Ostalon^® Calcium-D (Tablets) Instructions for Use

Marketing Authorization Holder

Gedeon Richter, Plc. (Hungary)

Manufactured By

Beres Pharmaceuticals Co. Ltd. (Hungary)

And

GEDEON RICHTER POLAND, Co. Ltd. (Poland)

ATC Code

M05BB05 (Alendronic acid, calcium and Colecalciferol for sequential administration)

Active Substances

Calcium carbonate (Ph.Eur. European Pharmacopoeia)

Colecalciferol (Rec.INN registered by WHO)

Alendronic acid (Rec.INN registered by WHO)

Dosage Form

Ostalon® Calcium-D

Film-coated tablets, in a set of 2 types: 32 or 96 pcs. per pack, incl.: film-coated tablets, 70 mg: 4 pcs. per blister; film-coated tablets, 400 IU+1.5 g: 14 pcs. per blister

Dosage Form, Packaging, and Composition

Tablets, film-coated, in a set of 2 types

Tablets, film-coated white, round, biconvex, with engraving “M14” on one side. (4 pcs. per blister).

Excipients : microcrystalline cellulose – 261.25 mg, colloidal silicon dioxide – 3.5 mg, croscarmellose sodium – 1.28 mg, magnesium stearate – 2.62 mg.

Film coating composition Lustre Clear LS103 – 7 mg (microcrystalline cellulose – 44%, carrageenan – 18%, macrogol 8000 – 38%).

Tablets, film-coated pale brownish-yellow, oblong, with a score on one side; on cross-section – a white core (14 pcs. per blister).

Excipients : D,L-α-tocopherol – 0.008 mg, hydrogenated soybean oil – 0.3 mg, gelatin – 1.52 mg, sucrose – 1.52 mg, corn starch – 0.642 mg, maltodextrin – 76 mg, polysorbate 80 – 2 mg, microcrystalline cellulose – 39 mg, copovidone – 17 mg, crospovidone – 8 mg, magnesium stearate – 4 mg.

Film coating composition: sepifilm 4202 yellow – 50 mg (hypromellose – 55-65%, macrogol – 10-16%, talc – 10-20%, titanium dioxide (E171) – 5-15%, iron oxide yellow (E172) – 5%).

14 pcs. (tab.) – blisters (2) +4 pcs. (tab.) – blisters (1) – cardboard packs.
14 pcs. (tab.) – blisters (6) +4 pcs. (tab.) – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Combined drug for the treatment of osteoporosis

Pharmacotherapeutic Group

Osteoporosis treatment agent (bone resorption inhibitor + calcium-phosphorus metabolism regulator)

Pharmacological Action

Combined drug.

Alendronic acid, as a bisphosphonate, penetrates into areas of active bone resorption, inhibits the resorption process without directly affecting the formation of new bone tissue, which leads to an increase in bone mass. During treatment, normal bone tissue is formed (at therapeutic doses, Alendronic acid does not cause osteomalacia).

Calcium carbonate contains calcium, which is an essential element that plays a key role in electrolyte balance. It is necessary for muscle contraction, nerve impulse conduction, and blood clotting. It plays a crucial role in intracellular signaling and in the control of various metabolic processes. Calcium is the main inorganic component of bone tissue, 99% of the total calcium content in the body is present in bone tissue.

Colecalciferol increases intestinal absorption of calcium and phosphates, regulates their excretion by the kidneys, and also regulates the concentration of calcium in blood plasma.

Pharmacokinetics

Alendronic acid

Absorption and distribution

Bioavailability when taken on an empty stomach 2 hours before meals is 0.64% (in women) and 0.6% (in men); when taken 1-1.5 hours before meals, it decreases by 40%. Coffee and orange juice reduce bioavailability by 60%. When taken at therapeutic doses, the concentration of the drug in plasma is less than 5 ng/ml.

