Aquadetrim (Tablets, Drops) Instructions for Use

ATC Code

A11CC05 (Colecalciferol)

Active Substance

Colecalciferol (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Drug regulating calcium and phosphorus metabolism

Pharmacotherapeutic Group

Vitamins; vitamin A and D, including their combinations; vitamin D and its analogues

Pharmacological Action

Vitamin D₃ is an active antirachitic factor.

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

Vitamin D₃ is the natural form of vitamin D that is formed in human skin under the influence of sunlight. Compared to vitamin D₂, it is characterized by 25% higher activity.

Vitamin D binds to the specific vitamin D receptor (VDR), which regulates the expression of many genes, including the genes for the TRPV6 ion channel (provides calcium absorption in the intestine), CALB1 (calbindin; provides calcium transport into the bloodstream), BGLAP (osteocalcin; provides bone tissue mineralization and calcium homeostasis), SPP1 (osteopontin; regulates osteoclast migration), REN (renin; provides blood pressure regulation, being a key element of the RAAS), IGFBP (insulin-like growth factor binding protein; enhances the action of insulin-like growth factor), FGF23 and FGFR23 (fibroblast growth factor 23; regulate calcium levels, phosphate anion, and fibroblast cell division processes), TGFB1 (transforming growth factor beta-1; regulates cell division and differentiation processes of osteocytes, chondrocytes, fibroblasts, and keratinocytes), LRP2 (LDL receptor-related protein 2; mediates endocytosis of low-density lipoproteins), INSR (insulin receptor; provides the effects of insulin on any cell types).

Colecalciferol plays a significant role in the absorption of calcium and phosphates in the intestine, in the transport of mineral salts, and in the process of bone calcification, and also regulates the excretion of calcium and phosphates by the kidneys.

The concentration of calcium ions in the blood determines the maintenance of skeletal muscle tone, myocardial function, promotes nerve impulse conduction, and regulates the blood clotting process.

Lack of vitamin D in the diet, impaired absorption, calcium deficiency, as well as insufficient exposure to sunlight during a child’s rapid growth period leads to rickets; in adults – to osteomalacia; in pregnant women, symptoms of tetany and impaired bone calcification processes in newborns may occur.

An increased need for vitamin D occurs in women during menopause, as they often develop osteoporosis due to hormonal disorders.

Vitamin D has a number of so-called extraskeletal effects.

Vitamin D is involved in the functioning of the immune system by modulating cytokine levels and regulates the division of T-helper lymphocytes and the differentiation of B-lymphocytes. A number of studies have noted a reduction in the incidence of respiratory tract infections while taking vitamin D.

It has been shown that vitamin D is an important link in immune system homeostasis: it prevents autoimmune diseases (including type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis, inflammatory bowel diseases).

Vitamin D has antiproliferative and prodifferentiating effects, which determine the oncoprotective action of vitamin D. It has been noted that the incidence of some tumors (breast cancer, colon cancer) increases against the background of low blood levels of vitamin D.

Vitamin D is involved in the regulation of carbohydrate and fat metabolism by influencing the synthesis of IRS1 (insulin receptor substrate 1; involved in intracellular signaling pathways of the insulin receptor), IGF (insulin-like growth factor; regulates the balance of adipose and muscle tissue), PPAR-δ (peroxisome proliferator-activated receptor, type δ; promotes the processing of excess cholesterol).

According to epidemiological studies, vitamin D deficiency is associated with the risk of metabolic disorders (metabolic syndrome and type 2 diabetes mellitus).

Vitamin D receptors and metabolizing enzymes are expressed in arterial vessels, the heart, and in almost all cells and tissues related to the pathogenesis of cardiovascular diseases. Animal models have shown antiatherosclerotic action, renin suppression, and prevention of myocardial damage, among others. Low levels of vitamin D in humans are associated with adverse risk factors for cardiovascular pathology, such as diabetes mellitus, dyslipidemia, arterial hypertension, and are associated with the risk of cardiovascular events, including strokes.

