Decristol® 500 iu

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEKRISTOL® 500 IU

Composition:

Active substance: cholecalciferol;

One tablet contains cholecalciferol (as concentrate [powder form]) 12.5 μg, equivalent to 500 IU of vitamin D3;

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

Pharmaceutical form. Tablets.

Main physicochemical properties: white or slightly yellowish, round, slightly convex tablets.

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

ATC code A11C C05.

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) in two stages of hydroxylation: first in the liver (position 25), then in kidney tissues (position 1). Together with parathyroid hormone and calcitonin, 1,25-dihydroxycholecalciferol plays an important role in regulating calcium-phosphate balance. In its biologically active form, vitamin D3 stimulates calcium absorption in the intestine, incorporation of calcium into osteoid, and release of calcium from bone tissue. In case of vitamin D deficiency, skeletal calcification does not occur (rickets) or decalcification of bones occurs (osteomalacia).

Deficiency of calcium and/or vitamin D induces reversible increased secretion of parathyroid hormone. This secondary hyperparathyroidism causes increased bone tissue 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 physiological synthesis in the skin, cholecalciferol can be supplemented through diet or as a medicinal product. In the latter case, overdose and intoxication are possible, since the drug 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 exerts effects identical in both qualitative and quantitative terms.

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.

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. It is then converted in the kidneys to 1,25-dihydroxycholecalciferol.

Vitamin D that is not metabolized is stored in muscle and adipose tissue, thus having a prolonged biological half-life. After administration of high doses of vitamin D, serum concentration 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, adolescents, and adults.
• Prevention of vitamin D deficiency in children, adolescents, and adults with identified risk of such deficiency.
• As an adjunct to specific therapy of 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 (vitamin D requirement may be lower than during normal vitamin sensitivity, and there is a risk of prolonged overdose).
• Kidney stones.
• 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

Plasma concentration of 25-OH D may decrease, and metabolism to inactive metabolites may increase.

Glucocorticoids

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

Rifampicin and isoniazid

Metabolism of vitamin D may increase, and its effectiveness may decrease.

Ion-exchange agents, laxatives, orlistat

Concomitant treatment with ion-exchange agents, e.g. cholestyramine, laxatives, e.g. liquid paraffin, or orlistat, may reduce vitamin D absorption.

Actinomycin and imidazole

May reduce conversion of vitamin D metabolites and thus decrease its effectiveness.

Vitamin D metabolites or analogs (e.g., calcitriol)

Use of Decristol® 500 IU in combination with these agents is possible only in exceptional cases. Serum calcium levels should be monitored.

Thiazide diuretics

Administration of thiazide diuretics may lead to hypercalcaemia due to reduced renal excretion of calcium. During prolonged treatment, serum and urinary calcium levels should be monitored.

Digitalis (cardiac glycosides)

Oral administration of vitamin D may enhance the efficacy and toxicity of cardiac glycosides due to elevated calcium levels (risk of cardiac arrhythmias). Patients should be monitored using 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 toxic effects of aluminium on bone and hypermagnesaemia in patients with renal insufficiency.

Ketoconazole

Ketoconazole may reduce 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, etidronate, pamidronate

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

Special precautions for use

When prescribing other medicinal products containing vitamin D, the dose of vitamin D in Decristol® 500 IU should be taken into account. Additional vitamin D or calcium preparations should be administered only under medical supervision. In such cases, serum and urinary calcium levels should be monitored.

In patients with renal insufficiency receiving Decristol® 500 IU, the effect on calcium-phosphate balance should be monitored.

Decristol® 500 IU should not be taken by patients prone to developing calcium-containing kidney stones.

Decristol® 500 IU should be used with particular caution in patients with impaired renal excretion of calcium and phosphates, in patients undergoing treatment with benzothiadiazine derivatives, and in immobilized patients (risk of hypercalcemia, hypercalciuria). In such patients, plasma and urinary calcium levels should be monitored.

Decristol® 500 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® 500 IU should not be used in patients with pseudohypoparathyroidism (vitamin D requirement may be reduced, sometimes to normal sensitivity to vitamin D; risk of prolonged overdose). In such cases, vitamin D derivatives with more easily adjustable doses are recommended.

For certain patients, additional calcium supplementation may be considered. Dietary supplements containing calcium should be used under strict medical supervision to prevent hypercalcemia.

Prior to initiating vitamin D therapy, a thorough evaluation of the patient's condition by a physician is required, including consideration of additional vitamin D intake from certain food products.

Infants and young children

Decristol® 500 IU should be used with particular caution in infants and young children, as they may not be able to swallow the tablets and could 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 prolonged treatment with Decristol® 500 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 concurrently receiving cardiac glycosides or diuretics. It also applies to patients particularly prone to developing calcium-containing kidney stones.