V_d– 28 L (excluding bone tissue). Protein binding – 78%.

Elimination

Renal clearance – 71 ml/min (at a dose of 10 mg IV). 6 hours after IV administration, the concentration in blood plasma decreases by more than 95%. T_1/2– 72 hours, terminal T_1/2– more than 10 years (reflects elimination from bone tissue). Excreted mainly by the kidneys, a small amount is removed through the intestines.

Colecalciferol

The bioavailability of colecalciferol in combination with alendronic acid is similar to the bioavailability of colecalciferol when taken alone.

Calcium carbonate

Absorption and distribution

Approximately 1/5-1/3 of the orally administered drug is absorbed in the small intestine; this process depends on the presence of vitamin D, pH, dietary characteristics, and the presence of factors affecting the ability to bind calcium. Calcium absorption increases with its deficiency and when using a diet with reduced calcium content. In blood plasma, about 45% is in complex with proteins.

Elimination

About 20% is excreted by the kidneys, the remaining amount (80%) is removed through the intestines.

Indications

• Osteoporosis in postmenopausal women (reducing the risk of fractures, including hip fractures and vertebral compression fractures);
• Osteoporosis in men (reducing the risk of fractures);
• Osteoporosis caused by long-term use of glucocorticoids.

ICD codes

Dosage Regimen

Tablets containing alendronic acid are prescribed orally, 1 tab. once a week. The drug is recommended to be taken on the same day of the week.

The tablet should be taken whole, in the morning on an empty stomach, with a glass of water, at least 30 minutes before the first meal, drink, or other medications. The tablet should not be chewed or dissolved. Wash down only with plain water, since other drinks (including mineral water, coffee, tea, orange juice) reduce absorption.

After taking the drug, the patient must maintain an upright body position (standing or sitting) for at least 30 minutes. Do not take the drug before bedtime or before getting out of bed in the morning.

The patient should be warned that if a dose of alendronic acid is missed, the missed tablet should be taken the next day. Under no circumstances should you take 2 tablets on the same day.

Tablets containing the combination Colecalciferol + Calcium carbonate, are prescribed orally, 1 tab. daily, after lunch or dinner, with a glass of water. Do not chew the tablet. On the day of taking alendronic acid, the drug should be taken no earlier than 3 hours after taking alendronic acid.

Adverse Reactions

Adverse reactions associated with taking alendronic acid

Definition of frequency of adverse reactions: common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10 000, <1/1000).

From the digestive system common – abdominal pain, dyspepsia, constipation, diarrhea, flatulence, esophageal ulcer, dysphagia, abdominal distension, heartburn; uncommon – nausea, vomiting, gastritis, esophagitis, esophageal erosion, melena; rare – esophageal stricture, oropharyngeal ulcer, perforation of the upper gastrointestinal tract, ulcer, bleeding (the relationship with treatment is not always clear).

From the musculoskeletal system common – bone pain, arthralgia, myalgia.

From the nervous system common – headache; irritability.

From the skin: uncommon – itching, rash, skin hyperemia.

Allergic reactions: rare – urticaria, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis).

From the organ of vision rare – uveitis, scleritis.

From metabolism rare – transient, mild asymptomatic hypocalcemia and hypophosphatemia.

From the body as a whole rare – transient symptoms that most often appear at the beginning of treatment (myalgia, weakness, malaise, in rare cases – fever), rash, photosensitivity, asymptomatic hypocalcemia (often accompanied by predisposing factors) and hypophosphatemia. Cases of osteonecrosis of the upper and lower jaw have been described during treatment with bisphosphonates in cancer patients against the background of anticancer treatment.

Adverse reactions associated with taking the combination Colecalciferol + Calcium carbonate

From the digestive system rare (≥1/10 000, <1/1000) – constipation, flatulence, nausea, abdominal pain, diarrhea.

From metabolism uncommon (≥1/1000, <1/100) – hypercalcemia, hypercalciuria.

