivatives, as well as to immobilized patients (due to the risk of developing hypercalcemia and hypercalciuria). In such patients, serum calcium and phosphate levels should be monitored. The risk of soft tissue calcification should be considered. In patients with severe renal insufficiency, normal metabolic conversion of cholecalciferol is impaired; therefore, other forms of vitamin D should be used (see section "Contraindications").

Videin, 20000 IU, should not be administered to patients with sarcoidosis due to the risk of accelerated conversion of vitamin D into its active metabolites. In such patients, serum and urinary calcium levels must be monitored.

When administering the medicinal product in an equivalent daily dose exceeding 1000 IU of vitamin D, serum calcium levels in blood and urine should be monitored, and renal function should be assessed by measuring serum creatinine concentration. This monitoring is particularly important for elderly patients and during concomitant therapy with cardiac glycosides or diuretics (see section "Interaction with other medicinal products and other forms of interaction"). This also applies to patients with a predisposition to formation of calcium-containing kidney stones.

For certain patients, additional calcium supplementation should be considered. Dietary supplements containing calcium should be used under strict medical supervision to prevent hypercalcemia.

Prior to initiating vitamin D therapy, a thorough patient assessment by a physician is required, including consideration of additional vitamin D intake from specific food products.

Elderly patients (> 65 years of age)

According to published data, in elderly individuals with a history of falls, the risk of falling increased when administering 60000 IU of vitamin D monthly. Therefore, use of the medicinal product Videin, 20000 IU, in elderly patients is recommended only after careful benefit-risk assessment and solely when clearly indicated. The dose should not exceed 24000 IU per month (one capsule). For elderly patients with a history of falls, daily supplementation with additional vitamin D should be considered.

In individuals aged > 70 years, serum 25(OH)D3 levels should be regularly monitored during vitamin D treatment with a loading dose regimen. Treatment should be discontinued if levels reach ≥ 50 ng/mL.

Use during pregnancy or breastfeeding

Pregnancy

During pregnancy, the medicinal product Videin, 20000 IU, may be prescribed only when clearly indicated and when it is absolutely necessary to correct vitamin D deficiency.

Vitamin D overdose should be avoided during pregnancy, as prolonged hypercalcemia may lead to delayed physical and mental development in the child, as well as supravalvular aortic stenosis and retinopathy.

Breastfeeding

Vitamin D and its metabolites are excreted in breast milk. Cases of overdose in breastfed newborns have not been reported. However, this should be taken into account when additional vitamin D is prescribed for the infant. High-dose vitamin D treatment (e.g., 20000 IU capsules) is not recommended for breastfeeding women.

Fertility

No effects on reproductive function or fertility were observed in animal studies with cholecalciferol. The benefit-risk ratio in humans remains unknown.

Ability to influence reaction speed when driving vehicles or operating machinery.
Videin, 20000 IU, has no effect or has a negligible effect on the ability to drive vehicles or operate machinery. However, particular caution is recommended when driving vehicles or operating machinery due to the potential for adverse reactions affecting the nervous system.

Method of Administration and Dosage

Method of Administration

For oral use.

Adults should swallow the capsule whole with plenty of water, preferably during the main meal of the day.

Dosage

Vitamin D dosage depends on the severity of the condition and the patient's response to treatment. Depending on individual needs, availability, and patient preference, daily, weekly, or monthly dosing regimens may be considered. Dosage forms with lower strengths (e.g., 400 IU, 500 IU, 800 IU, and 1000 IU) are suitable for daily vitamin D supplementation, whereas higher-dose formulations, such as 20000 IU capsules, contain amounts corresponding to weekly or monthly vitamin D doses and should be used accordingly. The dose must be prescribed by a physician in each individual case.

Certain patient groups have a higher risk of vitamin D deficiency and may require higher doses and monitoring of serum 25-hydroxycholecalciferol (25(OH)D3) concentration:

• individuals residing in specialized institutions or hospitalized patients;
• individuals with dark skin;
• individuals with limited effective sun exposure due to protective clothing or consistent use of sunscreen;
• patients with osteoporosis;
• individuals with obesity;
• individuals taking certain concomitant medications (e.g., anticonvulsants, glucocorticoids);
• individuals recently treated for vitamin D deficiency who require maintenance therapy;
• patients with malabsorption, including inflammatory bowel disease and celiac disease.

Dosage recommendations:

Initial treatment of vitamin D deficiency: 40000 IU weekly for 6–12 weeks.

Treatment of vitamin D deficiency and maintenance of its levels: 60000 to 120000 IU per month for up to 6 months.

Prevention of vitamin D deficiency: 20000 IU weekly regardless of baseline levels during the period from November to April.

