Calcemin^® Advance (Tablets) Instructions for Use

Marketing Authorization Holder

BAYER, JSC (Russia)

Manufactured By

Contract Pharmacal Corporation (USA)

Packaging and Quality Control Release

CONTRACT PHARMACAL CORPORATION (USA)

Contact Information

BAYER AG (Germany)

ATC Code

A12AX (Calcium preparations in combination with vitamin D and/or other drugs)

Dosage Form

Calcemin® Advance

Film-coated tablets: 30, 60, or 120 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets pink in color, oval in shape, biconvex, with a score on one side.

* contains gum arabic and maltodextrin.
** as dry vitamin D₃ 100000 IU/g – contains starch, sucrose, sodium ascorbate, triglycerides, silicon dioxide and tocopherols.

Excipients : maltodextrin – 25 mg, microcrystalline cellulose – 49.05 mg, croscarmellose sodium – 38 mg, stearic acid – 16.3 mg, soy polysaccharide – 15 mg, sodium lauryl sulfate – 5 mg.

Coating composition hypromellose – 26.328 mg, titanium dioxide – 12.643 mg, magnesium silicate – 5 mg, triacetin – 5.689 mg, mineral oil – 2.845 mg, aluminum lake based on Allura Red AC (Red No. 40) – 0.316 mg, aluminum lake based on Sunset Yellow FCF (Yellow No. 6) – 0.079 mg, aluminum lake based on Brilliant Blue FCF (Blue No. 1) – 0.04 mg.

30 pcs. – high-density polyethylene bottles (1) – cardboard packs.
60 pcs. – high-density polyethylene bottles (1) – cardboard packs.
120 pcs. – high-density polyethylene bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Drug affecting phosphorus-calcium metabolism

Pharmacotherapeutic Group

Calcium-phosphorus metabolism regulator

Pharmacological Action

A combined preparation containing vitamins, micro- and macroelements; the action is due to the properties of the ingredients included in the composition.

Calcium participates in the formation of bone tissue, reduces resorption and increases bone density, prevents diseases of the musculoskeletal system, promotes the strengthening of bone tissue and joints. Calcium citrate ensures calcium absorption regardless of the functional state of the gastrointestinal tract, which is applicable for the treatment of patients with reduced secretory function of the gastrointestinal tract, as well as during treatment with drugs to reduce secretion; reduces the level of bone resorption markers, which indicates a slowdown in the processes of bone tissue destruction; regulates the content of parathyroid hormone, which leads to improved regulation of calcium homeostasis; does not increase the content of oxalates and calcium in the urine, therefore does not cause the risk of kidney stones; does not block iron absorption, which reduces the risk of iron deficiency anemia.

Colecalciferol (vitamin D₃) regulates the metabolism of calcium and phosphorus in the body, participates in the formation of the bone skeleton, helps preserve bone structure, enhances calcium absorption in the intestine and phosphorus reabsorption in the renal tubules.

Magnesium participates in the formation of muscle and bone tissues, and is also involved in protein synthesis (including type I collagen).

Zinc promotes the synthesis of sex hormones, which prevents the destruction of bone tissue. It has a beneficial effect on bone density.

Zinc and Magnesium are necessary for the synthesis of the organic bone matrix.

Manganese participates in the formation of proteoglycans, which improves the quality of bone tissue and forms the protein (collagen) matrix of bone tissue.

Copper participates in the synthesis of collagen and elastin, which are part of bone and connective tissue, which affects the processes of bone mass formation.

Boron reduces excessive activity of parathyroid hormone, improves calcium absorption, reduces the risk of colecalciferol deficiency, and helps prevent osteoporosis.

Indications

• Prevention and complex therapy of osteoporosis of various origins: age-related, in women during menopause (natural and surgical), idiopathic, in persons taking glucocorticosteroids and immunosuppressants for a long time;
• Prevention and complex therapy of dental and periodontal diseases;
• Situations requiring additional intake of calcium, vitamin D and minerals (for example, to improve consolidation of traumatic fractures, during pregnancy, with nutritional deficiency);
• Prevention and treatment of calcium, vitamin D, magnesium, zinc, copper, manganese and boron deficiency.

