Decristol® 1000 iu

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEKRISTOL® 1000 IU

Composition:

Active substance: cholecalciferol;

1 tablet contains cholecalciferol (in the form of concentrate [powder form]) 25 mcg, equivalent to 1000 IU of vitamin D3;

Excipients: all-rac-alpha-tocopherol, modified corn starch, medium-chain triglycerides, sodium ascorbate crystalline, sucrose, silicon dioxide, lactose monohydrate, microcrystalline cellulose, corn starch, sodium starch glycolate (type A), colloidal anhydrous silicon dioxide, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white, elongated tablets with a score line on both sides. The tablet can be divided into two equal parts.

Pharmacotherapeutic group. Vitamins. Vitamin D and analogues. Cholecalciferol.

ATC code A11CC05.

Pharmacological properties.

Pharmacodynamics.

Cholecalciferol (vitamin D3) is synthesized in the skin under the influence of UV radiation from 7-dehydrocholesterol and is converted into its biologically active form (1,25-dihydroxycholecalciferol) through two hydroxylation steps: first in the liver (at position 25), then in kidney tissues (at position 1). Together with parathyroid hormone (PTH) and calcitonin, 1,25-dihydroxycholecalciferol plays an important role in regulating calcium-phosphate balance. In its biologically active form, vitamin D3 stimulates intestinal absorption of calcium, incorporation of calcium into osteoid, and release of calcium from bone tissue. In case of vitamin D deficiency, skeletal calcification does not occur (resulting in rickets), or decalcification of bones occurs (osteomalacia).

Deficiency of calcium and/or vitamin D induces reversible increased secretion of PTH. This secondary hyperparathyroidism causes increased bone metabolism, which may lead to bone fragility and fractures.

From the standpoint of its formation, physiological regulation, and mechanism of action, vitamin D3 can be considered a precursor of a steroid hormone.

In addition to its physiological synthesis in the skin, cholecalciferol can also be obtained from dietary sources or as a medicinal product. In the latter case, overdose and intoxication are possible, since the administered preparation does not physiologically suppress vitamin D synthesis in the skin.

Ergocalciferol (vitamin D2) is produced in plants. In humans, it is metabolically activated similarly to cholecalciferol. Ergocalciferol demonstrates effects equivalent to cholecalciferol both qualitatively and quantitatively.

Pharmacokinetics.

Absorption

Vitamin D is almost completely absorbed from food together with dietary lipids and bile acids. Higher doses are absorbed to approximately two-thirds of the administered amount.

Distribution and biotransformation

Cholecalciferol and its metabolites circulate in the blood bound to proteins. In the liver, it is metabolized by microsomal hydroxylase to 25-hydroxycholecalciferol, which is then converted in the kidneys to 1,25-dihydroxycholecalciferol.

Vitamin D that is not metabolized is stored in muscle and adipose tissue, resulting in a prolonged biological half-life. After administration of high doses, serum concentrations of 25-hydroxyvitamin D may remain elevated for months. Hypercalcemia caused by overdose may persist for weeks (see section "Overdose").

Elimination

Vitamin D and its metabolites are excreted via bile/feces.

Clinical characteristics.

Indications.

• Prevention of rickets and osteomalacia in children and adults.
• Prevention of vitamin D deficiency in children and adults at risk of such deficiency.
• As an adjunct to specific therapy for osteoporosis in adults.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients listed in the section "Composition".
• Hypercalcaemia.
• Hypercalciuria.
• Hypervitaminosis D.
• Pseudohypoparathyroidism (the requirement for vitamin D may be lower than during normal sensitivity to vitamin D; risk of prolonged overdose exists).
• Nephrolithiasis (urolithiasis).
• Renal insufficiency.
• Sarcoidosis.
• Tuberculosis.
• Additional intake of vitamin D may lead to overdose.

Interaction with other medicinal products and other forms of interaction.

Phenytoin or barbiturates

When anticonvulsant drugs such as phenobarbital, hydantoin derivatives including phenytoin, other barbiturates or primidone, and possibly other drugs that inhibit hepatic enzyme activity are used concomitantly, the effect of vitamin D3 may be reduced due to metabolic inactivation, for example, as a result of activation of the microsomal enzyme system.

Glucocorticoids

Due to enhanced metabolism of vitamin D, its effect may be reduced.

Rifampicin

Rifampicin may reduce the efficacy of cholecalciferol due to induction of hepatic enzymes.

Isoniazid

Isoniazid may reduce the efficacy of cholecalciferol by inhibiting the metabolic activation of cholecalciferol.

Ion-exchange agents, laxatives, orlistat

Concomitant treatment with ion-exchange agents such as cholestyramine or colestipol, laxatives such as liquid paraffin, or substances that impair fat absorption such as orlistat, may reduce the gastrointestinal absorption of vitamin D.

