Decristol capsules 20000 IU No. 20

Instructions for Decristol capsules 20000 IU No. 20

Composition

active ingredient: cholecalciferol;

1 soft capsule contains 20.0 mg of cholecalciferol (as a concentrate of 1.0 mIU/g (oil form)), which corresponds to 0.5 mg, or 20,000 IU, of vitamin D3;

Excipients: peanut oil, gelatin, glycerin 85%, medium chain triglycerides, purified water, alpha-tocopherol.

Dosage form

Soft capsules.

Main physicochemical properties: round, transparent, light yellow soft capsules.

Pharmacotherapeutic group

Vitamins. Vitamin D and analogues. Cholecalciferol. ATX code A11C C05.

Pharmacological properties

Pharmacodynamics

Cholecalciferol (vitamin D3) is synthesized in the skin from 7-dehydrocholesterol under the influence of ultraviolet radiation and is converted to its biologically active form (1,25-hydroxycholecalciferol) in two hydroxylation steps: first in the liver (position 25), and then in the kidney tissues (position 1). Together with parathyroid hormone and calcitonin, 1,25-dihydroxycholecalciferol plays a significant role in regulating the balance of calcium and phosphate. In its biologically active form, vitamin D3 stimulates calcium absorption in the intestine, calcium penetration into osteoid and calcium release from bone tissue. In the small intestine, it promotes rapid and delayed calcium absorption. In addition, passive and active phosphate transport is stimulated. In the kidneys, it inhibits the excretion of calcium and phosphate by stimulating tubular resorption. The biologically active form of cholecalciferol directly inhibits the production of parathyroid hormone in the parathyroid glands. Parathyroid hormone secretion is further inhibited by increased calcium absorption in the small intestine under the action of biologically active vitamin D3.

The so-called vitamin D3, from the point of view of its formation, physiological regulation and mechanism of action, can be considered as a precursor of a steroid hormone. Cholecalciferol, in addition to its physiological production in the skin, can enter the body with food or as a drug. This latter method can cause overdose and intoxication, since the physiological production of vitamin D as synthesis in the skin is not inhibited.

Presence in nature and satisfaction of needs

The recommended daily intake of vitamin D for adults is 20 mcg, which corresponds to 800 IU per day. Healthy adults can meet their vitamin D needs through endogenous synthesis, provided there is sufficient sunlight. Obtaining vitamin D from food is of secondary importance, but may be important under certain critical conditions (climate, lifestyle).

Fish liver oil and fish are particularly rich in vitamin D, although small amounts are also found in meat, eggs, egg yolks, milk, dairy products, and avocados.

Signs of vitamin D deficiency

Signs of vitamin D deficiency may occur, for example, in premature infants, in infants who are exclusively breastfed for more than 6 months without calcium supplementation, or in children who are on a strict vegetarian diet. Rare causes of vitamin D deficiency in adults may include insufficient dietary intake, lack of sufficient ultraviolet radiation, malabsorption and digestion, cirrhosis of the liver, and renal failure.

In case of vitamin D deficiency, skeletal calcification does not occur (leading to rickets) or decalcification of bones occurs (leading to osteomalacia). Calcium and/or vitamin D deficiency causes a reversible increase in parathyroid hormone secretion. This secondary hyperparathyroidism increases bone metabolism, which can lead to bone fragility and fractures.

Pharmacokinetics

Absorption

Vitamin D in the amounts found in food is almost completely absorbed from food. It is absorbed together with dietary lipids and bile acids, and therefore administration of vitamin D with the main meal of the day may contribute to its better absorption.

Distribution and biotransformation

Metabolic conversion of cholecalciferol occurs in the liver by microsomal hydroxylase to form 25-hydroxycholecalciferol (25(OH)D3). It is then converted in the kidneys to 1,25-dihydroxycholecalciferol, which is the biologically active form.

After a single oral dose of cholecalciferol, the maximum serum concentration of 25(OH)D3 as the main storage form is reached after about a week. 25(OH)D3 is then slowly eliminated with an apparent serum half-life of about 50 days. After high doses of vitamin D, serum concentrations of 25-hydroxycholecalciferol may increase for several months. Hypercalcemia caused by overdose may persist for several weeks (see section 4.4).

Breeding

Metabolites bound to specific α-globin that circulate in the blood are excreted mainly with bile and feces.

