Vitamin d3

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT VITAMIN D3 (VITAMIND3)

Composition:

Active substance: cholecalciferol (colecalciferol);

1 ml (30 drops) of the preparation contains 15,000 IU cholecalciferol (1 drop (1 dose) contains 500 IU cholecalciferol);

Excipients: sodium hydrogen phosphate; citric acid; sucrose; macrogol glycerol ricinoleate 35; benzyl alcohol; anise oil; purified water.

Medicinal form. Oral drops, solution.

Main physicochemical properties: clear colorless liquid with anise odor and taste. Slight opalescence of the preparation may be present.

Pharmacotherapeutic group. Vitamins. Vitamin D and its analogues.

ATC code A11CC05.

Pharmacological Properties.

Pharmacodynamics.

Vitamin D3 is the active antirachitic factor. The most important function of vitamin D is regulation of calcium and phosphate metabolism, which promotes proper skeletal mineralization and growth.

Vitamin D3 is the natural form of vitamin D produced in animals and humans. Compared to vitamin D2, it has approximately 25% higher biological activity. It is essential for the proper function of the parathyroid glands, intestines, kidneys, and skeletal system. Vitamin D3 plays a crucial role in the intestinal absorption of calcium and phosphates, in the transport of mineral salts, and in the process of bone calcification. It also regulates renal excretion of calcium and phosphates. Calcium ion concentration influences numerous vital biochemical processes, including maintenance of skeletal muscle tone, transmission of nerve impulses, and blood coagulation. Vitamin D3 also participates in immune system function by affecting lymphokine production.

Deficiency of vitamin D3 in the diet, impaired absorption, calcium deficiency, and lack of exposure to sunlight during periods of rapid growth in children may lead to rickets; in adults – to osteomalacia; in pregnant women – to symptoms of tetany and defective enamel formation in newborns.

Women during menopause, who are frequently affected by osteoporosis due to hormonal imbalances, require increased doses of vitamin D3.

Pharmacokinetics.

Absorption.

The aqueous solution of vitamin D3 is absorbed better than the oily solution. In premature infants, insufficient bile production and secretion into the intestine impair the absorption of fat-soluble vitamins, including vitamin D in oily formulations.

After oral administration, cholecalciferol is absorbed in the small intestine.

Distribution. Crosses the placental barrier and is excreted into breast milk.

Metabolism. Metabolized in the liver and kidneys into its active metabolite – calcitriol. Calcitriol binds to a carrier protein and is transported to target organs (intestines, bones, kidneys). The half-life in blood is several days and may be prolonged in case of kidney disease.

Excretion. Eliminated via urine and feces.

Vitamin D3 participates in the regulation of phosphorus and calcium metabolism within 6 hours after administration.

Significant elevation of serum cholecalciferol levels is observed as early as 48 hours after vitamin D3 intake.

Clinical characteristics.

Indications.

• Prophylaxis of rickets;
• prophylaxis of vitamin D3 deficiency in high-risk groups without malabsorption disorders;
• prophylaxis of rickets in premature newborns;
• prophylaxis of vitamin D3 deficiency in malabsorption;
• treatment of rickets and osteomalacia;
• supportive treatment of osteoporosis;
• treatment of hypoparathyroidism.

Contraindications.

Hypersensitivity to the components of the drug, hypercalcemia and/or hypercalciuria, hypervitaminosis D, sarcoidosis, renal insufficiency, nephrolithiasis, tuberculosis. Pseudohypoparathyroidism (vitamin D requirement may be lower than during normal vitamin sensitivity). Administration of vitamin D may lead to the risk of overdose. In such cases, vitamin D should be administered in other pharmaceutical forms that allow easier control of concentration. The drug is contraindicated in patients with rare hereditary fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency.

Interaction with other medicinal products and other types of interactions.

Antiepileptic agents such as phenytoin and phenobarbital, as well as rifampicin, reduce the absorption of vitamin D3.

Concomitant use of the drug with thiazides increases the risk of hypercalcemia.

Concomitant use with cardiac glycosides may enhance their toxic effects (increased risk of cardiac arrhythmias).