Actinomycin and imidazole

The cytostatic drug actinomycin and the antifungal agent 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-hydroxylase.

They may reduce the conversion of vitamin D metabolites and thus decrease its efficacy.

Vitamin D metabolites or analogues (e.g. calcitriol)

The use of Decristol® 1000 IU in combination with vitamin D metabolites or analogues should be avoided. Concomitant administration of vitamin D3 with vitamin D metabolites or analogues is possible only exceptionally and only under strict monitoring of serum calcium levels (increases the risk of toxic effects).

Thiazide diuretics

The use of thiazide diuretics may lead to the development of hypercalcaemia due to reduced renal excretion of calcium. During long-term treatment, serum and urinary calcium levels should be monitored.

Digitalis (cardiac glycosides)

Oral intake of vitamin D may enhance the efficacy and toxicity of cardiac glycosides due to elevated calcium levels (risk of cardiac arrhythmias). Patient status should be monitored by ECG, plasma and urinary calcium levels, and, if necessary, digoxin or digitoxin levels.

Antacids containing aluminium or magnesium

Concomitant use of the product with antacids containing aluminium or magnesium may provoke aluminium-related bone toxicity and hypermagnesaemia in patients with renal insufficiency.

Ketoconazole

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

Medicinal products containing high doses of calcium and phosphorus

Concomitant use with medicinal products containing high doses of calcium and phosphorus increases the risk of hyperphosphataemia.

Calcitonin, gallium nitrate, bisphosphonates, etidronate, pamidronate, piclamilacin

Vitamin D may antagonize medicinal products used in the treatment of hypercalcaemia, such as calcitonin, etidronate, pamidronate.

Special precautions for use

When prescribing other medicinal products containing vitamin D, the vitamin D dose in Decristol® 1000 IU should be taken into account. Additional vitamin D or calcium supplements should be used only under medical supervision to prevent hypercalcaemia. In such cases, serum and urinary calcium levels should be monitored.

In patients with renal insufficiency receiving Decristol® 1000 IU, the effect on calcium-phosphate balance should be monitored.

Recommended doses should not be exceeded due to the risk of developing hypervitaminosis.

In patients with severe renal impairment, cholecalciferol is not metabolized normally. Therefore, such patients may require other forms of vitamin D.

When using the medicinal product in patients with mild to moderate renal impairment, monitoring of calcium and phosphate levels is recommended. The risk of soft tissue calcification should be considered.

Decristol® 1000 IU should not be prescribed if patients are prone to developing calcium-containing kidney stones.

Decristol® 1000 IU should be used with particular caution in patients with impaired renal excretion of calcium and phosphate, in patients treated with benzothiadiazine derivatives, and in immobilized patients (risk of hypercalcaemia, hypercalciuria). In such patients, plasma and urinary calcium levels should be monitored.

Decristol® 1000 IU should be used with caution in patients with sarcoidosis, as there is a risk of enhanced conversion of vitamin D into its active metabolites. In such patients, serum and urinary calcium levels should be monitored.

Decristol® 1000 IU should not be used in patients with pseudohypoparathyroidism (the requirement for vitamin D may be reduced, sometimes to normal vitamin D sensitivity, and there is a risk of prolonged overdose). In such cases, vitamin D derivatives, the doses of which are easier to adjust, are recommended.

In patients with hepatic insufficiency, hepatic hydroxylation of cholecalciferol to 25 OHD may be impaired.

Infants and young children

Decristol® 1000 IU should be used with particular caution in infants and young children, as they may not swallow the tablets properly and may choke. For such patients, the tablets should preferably be dissolved according to the instructions (see section "Dosage and administration") or liquid formulations should be used.

Daily doses exceeding 500 IU

During long-term treatment with Decristol® 1000 IU, serum and urinary calcium levels should be monitored, and renal function should be assessed by measuring serum creatinine. This monitoring is particularly important for elderly patients and patients receiving concomitant treatment with cardiac glycosides or diuretics (see section "Interaction with other medicinal products and other forms of interaction").

This also applies to patients who are particularly prone to developing calcium-containing kidney stones.

If hypercalcaemia or signs of impaired renal function occur, the dose should be reduced or treatment discontinued. In case of hypercalciuria (more than 7.5 mmol, equivalent to 300 mg, calcium/day), the dose should be reduced or treatment discontinued.

Treatment should be discontinued if symptoms of hypervitaminosis occur, such as fatigue, nausea, diarrhoea, or polyuria. Since these symptoms are non-specific, medical advice should be sought to determine whether they may be related to vitamin D excess.

One tablet of Decristol® 1000 IU contains 175 mg of sucrose

Patients with rare hereditary fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency should not take this medicinal product. If you have been diagnosed with intolerance to certain sugars, consult your doctor before taking this medicinal product.

