Beres® calcium plus d3

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BEREŠâ CALCIUM PLUS D3 (BERES CALCIUM PLUS D3)

Composition:

Active ingredients: 1 film-coated tablet contains 600 mg of calcium (as calcium carbonate 1500 mg) and 10 μg (400 IU) of vitamin D3 (cholecalciferol in the form of cholecalciferol powder 100000 IU/g);

Excipients: magnesium stearate, crospovidone, copovidone, microcrystalline cellulose, sucrose, gelatin, dl-α-tocopherol, hydrogenated soybean oil, corn starch; film coating Sepifilm 4202 yellow (yellow iron oxide (E 172), hypromellose, titanium dioxide (E 171), polyethylene glycol 400, talc).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: oval, biconvex, film-coated tablets of yellow color with a score line on one side.

Pharmacotherapeutic group. Calcium, combinations with vitamin D and/or other agents.

ATC code A12AX.

Pharmacological properties.

Pharmacodynamics.

Vitamin D increases calcium absorption in the intestine.

Administration of calcium and vitamin D3 (cholecalciferol) counteracts the increase in parathyroid hormone (PTH) levels caused by calcium deficiency, which in turn leads to enhanced bone resorption.

A clinical study conducted in nursing homes involving patients with vitamin D deficiency demonstrated that daily intake of 2 tablets containing 500 mg calcium and 400 IU vitamin D over 6 months normalized serum levels of 25-hydroxyvitamin D3 and reduced manifestations of secondary hyperparathyroidism and alkaline phosphatase levels.

An 18-month double-blind, placebo-controlled study conducted in nursing homes involving 3270 women aged 84 ± 6 years, who received vitamin D supplements (800 IU/day) and calcium phosphate (equivalent to 1200 mg/day elemental calcium), demonstrated a significant reduction in PTH secretion. After 18 months, in the ITT population (intention-to-treat population), 80 hip fracture cases were observed in the calcium and vitamin D group versus 110 hip fracture cases in the placebo group (p = 0.004). After 36 months of additional follow-up, at least one hip fracture occurred in 137 women in the calcium and vitamin D group (n = 1176) compared to 178 in the placebo group (n = 1127, p ≤ 0.02).

Pharmacokinetics.

Calcium

Absorption

The amount of calcium absorbed in the gastrointestinal tract is approximately 30% of the oral dose.

Distribution and metabolism

99% of calcium in the body is concentrated in the hard tissues of bones and teeth. The remaining 1% is located in intracellular and extracellular fluids. Approximately 50% of total calcium in blood exists in the physiologically active ionized form, about 10% forms complexes with citrate, phosphate, or other anions, and the remaining 40% is bound to proteins, primarily albumin.

Excretion

Calcium is excreted in feces, urine, and sweat. Renal excretion depends on glomerular filtration and tubular reabsorption of calcium.

Vitamin D

Absorption

Vitamin D3 is absorbed in the small intestine.

Distribution and metabolism

Cholecalciferol and its metabolites circulate in the blood bound to a specific globulin. Cholecalciferol is converted in the liver via hydroxylation into the active form 25-hydroxycholecalciferol. This is further converted in the kidneys into 1,25-dihydroxycholecalciferol. 1,25-Dihydroxycholecalciferol is the metabolite responsible for increasing calcium absorption. Unmetabolized vitamin D is stored in adipose and muscle tissues.

Excretion

Vitamin D is excreted in feces and urine.

Clinical characteristics.

Indications.

Prevention and treatment of calcium and vitamin D deficiency in elderly patients.

Additional administration of vitamin D and calcium as an adjunct in the specific treatment of osteoporosis in patients at risk of developing vitamin D and calcium deficiency.

Contraindications.

Diseases and/or conditions leading to hypercalcemia and/or hypercalciuria (e.g., myeloma, bone metastases, primary hyperparathyroidism).

Nephrolithiasis/nephrocalcinosis.

Severe renal dysfunction and renal failure.

Hypervitaminosis D.

Sarcoidosis (due to the risk of increased metabolism of vitamin D into its active form) and bone metastases.

Hypersensitivity to the active substances or to any of the excipients. The product contains hydrogenated soybean oil. The use of the product is contraindicated in patients with soy or peanut allergy (due to the risk of cross-allergy).

