Calcium-d3 nicomed with orange flavor

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT CALCIUM-D3 NYCOMED with orange flavour (CALCIUM-D3 NYCOMED with orange flavour)

Composition:

Active substances: 1 tablet contains calcium carbonate 1250 mg, equivalent to 500 mg of calcium, cholecalciferol (vitamin D3) – 5 μg (200 IU), corresponding to cholecalciferol concentrate* 2 mg;

Excipients: xylitol (E 967), orange-flavoured granulate (isomalt (E 953), orange flavouring, mono- and diglycerides of fatty acids), povidone, magnesium stearate, sucralose (E 955).

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

Pharmaceutical form. Chewable tablets.

Main physicochemical properties: white, round, biconvex uncoated tablets. Speckles and minor edge irregularities are acceptable. A small amount of powder at the bottom of the bottle may be present.

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.

The use of calcium and vitamin D3 prevents an increase in parathyroid hormone (PTH) 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.

Calcium.

Absorption. Approximately 30 % of the administered calcium dose is 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 exists in physiologically active ionized form, nearly 10 % is complexed with citrates, phosphates, and other anions, and the remaining 40 % is bound to proteins, primarily albumins.

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

Cholecalciferol.

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

Distribution and biotransformation. Cholecalciferol and its metabolites circulate in the blood bound to a specific globulin. In the liver, cholecalciferol is converted via hydroxylation into 25-hydroxycholecalciferol. This is further 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.

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 other components of the medicinal product;
• Severe renal insufficiency (glomerular filtration rate <30 mL/min/1.73 m²);
• Diseases and/or conditions associated with hypercalcaemia and/or hypercalciuria;
• Nephrolithiasis (urinary stone disease);
• Hypervitaminosis D;
• Active-phase tuberculosis.

Interaction with other medicinal products and other types of interactions.

The activity of vitamin D3 may be reduced when used concomitantly with rifampicin.

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

Calcium carbonate may interfere with the absorption of tetracycline-class drugs. Tetracycline-class drugs should be taken at least 2 hours before or 4–6 hours after administration of Calcium-D3 Nicomed.

Hypercalcaemia may potentiate the toxicity of cardiac glycosides (possible development of arrhythmias, etc.) when calcium and vitamin D preparations are used. Concomitant use in patients receiving cardiac glycosides and high doses of calcium is not recommended. If concomitant therapy with cardiac glycosides is necessary, low doses of the medicinal product should be used. Monitoring of cardiac function by ECG and serum calcium levels in patients is required.

To prevent reduced absorption of bisphosphonates, Calcium-D3 Nicomed should be taken no sooner than 1 hour after bisphosphonate administration.

When calcium is used concomitantly, the efficacy of levothyroxine may be reduced due to decreased absorption. Levothyroxine should be taken at least 4 hours after administration of Calcium-D3 Nicomed.

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.

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 Calcium-D3 Nicomed.

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

Special precautions for use

During prolonged treatment with this medication, it is necessary to monitor serum calcium and creatinine levels and kidney function, especially in elderly patients receiving concomitant therapy with cardiac glycosides or diuretics (see section "Interaction with other medicinal products and other types of interactions") and in patients with a high predisposition to dental calculus formation. If signs of hypercalcemia or impaired kidney function occur, the dose should be reduced or administration of the medication discontinued.

This medication should be used with caution in patients with hypercalcemia or signs of impaired kidney function, and serum levels of calcium and phosphates should be monitored. The risk of soft tissue calcification should be taken into account. In patients with severe renal insufficiency, vitamin D3 in the form of cholecalciferol may not be properly metabolized; therefore, other forms of vitamin D should be used (see section "Contraindications").

Concomitant intake of vitamin D from other sources, including medicinal products or foods containing calcium (e.g., milk), may lead to hypercalcemia and milk-alkali syndrome, resulting in subsequent kidney dysfunction. Additional doses of calcium or vitamin D should be taken under medical supervision. Such patients require regular monitoring of serum calcium levels and kidney function.

Calcium-D3 Nycomed is contraindicated in patients with sarcoidosis and hypoparathyroidism due to the risk of increased metabolism of vitamin D3 into its active form.

Serum and urinary calcium levels should be monitored in such patients.

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

Calcium-D3 Nycomed contains sucrose, which may be harmful to teeth. The medication also contains isomalt (E 953). Therefore, the medication should not be used in patients with rare hereditary fructose intolerance, sucrase-isomaltase deficiency, or glucose-galactose malabsorption.

Calcium-D3 Nycomed contains less than 23 mg of sodium per tablet, i.e., it is essentially sodium-free.

Use during pregnancy or breastfeeding.

Pregnancy. Calcium-D3 Nycomed may 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 on Calcium-D3 Nycomed, as prolonged hypercalcemia 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 may be used during breastfeeding. Calcium, vitamin D3, and its metabolites may pass into breast milk; therefore, intake of calcium and vitamin D from other sources into the infant's body should be taken into account.

Ability to affect reaction rate when driving or operating machinery.

There are no known data regarding the effect of Calcium-D3 Nycomed on reaction rate when driving or operating machinery.

Dosage and Administration

The medication is intended for oral administration. The tablet should be chewed or sucked.

Calcium and vitamin D deficiency

Adults and elderly patients: 1 tablet 1–3 times daily.

Children aged 5 years and older: 1 tablet 1–2 times daily as recommended by a physician.

Adjunctive therapy in osteoporosis

Adults: 1 tablet 2–3 times daily.

Patients with hepatic impairment do not require dose adjustment.

Patients with severe renal impairment should not use the medication (see section "Contraindications").

Elderly patients: The same doses as recommended for adults are recommended.

Children: The medication may be used for the treatment of calcium and vitamin D deficiency in children aged 5 years and older as recommended by a physician.

Overdose

Symptoms: Overdose may lead to hypercalcemia and vitamin D hypervitaminosis. Symptoms of hypercalcemia include: anorexia, thirst, nausea, vomiting, constipation, abdominal pain, muscle weakness, increased fatigue, mental disorders, polydipsia, polyuria, bone pain, nephrocalcinosis, nephrolithiasis, and cardiac arrhythmias in severe cases. Severe hypercalcemia may result in coma and fatal outcome. Persistent high calcium levels in the body may lead to irreversible kidney damage and soft tissue calcification.

In patients taking large amounts of calcium and absorbable alkalis, milk-alkali syndrome may develop; such patients require hospitalization.

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 lavage should be performed in patients with impaired consciousness, and large amounts of fluid should be administered. Depending on the severity of overdose, treatment with loop diuretics, bisphosphonates, calcitonin, and corticosteroids, either alone or in combination, may be required. Serum electrolyte levels, renal function, and diuresis should be monitored. In severe cases, monitoring of electrocardiogram (ECG) and central venous pressure (CVP) parameters is required.

Adverse reactions.

Undesirable effects are classified by frequency of occurrence as follows:

uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), not known (frequency cannot be determined from available data).

From the immune system.

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

From the metabolism and nutrition disorders.

Uncommon: hypercalcemia, hypercalciuria.

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

From the gastrointestinal tract.

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

From the skin and subcutaneous tissue.

Very rare: pruritus, rash, urticaria.

Special patient groups.

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

Shelf life. 30 months.

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

Packaging. 20, 50 or 100 tablets in a bottle; 1 bottle in a cardboard box.

Prescription status. Over-the-counter.

Manufacturer. Asker Contract Manufacturing AS, Norway.

Manufacturer's address. Drammensveien 852, NO-1383 Asker, Norway.