In studies on experimental models of Alzheimer’s disease, it was shown that vitamin D₃ reduced the accumulation of amyloid in the brain and improved cognitive function. In non-interventional human studies, it was shown that the incidence of dementia and Alzheimer’s disease increases against the background of low vitamin D levels and low dietary intake of vitamin D. A worsening of cognitive function and incidence of Alzheimer’s disease was observed with low levels of vitamin D.

Pharmacokinetics

Absorption

The aqueous solution of colecalciferol is absorbed better than the oil solution (this is important when used in premature infants, since in this category of patients there is insufficiency in the production and entry of bile into the intestine, which impairs the absorption of vitamins in the form of oil solutions).

After oral administration, Colecalciferol is absorbed from the small intestine.

Distribution and Metabolism

It is metabolized in the liver and kidneys.

It crosses the placental barrier. It is excreted in breast milk. Colecalciferol accumulates in the body.

Excretion

The T_1/2 of colecalciferol from the blood is several days. It is excreted by the kidneys in small amounts; most is excreted in the bile.

Pharmacokinetics in Special Clinical Cases

In renal failure, an increase in T_1/2 is possible.

Indications

Prevention and treatment

• Of vitamin D deficiency;
• Rickets and rickets-like diseases;
• Hypocalcemic tetany;
• Osteomalacia;
• Bone diseases on a metabolic basis (such as hypoparathyroidism and pseudohypoparathyroidism).

Treatment of osteoporosis, including postmenopausal (as part of combination therapy).

ICD codes

Dosage Regimen

Drops

The drug is taken orally, in 1 spoonful of liquid (1 drop contains 500 IU of colecalciferol). Unless otherwise prescribed by a doctor, the drug is used in the following dosages.

For prevention in full-term newborns from 4 weeks of age to 2-3 years, with proper care and sufficient time spent outdoors, the drug is prescribed at a dose of 500 IU (1 drop)/day.

For premature infants from 4 weeks of age, twins, and children living in unfavorable conditions, 1000-1500 IU (2-3 drops)/day are prescribed.

During the summer, the dose can be reduced to 500 IU (1 drop)/day.

For healthy adults without malabsorption – 500 IU (1 drop)/day; for adult patients with malabsorption syndrome – 3000-5000 IU (6-10 drops)/day.

For pregnant women, 500 IU (1 drop)/day is prescribed daily throughout pregnancy, or 1000 IU (2 drops)/day, starting from the 28th week of pregnancy.

In the postmenopausal period, 500-1000 IU (1-2 drops)/day are prescribed.

For treatment of rickets, the drug is prescribed daily at a dose of 1000-5000 IU (2-10 drops)/day for 4-6 weeks, depending on the severity of rickets (I, II, or III) and the variant of the disease course. In this case, the patient’s clinical condition and biochemical parameters (levels of calcium, phosphorus, activity of ALP in blood and urine) should be monitored. The initial dose is 1000 IU/day for 3-5 days, then, with good tolerance, the dose is increased to an individual therapeutic dose (usually up to 3000 IU/day). A dose of 5000 IU/day is prescribed only for pronounced bone changes.

If necessary, after a 1-week break, the course of treatment can be repeated.

Treatment should be continued until a clear therapeutic effect is obtained, followed by a switch to a prophylactic dose of 500-1500 IU/day.

For the treatment of rickets-like diseases, 20,000-30,000 IU (40-60 drops)/day are prescribed, depending on age, body weight, and severity of diseases, under the control of blood biochemical parameters and urinalysis. The course of treatment is 4-6 weeks. Treatment is carried out under medical supervision.

For the treatment of postmenopausal osteoporosis (as part of combination therapy), 500-1000 IU (1-2 drops)/day are prescribed.

The dose is set individually, taking into account the amount of vitamin D coming from food.

Tablets

Individual, depending on the indications, the dosage form used, and the patient’s age.

Adverse Reactions

Symptoms of hypervitaminosis D: loss of appetite, nausea, vomiting; headache, muscle and joint pain; constipation; dry mouth; polyuria; weakness; mental disorders, including depression; weight loss; sleep disturbance; fever; protein, leukocytes, hyaline casts appear in the urine; increased calcium levels in the blood and its excretion in the urine; calcification of the kidneys, blood vessels, and lungs is possible. If signs of hypervitaminosis D appear, it is necessary to discontinue the drug, limit calcium intake, and prescribe vitamins A, C, and B.

Other: hypersensitivity reactions are possible.

Contraindications

• Hypervitaminosis D;
• Hypercalcemia;
• Hypercalciuria;
• Urolithiasis (formation of calcium oxalate stones in the kidneys);
• Sarcoidosis;
• Acute and chronic diseases of the liver and kidneys;
• Renal failure;
• Active form of pulmonary tuberculosis;
• Hypersensitivity to the components of the drug (especially to benzyl alcohol).

With caution, the drug should be used in patients in an immobilized state; when taking thiazides, cardiac glycosides (especially digitalis glycosides); during pregnancy and lactation (breastfeeding); in infants with a predisposition to early closure of fontanelles (when small sizes of the anterior fontanelle are established from birth).

Use in Pregnancy and Lactation

During pregnancy, vitamin D₃ should not be used in high doses due to the possibility of a teratogenic effect in case of overdose.

Vitamin D₃ should be prescribed with caution during lactation, because when the drug is used in high doses in a nursing mother, symptoms of overdose may develop in the child.

Use in Hepatic Impairment

Contraindicated in acute and chronic liver diseases.

Use in Renal Impairment

Contraindicated in acute and chronic kidney diseases; in renal failure.

Pediatric Use

With caution in infants with a predisposition to early closure of fontanelles (when small sizes of the anterior fontanelle are established from birth).

Special Precautions

Overdosing should be avoided.

Individual provision of a certain need should take into account all possible sources of this vitamin.

Too high doses of vitamin D₃, used for a prolonged period, or shock doses can cause chronic hypervitaminosis D₃.

The determination of the child’s daily requirement for vitamin D and the method of its administration should be established by the doctor individually and each time subjected to correction during periodic examinations, especially in the first months of life.

When an adequate blood concentration level of vitamin D (>30 ng/ml 25(OH)D) is achieved in adults, maintenance therapy with Aquadetrim at a dose of 1500-2000 IU (3-4 drops)/day may be continued.

Do not use high doses of calcium simultaneously with vitamin D₃.

During treatment, periodic monitoring of phosphate concentrations in blood and urine is necessary.

With long-term use of colecalciferol, it is necessary to regularly determine the level of calcium in the blood serum and urine, as well as assess renal function by measuring the serum creatinine level. If necessary, the dose of colecalciferol should be adjusted depending on the serum calcium level.

Overdose

Symptoms: decreased appetite, nausea, vomiting, constipation, restlessness, thirst, polyuria, diarrhea, intestinal colic. Frequent symptoms are headache, muscle and joint pain, mental disorders, including depression, ataxia, stupor, progressive weight loss. Impaired renal function develops with albuminuria, erythrocyturia and polyuria, increased loss of potassium, hyposthenuria, nocturia and increased blood pressure.

In severe cases, clouding of the cornea is possible, less often – edema of the optic disc, inflammation of the iris up to the development of cataract. Formation of kidney stones, calcification of soft tissues, including blood vessels, heart, lungs, and skin is possible.

Cholestatic jaundice rarely develops.

Treatment: discontinuation of the drug. Plenty of fluids are prescribed. Hospitalization may be required if necessary.

Drug Interactions

Antiepileptic drugs, rifampicin, cholestyramine reduce the reabsorption of vitamin D₃.

Concomitant use with thiazide diuretics increases the risk of hypercalcemia.

Concomitant use with cardiac glycosides may enhance their toxic effect (the risk of cardiac arrhythmias increases).

Storage Conditions

The drug should be stored in the original packaging in a place inaccessible to children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.