Aquavit-d3

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AQUAVIT-D3 (AQUAVIT-D3)

Composition:

Active substance: cholecalciferol (vitamin D3);

1 ml of solution contains cholecalciferol (vitamin D3) 375 μg (15,000 IU);

Excipients: polyoxyl 35 castor oil; white crystalline sugar; sodium hydrogen phosphate, dodecahydrate; citric acid monohydrate; benzyl alcohol; anise flavor; purified water.

Pharmaceutical form. Oral solution.

Main physicochemical properties: a clear, colorless liquid with a characteristic anise odor. Opalescence may be present.

Pharmacotherapeutic group. Vitamins. Vitamin D and its analogues preparations. Cholecalciferol. ATC code A11CC05.

Pharmacological properties.

Pharmacodynamics.

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

Vitamin D3 is a natural form of vitamin D produced in animals and humans. Compared to vitamin D2, it has higher biological activity (by 25%).

It is essential for the function of the parathyroid glands, intestine, kidneys, and skeletal system. It plays a crucial role in the absorption of calcium and phosphates from the intestine, in the transport of mineral salts, and in the process of bone calcification. It also regulates the renal excretion of calcium and phosphates. Calcium ion concentration affects numerous vital biochemical processes, maintaining skeletal muscle tone, participating in nerve impulse conduction, and influencing blood coagulation. Vitamin D3 also contributes to 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 lead to rickets, in adults—to osteomalacia, and in pregnant women—to tetany symptoms and, subsequently, defective enamel formation in children.

Women during menopause who suffer from osteoporosis require increased doses of vitamin D3 due to hormonal imbalances.

Pharmacokinetics.

Absorption. The aqueous solution of vitamin D3 is better absorbed than oily solutions. In premature infants, insufficient bile production and delivery to the intestine impair the absorption of vitamins administered in oily form.

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

Distribution. It crosses the placental barrier and is excreted into breast milk.

Metabolism. It is metabolized in the liver and kidneys, converting into the active metabolite—calcitriol—which binds to a carrier protein and is transported to target organs (intestine, bones, kidneys). The half-life in blood is several days and may be prolonged in case of kidney disease.

Excretion. It is excreted in urine and feces.

Vitamin D3 participates in the regulation of phosphorus and calcium metabolism in the body 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.

Contraindications.

Hypersensitivity to the components of the drug, hypercalcemia and/or hypercalciuria, hypervitaminosis D, sarcoidosis, renal insufficiency, nephrolithiasis, tuberculosis.

Pseudohypoparathyroidism (the requirement for vitamin D may be lower than during normal sensitivity to the vitamin). Administration of vitamin D may lead to a risk of overdose. In such cases, vitamin D should be used 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, particularly phenytoin and phenobarbital, as well as rifampicin, neomycin, cholestyramine, and liquid paraffin reduce the effect of vitamin D3.

Concomitant use 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 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 administration of vitamin D3 with metabolites or analogs of vitamin D is possible only exceptionally and only under conditions of serum calcium level monitoring (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-loss 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.

During administration of the drug, additional intake of vitamin D3 should be taken into account (concomitant use of other vitamin D-containing products). Combined therapy with vitamin D or calcium should be administered only under medical supervision with monitoring of calcium levels in blood serum and urine.

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

Very high doses administered over a prolonged period 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 administered with particular caution to infants born with a small anterior fontanelle.

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

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

The drug should be used with caution in patients with impaired renal function. Prolonged use of the drug requires monitoring of kidney function by measuring serum creatinine levels.

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

Use during pregnancy or breastfeeding.

During pregnancy or breastfeeding, vitamin D should be supplied to the body in adequate amounts. Intake of vitamin D should be monitored.

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

Daily doses exceeding 500 IU of vitamin D. The drug should be used during pregnancy only if clearly necessary and in strictly recommended doses. Prolonged vitamin D overdose should be avoided due to the possible 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 overdose are lacking.

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

There are currently no reports of harmful effects of the drug on the ability to drive vehicles or operate machinery. However, when driving vehicles or operating machinery, particular caution is recommended due to possible 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 dosage for treatment of vitamin D3 deficiency is individually determined by the physician based on the course and severity of the condition.

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

Duration and method of administration.

The drug is prescribed 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 required, 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 drug cannot be guaranteed. Add the drug to food immediately before consumption.

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

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 one year.

1 drop contains 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 drug, serum calcium levels should be monitored.

Children.

The drug may be used in children 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 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 function impairment 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; rarely, optic disc edema, uveitis, and even cataract development may be observed.

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

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, and administration of glucocorticoids and calcitonin are recommended.

With normal renal function, 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 calcium levels and ECG. In cases of oligoanuria, hemodialysis is required instead. There is no specific antidote.

Side effects.

Side effects are usually not observed when the drug is used at recommended doses.

In case of individual hypersensitivity to vitamin D3, which is rare, or with prolonged use of excessively high doses, vitamin D hypervitaminosis may occur.

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, urolithiasis and tissue calcification, uremia, polyuria.

Skin and subcutaneous tissue: allergic reactions, including urticaria, rash, pruritus, eczema.

Musculoskeletal system: myalgia, arthralgia, muscle weakness.

Eyes: conjunctivitis, photophobia.

Metabolism and nutrition: 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 drug may cause anaphylactoid reactions.

Shelf life. 2 years.

Storage conditions.

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

After opening the bottle, store with tightly closed cap in the refrigerator (at 2 to 8°C) for no more than 6 months.

Packaging.

10 mL in a dark glass bottle. 1 bottle with dropper cap in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

JSC "Tekhnolohiya".

Manufacturer's address and location of its business activity.

8 Stara Prorizhna Street, City of Uman, Cherkasy Region, 20300, Ukraine.