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

Active ingredient

Composition

1 ml:

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

Excipients:

propylene glycol – 100 mg,

macrogoal glyceryl hydroxystearate – 50 mg,

methyl parahydroxybenzoate – 1 mg,

sodium saccharinate – 0.7 mg,

anise flavoring – 0.7 mg,

sodium hydrophosphate dihydrate – 3 mg,

citric acid anhydrous – 0.6 mg,

d/i water – up to 1 ml.

How to take, the dosage

Oral.
The drug is taken in a spoonful of liquid.
1 drop contains about 500 ME of vitamin D3.

Prevention of rickets:
Premature infants from 4 weeks of life – 1 drop (500 ME) per day;
Premature infants from 4 weeks of life – 2 drops (1000 ME) per day during the first year of life, then 1 drop (500 ME) per day.
The drug should be used during the first two years of the child’s life during the periods of low insolation (especially in winter).

The treatment of rickets:
If there are no skeletal deformations (slight degree of rickets) – 2-3 drops (1000-1500 ME) a day and the treatment is continued for 30 days.
In case of bone deformations typical for medium and severe rickets – 4-8 drops (2000-4000 ME) per day, to be continued for 30-45 days. The preparation’s dose and duration of therapy depend on severity of the changes and are determined by the doctor (see section “Special indications”).

Prevention of vitamin D deficiency and diseases connected with its insufficiency (osteomalacia):
1 drop (500 ME) per day during the whole period of vitamin D deficiency. The minimum duration of the course of prophylaxis is 1 month.

In the complex treatment of osteoporosis:
In 1-2 drops (500-1000 ME) per day for 3 months. Repeated courses of therapy are possible on the recommendation of a physician, depending on the results of the evaluation of markers of bone metabolism and calcium metabolism (see section “Special indications”).

Interaction

Antiepileptic agents (especially phenytoin and phenobarbital, primidone), rifampicin, colestiramine reduce reabsorption of vitamin D3.

Simultaneous use with thiazide diuretics increases the risk of hypercalcemia. In these cases the calcium concentration in blood should be continuously monitored.

In hypervitaminosis of vitamin D3 the enhancement of cardiac glycosides action and the increase of risk of arrhythmia caused by hypercalcemia are possible (it is reasonable to monitor the calcium concentration in blood and electrocardiogram, and also to correct the cardiac glycoside dose.)

Concomitant therapy with glucocorticosteroids may decrease the efficiency of vitamin D3.

Prolonged use of antacids containing aluminum and magnesium in combination with vitamin D3 may increase the concentration of aluminum and magnesium in the blood and, consequently, the toxic effects of aluminum on bone tissue and hypermagnesemia in patients with renal insufficiency.

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

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

In concomitant use 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 analogues of vitamin D increases the risk of vitamin D hypervitaminosis.

Ketoconazole may inhibit both biosynthesis and catabolism of 1,25(OH)2-calciferol.

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

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

Special Instructions

Avoid overdose.

The amount of vitamin D and calcium taken with food and other medications must be taken into account when taking the drug.

High doses of vitamin D3 used for prolonged periods or shock doses can cause chronic hypervitaminosis of D3.

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

The drug should be used with caution in patients with impaired urinary calcium and phosphate excretion, when treated with benzothiadiazine derivatives and in immobilized patients (risk of hypercalcemia and hypercalciuria). In these patients the calcium concentration in plasma and urine should be monitored.

Vitamin D3 should not be taken in pseudohypoparathyroidism because in this disease the vitamin D requirement may be reduced, which could lead to the risk of long-term overdose.

The main clinical manifestations of mild rickets include nervous excitability, restlessness, startle at loud sounds and light flashes, sleep disturbances, restless sleep, sweating, itchy skin, baldness in the back of the head, and suppleness of the edges of the great fontanelle.

The presence of visible bone deformities is characteristic of moderate and severe rickets which, as a rule, require hospitalization and complex therapy prescribed by a physician after examination.

Renew courses of therapy for osteoporosis may be recommended by the doctor, depending on the results of the assessment of bone and calcium metabolism markers.

If a physician has prescribed a longer course of therapy than indicated, the serum calcium and urine calcium concentrations should be determined regularly (every three months of therapy), and renal function should be assessed by measuring serum creatinine concentrations.

If necessary, the dose can be adjusted by the physician according to the serum calcium concentration.

In case of hypercalcemia or signs of renal dysfunction, the dose should be reduced or the treatment should be stopped. If urinary calcium concentration exceeds 7.5 mmol/24 h (300 mg/24 h), it is recommended to reduce the dose of the drug or suspend treatment.

There are no data on possible effect of the drug on driving and operating ability.

Features

Calciferol is absorbed from the small intestine after oral administration.

T1/2 is several days. It is excreted with urine and feces.

The T1/2 may increase if impaired.

It penetrates the placental barrier. It is excreted with breast milk.

Contraindications

Side effects

Metabolic and nutritional disorders: hypercalcemia and hypercalciuria, decreased appetite.
Nervous system disorders: headache.
Cardiac disorders: arrhythmias.
Vascular disorders: increased blood pressure.
Respiratory system, chest and mediastinal organs: exacerbation of tuberculosis 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.

In case of adverse reactions, a physician should be consulted.

Overdose

Symptoms of acute vitamin D3 overdose:

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

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

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

Treatment: If the above symptoms occur, discontinue use and see a physician.

A low-calcium diet (for several weeks), increased fluid intake, forced diuresis with furosemide, electrolytes, and administration of glucocorticosteroids, calcitonin are indicated.

With proper renal function, plasma calcium concentration can be significantly reduced by infusion of isotonic sodium chloride solution (3-6 liters over 24 hours) with furosemide and, in some cases, also sodium edetate at a dose of 15 mg/kg/h, while continuous monitoring of plasma calcium concentration and electrocardiogram data.

In contrast, hemodialysis (dialysate without calcium) is necessary in oligoanuria. A specific antidote is not known.

To prevent overdose, blood calcium concentration control is recommended in some cases.

Pregnancy use

Similarities