Vitamin d3

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT VITAMIN D3 (VITAMIN D3)

Composition:

Active ingredient: cholecalciferol;

1 ml of solution contains 15,000 IU of cholecalciferol;

Excipients: macrogolglycerol ricinoleate, sucrose, disodium phosphate dodecahydrate, citric acid monohydrate, banana flavoring, benzyl alcohol, purified water.

Pharmaceutical form. Aqueous oral solution.

Main physicochemical properties: colorless or slightly yellowish liquid with a banana odor. Opalescence 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 the 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 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 the renal excretion of calcium and phosphates. The concentration of calcium ions influences numerous vital biochemical processes that maintain skeletal muscle tone, participate in nerve impulse conduction, and affect blood coagulation. Vitamin D3 also contributes to immune system function by influencing 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; and in pregnant women, to symptoms of tetany and defective enamel formation in infants.

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 delivery to the intestine impair the absorption of vitamins 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, where it is converted 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 kidney disease.

Excretion. Excreted in urine and feces.

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

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

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). Vitamin D administration 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 forms of interaction.

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

Concomitant use of Vitamin D3 with thiazide diuretics increases the risk of hypercalcemia.

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

Concomitant use of Vitamin D3 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 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 agents 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.

When using the Vitamin D3 preparation, additional intake of vitamin D3 should be taken into account (concomitant use of other 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 assessment of required intake should consider all possible sources of vitamin D intake.

Excessively high doses of Vitamin D3 used long-term or as 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 infants born with a small anterior fontanelle.

Do not take Vitamin D3 preparation simultaneously with high doses of calcium.

During treatment with this preparation, monitoring of serum and urinary levels of calcium, phosphates, and glucose is recommended.

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

The preparation should be used with caution during pregnancy and in breastfeeding women.

If a patient has known sugar intolerances, 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. The risks associated with using vitamin D within this dosage range are unknown. Prolonged vitamin D overdosing should be avoided due to the potential development of hypercalcemia.

Daily doses exceeding 500 IU of vitamin D. Vitamin D3 should be used during pregnancy only when clearly necessary and strictly according to recommended dosing. Prolonged vitamin D overdosing should be avoided due to the potential development 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 overdosing are lacking.

Ability to influence reaction speed when driving vehicles or operating machinery.

There are no reports indicating that the medicinal product affects the ability to drive vehicles or operate machinery. However, when driving vehicles or operating machinery, particular caution is recommended, taking into account the possibility of adverse reactions affecting the nervous system.

Dosage and Administration

Administer orally.

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

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

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

Prophylaxis of rickets in preterm newborns: dosage is determined by the physician. The general recommended dose is 2 drops (approximately 1000 IU of vitamin D3) daily.

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

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

Treatment of hypoparathyroidism: the recommended dose depends on serum calcium levels and ranges from 20–40 drops (approximately 10,000–20,000 IU of vitamin D3) daily. If higher doses of cholecalciferol are required, medicinal products with higher dosage strengths should be used.

During long-term treatment with Vitamin D3, it is necessary to regularly monitor serum creatinine, serum calcium, and urinary calcium levels. If necessary, the dose should be adjusted according to serum calcium concentration.

Duration and method of administration.

Vitamin D3 should be prescribed to infants for rickets prophylaxis starting from the second week of life up to the end of the first year of life. During the second year of life, continued use of Vitamin D3 may be necessary, especially during winter months.

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

Adults and older children should take the medication in a spoon with liquid.

The duration of treatment depends on the course and severity of the disease and is individually determined by the physician. Treatment of rickets and osteomalacia caused by vitamin D3 deficiency lasts for 1 year.

1 ml of the medicinal product contains approximately 30 drops. 1 drop contains approximately 500 IU of vitamin D3. To accurately measure the dose, hold the bottle at a 45° angle during administration.

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

Children.

Use in children starting from the second week of life.

Overdose.

Vitamin D3 regulates calcium and phosphate metabolism. Overdose may lead to hypercalcemia, hypercalciuria, renal calcifications, bone damage, and cardiovascular system changes. Hypercalcemia may occur after administration of 50,000–100,000 IU of vitamin D3 daily.

Symptoms of overdose may 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 increase in blood pressure.

In severe cases, corneal clouding may occur; less frequently, 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. Discontinue the medication immediately. Depending on the degree of hypercalcemia, a low-calcium or calcium-free diet, high fluid intake, forced diuresis induced by furosemide, and administration of glucocorticoids and calcitonin are recommended.

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

Side effects.

Generally, no adverse reactions are observed when administered at recommended doses.

In cases of individual hypersensitivity to Vitamin D3, which is rare, or as a result of prolonged use of excessively high doses, vitamin D hypervitaminosis may occur.

Cardiovascular system. Arrhythmia, hypertension.

Gastrointestinal tract. Loss of appetite, nausea, vomiting, constipation, dryness in the 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: Decreased libido.

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

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

Shelf life. 3 years.

After opening the bottle, store with tightly closed cap for up to 6 months.

Storage conditions.

Store in original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging.

10 mL in a dark glass bottle closed with a dropper stopper and a tamper-evident screw cap; 1 bottle per carton.

Prescription status.

Prescription only.

Manufacturer.

PJSC "Halychpharm".

Manufacturer's address and location of business activity.

6/8 Opryshkivska St., Lviv, 79024, Ukraine.