DeTriFerol (Drops) Instructions for Use

Marketing Authorization Holder

Grotex, LLC (Russia)

ATC Code

A11CC05 (Colecalciferol)

Active Substance

Colecalciferol (Rec.INN registered by WHO)

Dosage Form

DeTriFerol

Oral drops (with anise flavor, with banana flavor, with cherry flavor, with orange flavor) 15000 IU/1 ml: 10 ml, 15 ml, 20 ml, 25 ml, or 30 ml bottle

Dosage Form, Packaging, and Composition

Oral drops, with anise flavor, with banana flavor, with cherry flavor, with orange flavor in the form of a transparent or slightly opalescent, colorless or weakly colored liquid with a characteristic odor.

Excipients: propylene glycol – 100 mg, macrogol glyceryl hydroxystearate – 50 mg, methylparaben – 1 mg, sodium saccharin – 0.7 mg, anise flavor, banana flavor, cherry flavor or orange flavor – 0.7 mg, sodium phosphate dibasic dihydrate – 3 mg, anhydrous citric acid – 0.6 mg, purified water – up to 1 ml.

10 ml – colored glass bottles^× (1) – cardboard boxes.
15 ml – colored glass bottles^× (1) – cardboard boxes.
20 ml – colored glass bottles^× (1) – cardboard boxes.
25 ml – colored glass bottles^× (1) – cardboard boxes.
30 ml – colored glass bottles^× (1) – cardboard boxes.

^× with a dropper cap and a screw cap with or without a child-resistant mechanism.

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

Vitamin D₃ is an active anti-rachitic factor. The most important function of vitamin D₃ is the regulation of 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 skeletal muscle tone, myocardial function, promotes nerve impulse conduction, and regulates the blood clotting process.

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

An increased need for vitamin D occurs in women during menopause, since 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 regulating 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 cancer-protective effect of vitamin D. It has been noted that the incidence of some 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; 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 effects, 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 studies in humans, it was shown that the incidence of dementia and Alzheimer’s disease increases against the background of low levels of vitamin D and low dietary intake of vitamin D. A deterioration in cognitive function and the 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 of bile production and entry into the intestine, which impairs the absorption of vitamins in the form of oil solutions).

After oral administration, Colecalciferol is rapidly absorbed from the distal part of the small intestine, enters the lymphatic system, reaches the liver and the systemic circulation.

Distribution

In the blood, it binds to α₂-globulins and partially to albumin. Colecalciferol accumulates in the liver, bones, skeletal muscles, kidneys, adrenal glands, myocardium, and adipose tissue. C_max in tissues is reached after 4-5 hours, after which it decreases somewhat, remaining at a constant level for a long time. It cumulates. Penetrates 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. It undergoes enterohepatic recirculation.

Excretion

It is excreted mainly with bile and a small amount – by the kidneys.

Indications

• Prevention of vitamin D deficiency;
• Prevention and treatment of rickets;
• Complex treatment of osteoporosis, including postmenopausal.

ICD codes

Dosage Regimen

Orally.

The drug should be taken in a spoonful of liquid.

Prophylactic doses

Full-term newborns from 4 weeks of life to 2-3 years with proper care and sufficient exposure to fresh air: 500 IU per day.

Premature infants from 4 weeks of life, twins, infants living in poor conditions 1000-1500 IU (2-3 drops) per day.

During the summer, the dose can be limited to 500 IU per day.

In adults without malabsorption: 500 IU per day.

In adult patients with malabsorption syndrome: 3000-5000 IU per day.

Pregnant women daily dose of 500 IU for the entire period of pregnancy, or 1000 IU per day, starting from the 23rd week of pregnancy.

In the postmenopausal period 500-1000 IU per day.

Therapeutic doses

For rickets 1000-5000 IU daily, depending on the severity of rickets (I, II or III) and the course variant, for 4-6 weeks, under careful monitoring of the clinical condition and investigation of biochemical parameters (calcium, phosphorus, alkaline phosphatase) in blood and urine. Start with 1000 IU for 3-5 days. Then, with good tolerance, the dose is increased to an individual therapeutic dose (most often 3000 IU).

A dose of 5000 IU is prescribed only for severe bone changes.

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

Treatment is carried out until a clear therapeutic effect is achieved, followed by a switch to a prophylactic dose of 500-1500 IU per day.

In the complex treatment of postmenopausal osteoporosis 500-1000 IU per day.

The dose is usually prescribed taking into account the amount of vitamin D coming from food.