Special patient groups

In cases of malabsorption, absorption is reduced and elimination of vitamin D3 is increased. Obese individuals have a reduced ability to maintain vitamin D3 levels during sun exposure and may require higher doses of oral vitamin D3 to correct the deficiency.

Indication

Treatment of clinically confirmed vitamin D deficiency in adults.

Prevention of vitamin D deficiency in high-risk patients.

As an adjunct to specific osteoporosis therapy in patients with vitamin D deficiency or at high risk of vitamin D deficiency.

Contraindication

Hypersensitivity to the active substance, peanut, soy or any other excipients contained in the medicinal product. Hypercalcemia. Hypercalciuria. Hypervitaminosis D. Pseudohypoparathyroidism (the need for vitamin D may be lower than during the period of normal sensitivity to the vitamin, with the risk of prolonged overdose). Nephrolithiasis (urinary stone disease). Renal failure. Sarcoidosis. Tuberculosis. Additional intake of vitamin D (may lead to overdose).

Interaction with other medicinal products and other types of interactions

Concomitant use of anticonvulsants (such as phenytoin and phenobarbital) or barbiturates (and possibly other drugs that induce liver enzymes) may lead to a reduction in the effect of vitamin D3 due to metabolic inactivation.

Rifampicin may reduce the effectiveness of cholecalciferol due to induction of liver enzymes.

Isoniazid may reduce the effectiveness of cholecalciferol due to inhibition of the metabolic activation of cholecalciferol.

Ion exchangers, laxatives, orlistat may reduce the absorption of vitamin D in the gastrointestinal tract.

The cytotoxic agent actinomycin and imidazole antifungals reduce the activity of vitamin D3 by inhibiting the conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol by renal enzymes to form 25-hydroxyvitamin D-1-hydrolase.

Glucocorticoids increase vitamin D metabolism, which may lead to decreased vitamin D effectiveness.

Concomitant administration of benzothiadiazine derivatives (thiazide diuretics) increases the risk of hypercalcemia due to decreased renal calcium excretion. Therefore, it is necessary to monitor the level of calcium in the blood plasma and urine.

The combination of Decristol® 20,000 IU with metabolites or analogues of vitamin D should be avoided. Simultaneous administration of vitamin D3 with metabolites or analogues of vitamin D is possible only as an exception and only with monitoring of serum calcium levels (increases the risk of toxic effects).

Oral vitamin D intake with concomitant use of cardiac glycosides may enhance the efficacy and toxicity of digitalis due to increased calcium levels (risk of cardiac arrhythmias). In such patients, regular ECG monitoring and monitoring of plasma and urinary calcium levels, as well as determination of digoxin or digitoxin concentrations, if possible, should be performed.

Concomitant use of the drug with antacids containing aluminum or magnesium may provoke aluminum toxicity on bones and hypermagnesemia in patients with renal failure.

Ketoconazole may reduce the biosynthesis and catabolism of 1,25(OH)2-cholecalciferol.

Concomitant use with drugs containing high doses of calcium and phosphorus increases the risk of hyperphosphatemia.

Vitamin D may antagonize drugs prescribed for hypercalcemia, such as calcitonin, etidronate, and pamidronate.

Application features

Decristol® 20,000 IU is not recommended for people who are prone to the formation of calcium-containing kidney stones.

Decristol® 20000 IU should be used with special caution in patients with impaired renal function during treatment with benzothiadiazine derivatives, as well as in immobilized patients (due to the risk of hypercalcemia, hypercalciuria). In such patients, it is necessary to monitor the level of calcium and phosphates. The risk of soft tissue calcification should be taken into account. In patients with severe renal failure, the normal metabolic transformation of cholecalciferol is impaired, and therefore other forms of vitamin D should be used (see section "Contraindications").

Decristol® 20000 IU should not be used in patients with sarcoidosis due to the risk of accelerated conversion of vitamin D to its active metabolites. In such patients, it is necessary to monitor the level of calcium in the blood plasma and urine.

When using the drug in an equivalent daily dose exceeding 1000 IU of vitamin D, it is necessary to monitor the level of calcium in the blood serum and urine, as well as to check the renal function by determining the concentration of creatinine in the blood serum. Such monitoring is especially important for elderly patients and during concomitant treatment with cardiac glycosides or diuretics (see section "Interaction with other medicinal products and other types of interactions"). This also applies to patients with a tendency to form calcium-containing kidney stones.

Before starting vitamin D treatment, a careful assessment of the patient's condition by the doctor is required and consideration is given to the additional amount of vitamin D that the patient consumes with certain foods.

Elderly (aged > 65 years)

A recent study in elderly people with a history of falls showed an increased risk of falls with monthly administration of 60,000 IU of vitamin D. Therefore, the use of Decristol® 20,000 IU in elderly people is recommended only after a careful benefit-risk analysis and only if there are clear indications. In this case, the dose should not exceed 24,000 IU per month (one capsule). For elderly patients with a history of falls, it is recommended to consider the possibility of daily administration of additional amounts of vitamin D.

For elderly people aged > 70 years

When treating with vitamin D with a loading dose protocol, serum 25(OH)D3 levels should also be monitored regularly. Treatment should be discontinued at levels ≥ 50 ng/mL.

This medicine contains peanut oil. If you are allergic to peanut or soya, do not take this medicine.

Ability to influence reaction speed when driving vehicles or other mechanisms

Decristol® 20000 IU has no or negligible influence on the ability to drive or use machines.

Use during pregnancy or breastfeeding

Pregnancy

During pregnancy, Decristol® 20,000 IU can be prescribed only if there are clear indications and only when it is absolutely necessary to eliminate vitamin D deficiency.

During pregnancy, vitamin D overdose should be avoided, as prolonged hypercalcemia can lead to a slowdown in the child's physical and mental development and the appearance of supravalvular aortic stenosis and retinopathy in the child.

Breast-feeding

Vitamin D and its metabolites are excreted in breast milk. No cases of overdose in breastfed infants have been observed. However, this should be taken into account when prescribing additional vitamin D to the child. It is not recommended to prescribe high-dose vitamin D treatment, for example, in capsules of 20,000 IU, to women who are breastfeeding.

Fertility

In animal studies of the effects of cholecalciferol on reproductive function and fertility, no effects were observed. The potential benefit-risk balance for humans remains unknown.

Method of administration and doses

Method of application.

For oral use.

Adults should take the capsule by swallowing it whole and drinking plenty of water, preferably during the main meal of the day.

Dosage.

The dosage of vitamin D depends on the severity of the disease and the patient's response to treatment. Depending on the needs, possibilities and choice of the patient, daily, weekly or monthly dosing regimens can be offered. Lower dosage forms (e.g. 400 IU, 500 IU, 800 IU and 1000 IU) are suitable for daily vitamin D supplementation, while higher dosage forms, e.g. 20,000 IU capsules, contain amounts corresponding to weekly and monthly vitamin D doses, which should be taken into account. The dosage is prescribed by the doctor in each individual case.

Some groups of patients are at higher risk of vitamin D deficiency and may require higher doses and monitoring of serum 25-hydroxycholecalciferol (25(OH)D3) concentrations:

persons in specialized institutions or hospitalized persons; dark-skinned persons; persons with limited effective sun exposure due to wearing protective clothing or constant use of sunscreens; patients with osteoporosis; persons with obesity; persons taking certain concomitant medications (e.g. anticonvulsants, glucocorticoids); persons who have recently been treated for vitamin D deficiency and who require maintenance therapy; patients with malabsorption, including inflammatory bowel disease and celiac disease.

Dosage recommendations:

Initial treatment for vitamin D deficiency:

40,000 IU per week for 6–12 weeks.

Treatment of vitamin D deficiency and maintenance of its levels:

from 60,000 to 120,000 IU per month for a period of up to 6 months.

Prevention of vitamin D deficiency:

20,000 IU per week regardless of initial level from November to April.

As an adjunct to specific osteoporosis therapy in patients with vitamin D deficiency or in patients at risk of vitamin D deficiency:

Adults and the elderly:

20,000 to 40,000 IU per month in combination with a calcium supplement, if needed.

Elderly people with a history of falls should avoid doses exceeding 24,000 IU per month (see also section “Special warnings and precautions for use”).

Patients with renal impairment/hypercalcemia

If hypercalcemia or signs of decreased renal function occur, the dose should be reduced or treatment discontinued. If hypercalciuria occurs (more than 7.5 mmol, corresponding to 300 mg of calcium per 24 hours), the dose should be reduced or treatment discontinued.

Children

The drug is not recommended for use in children and adolescents (under 18 years of age) due to the lack of data on the dosage regimen and the risk of choking when children take capsules. Instead, it is advisable to use drops or dissolvable tablets.

Overdose

Vitamin D3 regulates calcium and phosphate metabolism, and overdose causes hypercalcemia, hypercalciuria, renal calcifications, and bone damage, as well as changes in the cardiovascular system. Hypercalcemia occurs after the use of 50,000–100,000 IU of vitamin D3 per day.

Symptoms of overdose

Acute and chronic overdose of vitamin D3 can cause hypercalcemia, which can be persistent and life-threatening. Symptoms can be nonspecific and include cardiac arrhythmia, thirst, dehydration, adynamia, and impaired consciousness. In addition, chronic overdose can lead to calcium deposition in blood vessels and tissues.

In addition to increasing the phosphorus content in the blood serum and urine, overdose can also cause hypercalcemic syndrome, which subsequently leads to calcium deposition in the tissues and, in particular, in the kidneys (nephrolithiasis, nephrocalcinosis, renal failure), as well as in the blood vessels.

Symptoms of intoxication are not very characteristic and manifest as muscle weakness, loss of appetite, nausea, vomiting, initial frequent diarrhea, which is replaced by constipation, anorexia, shortness of breath, headache, myalgia, arthralgia, muscle weakness and constant drowsiness, arrhythmia, azotemia, polydipsia and polyuria, as well as (in the pre-terminal stage) dehydration, photosensitivity, pancreatitis, rhinorrhea, hyperthermia, decreased libido, conjunctivitis, hypercholesterolemia, increased transaminase activity, arterial hypertension, uremia. Common symptoms are pain in the muscles and joints.

Renal dysfunction develops with albuminuria, erythrocyturia and polyuria, increased potassium loss, hyposthenuria, nocturia and moderate increase in blood pressure.

In severe cases, corneal clouding is possible, less often - swelling of the optic nerve papilla, inflammation of the iris, up to the development of cataracts.

Kidney stones and calcifications in soft tissues such as blood vessels, heart, lungs, and skin may form.

Cholestatic jaundice rarely develops.

Characteristic biochemical abnormalities are hypercalcemia, hypercalciuria, and increased serum 25-hydroxycalciferol concentration.

Treatment. The appearance of symptoms of chronic vitamin D overdose may require forced diuresis, as well as the administration of glucocorticoids and calcitonin.

In the event of overdose, measures should be taken to eliminate the often chronic and potentially life-threatening hypercalcemia.

As a primary measure, vitamin D should be discontinued; normalization of calcium levels in hypercalcemia resulting from vitamin D intoxication takes several weeks.

Depending on the degree of hypercalcemia, a calcium-free or low-calcium diet may be used, and it is also recommended to drink plenty of fluids, forceful diuresis with furosemide, and administer glucocorticoids and calcitonin.

In normal renal function, calcium levels can be reduced with a high degree of certainty by infusion of isotonic sodium chloride solution (3–6 liters over 24 hours) with the addition of furosemide, in some cases, the administration of sodium edetate at a dose of 15 mg/kg body weight/hour is also recommended under constant monitoring of calcium levels and ECG. However, in oligoanuria, hemodialysis (using calcium-free dialysate) is necessary.

There is no known specific antidote.

Patients receiving long-term treatment with higher doses of vitamin D are advised to report symptoms of possible overdose (nausea, vomiting, initial frequent diarrhea followed by constipation, anorexia, dizziness, headache, myalgia, arthralgia, muscular weakness, drowsiness, azotemia, polydipsia, and polyuria).

Adverse reactions

As a rule, adverse reactions are not observed when taken in recommended doses.

In case of individual sensitivity to the drug, which is rare, or as a result of using very high doses over a long period, hypervitaminosis D may occur.

Adverse reactions are listed below for each system organ class by frequency of occurrence.

There have also been reports of rhinorrhea and hyperthermia.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions is very important. Healthcare professionals and patients should report any suspected adverse reactions via the national reporting system.

Expiration date

3 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C in a place protected from light and moisture. Keep out of the reach of children.

Packaging

10 capsules in a blister. 2 blisters in a pack.

Vacation category

According to the recipe.

Producer

mibe GmbH Arcnaymittel.

Location of the manufacturer and its business address

Münchenerstrasse 15, Brena, Saxony-Anhalt, 06796, Germany.