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

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

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

Concomitant administration of vitamin D3 with metabolites or analogs of vitamin D is possible only exceptionally and only with monitoring of serum calcium levels (increased risk of toxic effects).

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

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

Concomitant use with weight-reducing agents (orlistat) and cholesterol-lowering drugs may reduce the absorption of vitamin D and other fat-soluble vitamins.

Special precautions for use

The medicinal product should be used with caution in immobilized patients, patients taking thiazides, cardiac glycosides, and in patients with cardiovascular diseases.

During treatment with this drug, additional intake of vitamin D3 should be taken into account (concomitant use of other medicinal products containing vitamin D). Combined therapy with vitamin D or calcium should be administered only under medical supervision and with monitoring of serum and urinary calcium levels.

Individual supplementation to meet specific requirements should take into account all possible sources of vitamin intake.

Very high doses used long-term or bolus doses may lead to chronic vitamin D3 hypervitaminosis.

The determination of a child's daily requirement for vitamin D and the method of administration should be established individually and verified periodically, especially during the first months of life.

The medicinal product should be used with particular caution in newborns with a small anterior fontanelle.

Do not take the drug simultaneously with high doses of calcium.

During treatment with this product, monitoring of calcium, phosphate, and glucose levels in blood serum and urine is recommended.

The drug should be used cautiously in patients with impaired renal function. Long-term use requires monitoring of kidney function through serum creatinine levels.

The drug should be used with caution during pregnancy and breastfeeding.

The medicinal product contains sucrose and therefore may be harmful to teeth. If a patient has known intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

Use during pregnancy or breastfeeding

During pregnancy and breastfeeding, vitamin D should be supplied in adequate amounts. Intake of vitamin D should be monitored.

Daily doses up to 500 IU of vitamin D. Risks associated with using vitamin D within this dosage range are unknown. Prolonged vitamin D overdose should be avoided due to the potential risk of hypercalcemia.

Daily doses exceeding 500 IU of vitamin D. The drug should be used during pregnancy only if clearly necessary and at strictly recommended doses. Prolonged vitamin D overdose should be avoided due to the potential risk of hypercalcemia, which may lead to physical and mental developmental abnormalities in the fetus, aortic stenosis, and retinopathy in children.

Vitamin D and its metabolites pass into breast milk. Data regarding possible overdose are lacking.

Effect on the ability to drive or operate machinery

There are no reports on the effect of the medicinal product on the ability to drive or operate machinery. However, when driving or operating machinery, particular caution is recommended due to the potential for adverse reactions affecting the nervous system.

Method of Administration and Dosage

Administer orally.

Prophylaxis of rickets: the recommended dose is 1 drop (500 IU vitamin D3) daily.

Prophylaxis of vitamin D3 deficiency in high-risk patients without malabsorption disorders: the recommended dose is 1 drop (500 IU vitamin D3) daily.

Supportive treatment of osteoporosis: the recommended dose is 2 drops (1000 IU vitamin D3) daily.

Prophylaxis of rickets in premature infants: dosage is determined by a physician. The general recommended dose is 2 drops (1000 IU vitamin D3) daily.

Prophylaxis of vitamin D3 deficiency in malabsorption: dosage is individually determined by a physician. The general recommended dose is 6–10 drops (3000–5000 IU vitamin D3) daily.

Treatment of rickets and osteomalacia: as in the treatment of vitamin D3 deficiency, dosage is individually determined by a physician depending on the course and severity of the disease. The general recommended treatment dose of vitamin D3 deficiency in infants and children is 2–10 drops (1000–5000 IU vitamin D3) daily.

Treatment of hypoparathyroidism: the recommended dose depends on serum calcium levels and ranges from 20–40 drops (10000–20000 IU vitamin D3) daily. If higher doses of cholecalciferol are required, medicinal products with higher dosage strengths should be used.

During long-term treatment with the drug, it is necessary to regularly monitor serum creatinine levels as well as calcium levels in blood serum and urine. If necessary, the dose should be adjusted according to serum calcium concentration.

Duration and method of administration.