Adverse Reactions

The frequency of adverse reactions is not determined.

Metabolism and nutrition disorders hypercalcemia and hypercalciuria, decreased appetite.

Nervous system disorders headache.

Cardiac disorders arrhythmias.

Vascular disorders increased blood pressure.

Respiratory, thoracic and mediastinal disorders exacerbation of the tuberculous 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 disorders renal function impairment, polyuria.

If adverse reactions occur, the patient should consult a doctor.

Contraindications

• Hypersensitivity to colecalciferol and/or to any of the excipients in the drug;
• Hypervitaminosis D;
• 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 under 4 weeks of age.

With caution

Intake of additional amounts of vitamin D and calcium (for example, as part of other drugs), in case of impaired excretion of calcium and phosphates in the urine, with simultaneous use of thiazides, cardiac glycosides (especially digitalis glycosides), benzothiadiazine derivatives, in patients with atherosclerosis, in immobilized patients, during pregnancy and 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 D should not be taken in high doses due to the possibility of a teratogenic effect in case of overdose.

The recommended doses of the drug should not be exceeded, as hypercalcemia may develop, which can lead to delayed mental and physical development of the fetus.

During breastfeeding, vitamin D should be prescribed with caution, since the drug taken by the mother in high doses can cause symptoms of overdose in the child.

Use in Hepatic Impairment

Contraindication: acute and chronic liver diseases.

Use in Renal Impairment

Contraindication: acute and chronic kidney diseases, renal failure.

Pediatric Use

Contraindicated for use in children under 4 weeks of age.

Geriatric Use

Use with caution in elderly patients to avoid the risk of exacerbation of chronic diseases.

Special Precautions

Overdosing should be avoided. When other drugs containing Colecalciferol are prescribed simultaneously, this dose of colecalciferol should be taken into account. Additional use of colecalciferol or calcium should only be carried out under medical supervision. The use of high doses of vitamin D₃ 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 individually by a doctor and each time subjected to correction during periodic examinations, especially in the first months of life. It is necessary to control the concentration of calcium in the blood and urine.

The drug should not be used for pseudohypoparathyroidism, since in the phase of normal sensitivity to colecalciferol, the need for colecalciferol may decrease, which leads to the risk of delayed overdose. In such cases, it is better to use active metabolites of vitamin D, which allow more precise dose adjustment.

The drug should be taken with caution in patients with impaired excretion of calcium and phosphates in the urine, when treated with benzothiazidine derivatives and in immobilized patients (risk of developing hypercalcemia and hypercalciuria). In such patients, the concentration of calcium in blood plasma and urine should be monitored.

During long-term treatment with colecalciferol, the concentration of calcium in blood plasma and urine should be monitored, and renal function should be assessed by measuring serum creatinine concentration.

This is especially important for elderly patients and during concomitant treatment with cardiac glycosides and diuretics.

Effect on ability to drive vehicles and mechanisms

Data on the possible effect of the drug on the ability to drive vehicles and mechanisms are absent.

Drug Interactions

Concomitant use of anticonvulsant drugs (such as phenytoin) or barbiturates (and possibly other drugs that induce liver enzymes) may reduce the effectiveness of colecalciferol by increasing the rate of biotransformation of colecalciferol into inactive metabolites.

Concomitant therapy with corticosteroid drugs may reduce the effectiveness of colecalciferol.

Oral intake of colecalciferol may enhance the therapeutic effect and toxic potential of digitalis and other cardiac glycosides (risk of arrhythmia) due to the development of hypercalcemia. Careful medical supervision, monitoring of ECG parameters and calcium levels in blood plasma and urine, and, if necessary, adjustment of the dose of cardiac glycosides is required.

In case of concomitant therapy with thiazide diuretics, which reduce the excretion of calcium in the urine, it is recommended to monitor the calcium content in the blood serum and urine.

Concomitant treatment with ion-exchange resins (such as cholestyramine), orlistat preparations or laxatives (such as paraffin oil) may reduce the absorption of colecalciferol in the digestive tract.

Concomitant use of rifampicin and isoniazid may reduce the effectiveness of the drug due to an increase in the rate of biotransformation of colecalciferol.

Against the background of simultaneous use of antacids containing aluminum and colecalciferol, the concentration of magnesium in the blood may increase.

Against the background of simultaneous use of antacids containing aluminum and colecalciferol, the concentration of aluminum in the blood may increase, which increases the risk of toxic effects of aluminum.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

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.