Interaction with other medicinal products and other forms of interaction.

Thiazide diuretics reduce urinary calcium excretion. Due to the increased risk of hypercalcemia, serum calcium levels should be monitored regularly during concomitant use of thiazide diuretics.

Systemic corticosteroids reduce calcium absorption. During concomitant use, it may be necessary to increase the dose of "Beres® Calcium plus D3", film-coated tablets.

Concomitant treatment with ion-exchange resins such as cholestyramine or with laxatives such as liquid paraffin may reduce gastrointestinal absorption of vitamin D.

Calcium carbonate may interfere with the absorption of concurrently administered tetracycline antibiotics. Therefore, tetracycline preparations should be taken at least 2 hours before or 4–6 hours after oral administration of calcium preparations.

Hypercalcemia may enhance the toxicity of cardiac glycosides during treatment with calcium and vitamin D. Patients require monitoring including electrocardiography (ECG) and determination of serum calcium levels.

When co-administering bisphosphonates or sodium fluoride, these medicinal products should be administered at least 3 hours before taking "Beres® Calcium plus D3", film-coated tablets, as gastrointestinal absorption may be reduced.

Rifampicin, phenytoin, and barbiturates may reduce the activity of vitamin D3, as they increase its metabolic rate.

Absorption of quinolone antibiotics may be impaired when administered concomitantly with calcium preparations. Quinolone antibiotics should be taken at least 2 hours before or 6 hours after calcium intake.

Calcium salts may reduce the absorption of iron, zinc, or strontium. Therefore, preparations containing iron, zinc, or strontium and calcium preparations should be taken at least 2 hours apart.

Calcium salts may reduce the absorption of estramustine or thyroid hormones. It is recommended to take "Beres® Calcium plus D3", film-coated tablets, at least 2 hours apart from these medicinal products.

Oxalic acid (found in spinach, sorrel, and rhubarb) and phytic acid (found in whole cereal grains) may inhibit calcium absorption by forming insoluble complexes with calcium ions. Patients should not take calcium preparations within 2 hours after consuming foods high in oxalic and phytic acids.

Special precautions for use.

During prolonged treatment with the drug, it is necessary to monitor serum calcium levels and perform kidney function monitoring by measuring serum creatinine levels. Monitoring is especially important for elderly patients, particularly when concomitant therapy with cardiac glycosides or thiazide diuretics is administered (see section "Interaction with other medicinal products and other forms of interaction"), as well as for patients with a high predisposition to stone formation. In case of hypercalcemia or signs of impaired kidney function, the dose should be reduced or treatment discontinued. It is recommended to reduce the dose or temporarily discontinue treatment if urinary calcium excretion exceeds 7.5 mmol/day (300 mg/day).

Vitamin D should be administered with caution to patients with impaired renal function, with regular monitoring of calcium and phosphate levels. The risk of soft tissue calcification should be considered. In patients with severe renal impairment, vitamin D in the form of cholecalciferol cannot be normally metabolized; therefore, other forms of vitamin D should be used (see section "Contraindications").

Administration of "Beres® Calcium plus D3", film-coated tablets, should be avoided in patients with sarcoidosis due to the risk of enhanced vitamin D metabolism leading to formation of its active form. These patients require monitoring of serum and urinary calcium levels.

"Beres® Calcium plus D3", film-coated tablets, should be prescribed with caution to immobilized patients with osteoporosis, due to the increased risk of hypercalcemia. When prescribing other medicinal products containing vitamin D, the vitamin D content (400 IU) in "Beres® Calcium plus D3", film-coated tablets, should be taken into account. Additional doses of calcium or vitamin D should be taken under strict medical supervision. In such cases, serum calcium levels and urinary calcium excretion should be monitored frequently. Milk-alkali syndrome (Burnett's syndrome) may develop, characterized by hypercalcemia, alkalosis, and impaired kidney function, when large amounts of calcium are consumed together with absorbable alkali substances.

Excipients

One tablet of the medicinal product "Beres® Calcium plus D3" contains 0.3 mg of hydrogenated soybean oil. The use of the drug is contraindicated in patients with soy or peanut allergy (due to risk of cross-reactivity).

One tablet of "Beres® Calcium plus D3" contains 1.52 mg of sucrose. This medicinal product should not be administered to patients with rare hereditary fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency.

