Calcium-d3 nicomed comfort

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT CALCIUM-D3 NYCOMED COMFORTE (CALCIUM-D3 NYCOMED COMFORTE)

Composition:

Active substances:
calcium carbonate, cholecalciferol;

One tablet contains calcium carbonate 1250 mg, equivalent to 500 mg of calcium, cholecalciferol (vitamin D3) – 10 μg (400 IU) in the form of cholecalciferol concentrate* 4 mg;

Excipients:
sorbitol (E 420), mannitol (E 421), acesulfame potassium, lemon-flavoured powder, sodium croscarmellose, microcrystalline cellulose;

Film coating: hypromellose, talc, propylene glycol.

* Composition of cholecalciferol concentrate: cholecalciferol, tocopherol, medium-chain triglycerides, modified maize starch, sucrose, sodium ascorbate, silicon dioxide anhydrous colloidal.

Pharmaceutical form.
Film-coated tablets.

Main physicochemical properties:
White or almost white, oval film-coated tablets. Grey specks may be present. Embossed with 500/400.

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

ATC code A12AX.

Pharmacological properties.

Pharmacodynamics.

Vitamin D3 increases calcium absorption in the intestine.

Administration of calcium and vitamin D3 prevents the increase in parathyroid hormone levels caused by calcium deficiency, which leads to enhanced bone resorption (leaching of calcium from bones).

A clinical study in hospitalized patients with vitamin D deficiency showed that daily intake of 2 calcium tablets of 500 mg and vitamin D at a dose of 400 IU for 6 months normalized the level of 25-hydroxylated metabolite of vitamin D3 and reduced manifestations of secondary hyperparathyroidism and alkaline phosphatase levels.

Pharmacokinetics.

Absorption. Approximately 30 % of the administered calcium dose is generally absorbed through the gastrointestinal tract.

Distribution and biotransformation. 99 % of calcium is concentrated in hard tissues of the body (bones, teeth); 1 % of calcium is present in intracellular and extracellular environments. Approximately 50 % of calcium in blood is in physiologically active ionized form, nearly 10 % is complexed with citrates, phosphates and other anions, and the remaining 40 % is bound to proteins, mainly to albumins.

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

Absorption. Vitamin D3 is readily absorbed in the small intestine.

Distribution and biotransformation. Cholecalciferol and its metabolites circulate in the blood in a bound state with a specific globulin. In the liver, cholecalciferol is converted by hydroxylation into 25-hydroxycholecalciferol. Subsequently, it is transformed into the active form, 1,25-dihydroxycholecalciferol, in the kidneys. 1,25-Dihydroxycholecalciferol is the metabolite responsible for enhanced calcium absorption. Vitamin D3 that has not undergone metabolism is stored in adipose and muscle tissues.

Excretion. Vitamin D3 is excreted in feces and urine.

Clinical characteristics.

Indications.

Prevention and treatment of calcium and vitamin D deficiency in adult patients at risk.

Additional use of vitamin D and calcium as a supplement to specific osteoporosis therapy in patients at risk of developing calcium and vitamin D deficiency.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients;
• severe renal impairment (glomerular filtration rate < 30 mL/min/1.73 m²);
• diseases and/or conditions associated with hypercalcaemia and/or hypercalciuria;
• urolithiasis (nephrolithiasis);
• hypervitaminosis D.

Interaction with other medicinal products and other forms of interaction.

Thiazide diuretics reduce urinary excretion of calcium. During concomitant therapy, serum calcium levels should be monitored, as the risk of hypercalcaemia increases.

Calcium carbonate may interfere with the absorption of tetracycline-class drugs when administered simultaneously; therefore, these drugs should be taken at least 2 hours before or 4–6 hours after oral administration of Calcium-D3 Nicomed COMFORT.

Hypercalcaemia may potentiate the toxicity of cardiac glycosides when calcium and vitamin D preparations are used. It is necessary to monitor cardiac function by electrocardiogram (ECG), serum calcium levels, and the patient's clinical status.

To prevent reduced absorption of bisphosphonates when Calcium-D3 Nicomed COMFORT is used concomitantly, it is recommended to take the product no earlier than 1 hour after bisphosphonate administration.

Concomitant use of calcium may reduce the effectiveness of levothyroxine due to decreased absorption. Therefore, levothyroxine should be taken 4 hours before or 4 hours after administration of the product.

Concomitant use of calcium may impair the absorption of quinolone antibiotics. Quinolone antibiotics should be taken at least 2 hours before or 6 hours after administration of Calcium-D3 Nicomed COMFORT.

Calcium salts may reduce the absorption of iron, zinc, and strontium ranelate. Therefore, iron, zinc, and strontium ranelate preparations should be taken at least 2 hours before or after administration of the product.

Treatment with orlistat may potentially impair the absorption of fat-soluble vitamins (e.g., vitamin D3).

Special precautions for use.

During prolonged treatment with the medicinal product, serum calcium and creatinine levels and renal function should be monitored, especially in elderly patients receiving concomitant therapy with cardiac glycosides or diuretics (see section "Interaction with other medicinal products and other forms of interaction") and in patients with a high predisposition to stone formation. If signs of hypercalcaemia or impaired renal function occur, the dose should be reduced or treatment discontinued.

Vitamin D should be used with caution in patients with hypercalcaemia or signs of impaired renal function, and levels of calcium and phosphates should be monitored. The potential risk of soft tissue calcification should be kept in mind. In patients with severe renal insufficiency, vitamin D in the form of cholecalciferol may not be properly metabolized; therefore, other forms of vitamin D should be used.

Concomitant intake of vitamin D from other sources, including medicinal products or foods containing calcium (e.g. milk), may lead to hypercalcaemia and milk-alkali syndrome, resulting in subsequent renal dysfunction. To avoid overdose when other medicinal products containing vitamin D are prescribed simultaneously, the vitamin D content in Calcium-D3 Nycomed COMFORT (400 IU) should be taken into account. Additional doses of calcium or vitamin D should be taken only under medical supervision. Such patients require regular monitoring of serum calcium levels and renal function.

Calcium-D3 Nycomed COMFORT should be used with caution in patients with sarcoidosis due to the risk of increased metabolism of vitamin D3 into its active form. Serum and urinary calcium levels should be monitored.

Calcium-D3 Nycomed COMFORT should be used with caution in immobilized patients with osteoporosis due to the risk of developing hypercalcaemia.

The medicinal product should not be used in patients with rare hereditary fructose intolerance, sucrase-isomaltase deficiency, or glucose-galactose malabsorption, as it contains sorbitol (E 420) and sucrose.

Use during pregnancy or breastfeeding.

Pregnancy.
Calcium-D3 Nycomed COMFORT can be used during pregnancy in cases of calcium and vitamin D deficiency. The daily dose should not exceed 2500 mg of calcium and 4000 IU of vitamin D. Animal studies have shown that high doses of vitamin D have reproductive toxicity. Pregnant women should avoid overdosing, as prolonged hypercalcaemia may have adverse effects on the fetus. There is no evidence that vitamin D at recommended doses causes teratogenic effects in humans.

Breastfeeding.
Calcium-D3 Nycomed COMFORT can be used during breastfeeding. Calcium, vitamin D3, and its metabolites may pass into breast milk; therefore, intake of calcium and vitamin D3 from other sources into the infant's body should be taken into account.

Ability to influence the speed of reactions while driving or operating machinery.
There are no known data regarding the influence of Calcium-D3 Nycomed COMFORT on the ability to drive or operate machinery.

Dosage and Administration.

The medication is intended for oral use. The tablet should be swallowed or chewed.

Adults and elderly patients: 1 tablet twice daily.

Patients with hepatic impairment: Dose adjustment is not required.

Patients with severe renal impairment: The medication should not be used (see section "Contraindications").

Children: The medication is not intended for use in children.

Overdose.

Symptoms.

Overdose of the medication may lead to vitamin D toxicity (hypervitaminosis D) and hypercalcemia.

Symptoms of hypercalcemia include: anorexia, thirst, nausea, vomiting, constipation, abdominal pain, muscle weakness, fatigue, mental disturbances, polydipsia, polyuria, bone pain, nephrocalcinosis, nephrolithiasis, and cardiac arrhythmias in severe cases. In very severe cases, hypercalcemia may lead to coma and death. Prolonged overdose with high doses of the medication may cause irreversible kidney damage and soft tissue calcinosis. Milk-alkali syndrome may develop with the use of high doses of calcium and easily absorbable alkaline substances.

Treatment.

Symptomatic and supportive therapy. The medication should be discontinued. Therapy with thiazide diuretics and cardiac glycosides should also be discontinued (see section "Interaction with other medicinal products and other forms of interaction").

Gastric emptying should be performed in patients with impaired consciousness. Rehydration and a diet restricted in calcium intake should be implemented. Depending on the severity of overdose, administration of loop diuretics, bisphosphonates, calcitonin, and corticosteroids, either alone or in combination, may be necessary. Serum electrolyte levels, renal function, and diuresis should be monitored. In severe cases, ECG and central venous pressure monitoring should be performed.

Adverse Reactions

Undesirable effects are classified by frequency of occurrence as follows:

Uncommon (> 1/1000, < 1/100), rare (> 1/10000, < 1/1000), very rare (< 1/10000), not known (frequency cannot be estimated from available data).

Immune system disorders.

Not known: hypersensitivity reactions, including angioedema, laryngeal edema.

Metabolic and nutritional disorders.

Uncommon: hypercalcaemia, hypercalciuria.

Very rare: milk-alkali syndrome (frequent urge to urinate, persistent headache, prolonged loss of appetite, nausea or vomiting, unusual fatigue or weakness, hypercalcaemia, alkalosis, renal failure) – observed only in cases of overdose (see section "Overdose").

Gastrointestinal disorders.

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

Skin and subcutaneous tissue disorders.

Very rare: pruritus, rash, urticaria.

Special patient groups.

Patients with renal impairment: risk of developing hyperphosphataemia, nephrolithiasis, and nephrocalcinosis is possible (see section "Special precautions for use").

Shelf life. 2 years.

Storage conditions. Keep the bottle tightly closed at a temperature not exceeding 30 °C. Keep out of the reach of children!

Packaging. 30, 60 or 90 tablets in a bottle; 1 bottle in a cardboard box.

Availability. Over-the-counter.

Manufacturer.

Takeda GmbH, Oranienburg site, Germany / Takeda GmbH, Betriebsstätte Oranienburg, Germany.

Acino Estonia OU, Estonia / Acino Estonia, OU, Estonia.

Manufacturer's name and address.

Lehnitzstrasse 70-98, 16515 Oranienburg, Germany.

Jaama 55b, Polva, Polva county 63308, Estonia.