ICD codes

Dosage Regimen

The drug is taken orally, with meals, with a sufficient amount of water (200 ml).

Adults, children over 12 years of age and elderly persons

For prevention of osteoporosis, calcium, vitamin D and mineral deficiency – 1 tablet 2 times/day. The average duration of the course is 2 months.

In addition to specific therapy for osteoporosis, treatment of calcium, vitamin D and mineral deficiency – 1 tablet 2-3 times/day. The average duration of the course is 3 months.

In situations requiring therapeutic use of calcium, vitamin D and mineral supplements – 1 tablet 1-2 times/day. The average duration of the course is 4-6 weeks.

The duration of individual treatment is determined by the attending physician.

Special patient groups

Dosage during pregnancy – 1 tablet 1-2 times/day.

In patients with hepatic insufficiency, there is no need for dose adjustment. The maximum daily dose should not exceed 3 tablets.

Adverse Reactions

The following adverse reactions have been identified during post-registration use of the drug (since information about such reactions is voluntarily reported from an unknown number of people, it is not always possible to reliably assess their frequency or establish a causal relationship with the drug).

From the digestive system: abdominal pain, constipation, diarrhea, flatulence, nausea and vomiting may occur.

From the immune system allergic reactions, anaphylactic reactions, anaphylactic shock. Rare hypersensitivity reactions with corresponding laboratory and clinical manifestations, including asthmatic syndrome, from mild to moderate skin and/or respiratory and/or gastrointestinal and/or cardiovascular reactions. Symptoms may include rash, urticaria, swelling, itching, respiratory distress syndrome, and very rarely, severe reactions including anaphylactic shock.

Contraindications

• Increased individual sensitivity to the components of the drug;
• Hypervitaminosis of vitamin D;
• Hypercalcemia and/or conditions leading to hypercalcemia, such as sarcoidosis, malignant tumors and primary hyperthyroidism;
• Hypercalciuria;
• Renal failure;
• Urolithiasis, nephrolithiasis;
• Active form of tuberculosis;

• Children under 12 years of age;
• Allergic reaction to peanut oil and soy, because the drug contains soy polysaccharide;

With caution: pregnancy, breastfeeding period, renal failure.

Use in Pregnancy and Lactation

The use of the drug during pregnancy and breastfeeding should be agreed with a doctor.

The daily dose for pregnant women should not exceed 1500 mg of calcium and 600 IU of vitamin D₃, because hypercalcemia developing due to overdose during pregnancy can cause mental and physical developmental defects in the child.

In nursing women, it should be taken into account that Colecalciferol and its metabolites are excreted in breast milk. This should be taken into account when additionally prescribing calcium and vitamin D₃ to the child.

Use in Hepatic Impairment

In patients with hepatic insufficiency, there is no need for dose adjustment.

Use in Renal Impairment

The use of the drug is contraindicated in renal failure and urolithiasis.

The drug should be prescribed with caution in renal failure.

Pediatric Use

The use of the drug is contraindicated in children under 12 years of age.

Special Precautions

The recommended dose should not be exceeded, because increased calcium intake can inhibit the absorption of iron, zinc and other essential minerals in the intestine.

Effect on the ability to drive vehicles and mechanisms

There are no data on the effect of the drug on the speed of psychomotor reactions when driving a car and working with mechanisms.

Overdose

Overdose of the drug can lead to hypervitaminosis of vitamin D₃, hypercalcemia and hypercalciuria.

Symptoms thirst, polyuria, decreased appetite, constipation, nausea, vomiting, dizziness, muscle weakness, headache, fainting, coma, increased fatigue, bone pain, mental disorders, nephrocalcinosis, abdominal pain, urolithiasis, in severe cases – cardiac arrhythmias. With long-term use of calcium in doses above 2500 mg – kidney damage, calcification of soft tissues.

If the first signs of overdose are detected, the patient should reduce the dose or stop using the drug and consult a doctor.

In case of hypercalciuria exceeding 7.5 mmol/day (300 mg/day), it is necessary to reduce the dose or stop taking the drug.

