DeTriFerol anise-flavored drops 15000 me/ml 15 ml

Pharmacodynamics

Vitamin D3 is a natural form of vitamin D, which is formed in the human skin under the influence of sunlight. Compared with vitamin D2 is characterized by 25% higher activity.
Vitamin D3 is an active anti-rachitis factor.

The most important function of vitamin D3 is to regulate calcium and phosphate metabolism to promote proper mineralization and skeletal growth.

Calciferol plays an essential role in the absorption of calcium and phosphate in the intestine, in the transport of mineral salts and in the calcification of bones, and also regulates the excretion of calcium and phosphate by the kidneys.

The concentration of calcium ions in blood determines the muscle tone of skeletal muscles, myocardial function, contributes to nerve stimulation and regulates the process of blood clotting.

Deficiency of vitamin D in food, disorders of its absorption, calcium deficiency, as well as lack of exposure to the sun during rapid growth of children leads to rickets, osteomalacia in adults, pregnant women may show symptoms of tetany, disruption of bone calcification in newborns.

The 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 extracellular 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 shown a decrease in the incidence of respiratory tract infections with vitamin D supplementation.

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

Vitamin D has antiproliferative and pro-differentiation effects, which determine the oncoprotective effect of vitamin D. It is noted that the incidence of some tumors (breast cancer, colon cancer) is increased with low levels of vitamin D in the blood.

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

According to epidemiological studies, vitamin D deficiency is associated with the risk of metabolic disorders (metabolic syndrome and type 2 diabetes). Vitamin D receptors and metabolizing enzymes are expressed in arterial vessels, the heart and virtually all cells and tissues relevant to the pathogenesis of cardiovascular disease.

In animal models antiatherosclerotic effects, suppression of renin and prevention of myocardial damage, etc., have been shown. Low levels of vitamin D in humans are associated with adverse cardiovascular risk factors such as diabetes, dyslipidemia, arterial hypertension, and are associated with the risk of cardiovascular accidents, including strokes.

In studies in experimental models of Alzheimer’s disease, vitamin D3 has been shown to reduce amyloid accumulation in the brain and improve cognitive function. In non-interventional studies in humans, the incidence of dementia and Alzheimer’s disease has been shown to increase with low vitamin D levels and low dietary intake of vitamin D. There has been a worsening of cognitive function and the incidence of Alzheimer’s disease at low levels of vitamin D.

Pharmacokinetics

Intake. Water solution of colecalciferol is absorbed better than oil solution (this is important when used in premature infants, since this category of patients has insufficient production and intestinal flow of bile, which impairs absorption of vitamins in the form of oil solutions).

After oral administration, colecalciferol is quickly absorbed from the distal small intestine, enters the lymphatic system, enters the liver and the general bloodstream.

Distribution. In the blood it binds with α2-globulins and partially with albumin. Colecalciferol accumulates in the liver, bones, skeletal muscles, kidneys, adrenal glands, myocardium, adipose tissue.

The maximum concentration in the tissue is reached after 4-5 hours, after this time it decreases slightly, remaining constant for a long time.

Cumulative. Passes through the placental barrier and into the breast milk.

Metabolism.

Biotransformation occurs in the liver and kidneys: In the liver, colecalciferol is converted to the inactive metabolite calcifediol (25-dihydrocolecalciferol); in the kidneys, it is converted from calcifediol to the active metabolite calcitriol (1,25-dihydroxycolecalciferol) and the inactive metabolite 24,25-dihydroxycolecalciferol. It is subject to intestinal-hepatic recirculation.

Excretion. The drug is excreted mainly with the bile and a small amount with the kidneys.

Indications

Prevention of vitamin D deficiency and diseases associated with its deficiency (rickets, osteomalacia).
Treatment of rickets.
Complex therapy of osteoporosis of various origins.

Pharmacological effect

Pharmacodynamics

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

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

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 muscle tone of skeletal muscles, myocardial function, promotes nervous stimulation, and regulates the process of blood clotting.

Lack of vitamin D in food, impaired absorption, calcium deficiency, as well as insufficient exposure to the sun during the period of rapid growth of a child leads to rickets, in adults – to osteomalacia, pregnant women may experience symptoms of tetany, disruption of the calcification processes of the bones of newborns.