Supplement to specific osteoporosis therapy in patients with vitamin D deficiency or at risk of vitamin D insufficiency:

Adults and elderly patients: 20000 to 40000 IU per month in combination with a calcium supplement, if required.

Elderly patients with a history of falls should avoid doses exceeding 24000 IU per month (see also section “Special Warnings and Precautions for Use”).

Patients with renal impairment / hypercalcemia: In the presence of hypercalcemia or signs of reduced renal function, the dose should be reduced or treatment discontinued. If hypercalciuria develops (more than 7.5 mmol, corresponding to 300 mg calcium over 24 hours), the dose should be reduced or treatment stopped.

Children. The use of this medicinal product is not recommended in children and adolescents (under 18 years of age) due to lack of dosing data and the risk of choking on capsules. Instead, drops or dissolvable tablets are preferable.

Overdose

Vitamin D3 regulates calcium and phosphate metabolism; overdose leads to hypercalcemia, hypercalciuria, renal calculi, bone damage, and cardiovascular changes. Hypercalcemia may occur after daily intake of 50000–100000 IU of vitamin D3.

Symptoms of overdose. Acute and chronic vitamin D3 overdose may cause hypercalcemia, which can become persistent and life-threatening. Symptoms may be nonspecific and include cardiac arrhythmias, thirst, dehydration, adynamia, and impaired consciousness. Chronic overdose may additionally lead to calcium deposition in blood vessels and tissues.

In addition to elevated serum and urinary phosphate levels, overdose may cause a hypercalcemic syndrome, eventually resulting in tissue calcium deposition, particularly in the kidneys (nephrolithiasis, nephrocalcinosis, renal failure), as well as in blood vessels.

Symptoms of intoxication are not very specific and may include muscle weakness, loss of appetite, nausea, vomiting, initial frequent diarrhea followed by constipation, anorexia, dyspnea, headache, myalgia, arthralgia, muscle weakness, persistent drowsiness, arrhythmia, azotemia, polydipsia, and polyuria, as well as (in preterminal stages) dehydration, photosensitivity, pancreatitis, rhinorrhea, hyperthermia, decreased libido, conjunctivitis, hypercholesterolemia, increased transaminase activity, arterial hypertension, and uremia. Common symptoms include muscle and joint pain.

Renal dysfunction may develop, characterized by albuminuria, erythrocyturia, polyuria, increased potassium loss, hypostenuria, nocturia, and moderate elevation of blood pressure.

In severe cases, corneal clouding may occur, rarely papilledema, uveitis, and even cataract development.

Kidney stones and calcification in soft tissues such as blood vessels, heart, lungs, and skin may form.

Cholestatic jaundice may rarely develop.

Characteristic biochemical abnormalities include hypercalcemia, hypercalciuria, and elevated serum 25-hydroxycalciferol concentration.

Treatment. The onset of symptoms of chronic vitamin D overdose may require forced diuresis and administration of glucocorticoids and calcitonin.

In case of overdose, measures should be taken to correct often chronic and potentially life-threatening hypercalcemia.

The primary measure is discontinuation of vitamin D intake; normalization of calcium levels after vitamin D intoxication–induced hypercalcemia may take several weeks.

Depending on the degree of hypercalcemia, a calcium-free or low-calcium diet may be used, along with recommendations for high fluid intake, forced diuresis with furosemide, and administration of glucocorticoids and calcitonin.

With normal renal function, calcium levels can usually be reduced by infusion of isotonic sodium chloride solution (3–6 liters within 24 hours) combined with furosemide. In some cases, intravenous sodium edetate at a dose of 15 mg/kg body weight/hour may also be recommended, with continuous monitoring of calcium levels and ECG. However, in cases of oligoanuria, hemodialysis (using a calcium-free dialysate) should be performed.

There is no known specific antidote.

Patients undergoing long-term treatment with high-dose vitamin D should be informed about the symptoms of possible overdose (nausea, vomiting, initial frequent diarrhea followed by constipation, anorexia, dizziness, headache, myalgia, arthralgia, muscle weakness, drowsiness, azotemia, polydipsia, and polyuria).

Adverse Reactions

Adverse reactions are generally not observed when the product is used at recommended doses.

In cases of individual hypersensitivity to the drug, which is rare, or as a result of using very high doses over a prolonged period, vitamin D hypervitaminosis may occur.

The adverse reactions listed below are classified by organ systems according to MedDRA (Medical Dictionary for Regulatory Activities) by frequency of occurrence.

Cases of rhinorrhea and hyperthermia have also been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical 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: https://aisf.dec.gov.ua

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging. 10 capsules in a blister; 2 blisters per carton.

10 capsules in a blister; 6 blisters per carton.

Prescription status. Prescription only.

Manufacturer. JSC "KYIV VITAMIN PLANT".

Manufacturer's address and place of business. 38 Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua