Instructions for use Decristol Drops solution 20,000 IU/ml oral drops 10 ml bottle
Composition
active ingredient: cholecalciferol;
1 ml of solution (40 drops) contains 0.5 mg of cholecalciferol (corresponding to 20,000 IU of vitamin D3). 1 drop contains approximately 500 IU of vitamin D3.
excipients: medium chain triglycerides, butylhydroxytoluene.
Dosage form
Oral drops, solution.
Main physicochemical properties: transparent, colorless to pale yellow oily solution.
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 into its biologically active form (1,25-hydroxycholecalciferol) as a result of two stages of hydroxylation: 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 the absorption of calcium in the intestine, the penetration of calcium into osteoid and the release of calcium from bone tissue. In the small intestine, it promotes rapid and delayed absorption of calcium. 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 (PTH) in the parathyroid glands. PTH 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 there is no physiological inhibition of vitamin D synthesis in the skin.
Presence in nature and satisfaction of needs
The vitamin D requirement 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. Dietary intake of vitamin D is of secondary importance, but may be important under certain critical conditions (climate, lifestyle).
Fish 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
- Prevention of nutritional rickets in infants, newborns and premature children.
- Prevention of vitamin D deficiency in adults and children with identified risk factors.
- Treatment of vitamin D deficiency in adults and children.
- As an adjunct to specific osteoporosis therapy in patients with vitamin D deficiency or at risk of vitamin D insufficiency.
Contraindication
- Hypersensitivity to the active substance or to any of the excipients listed in the "Composition" section.
- Hypercalcemia.
- Hypercalciuria.
- Vitamin D hypervitaminosis.
- Pseudohypoparathyroidism (vitamin D requirements may be lower than during periods of normal vitamin sensitivity, there is a risk of prolonged overdose).
- Nephrolithiasis (urinary stone disease).
- Renal failure of high severity.
- Sarcoidosis.
- Tuberculosis.
- Taking additional vitamin D can lead to an overdose.
Interaction with other medicinal products and other types of interactions
Anticonvulsants and epilepsy drugs
In the case of simultaneous use of anticonvulsants such as phenobarbital, hydantoin derivatives, in particular phenytoin, and other barbiturates or primidone, as well as, possibly, other drugs that inhibit the activity of liver enzymes, a decrease in the effect of vitamin D3 may occur due to metabolic inactivation, for example, as a result of activation of the microsomal enzyme system.
Rifampicin
Rifampicin may reduce the effectiveness of cholecalciferol due to activation of liver enzymes.
Isoniazid
Isoniazid may reduce the effectiveness of cholecalciferol due to inhibition of the metabolic activation of cholecalciferol.
Ion exchange drugs, laxatives, orlistat
Concomitant treatment with drugs that impair fat absorption, such as orlistat, laxatives (liquid paraffin, mineral oils) or exchange resins (cholestyramine or colestipol), may reduce the absorption of vitamin D in the gastrointestinal tract.
Actinomycin and imidazoles
The cytostatic drug actinomycin and the antifungal drug imidazole interfere with the activity of vitamin D3 by inhibiting the conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol by the renal enzyme 25-hydroxyvitamin D-1-hydrolase.
May reduce the conversion of vitamin D metabolites and therefore reduce its effectiveness.
Glucocorticoids
Due to increased metabolism of vitamin D, its effect may decrease.
Thiazide diuretics, hydrochlorothiazide
In case of simultaneous use with benzothiadiazine derivatives (thiazide diuretics), the risk of hypercalcemia increases due to reduced renal calcium excretion. Therefore, monitoring of calcium levels in blood plasma and urine is necessary.
Vitamin D metabolites or analogues (e.g. calcitriol)
It is necessary to avoid the use of the combination of the drug Decristol® drops with metabolites or analogues of vitamin D. The simultaneous administration of vitamin D3 with metabolites or analogues of vitamin D is possible only as an exception and only under the condition of monitoring the level of calcium in the blood serum (increases the risk of toxic effects).
Cardiac glycosides
Oral vitamin D may increase the efficacy and toxicity of cardiac glycosides due to increased calcium levels (risk of cardiac arrhythmias). Patients should be monitored with ECG, plasma and urine calcium levels, and, if necessary, digoxin or digitoxin levels.
Dietary calcium supplements
In case of simultaneous use of dietary calcium supplements, all sources of calcium should be taken into account, the total dose should not exceed 1000 mg/day.
Calcitonin, gallium nitrate, bisphosphonates, etidronate, pamidronate, plicamycin
In the case of simultaneous use of calcitonin, gallium nitrate, bisphosphonates or plicamycin and vitamin D, an antagonistic effect on the action of these drugs used to eliminate hypercalcemia is possible.
Magnesium
Magnesium-containing drugs (such as antacids) should not be taken during vitamin D therapy due to the risk of developing hypermagnesemia.
Phosphorus
High-dose phosphorus medications used concurrently may increase the risk of hyperphosphatemia.
Aluminum
Vitamin D may increase the absorption of aluminum in the intestine, and therefore increase serum aluminum levels. Long-term or excessive use of aluminum-containing antacids should be avoided.
Ketoconazole
Ketoconazole may reduce the biosynthesis and catabolism of 1,25(OH)2-cholecalciferol.
Application features
In patients with mild to moderate renal insufficiency, who use Dekristol® drops, it is necessary to monitor the effect on calcium and phosphate balance. In patients with severe renal insufficiency, the normal metabolic transformation of cholecalciferol is impaired, and therefore such patients should use other forms of vitamin D (see section "Contraindications").
In patients with hepatic insufficiency, the hepatic hydroxylation of cholecalciferol to 25 OHD may be impaired.
Dekristol® drops should not be used in the presence of pseudohypoparathyroidism (the need for vitamin D may be reduced sometimes to normal sensitivity to vitamin D, there is a risk of prolonged overdose). In such cases, it is recommended to use vitamin D derivatives, the doses of which are easier to adjust.
Decristol® drops should not be taken if patients are prone to the formation of calcium-containing kidney stones.
Dekristol® drops should be used with special caution in patients with impaired renal excretion of calcium and phosphate, in patients receiving treatment with benzothiadiazine derivatives and in immobilized patients (risk of hypercalcemia, hypercalciuria). In such patients, the level of calcium in the blood plasma and urine should be monitored. The risk of soft tissue calcification should be taken into account.
When using the drug Decristol® drops in patients with sarcoidosis, there is a risk of increased conversion of vitamin D to its active metabolites. In such patients, calcium levels in blood plasma and urine should be monitored.
During treatment with vitamin D, equivalent daily doses of which exceed 1000 IU, serum and urine calcium levels should be monitored and renal function should be checked by measuring serum creatinine. Such monitoring is particularly important in elderly patients and in patients receiving concomitant treatment with cardiac glycosides or diuretics (see section 4.5). If hypercalcaemia or signs of reduced renal function occur, the dose should be reduced or treatment discontinued. If hypercalciuria (more than 7.5 mmol, equivalent to 300 mg, calcium/day) develops, the dose should be reduced or treatment discontinued.
For elderly people aged > 70 years
When treating with vitamin D in a loading dose protocol, serum 25(OH)D3 levels should also be monitored regularly. Treatment should be discontinued at levels ≥ 50 ng/mL.
Use during pregnancy or breastfeeding
Pregnancy
There are no or limited data from the use of cholecalciferol in pregnant women. There is no evidence that vitamin D3 is harmful to the embryo/fetus when used at recommended doses. Animal studies have shown that high doses of vitamin D are teratogenic.
Long-term overdose should be avoided during pregnancy, as the resulting prolonged hypercalcemia may lead to retardation of physical and mental development, supravalvular aortic stenosis and retinopathy in the child. Dekristol® drops are not recommended during pregnancy in patients without vitamin D deficiency. In the presence of vitamin D deficiency, the recommended dose should be selected according to national guidelines, but usually the dose does not exceed 600 IU/day, and the maximum dose should not exceed 4000 IU/day.