An increased need for vitamin D occurs in women during menopause, as they often develop osteoporosis due to hormonal imbalances. 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 regulating the division of T-helper lymphocytes and the differentiation of B-lymphocytes. A number of studies have noted a decrease in the incidence of respiratory tract infections with vitamin D supplementation.

It has been shown that vitamin D is an important part of the homeostasis of the immune system: it prevents autoimmune diseases (type 1 diabetes, multiple sclerosis, rheumatoid arthritis, inflammatory bowel diseases, etc.).

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

Vitamin D is involved in the regulation of carbohydrate and fat metabolism by influencing the synthesis of IRS1 (insulin receptor substrate 1; participates in the intracellular pathways of the insulin receptor signal), IGF (insulin-like growth factor; regulates the balance of adipose and muscle tissue), PPAR-σ (activated peroxisome proliferator receptor, type σ; 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 virtually all cells and tissues relevant to the pathogenesis of cardiovascular disease.

Animal models show anti-atherosclerotic effects, renin suppression and prevention of myocardial damage, etc. Low levels of vitamin D in humans are associated with unfavorable risk factors for cardiovascular pathology, such as diabetes mellitus, dyslipidemia, arterial hypertension, and are associated with the risk of cardiovascular accidents, including strokes.

Studies in experimental models of Alzheimer’s disease showed that vitamin D3 reduced amyloid accumulation in the brain and improved cognitive function. Non-interventional human studies have shown that the incidence of dementia and Alzheimer’s disease increases with low vitamin D levels and low dietary intake of vitamin D. Cognitive function and the incidence of Alzheimer’s disease have been impaired with low vitamin D levels.

Pharmacokinetics

Suction. An aqueous solution of colecalciferol is absorbed better than an oil solution (this is important when used in premature infants, since in this category of patients there is insufficient production and flow of bile into the intestines, which impairs the absorption of vitamins in the form of oil solutions).

After oral administration, colecalciferol is rapidly absorbed from the distal small intestine, enters the lymphatic system, enters the liver and the general bloodstream.

Distribution. In the blood it binds to α2-globulins and partially to albumins. Colecalciferol accumulates in the liver, bones, skeletal muscles, kidneys, adrenal glands, myocardium, and adipose tissue.

The maximum concentration in tissues is reached after 4-5 hours, after which it decreases slightly, remaining at a constant level for a long time.

Cumulates. Penetrates through the placental barrier and into breast milk.

Metabolism.

Biotransformation occurs in the liver and kidneys: in the liver, colecalciferol is converted into the inactive metabolite calcifediol (25-dihydrocolecalciferol), in the kidneys, from calcifediol it is converted into the active metabolite calcitriol (1,25-dihydroxycolecalciferol) and the inactive metabolite 24,25-dihydroxycolecalciferol. Subject to enterohepatic recirculation.

Excretion. The drug is excreted mainly through bile and a small amount through the kidneys.

Special instructions

Avoid overdose.

When taking the drug, the amount of vitamin D and calcium obtained from food and other medications should be taken into account.

Too high doses of vitamin D3, used over a long period of time, or shock doses can cause chronic hypervitaminosis D3.

High doses of calcium should not be taken at the same time as vitamin D3.

The drug should be used with caution in patients with impaired urinary excretion of calcium and phosphate, during treatment with benzothiadiazine derivatives and in immobilized patients (risk of developing hypercalcemia and hypercalciuria). In such patients, calcium concentrations in blood plasma and urine should be monitored.

Vitamin D3 should not be taken if you have pseudohypoparathyroidism, as in this disease the need for vitamin D may be reduced, which may lead to a risk of long-term overdose.

The main clinical manifestations of mild rickets include nervous excitability, anxiety, flinching at a sharp sound, a flash of light, sleep rhythm disturbances, superficial “anxious” sleep, sweating, itchy skin, baldness of the back of the head, pliability of the edges of the large fontanel.

The presence of visible deformations of bone tissue is characteristic of moderate and severe rickets, which, as a rule, require hospitalization and complex therapy prescribed by a doctor based on the results of the examination.

Repeated courses of therapy for osteoporosis are possible on the recommendation of a doctor, depending on the results of assessing markers of bone metabolism and calcium metabolism.

If the doctor has prescribed a longer treatment than recommended in the instructions, then you should regularly (every three months of therapy) determine the concentration of calcium in the blood serum and urine, and also assess kidney function by measuring the concentration of creatinine in the blood serum.

If necessary, the dose can be adjusted by the doctor in accordance with the concentration of calcium in the blood serum.

In case of hypercalcemia or signs of renal impairment, the dose of the drug should be reduced or treatment should be suspended. If the concentration of calcium in the urine exceeds 7.5 mmol/24 hours (300 mg/24 hours), it is recommended to reduce the dose of the drug or suspend treatment.

Impact on the ability to drive vehicles and machinery

There are no data on the possible effect of the drug on the ability to drive vehicles and machines.

Active ingredient

Colecalciferol

Composition

1 ml:

colecalciferol (Vit. D) 15000 IU (0.375 mg)

Excipients:

propylene glycol – 100 mg,

macrogol glyceryl hydroxystearate – 50 mg,

methyl parahydroxybenzoate – 1 mg,

sodium saccharinate – 0.7 mg,

anise flavor – 0.7 mg,

sodium hydrogen phosphate dihydrate – 3 mg,

anhydrous citric acid – 0.6 mg,

water for d/i – up to 1 ml.

Pregnancy

During pregnancy, the drug should not be used in doses exceeding those recommended for the prevention of vitamin D deficiency (see section “Method of administration and dosage”), due to the possibility of teratogenic effects in case of overdose.

Vitamin D3 should be prescribed with caution to women during breastfeeding, since the drug taken in high doses by the mother can cause overdose symptoms in the child.

When using the drug during pregnancy and breastfeeding, it is necessary to take into account the intake of vitamin D from other sources; the daily dose of vitamin D should not exceed 600 IU.

Contraindications

Hypersensitivity to colecalciferol and/or to any of the excipients in the drug.
Vitamin D hypervitaminosis.
Increased concentration of calcium in the blood (hypercalcemia), increased excretion of calcium in the urine (hypercalciuria), urolithiasis (formation of calcium oxalate stones), renal osteodystrophy with hyperphosphatemia, pseudohypoparathyroidism.
Sarcoidosis.
Acute and chronic diseases of the liver and kidneys, renal failure.
Active form of pulmonary tuberculosis.
Children up to 4 weeks of age.

With caution

In patients in a state of immobilization.
In patients taking thiazide diuretics, as well as in patients with cardiovascular diseases taking cardiac glycosides (see section “Interaction with other drugs”).
During pregnancy and breastfeeding (see section “Use during pregnancy and breastfeeding”).
In infants with a predisposition to early overgrowth of fontanelles (when the size of the anterior crown is small from birth).
When taking additional amounts of vitamin D and calcium (for example, as part of other drugs), in case of impaired urinary excretion of calcium and phosphate, during treatment with benzothiadiazine derivatives and in immobilized patients (risk of developing hypercalcemia and hypercalciuria) (see section “Special Instructions”).
In patients with the following concomitant diseases: atherosclerosis, heart failure, organic heart disease, granulomatosis, hyperphosphatemia, phosphate nephrolithiasis, gastrointestinal diseases, gastric and duodenal ulcers, hypothyroidism.
If you have one or more of the listed diseases and conditions, you should consult your doctor before taking the drug.

Side Effects

The frequency of adverse reactions has not been determined.
Metabolic and nutritional disorders: hypercalcemia and hypercalciuria, decreased appetite.
Nervous system disorders: headache.
Cardiac disorders: arrhythmias.
Vascular disorders: increased blood pressure.
Disorders of the respiratory system, chest and mediastinal organs: exacerbation of the tuberculosis process in the lungs.
Gastrointestinal disorders: constipation, flatulence, nausea, abdominal pain or diarrhea.
Skin and subcutaneous tissue disorders: hypersensitivity reactions such as itching, skin rash and urticaria.
Musculoskeletal and connective tissue disorders: arthralgia, myalgia.
Renal and urinary tract disorders: renal dysfunction, polyuria.

If undesirable reactions occur, you should consult a doctor.