Treatment: rehydration, use of “loop” diuretics (e.g., furosemide), glucocorticosteroids, calcitonin, bisphosphonates, in severe cases – hemodialysis.

In case of accidental overdose, induce vomiting and perform gastric lavage. If necessary – symptomatic therapy.

Drug Interactions

Calcium salts

Calcium salts can interact with many substances due to changes in gastric juice pH, affecting gastric emptying or forming complexes with certain substances, leading to reduced absorption of both substances. Since these interactions occur in the gastrointestinal tract, to minimize the possibility of interaction, calcium preparations should be taken separately from other medicines. As a rule, it is sufficient to observe an interval between taking the drugs, at least 2 hours before or 4-6 hours after taking the calcium preparation, unless otherwise indicated.

Antibiotics and antiviral drugs (e.g., tetracyclines, fluoroquinolones)

Calcium reduces the absorption of tetracycline antibiotics by forming insoluble complexes. Patients should take these drugs at least 2 hours before or 4-6 hours after taking the calcium preparation.

Levothyroxine

Calcium reduces the absorption of levothyroxine, probably due to the formation of insoluble complexes. Patients should take levothyroxine at least 4 hours before or 4 hours after taking calcium preparations.

Phosphates, bisphosphonates and fluorides

Calcium preparations reduce the absorption of bisphosphonates. Patients should take bisphosphonates at least 30 minutes before taking calcium, but preferably at different times of the day.

Eltrombopag

A 59% reduction in plasma eltrombopag levels was observed when consumed with a high-fat, high-calcium (427 mg) breakfast, while a low-calcium (<50 mg) meal did not significantly affect plasma eltrombopag levels. Calcium-rich foods and antacids containing aluminum, Calcium and Magnesium showed a significant reduction in systemic exposure.

Sodium fluoride

Calcium preparations impair the absorption of sodium fluoride. Patients should take sodium fluoride at least 2 hours before or 2 hours after taking calcium preparations.

Cardiac glycosides and calcium channel blockers

Hypercalcemia increases the likelihood of fatal cardiac arrhythmias when using cardiac glycosides such as digoxin and reduces the effectiveness of calcium channel blockers such as verapamil in atrial fibrillation. It is recommended to monitor serum calcium levels in people taking Calcium and/or vitamin D or these drugs simultaneously.

Protease inhibitor

If products containing Calcium or Magnesium, including buffered preparations, are administered together with some protease inhibitors, a decrease in the plasma concentration of all these substances is possible. Therefore, it is recommended to take the protease inhibitor 2 hours before or 1 hour after taking preparations containing aluminum, Calcium or Magnesium. This effect has been observed with the following drugs: amprenavir, atazanavir and tipranavir.

Thiazide diuretics

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

Some medications may reduce the gastrointestinal absorption of vitamin D. To minimize such interaction, these drugs and vitamin D should be taken separately, at least 2 hours before or 4-6 hours after taking vitamin D. These drugs include: ion-exchange resins (e.g., cholestyramine), laxatives, orlistat, carbamazepine, phenytoin and barbiturates increase the conversion of vitamin D to its inactive metabolite, reducing the effect of vitamin D₃.

Interaction with food components

Oxalic acid, phytic acid. Oxalic acid, found in spinach and rhubarb, and phytic acid, found in grains, can interfere with calcium absorption. It is not recommended to take calcium preparations within 2 hours after eating foods high in oxalic and phytic acids.

Iron, Zinc, Magnesium

Calcium preparations may reduce the absorption of iron, zinc and magnesium from food. However, in people with normal levels of these minerals, this has no clinical significance in the long term. Patients at risk of iron, zinc or magnesium deficiency should take calcium preparations at bedtime, rather than with meals, to avoid slowing the absorption of trace elements.

Dietary fiber

Some components of dietary fiber may slow down calcium absorption. These include phytic acid (found in wheat bran), oxalic acid (found in spinach and rhubarb) and uronic acid (a common component of plant fibers).

Storage Conditions

The drug should be stored out of the reach of children, in a dry place at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.