Breast-feeding
Vitamin D and its metabolites are excreted in breast milk. No adverse reactions have been observed in breastfed infants. Dekristol® drops can be used in recommended doses during breastfeeding in the presence of vitamin D deficiency, however, the feasibility of additional vitamin D administration to the child should be considered.
Fertility
Normal endogenous vitamin D levels are not expected to have any adverse effect on fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
Decristol® drops have no or negligible influence on the ability to drive or use machines.
When using the drug, caution is recommended due to the possibility of developing adverse reactions from the nervous system.
Method of administration and doses
Dosage
The dosage regimen is determined by the doctor individually, in accordance with the recommendations of national protocols.
As a rule, the following dosage recommendations are followed:
Adults
Prevention of vitamin D deficiency:
- 1–2 drops of Decristol® drops per day (500 IU – 1000 IU of vitamin D).
Treatment of vitamin D deficiency:
- 2 drops of Dekristol® drops per day (1000 IU vitamin D). Higher doses may be required in patients with severe disease or in patients with malabsorption syndrome. Higher doses should be adjusted depending on the desired serum level of 25-hydroxycholecalciferol (25[OH]D), the severity of the disease and the response to treatment.
The daily dose should not exceed 8 drops of Decristol® drops (4000 IU of vitamin D).
Adjunct to specific osteoporosis therapy in patients with vitamin D deficiency or at risk of vitamin D insufficiency:
- 2 drops of Decristol® drops per day (1000 IU of vitamin D).
Children
Prevention of vitamin D deficiency (hypovitaminosis due to vitamin D deficiency in the diet, alimentary rickets):
premature newborns with a birth weight > 1500 g: 1 drop of Decristol® drops per day (500 IU of vitamin D); premature newborns with a birth weight < 1500 g (700 – 1500 g): 2 drops of Decristol® drops per day (1000 IU of vitamin D); newborns and infants (up to 23 months of age): 1 drop of Decristol® drops per day (500 IU of vitamin D). Prevention of vitamin D deficiency in patients at identified risk:
- children aged 2–18 years: 1–2 drops of Decristol® drops per day (500 IU–1000 IU of vitamin D).
Treatment of vitamin D deficiency and nutritional rickets:
The dose should be adjusted based on the desired serum 25-hydroxycholecalciferol (25[OH]D) level, disease severity, and response to treatment.
The following doses should not be exceeded:
- infants aged 1–23 months: 2 drops of Decristol® drops per day (1000 IU of vitamin D);
- children aged 2–11 years: 4 drops of Decristol® drops per day (2000 IU of vitamin D);
- children aged 12–18 years: 8 drops of Decristol® drops per day (4000 IU of vitamin D).
Higher doses may be required for the treatment of nutritional rickets. The attending physician selects the appropriate dose taking into account the severity and course of the disease.
Alternatively, national guidelines for the treatment of vitamin D deficiency and nutritional rickets can be followed.
Special patient groups
Patients with hepatic insufficiency
In case of severe liver dysfunction, the dose should be adjusted by the attending physician (see also the section "Special instructions").
Patients with renal insufficiency/hypercalcemia
No dose adjustment is required for patients with an estimated glomerular filtration rate (eGFR) > 30 ml/min without hyperparathyroidism and hyperphosphatemia (see section "Special warnings and precautions for use"). Decristol® drops should not be used in patients with severe renal insufficiency (see section "Contraindications").
During long-term treatment with Decristol® drops, serum and urine calcium levels should be monitored regularly and renal function should be checked by measuring serum creatinine. If necessary, the dose should be adjusted depending on the serum calcium level (see sections "Special warnings and precautions for use" and "Interaction with other medicinal products and other forms of interaction").
Method and duration of application
For oral use.
Prevention of nutritional rickets in newborns and infants:
Newborns and infants should be given Decristol® drops from the second week of life until the end of the first year of life. In the second year of life, they should be advised to continue taking Decristol® drops, especially during the winter months.
Drops are added to a teaspoon of water, milk or puree. If drops are added to a bottle of baby food or puree, you need to make sure that the child eats the entire contents, otherwise he will not receive the full amount of the active substance. Drops should be added only after cooking the food and cooling it.
