Fortedetrim capsules 10000IU, 30pcs

Composition

Capsules – 1 capsule:

• Active ingredient: colecalciferol 10000 IU (0.25 mg);
• excipients: refined safflower oil;
• capsule: gelatin, glycerol, purified water.

15 capsules in a PVC blister/PVDC and aluminum foil.

Pharmacological action

of Calcium-phosphorus metabolism regulator.

Pharmacokinetics

Suction

Colecalciferol (vitamin D3) when taken orally is almost completely absorbed (80%) in the small intestine. The maximum concentration in the tissues is reached after 4-5 hours, after which the concentration decreases slightly, remaining at a constant level for a long time. After a single oral use of colecalciferol, the maximum concentration in the blood serum of the main form is reached in about 7 days.

Distribution

Colecalciferol accumulates in the liver, bones, skeletal muscles, kidneys, adrenal glands, myocardium, and adipose tissue. The maximum concentration in the tissues is reached after 4-5 hours, after which the concentration decreases slightly, remaining at a constant level for a long time.

Undergoes intestinal-hepatic recirculation. Serum concentration of the inactive metabolite 25-hydroxycalciferol (25(OH)D3, calcidiol) may be increased for several months after taking large doses of colecalciferol. Hypercalcemia caused by an overdose can persist for several weeks.

Metabolism

Colecalciferol in blood plasma binds to alpha-2 globulins and partially to albumins and is transported to the liver, where microsomal hydroxylation occurs to form the inactive metabolite 25-hydroxycalciferol (25(OH)D3, calcidiol).

The concentration of calcidiol circulating in the blood is an indicator of the level of vitamin D in the body. Calcidiol undergoes repeated hydroxylation in the kidneys to form the dominant active metabolite 1,25 hydroxycolecalciferol (1,25 (OH) 2D3, calcitriol).

Elimination

of 25 (OH) D3 is slowly eliminated with a half-life of about 50 days. The main route of excretion of colecalciferol, as well as its metabolites, is bile (feces), and at least 2% of these substances are excreted by the kidneys. Colecalciferol crosses the placental barrier and enters breast milk.

Pharmacodynamics

Vitamin D3 is a naturally occurring form of vitamin D that is formed in humans in the skin when exposed to 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 TRPV6 ion channel genes (provides calcium absorption in the intestine), CALB1 (calbindin; provides calcium transport to the bloodstream), BGLAP (osteocalcin; provides bone mineralization and calcium homeostasis), SPP1 (osteopontin; regulates osteoclast migration), REN (renin; regulates blood pressure, being a component of the immune system). key element of the renin-angiotensin-aldosterone regulatory system), IGFBP (binding protein of insulin-like growth factor; enhances the action of insulin-like growth factor), FGF23 and FGFR23 (fibroblast growth factor 23; regulate the levels of calcium, phosphate anion, fibroblast cell division processes), TGFB1 (transforming growth factor beta-1; regulates the processes of cell division and differentiation of osteocytes, chondrocytes, fibroblasts and keratinocytes), LRP2 (LDL receptor-bound protein 2; mediates endocytosis of low-density lipoproteins), INSR (insulin receptor; provides the effects of insulin on any cell types).

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 regulates the excretion of calcium and phosphates by the kidneys.

The concentration of calcium ions in the blood causes the maintenance of skeletal muscle tone, myocardial function, promotes nervous excitement, and regulates the blood clotting process.

A lack of vitamin D in food, a violation of its absorption, a lack of calcium, as well as insufficient sun exposure during the rapid growth of the child leads to rickets, in adults – to osteomalacia, pregnant women may experience symptoms of tetany, violation of the processes of calcification of the bones of 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 extra-skeletal effects.

Vitamin D is involved in the functioning of the immune system by modulating cytokine levels and regulating T helper cell division and B cell differentiation. A number of studies have shown a reduction in the incidence of respiratory tract infections with vitamin D supplementation.

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

Vitamin D has antiproliferative and prodifferentiating effects, which determine the oncoprotective effect of vitamin D. It is noted that the frequency 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 (a substrate of the insulin receptor 1; participates in the intracellular pathways of insulin receptor signaling), IGF (insulin-like growth factor; regulates the balance of fat and muscle tissue), PPAR-δ (activated peroxisome proliferator 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 virtually all cells and tissues related to the pathogenesis of cardiovascular diseases.

Anti-atherosclerotic action, renin suppression and prevention of myocardial damage are shown in animal models. Low levels of vitamin D in humans are associated with unfavorable risk factors for cardiovascular diseases, such as diabetes mellitus, dyslipidemia, arterial hypertension, and are associated with the risk of cardiovascular disasters, including strokes.

Studies in experimental models of Alzheimer’s disease have shown that vitamin D3 reduced amyloid accumulation in the brain and improved cognitive function.

Non-conservative 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 were reported to be impaired when vitamin D levels were low.

Indications

Treatment and prevention of vitamin D deficiency and insufficiency and conditions caused by vitamin D deficiency in adults.

Use during pregnancy and lactation

The use of Fortedetrim during pregnancy and lactation is not recommended in these dosages due to exceeding the recommended daily dose of 1000 IU. During pregnancy and lactation, the use of colecalciferol preparations in lower doses, such as Aquadetrim, is recommended.

Contraindications

• Hypersensitivity to the Active ingredient or any of the excipients listed in the “Composition” section;
• Hypercalcemia and / or hypercalciuria;
• Urolithiasis (formation of calcium oxalate stones);
• Hypervitaminosis D;
• Pseudohypoparathyroidism;
• Sarcoidosis.
• Active form of pulmonary tuberculosis;
• Severe renal failure;
• Pregnancy and breast-feeding period (in these dosages);
• Children under 18 years of age.

With caution

Taking additional amounts of colecalciferol and calcium (for example, as part of other drugs), with impaired excretion of calcium and phosphates in the urine, in the treatment of immobilized patients, while taking thiazides, cardiac glycosides (especially digitalis glycosides), benzothiadiazine derivatives, in patients with atherosclerosis.

Side effects

Classification of the frequency of adverse reactions: infrequent (≥1/1000 –

Immune system disorders: Unknown-Hypersensitivity reactions, such as angioedema or laryngeal edema.

Metabolic and nutritional disorders: Infrequently-Hypercalcemia or hypercalciuria.

Gastrointestinal disorders: Unknown-Constipation, bloating, nausea, abdominal pain, diarrhea.

Skin and subcutaneous tissue disorders: Rarely-Pruritus, rash, urticaria.

Interaction

Concomitant use of anticonvulsant medications (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 glucocorticosteroids may reduce the effectiveness of colecalciferol.

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

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

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

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

When taking antacids containing magnesium and colecalciferol at the same time, the concentration of magnesium in the blood may increase.

Concomitant use of aluminum-containing antacids and colecalciferol may increase the concentration of aluminum in the blood, which increases the risk of toxic aluminum exposure.

How to take, course of use and dosage

Capsules should be taken orally, swallowed whole and washed down with water, preferably during the main meal.

Treatment of vitamin D deficiency (level 25 (OH)D ≤ 20 ng / ml) in adults-8000 IU (4 capsules 2000 IU or 2 capsules 4000 IU) per day for 8 weeks.

Treatment of vitamin D deficiency (level 25 (OH)D-20-29 ng / ml) in adults-8000 IU (4 capsules 2000 IU or 2 capsules 4000 IU) per day for 4 weeks.

Maintaining normal levels of vitamin D (level 25 (OH))D ≥30 ng / ml) in adults-2000 IU (1 capsule) per day.

During long-term treatment, blood and urine calcium concentrations should be regularly measured, and renal function should be determined by measuring serum creatinine. If necessary, the dose should be adjusted to take into account the concentration of calcium in the blood serum.

Liver diseases

No dose adjustment is required.

Impaired renal function

The drug should not be used in patients with severe renal insufficiency.

Overdose

Symptoms

The intoxication threshold for colecalciferol varies between 40,000 and 100,000 IU / day for 1-2 months in adults with normal parathyroid function. Newborns and young children may be sensitive to much lower concentrations.

Acute and chronic overdose can lead to increased serum and urinary phosphorus levels, and hypercalcemia, which can be persistent and potentially life-threatening.

Typical changes in biochemical parameters include hypercalcemia, hypercalciuria, and increased serum levels of 25-hydroxycalciferol (25 (OH) D3, calcidiol). Chronic colecalciferol overdose can lead to calcium deposition in tissues and parenchymal organs, primarily in the kidneys (urolithiasis, nephrocalcinosis) and blood vessels.

Symptoms are general and manifest as nausea, vomiting, also initially as diarrhea, later as constipation, loss of appetite, weakness, headache, muscle and joint pain, muscle weakness, azotemia, persistent drowsiness, polydipsia and polyuria, and, in the final stage, as dehydration of the body. An overdose of colecalciferol can cause ECG changes, cardiac arrhythmias, pancreatitis, and kidney failure.

Overdose treatment

First of all, you need to stop taking colecalciferol. Hypercalcemia caused by colecalciferol overdose takes several weeks to resolve. Depending on the degree of hypercalcemia, a low-calcium or completely calcium-free diet, high fluid intake, forced diuresis with furosemide, as well as glucocorticosteroids and calcitonin are prescribed as treatment measures.

If renal function is preserved, the calcium concentration can be significantly reduced by infusion of an isotonic solution of sodium chloride (3-6 liters per 24 hours) with the addition of furosemide and, in some cases, also sodium edetate at a dose of 15 mg / kg / h, while monitoring the calcium level and ECG data.

Phosphate infusion should not be used to reduce hypercalcemia caused by colecalciferol overdose, as there is a risk of developing metastatic calcification. In case of oligoanuria, hemodialysis (dialysate without calcium) should be performed.

There is no specific antidote.

It is recommended that patients pay attention to the symptoms of possible overdose with prolonged use of high doses of the drug (nausea, vomiting, initially-diarrhea, later-constipation, loss of appetite, weakness, headache, muscle and joint pain, muscle weakness, persistent drowsiness, polydipsia and polyuria).

Special instructions

If other medications containing colecalciferol are prescribed at the same time, the dose of colecalciferol contained in Fortedetrim should be considered. Additional use of colecalciferol or calcium should only be carried out under the supervision of a doctor.

In this case, it is necessary to monitor the concentration of calcium in the blood serum and urine. Calcium and phosphate metabolism should be monitored in patients with renal insufficiency treated with Fortedetrim. The drug should not be used in patients with a predisposition to calcium nephrourolithiasis.

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

The drug should not be taken in patients with pseudohypoparathyroidism, since in the phase of normal sensitivity to colecalciferol, the need for colecalciferol may decrease, which leads to the risk of developing a delayed overdose. In such cases, it is better to use active metabolites of vitamin D, which allow you to more accurately adjust the dosage.

During long-term treatment with Fortedetrim, the concentration of calcium in blood plasma and urine should be monitored, as well as renal function should be evaluated by measuring the concentration of serum creatinine. This is especially important for elderly patients and for concomitant treatment with cardiac glycosides or diuretics.

If hypercalcemia develops during treatment with Fortedetrim (blood calcium concentration exceeds 7.5 mmol/24 h (300 mg/24 h)) or there are signs of impaired renal function, the dose of the drug should be reduced or suspended.

Influence on the ability to drive motor vehicles and manage mechanisms

Studies on the effect on the ability to drive a vehicle and work with mechanisms have not been conducted.

Active ingredient

Colecalciferol

Conditions of release from pharmacies

By prescription

Dosage form

Capsules