One tablet of Decristol® 1000 IU contains 68.94 mg of monohydrate lactose.

Patients with rare hereditary conditions of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

One tablet of Decristol® 1000 IU contains less than 1 mmol of sodium (23 mg).

Caution should be exercised when administering to patients on a sodium-controlled diet.

Use during pregnancy or breastfeeding

Pregnancy

Daily use at doses up to 500 IU/day

To date, risks are unknown when the product is used within this dosage range.

Vitamin D overdose during pregnancy should be avoided, as prolonged hypercalcaemia may lead to delayed physical and mental development of the fetus, aortic stenosis, and retinopathy in children.

Daily use at doses exceeding 500 IU/day

During pregnancy, Decristol® 1000 IU should be used only if clearly needed and at doses strictly necessary to correct vitamin D deficiency.

Prolonged vitamin D overdose should be avoided due to the potential risk of hypercalcaemia, which may lead to physical and mental developmental abnormalities in the fetus, aortic sten0sis, and retinopathy in the child.

Breastfeeding

Vitamin D and its metabolites are excreted in breast milk. Cases of overdose in infants have not been reported. However, this should be taken into account when prescribing additional vitamin D to the infant.

Fertility

In fertility studies using cholecalciferol, no effects on reproductive performance were observed. The human benefit-risk ratio is unknown.

Ability to influence reaction speed when driving or operating machinery

Not observed.

Method of Administration and Dosage

Dosage

Prevention of rickets and osteomalacia in children and adults

1/2 tablet of Decristol® 1000 IU per day (equivalent to 0.0125 mg or 500 IU of vitamin D3) (see section "Special Instructions").

Dosage should be determined by a physician. Generally, for rickets prophylaxis in preterm newborns:

• infants with birth weight > 1500 g: 1/2 tablet of Decristol® 1000 IU per day (equivalent to 0.0125 mg or 500 IU of vitamin D3);
• infants with birth weight < 1500 g (700–1500 g): 1 tablet of Decristol® 1000 IU per day (equivalent to 0.025 mg or 1000 IU of vitamin D3)

(see section "Special Instructions").

Prevention of vitamin D deficiency in children and adults with identified risk factors

Infants aged 0–12 months:

1/2 tablet of Decristol® 1000 IU per day (equivalent to 0.0125 mg or 500 IU of vitamin D3) (see section "Special Instructions").

Children, adolescents, and adults:

1/2–1 tablet of Decristol® 1000 IU per day (equivalent to 0.0125–0.025 mg or 500–1000 IU of vitamin D3) (see section "Special Instructions").

As an adjunct to specific osteoporosis therapy in adults

1 tablet of Decristol® 1000 IU per day (equivalent to 0.025 mg or 1000 IU of vitamin D3) (see section "Special Instructions").

During prolonged use of Decristol® 1000 IU at daily doses exceeding 500 IU, serum and urinary calcium levels should be monitored regularly, and kidney function should be assessed by measuring serum creatinine. If necessary, the dose should be adjusted according to serum calcium levels (see section "Special Instructions").

Alternatively, national recommendations for vitamin D dosing in prevention and treatment of deficiency may be followed.

Method of Administration

Infants and young children

Prevention of rickets in infants

Infants should receive Decristol® 1000 IU starting from the second week of life until the end of the first year of life. Continued administration of Decristol® 1000 IU during the second year of life is recommended, especially during winter months.

The tablet should be dissolved in a teaspoon of water or milk. The dissolved tablet should be administered directly into the infant’s mouth, preferably during a meal. The tablet dissolves within 1–2 minutes. Gently stirring the spoon may accelerate dissolution.

It is not recommended to add the dissolved tablet to a feeding bottle or soft puree, as complete dose delivery cannot be guaranteed. However, if the tablet must be administered with food, the food should first be prepared and cooled before adding the tablet.

When consuming vitamin-fortified foods, the amount of vitamin D contained in them should be taken into account.

Adults

Tablets should be taken with a sufficient amount of water, preferably during a meal.

Duration of treatment depends on the course of the disease.

Special Patient Groups

Patients with hepatic impairment

In cases of severe liver dysfunction, the dose should be adjusted by the treating physician (see also section "Special Instructions").

Patients with renal impairment / hypercalcemia

In the presence of hypercalcemia or signs of impaired kidney function, the dose should be reduced or treatment discontinued. If hypercalciuria occurs (more than 7.5 mmol, corresponding to 300 mg calcium in 24 hours), the dose should be reduced or treatment stopped.

Elderly patients

Elderly individuals with a history of falls should avoid doses exceeding 24,000 IU per month.

For elderly patients aged > 70 years

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

Children

For prevention of vitamin D deficiency, administration may begin from birth.