Prescribe Vitamin D3 to children for rickets prophylaxis starting from the second week of life until the end of the first year of life. During the second year of life, continued use of the drug may be necessary, especially during winter months.

For young children, add drops to a teaspoon of water, milk, or infant formula. If drops are added to a feeding bottle or food dish, ensure complete consumption of the food; otherwise, the full dose of the drug cannot be guaranteed. Add the drug to food immediately before consumption.

Adults and older children should take the drug mixed with a spoonful of liquid.

The duration of treatment depends on the course and severity of the disease and is individually determined by a physician. Treatment of rickets and osteomalacia caused by vitamin D3 deficiency lasts for one year.

1 drop contains 500 IU vitamin D3. To accurately measure the dose, invert the bottle and hold it vertically while dispensing drops.

When administering doses exceeding 1000 IU vitamin D3 daily, as well as during continuous use of the drug, serum calcium levels should be monitored.

Children.

To be used in children from the second week of life.

Overdose.

Vitamin D3 regulates calcium and phosphate metabolism. After overdose, hypercalcemia, hypercalciuria, renal calcifications, and bone damage may occur, as well as cardiovascular changes. Hypercalcemia occurs after administration of 50000–100000 IU vitamin D3 daily.

Effects that may develop in overdose include: muscle weakness, loss of appetite, nausea, vomiting, constipation, polydipsia, polyuria, drowsiness, photophobia, pancreatitis, rhinorrhea, hyperthermia, decreased libido, conjunctivitis, hypercholesterolemia, increased transaminase activity, arterial hypertension, cardiac arrhythmia, and uremia. Common symptoms include muscle and joint pain, headache, and weight loss. 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; more rarely, optic disc edema, uveitis, and even cataract development may be observed.

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

Cholestatic jaundice may rarely develop.

Treatment. Overdose requires treatment of hypercalcemia. Administration of the drug must be discontinued. Depending on the degree of hypercalcemia, a low-calcium or calcium-free diet, high fluid intake, forced diuresis induced by furosemide administration, and glucocorticoids and calcitonin may be recommended.

With normal renal function, calcium levels are reliably reduced by intravenous infusion of sodium chloride solution (3–6 liters within 24 hours) with added furosemide. In some cases, 15 mg/kg body weight/hour of sodium edetate may also be administered, with continuous monitoring of calcium levels and ECG. In cases of oligoanuria, hemodialysis is required instead. There is no specific antidote.

Adverse Reactions

Generally, no adverse reactions are observed when the product is used at recommended doses.

However, in rare cases of individual hypersensitivity to the drug, or as a result of prolonged use of very high doses, vitamin D hypercalcemia may occur.

Cardiovascular system: arrhythmia, arterial hypertension.

Gastrointestinal tract: loss of appetite, nausea, vomiting, constipation, dry mouth, flatulence, abdominal pain, diarrhea, dyspepsia.

Nervous system: headache, drowsiness, psychiatric disturbances, depression.

Urinary system: elevated calcium levels in blood and/or urine, nephrolithiasis and tissue calcification, uremia, polyuria.

Skin: hypersensitivity reactions, including urticaria, rash, pruritus.

Musculoskeletal system: myalgia, arthralgia, muscle weakness.

Eyes: conjunctivitis, photophobia.

Metabolism: hypercholesterolemia, weight loss, polydipsia, increased sweating, pancreatitis.

Hepatobiliary system: increased aminotransferase activity.

Psychiatric disorders: decreased libido.

There have also been reports of rhinorrhea, hyperthermia, and dry mouth.

Due to the presence of benzyl alcohol (15 mg/mL), the product may cause anaphylactoid reactions.

Shelf life. 2 years.

The shelf life of the product after opening the bottle is not more than 6 months.

Storage conditions.

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

Keep out of reach of children.

Packaging.

8 mL of solution in a dark glass bottle with a dropper stopper, closed with a cap, packed in a box.

Prescription status.

Prescription only.

Manufacturer.

LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVTYA".

Manufacturer's address and place of business.

22, Shevchenka Street, Kharkiv, Kharkiv Oblast, 61013, Ukraine.