Interaction

Antiepileptic drugs (especially phenytoin and phenobarbital, primidone), rifampicin, cholestyramine reduce the reabsorption of vitamin D3.

Use simultaneously with thiazide diuretics increases the risk of developing hypercalcemia. In such cases, it is necessary to constantly monitor the concentration of calcium in the blood.

With hypervitaminosis of vitamin D3, it is possible to enhance the effect of cardiac glycosides and increase the risk of arrhythmia due to the development of hypercalcemia (monitoring the concentration of calcium in the blood, an electrocardiogram, as well as adjusting the dose of cardiac glycoside are advisable).

Concomitant therapy with corticosteroids may reduce the effectiveness of vitamin D3.

Long-term use of antacids containing aluminum and magnesium in combination with vitamin D3 may increase the concentration of aluminum and magnesium in the blood and, as a result, the toxic effect of aluminum on bone tissue and hypermagnesemia in patients with renal failure.

Cholestyramine, colestipol and mineral oils reduce the absorption of fat-soluble vitamins in the gastrointestinal tract and require an increase in their dose.

Concomitant use of benzodiazepines increases the risk of hypercalcemia.
Drugs containing high concentrations of calcium and phosphorus increase the risk of developing hyperphosphatemia.

When used simultaneously with sodium fluoride, the interval between doses should be at least 2 hours; with oral forms of tetracyclines – at least 3 hours.

Concomitant use with other vitamin D analogues increases the risk of developing vitamin D hypervitaminosis.

Ketoconazole can inhibit both the biosynthesis and catabolism of 1,25(OH)2-colecalciferol.

Vitamin D is an antagonist of drugs used for hypercalcemia: calcitonin, etidronate, pamidronate, plicamycin, gallium nitrate.

Isoniazid and rifampicin can reduce the effect of the drug due to an increase in the rate of biotransformation.
Vitamin D3 does not interact with food.

Overdose

Symptoms of acute vitamin D3 overdose:

early manifestations (due to hypercalcemia) – constipation or diarrhea, dry oral mucosa, headache, thirst, Pollakiuria, nocturia, polyuria, anorexia, metallic taste in the mouth, nausea, vomiting, general weakness and fatigue, hypercalcemia, hypercalciuria, dehydration;

late manifestations – bone pain, cloudiness of urine (appearance of hyaline casts in the urine, proteinuria, leukocyturia), increased blood pressure, skin itching, photosensitivity of the eyes, conjunctival hyperemia, arrhythmia, drowsiness, myalgia, nausea, vomiting, pancreatitis, gastralgia, weight loss, rarely – psychosis (mental changes) and mood changes.

Symptoms of chronic overdose of vitamin D3 (when taken for several weeks or months for adults in doses of 20000-60000 IU / day, children – 2000-4000 IU / day): calcification of soft tissues, kidneys, lungs, blood vessels, arterial hypertension, renal and chronic heart failure (these effects most often occur when associated with hypercalcemia hyperphosphatemia), growth disturbance in children (long-term use at a dose of 1800 IU/day).

Treatment: if the above symptoms appear, you should stop using the drug and consult a doctor.

A diet low in calcium (for several weeks), consumption of large amounts of fluid, forced diuresis using furosemide, electrolytes, as well as the administration of glucocorticosteroids and calcitonin are indicated.

If the kidneys are functioning properly, the plasma calcium concentration can be significantly reduced by infusion of an isotonic sodium chloride solution (3-6 liters over 24 hours) with the addition of furosemide and, in some cases, also sodium edetate at a dose of 15 mg/kg/h, while continuously monitoring the plasma calcium concentration and electrocardiogram data.

With oligoanuria, on the contrary, hemodialysis (dialysate without calcium) is necessary. A specific antidote is unknown.

To prevent overdose, in some cases it is recommended to monitor the concentration of calcium in the blood.

Functional features

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

T1/2 is several days. Excreted in urine and feces.

If the function is impaired, T1/2 may increase.

Penetrates through the placental barrier. Excreted in breast milk.

Storage conditions

At a temperature not exceeding 25 °C.
Keep out of the reach of children.

Shelf life

3 years.

Manufacturer

Grotex LLC, Russia