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

Decristol® 500 IU contains sucrose

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

One tablet of Decristol® 500 IU contains 34.47 mg of monohydrate lactose.

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

One tablet of Decristol® 500 IU contains 0.87 mg of sucrose.

If you have been diagnosed with intolerance to certain sugars, consult your doctor before taking this medicinal product.

One tablet of Decristol® 500 IU contains less than 1 mmol of sodium (23 mg).

Caution is advised 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, no risks have been identified when the product is used within this dosage range.

Vitamin D overdose during pregnancy should be avoided, as prolonged hypercalcemia 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® 500 IU should be used only if clearly necessary and at doses truly required to correct vitamin D deficiency.

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

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 benefit-risk ratio in humans 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, adolescents, and adults

1 tablet of Decristol® 500 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. For prevention of rickets in preterm newborns, the usual dosage is:

• Birth weight > 1500 g: 1 tablet of Decristol® 500 IU per day (equivalent to 0.0125 mg, or 500 IU, of vitamin D3);

• Birth weight < 1500 g (700–1500 g): 2 tablets of Decristol® 500 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, adolescents, and adults at risk of deficiency

Infants (0–12 months)

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

Children, adolescents, and adults

1–2 tablets of Decristol® 500 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

2 tablets of Decristol® 500 IU per day (equivalent to 0.025 mg, or 1000 IU, of vitamin D3) (see section "Special Instructions").

During prolonged use of Decristol® 500 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. Dosage adjustments may be necessary based on 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® 500 IU from the second week of life until the end of the first year of life. Continued administration of Decristol® 500 IU during the second year of life may be necessary, especially during winter months.

The tablet should be dissolved in a teaspoon of water or milk and administered directly into the infant’s mouth, preferably during a meal. The tablet dissolves within 1–2 minutes. Stirring the spoon gently 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 allowed to cool before adding the tablet.

When consuming vitamin-fortified foods, the amount of vitamin D in the diet 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.

Children

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

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

Overdose

Vitamin D3 regulates calcium and phosphate metabolism. Overdose may lead to hypercalcemia, hypercalciuria, renal calcifications, bone damage, and cardiovascular system disorders. Hypercalcemia may occur after daily intake of 50,000–100,000 IU of vitamin D3.

Symptoms of overdose

Acute and chronic vitamin D3 overdose can lead to hypercalcemia, which may persist and potentially become life-threatening. Symptoms are nonspecific and may include cardiac arrhythmias, thirst, dehydration, lethargy, and impaired consciousness. Chronic overdose may additionally cause calcium deposition in 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), as well as in blood vessels.

Signs of intoxication are not highly specific and may manifest as muscle weakness, loss of appetite, nausea, vomiting, initial frequent diarrhea progressing to constipation, anorexia, dyspnea, headache, myalgia, arthralgia, muscle weakness, persistent drowsiness, arrhythmia, azotemia, polydipsia, and polyuria. In pre-terminal stages, symptoms may include dehydration, 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 cases 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 the condition after vitamin D intoxication-induced hypercalcemia may take several weeks.

Depending on the severity of hypercalcemia, a low-calcium or calcium-free diet, high fluid intake, forced diuresis with furosemide, and administration of glucocorticoids and calcitonin may be used.

With normal kidney function, infusions of isotonic NaCl solution (3–6 L over 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, are highly effective in reducing calcium levels.

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

No specific antidote is known.

Patients undergoing long-term treatment with higher doses of vitamin D should be informed about symptoms of possible overdose (nausea, vomiting, initial frequent 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 to assess frequency have not been conducted.

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

Eye disorders: conjunctivitis, photophobia.

Cardiovascular disorders: arrhythmia, arterial hypertension.

Metabolism and nutrition disorders: hypercalcaemia and hypercalciuria.

Gastrointestinal disorders: gastrointestinal symptoms such as constipation, flatulence, nausea, abdominal pain, or diarrhoea.

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

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

Hepatobiliary disorders: increased aminotransferase activity.

Psychiatric disorders: decreased libido.

Reporting of suspected adverse reactions

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

Shelf life. 30 months.

Storage conditions.

Store at a temperature not exceeding 25°C. Keep the blister in the outer carton to protect from light. Store out of reach of children.

Packaging. 10 tablets per blister. 5 or 10 blisters per carton.

Pharmaceutical category. Over-the-counter (without prescription).

Manufacturer. mibe GmbH Arzneimittel.

Manufacturer's address and place of business.

Muenchener Strasse 15, Brehna, Saxony-Anhalt, 06796, Germany.