Children and adults
Children and adults should take Decristol® drops with a teaspoon of liquid.
The duration of use depends on the course of the disease.
Treatment of rickets caused by vitamin D deficiency should last one year.
Children
For information on the method of administration and dosage for children, see the section “Method of administration and dosage”.
Overdose
Symptoms of overdose
Acute and chronic overdose of vitamin D3 can lead to hypercalcemia, which can become persistent and even life-threatening.
Symptoms of intoxication are not very characteristic and are manifested by thirst, dehydration, nausea, vomiting, initial frequent diarrhea, which later turns into constipation, anorexia, dizziness, headache, myalgia, arthralgia, muscle weakness and constant drowsiness, impaired consciousness, arrhythmia, azotemia, polydipsia and polyuria, as well as (in the preterminal stage) exsicosis.
Daily doses up to 500 IU/day
Chronic overdose of vitamin D can lead to hypercalcemia and hypercalciuria. If the dose is exceeded for a long time, calcification of parenchymal organs is possible.
Daily doses above 500 IU/day
Ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) have only a relatively narrow therapeutic range. For adults with normal parathyroid function, the maximum dose of vitamin D that does not cause intoxication is 40,000 to 100,000 IU per day for 1–2 months. However, in newborns and infants, sensitivity reactions are possible at much lower concentrations. Therefore, the use of vitamin D preparations without medical supervision is not recommended.
In addition to an increase in serum and urine phosphorus levels, overdose may also cause hypercalcemia syndrome, which leads to the accumulation of calcium in tissues, particularly in the kidneys (nephrolithiasis, nephrocalcinosis, renal failure), as well as in blood vessels.
Treatment in case of overdose
Daily doses up to 500 IU/day
If symptoms of chronic vitamin D overdose are present, forced diuresis is necessary, as well as the administration of glucocorticoids and calcitonin.
Daily doses above 500 IU/day
In case of overdose, measures are necessary due to hypercalcemia, which can often be chronic and even life-threatening.
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 l over 24 hours) with the addition of furosemide, and in some cases, the administration of sodium edetate at a dose of 15 mg/kg body weight/hour is recommended under constant monitoring of calcium levels and ECG. However, in oligoanuria, hemodialysis (with dialysate that does not contain calcium) 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).
Side effects
Adverse reactions are listed below for each system organ class by frequency of occurrence.
| System organ class (MedDRA) | Frequency of adverse reactions | |
Infrequently (≥ 1/1000 to < 1/100) | Rarely (≥ 1/10,000 to < 1/1,000) | Frequency unknown (cannot be estimated based on available data) |
| Cardiovascular system | Arrhythmia, hypertension | |
| Gastrointestinal tract | Loss of appetite, nausea, vomiting, colic (including exacerbation of colic), spasms, dyspepsia, dry mouth | |
| From the nervous system | Headache, mental disorders, depression, drowsiness | |
| From the urinary system | Increased calcium levels in the blood and/or urine, urolithiasis and tissue calcification, polyuria, uremia | |
| Musculoskeletal system | Muscle and joint pain, muscle weakness | |
| From the organs of vision | Conjunctivitis, photosensitivity | |
| Metabolism and nutrition disorders | Hypercalcemia and hypercalciuria | Hypercholesterolemia, weight loss, polydipsia, increased sweating, pancreatitis |
| Skin and subcutaneous tissue disorders | Itching, skin rashes and hives | |
| On the part of the immune system | Hypersensitivity reaction (e.g. angioedema or laryngeal edema) | |
| Hepatobiliary system | Increased aminotransferase activity | |
| From the psyche | Decreased libido | |
There have also been reports of rhinorrhea and hyperthermia.
Reporting of suspected adverse reactions
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of a medicinal product via the Automated Pharmacovigilance Information System at https//aisf.dec.gov.ua.
Expiration date
36 months.
The shelf life after first opening is 12 months.
Storage conditions
Store in the original package in order to protect from light. Keep out of the reach of children.
Packaging
10 ml of solution in a dropper bottle with a screw cap; 1 bottle 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.