For prevention of rickets, administration should start from the second week of life.

Overdose

Vitamin D3 regulates calcium and phosphate metabolism. In case of overdose, hypercalcemia, hypercalciuria, renal calcifications, bone lesions, and cardiovascular changes may occur. Hypercalcemia may develop after daily intake of 50,000–100,000 IU of vitamin D3.

Symptoms of overdose

Acute or chronic vitamin D3 overdose may lead to hypercalcemia, which can persist and potentially become life-threatening. Symptoms are non-specific and may include cardiac arrhythmias, thirst, dehydration, lethargy, and impaired consciousness. Chronic overdose may also lead to calcium deposition in blood vessels and tissues.

In addition to elevated serum and urinary phosphate levels, overdose may lead to a hypercalcemia syndrome, resulting in calcium deposition in tissues, particularly in the kidneys (nephrolithiasis, nephrocalcinosis, renal failure) and blood vessels.

Symptoms of intoxication are not highly specific and may include nausea, vomiting, initial frequent diarrhea progressing to constipation, anorexia, apathy, headache, myalgia, arthralgia, muscle weakness, persistent drowsiness, arrhythmias, azotemia, polydipsia, and polyuria; in pre-terminal stages, dehydration may occur. Other symptoms of intoxication include photosensitivity, pancreatitis, rhinorrhea, hyperthermia, decreased libido, conjunctivitis, hypercholesterolemia, elevated transaminase activity, arterial hypertension, and uremia. Common symptoms include muscle and joint pain.

Standard biochemical findings include hypercalcemia, hypercalciuria, and elevated serum 25-hydroxycalciferol levels.

Treatment

Symptoms of chronic vitamin D overdose may require forced diuresis and administration of glucocorticoids and calcitonin.

In case of overdose, measures to treat often chronic and potentially life-threatening hypercalcemia are required.

As an initial step, vitamin D-containing medication should be discontinued. Normalization of hypercalcemia due to vitamin D intoxication may take several weeks.

Depending on the severity of hypercalcemia, a low-calcium or calcium-free diet may be used. Adequate hydration is recommended, along with forced diuresis using furosemide, and administration of glucocorticoids and calcitonin.

With normal kidney function, infusions of isotonic NaCl solution (3–6 L within 24 hours) combined with furosemide, and in some cases 15 mg/kg body weight/hour of sodium edetate, administered under continuous monitoring of calcium levels and ECG, have shown high efficacy in reducing calcium levels.

However, in cases of oligoanuria, hemodialysis (using calcium-free dialysate) is indicated.

There is no specific antidote.

Patients on long-term treatment with higher doses of vitamin D should be informed about the symptoms of possible overdose (nausea, vomiting, initial diarrhea progressing to constipation, anorexia, apathy, headache, myalgia, arthralgia, muscle weakness, drowsiness, azotemia, polydipsia, and polyuria).

Adverse Reactions

The frequency of adverse reactions is unknown, as large-scale clinical studies enabling assessment of frequency have not been conducted.

Immune system disorders: hypersensitivity reactions, such as angioneurotic edema or laryngeal edema.

Eye disorders: conjunctivitis, photosensitivity.

Cardiovascular system disorders: arrhythmia, hypertension.

Metabolism and nutrition disorders: hypercholesterolemia, weight loss, polydipsia, increased sweating, pancreatitis, hypercalcemia and hypercalciuria.

Gastrointestinal disorders: gastrointestinal symptoms such as constipation, flatulence, nausea, abdominal pain or diarrhea, loss of appetite, colic (including colic exacerbation), spasms, dyspepsia, dry mouth.

Renal and urinary disorders: elevated levels of calcium in blood and/or urine, nephrolithiasis and tissue calcification, polyuria, uremia.

Musculoskeletal and connective tissue disorders: muscle and joint pain, muscle weakness.

Nervous system disorders: headache, drowsiness, mental disturbances, depression.

Skin and subcutaneous tissue disorders: pruritus, skin rash or urticaria.

Hepatobiliary disorders: increased aminotransferase activity.

Psychiatric disorders: decreased libido.

Cases of rhinorrhea and hyperthermia have also been reported.

Reporting of suspected adverse reactions

Reporting of adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at https://aisf.dec.gov.ua.

Shelf life. 36 months.

Storage conditions.

Store at a temperature not exceeding 25°C. Keep the blister in the carton to protect from light. Store in a place inaccessible to children.

Packaging. 10 tablets per blister. 2 blisters per carton.

25 tablets per blister. 2, 4, or 8 blisters per carton.

Dispensing category. Over-the-counter.

Manufacturer. mibe GmbH Arzneimittel.

Manufacturer's location and address of business operations.

Muenchenstrasse 15, Brehna, Saxony-Anhalt, 06796, Germany.