Calcemin® advance

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT KALCIUMIN® ADVANCE

Composition:

Active substances:

One tablet contains: calcium (calcium carbonate, calcium citrate) 500 mg, vitamin D3 (cholecalciferol) 200 IU, magnesium (magnesium oxide) 40 mg, zinc (zinc oxide) 7.5 mg, copper (copper oxide) 1 mg, manganese (manganese sulfate) 1.8 mg, boron (sodium borate) 250 mcg;

Excipients: maltodextrin, microcrystalline cellulose, sodium croscarmellose, acacia, hypromellose, stearic acid, soy polysaccharide, titanium dioxide (E 171), sodium lauryl sulfate, magnesium silicate, triacetin, mineral oil, Special Red AC (E 129), Yellow FCF (E 110), Diamond Blue FCF (E 133).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: oval, pink film-coated tablets with a cross-score on one side.

Pharmacotherapeutic group.

Calcium, combinations with vitamin D and/or other agents. ATC code: A12AX.

Pharmacological properties.

Pharmacodynamics.

Calcium is an important structural component of bone tissue. Calcium supplementation corrects dietary calcium deficiency, particularly in conditions of increased calcium demand or reduced calcium absorption.

Calcium carbonate is the salt containing the highest amount of elemental calcium. Calcium citrate enhances drug bioavailability in patients with reduced gastric acidity, achlorhydria, or those taking H2-histamine receptor blockers; reduces the risk of kidney stone formation during long-term use, and has a high anti-resorptive potential due to inhibition of parathyroid hormone.

Vitamin D is essential for the absorption of calcium, phosphates, and magnesium in the small intestine. It regulates the levels of these elements in body fluids, helps maintain normal blood calcium levels, and participates in the synthesis of organic bone components and skeletal calcification.

Magnesium is involved in bone tissue metabolism, prevents bone demineralization, inhibits calcium deposition in blood vessel walls, heart valves, muscles, and urinary tract.

Zinc acts as a cofactor for more than 200 enzymes and influences the process of bone tissue remodeling.

Copper participates in the formation of the most important connective tissue proteins—collagen and elastin—which form the matrix of bone and cartilage tissue.

Manganese normalizes the synthesis of glycosaminoglycans necessary for the formation of bone and cartilage tissue. It duplicates the calcium-conserving functions of vitamin D.

Boron regulates the activity of parathyroid hormone and thereby influences the metabolism of calcium, magnesium, phosphorus, and cholecalciferol.

Clinical characteristics.

Indications.

For slowing the rate of bone mass loss and correcting disorders of calcium metabolism, for the treatment of musculoskeletal system diseases and dental diseases. Recommended for children aged 12 years and older, adults, including women in perimenopausal and postmenopausal periods, especially in the presence of contraindications to hormone replacement therapy.

As part of complex therapy for conditions associated with significant loss of bone tissue mass.

As a baseline agent when using anti-resorptive drugs (hormone replacement therapy, calcitonin, bisphosphonates) and bone tissue formation stimulators.

Osteopenic conditions, systemic osteoporosis and its complications.

Contraindications.

Hypersensitivity to any component of the drug (allergic reactions); hypercalcemia and/or conditions leading to hypercalcemia (sarcoidosis, malignant neoplasms, and primary hyperthyroidism), severe hypercalciuria, impaired renal function, nephrolithiasis; hypervitaminosis D.

Interaction with other medicinal products and other types of interactions.

When using this drug concurrently with other medicinal products, consultation with a physician is required.

Interaction with other medicinal products.

Calcium may reduce the absorption of other medicinal substances by forming insoluble complexes in the gastrointestinal tract, including antibiotics (e.g., tetracyclines, quinolones) and antiviral agents, eltrombopag, sodium fluoride. In such cases, calcium absorption may also be reduced. To prevent potential interactions, these drugs should be administered at least 2 hours before or 4–6 hours after calcium administration, unless otherwise specified.

Interaction with protease inhibitors. Concomitant use of drugs containing calcium or magnesium, including buffered medicinal products, leads to decreased plasma concentrations of these compounds. Therefore, it is recommended to administer protease inhibitors 2 hours before or 1 hour after drugs containing aluminum, calcium, or magnesium. Such effects have been observed with amprenavir, atazanavir, and tipranavir.

Levothyroxine should be administered at least 4 hours before or 4 hours after calcium intake, as calcium reduces its absorption, possibly due to the formation of insoluble complexes.

Phosphates, bisphosphonates, and fluorides. Calcium preparations reduce the absorption of bisphosphonates; therefore, they should be taken at least 30 minutes before calcium administration, but preferably at another time or on another day. Concurrent use of the drug with antacids containing aluminum is not recommended due to reduced efficacy.

Eltrombopag. When taken with a high-fat meal containing high calcium levels (427 mg), a 59% reduction in eltrombopag plasma levels was observed. No effect on plasma eltrombopag levels was observed when consuming food with low calcium content (< 50 mg). Food high in calcium and antacids containing aluminum, calcium, or magnesium significantly reduce systemic absorption.

Calcium and/or vitamin D. Thiazide diuretics reduce urinary calcium excretion. Due to the increased risk of hypercalcemia when thiazide diuretics are used concomitantly, serum calcium levels should be monitored regularly.

Concomitant use with furosemide and other loop diuretics increases renal calcium excretion.

Cardiac glycosides and calcium channel blockers. Hypercalcemia increases the risk of fatal arrhythmias when using cardiac glycosides such as digoxin, and reduces the effectiveness of calcium channel blockers such as verapamil in atrial fibrillation. Monitoring of serum calcium levels, ECG, and the patient's clinical status is recommended.

Glucocorticoids and hormonal contraceptives impair calcium ion absorption.

Vitamin D. Some medicinal products may reduce vitamin D absorption in the gastrointestinal tract. To minimize interactions, these drugs and vitamin D should be administered at least 2 hours before or 4–6 hours after vitamin D intake.

Such medicinal products include: ion-exchange resins (e.g., cholestyramine), laxatives, orlistat. Carbamazepine, phenytoin, or barbiturates increase vitamin D metabolism to inactive metabolites and thus reduce its effect.

When using Calce**®**min Advance together with vitamin A, the toxicity of vitamin D3 is reduced.

Interaction of calcium with food and supplements. Oxalic acid found in spinach and rhubarb, and phytic acid present in whole grains, may inhibit calcium absorption. Therefore, it is not recommended to consume calcium-containing products within two hours after eating foods rich in oxalic and phytic acids.

Iron, zinc, magnesium. Calcium preparations may reduce the absorption of iron, zinc, and copper from food. However, for individuals with adequate iron, zinc, or magnesium stores, this has no clinical significance during long-term use. For individuals at risk of iron, zinc, or magnesium deficiency, to prevent inhibition of mineral absorption from food, it is recommended to take calcium supplements before bedtime rather than with meals.

Fiber. Some components of dietary fiber may reduce calcium absorption. Concurrent use of psyllium with calcium does not lead to a significant reduction in calcium absorption.

Special precautions for use.

Do not exceed the recommended dose. Calciummin® Advance should not be used simultaneously with other calcium or vitamin D preparations.

Overdose of calcium and vitamin D may result in adverse effects, including hypercalcemia and hypercalciuria. Calcium and vitamin D should be used with caution to avoid exceeding the total daily intake of 2500 mg of calcium and 4000 IU of vitamin D, taking into account dietary intake (see section "Overdose").

Patients receiving other medications containing vitamin D and/or calcium or any other medicinal products should consult a physician before starting this medication.

During long-term treatment with calcium-containing preparations in combination with vitamin D, as well as in cases of mild or moderate renal impairment (including elderly patients), serum levels of calcium, phosphates, and creatinine should be monitored; calcium and phosphates should also be monitored in urine. If signs of hypercalcemia or impaired renal function appear, or if calciuria exceeds 7.5 mmol/day (300 mg/day), the dose should be reduced or treatment discontinued. In cases of renal impairment and concomitant use of cardiac glycosides, calcium channel blockers, and/or thiazide diuretics, monitoring of renal function should be performed by measuring serum creatinine levels (see section "Interaction with other medicinal products and other forms of interaction").

Combined preparations should be used with caution in immobilized patients due to an increased risk of hypercalcemia.

Dose adjustment is not required for patients with impaired liver function. This medicinal product should not be used in patients with impaired renal function, nephrolithiasis, or predisposition to calcium deposition.

Use during pregnancy or breastfeeding.

During pregnancy and lactation, the daily dose should not exceed 2 coated tablets.

The drug should be used during pregnancy and breastfeeding only when indicated and under medical supervision. Use of the drug at recommended doses is considered safe. Recommended doses should not be exceeded, as chronic overdose may be harmful to the fetus and newborn.

During pregnancy and lactation, the total daily intake of calcium and vitamin D, including dietary sources and supplements, should not exceed 2500 mg of calcium and 4000 IU of vitamin D.

In animal studies, vitamin D overdose during pregnancy has been associated with teratogenic effects. There are no data indicating a potential teratogenic effect of vitamin D in humans when used at recommended doses.

Hypercalcemia in pregnant women due to excessive intake of vitamin D has been linked to fetal hypercalcemia, which may lead to adverse effects in the newborn, including suppression of parathyroid hormone, hypocalcemia, tetany, epileptic seizures, and aortic stenosis syndrome, the symptoms of which may include retinopathy, delayed mental development, or growth disorders; it may also lead to the development of hypercalcemia in newborns.

Vitamin D and calcium are excreted in breast milk. This should be taken into account if the infant is receiving any supplements containing vitamin D and calcium.

Fertility. Currently, there are no data indicating a potential adverse effect of vitamin D and/or calcium on human fertility.

Ability to affect reaction speed when driving or operating machinery. No effect on the ability to drive or operate machinery has been observed.

Dosage and Administration

For adults and children aged 12 years and older: take 1 tablet during a meal, 1–2 times daily. Swallow with sufficient amount of water (200 ml). The maximum daily dose should not exceed 3 coated tablets. The duration of treatment is determined by a physician depending on the nature of the disease.

Children. Not recommended for children under 12 years of age.

Overdose.

No cases of overdose have been observed when used at recommended doses. Most reports of overdose are associated with concomitant use of high doses of single-component or multivitamin preparations. In case of accidental overdose, symptomatic treatment is recommended: gastric lavage, increased fluid intake, and a low-calcium diet.

Prolonged intake of calcium and vitamin D in excessive doses exceeding 2500 mg of calcium and 4000 IU/day of vitamin D may lead to toxic effects.

In patients with hypercalcemia or conditions associated with hypercalcemia, renal insufficiency, and/or predisposition to nephrolithiasis, toxic effects of calcium and vitamin D may occur even with lower doses.

Acute or chronic overdose of calcium and vitamin D may cause hypervitaminosis D, hypercalcemia, hypercalciuria, hyperphosphatemia, and increased calcium absorption. Consequences include renal failure, milk-alkali syndrome—especially in patients with impaired renal function—vascular and soft tissue calcification, including nephrocalcinosis and nephrolithiasis, particularly in patients predisposed to kidney stones.

Non-specific initial symptoms such as sudden onset of headache, muscle weakness, depressed consciousness, and gastrointestinal disturbances (abdominal pain, constipation, diarrhea, nausea, and vomiting) may indicate acute overdose.

If such symptoms occur, discontinue use of the product immediately and seek medical advice without delay.

Laboratory and clinical signs of poisoning and hypercalcemia may include: anorexia, weight loss, increased fatigue, thirst, polyuria, bone pain, cardiac arrhythmias, and impaired absorption of other minerals. Laboratory abnormalities may include elevated plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Chronic overdose may lead to vascular and organ calcification due to hypercalcemia. Extremely high hypercalcemia may result in coma and fatal outcomes.

Side effects.

Gastrointestinal system. Gastrointestinal pain and abdominal pain, dyspepsia (including abdominal discomfort), constipation, diarrhea, flatulence, nausea, and vomiting.

Immune system (allergic reactions, anaphylactic reactions, anaphylactic shock). Hypersensitivity reactions, accompanied by corresponding laboratory and clinical manifestations, including asthma syndrome and mild to moderate reactions affecting the skin and/or respiratory system, gastrointestinal tract and/or cardiovascular system, have been reported rarely. Symptoms may include rash, urticaria, swelling, skin redness, itching, non-cardiogenic pulmonary edema. Very rare cases of severe reactions have been reported, including anaphylactic shock.

Laboratory findings. With prolonged use at high doses, hypercalcemia, hypercalciuria, and hypervitaminosis D may occur.

Shelf life.

3 years. Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

No special storage conditions required. Store in a tightly closed container. Keep out of reach of children.

Packaging.

Primary packaging: plastic bottle containing 30, 60, or 120 film-coated tablets; with a screw cap and protective film. Secondary packaging: cardboard box.

Availability.

Over-the-counter (without prescription).

Manufacturer.

Contract Pharmacal Corporation

Manufacturer's address.

135 Adams Avenue, Hauppauge, New York 11788, USA