Use during pregnancy or breastfeeding.

"Beres® Calcium plus D3", film-coated tablets, may be taken during pregnancy in cases of calcium and vitamin D3 deficiency.

During pregnancy, the daily dose should not exceed 1500 mg of calcium and 600 IU of vitamin D. Animal studies have demonstrated toxic effects on reproductive function with high doses of vitamin D. Any overdose of calcium or vitamin D in pregnant women should be avoided, as prolonged hypercalcemia during pregnancy may lead to delayed physical and mental development, supravalvular aortic stenosis, and retinopathy in the child. There is no evidence that vitamin D3 at therapeutic doses is teratogenic in humans.

"Beres® Calcium plus D3", film-coated tablets, may be taken during breastfeeding. Calcium and vitamin D are excreted in breast milk. This should be considered when administering additional vitamin D to the infant.

There is no information indicating harmful effects of endogenous calcium and vitamin D levels within normal ranges on fertility. Data on the effect of "Beres® Calcium plus D3", film-coated tablets, on fertility are lacking.

Ability to affect reaction speed while driving or operating machinery.

There are no data on the effect of the medicinal product on reaction speed while driving or operating machinery. The effect is unlikely.

Method of Administration and Dosage

Dosage

Adults and elderly patients

1 tablet twice daily (e.g., 1 tablet in the morning and 1 tablet in the evening). If necessary, dose reduction should be considered based on monitoring results of calcium levels, as specified in the sections "Special Instructions" and "Interaction with Other Medicinal Products and Other Forms of Interaction".

Hepatic impairment

Dose adjustment is not required.

Renal impairment

"Beres® Calcium plus D3" film-coated tablets should not be administered to patients with severe renal impairment.

Method of Administration

The film-coated tablet should be taken within one and a half hours after a meal, without chewing, and swallowed with a glass of water or juice. If necessary, the tablet may be divided in half.

Children

The medicinal product "Beres® Calcium plus D3" film-coated tablets is not intended for use in children and adolescents.

Overdose

Overdose may lead to hypervitaminosis and hypercalcemia. Symptoms of hypercalcemia may include anorexia, thirst, nausea, vomiting, constipation, abdominal pain, muscle weakness, increased fatigue, mental disturbances, polydipsia, polyuria, bone pain, nephrocalcinosis, kidney stone formation, and in severe cases, cardiac arrhythmias. Extreme hypercalcemia may result in coma and fatal outcome. Prolonged elevated calcium levels may lead to irreversible kidney damage and soft tissue calcification.

In patients consuming large amounts of calcium and absorbable alkalis, milk-alkali syndrome may develop. Symptoms include frequent urination, persistent headache, prolonged loss of appetite, nausea or vomiting, unusual fatigue or weakness, hypercalcemia, alkalosis, and impaired kidney function.

Treatment of hypercalcemia: discontinue calcium and vitamin D intake. Also discontinue thiazide diuretics, lithium, vitamin A, vitamin D, and cardiac glycosides. In case of impaired consciousness, gastric lavage is required. Perform rehydration and, depending on severity, administer monotherapy or combination therapy with loop diuretics, bisphosphonates, calcitonin, and corticosteroids. Monitor serum electrolyte levels, kidney function, and diuresis. In severe cases, ECG and central venous pressure monitoring are required.

Side effects

Side effects are grouped by organ systems and frequency. Frequency is defined as follows: uncommon (from ≥ 1/1000 to < 1/100); rare (from ≥ 1/10,000 to < 1/1000); or very rare (< 1/10,000).

Metabolism and nutrition disorders

Uncommon: hypercalcaemia and hypercalciuria.

Very rare: milk-alkali syndrome (usually observed only in cases of overdose).

Gastrointestinal disorders

Rare: constipation, flatulence, nausea, abdominal pain, and diarrhoea.

Very rare: dyspepsia.

Skin and subcutaneous tissue disorders

Rare: pruritus, rash, and urticaria.

Shelf life.

2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C, in the original packaging and out of reach of children.

Packaging.

10 tablets in a blister. 3 or 6 blisters in a cardboard box.

Supply category. Over-the-counter.

Manufacturer.

ZAO "Beres Pharma".

Manufacturer's location and address of business operations.

39 Nadzsandor József Street, Szolnok, 5000, Hungary.