From the skin rare (≥1/10 000, <1/1000) – itching, rash, urticaria.

Contraindications

For alendronic acid

• Hypocalcemia;
• Abnormalities of the esophagus and other factors that impede esophageal patency (achalasia, stricture);
• Inability of the patient to remain in an upright position (standing or sitting upright) for 30 minutes;
• Chronic renal failure (CrCl <35 ml/min);
• Pregnancy;
• Lactation period;
• Childhood;
• Individual intolerance to the drug.

For the combination Colecalciferol + Calcium carbonate

• Hypercalcemia (including as a result of primary or secondary hyperparathyroidism);
• Hypercalciuria;
• Calcium nephrolithiasis;
• Hypervitaminosis D;
• Sarcoidosis;
• Osteoporosis due to immobilization;
• Pulmonary tuberculosis (active form);
• Increased individual sensitivity to the components of the drug.

With caution gastrointestinal diseases in the acute phase – dysphagia, esophagitis, gastritis, gastric and duodenal ulcers.

Use in Pregnancy and Lactation

Ostalon^® Calcium-D is contraindicated during pregnancy and lactation.

Use in Renal Impairment

Contraindication: chronic renal failure (CrCl <35 ml/min).

Pediatric Use

Contraindication: childhood.

Special Precautions

For alendronic acid

To reduce the irritating effect on the esophagus, it is necessary to take immediately after getting up in the morning, with a full glass of water, and after taking, you should not lie down for 30 minutes (dangerous to use if the patient is unable to stand or sit upright for 30 minutes). Taking before bedtime or in a horizontal position increases the risk of esophagitis.

In patients with hypocalcemia, corrective therapy for mineral metabolism disorders, including vitamin D deficiency and hypoparathyroidism, must be carried out before starting treatment with alendronic acid.

During treatment, due to the positive effect of alendronic acid on bone mineral density, a slight asymptomatic decrease in the concentration of calcium and phosphates in the blood serum may be observed.

When taking bisphosphonates (especially with concomitant glucocorticoid therapy), it is necessary to ensure adequate intake of calcium and vitamin D with food or in the form of medications.

There are reports of osteonecrosis of the jaw, usually associated with tooth extraction and/or local infection (including osteomyelitis) in cancer patients who mainly received bisphosphonates IV. Many of these patients also received chemotherapy and glucocorticoids. There are also reports of osteonecrosis of the jaw in patients with osteoporosis receiving oral bisphosphonates.

Before prescribing bisphosphonate therapy, patients with concomitant risk factors (e.g., cancer, chemotherapy, radiation therapy, glucocorticoid use, poor oral hygiene) should undergo a dental examination with appropriate preventive dental treatment.

Patients undergoing bisphosphonate treatment should, if possible, avoid invasive dental procedures. In patients undergoing bisphosphonate therapy who have developed osteonecrosis of the jaw, dental surgical interventions may worsen the condition. If surgical interventions are necessary, it should be taken into account that there is no data on the possibility of reducing the risk of osteonecrosis of the jaw after discontinuation of the bisphosphonate.

For the combination Colecalciferol + Calcium carbonate

To avoid overdose, additional intake of vitamin D from other sources must be taken into account.

Consumption of foods containing oxalates (sorrel, spinach) and phytic acid (cereals) reduces the absorption of calcium, so Colecalciferol + Calcium carbonate should not be taken within 2 hours after consuming sorrel, spinach, or cereals.

Effect on the ability to drive vehicles and mechanisms

No adverse effects of the drugs on the ability to drive vehicles and engage in other activities requiring concentration and speed of psychomotor reactions have been reported.

Overdose

Alendronic acid

Symptoms hypocalcemia, hypophosphatemia, as well as adverse reactions from the gastrointestinal tract (diarrhea, heartburn, esophagitis, gastritis or erosive-ulcerative lesions of the gastrointestinal tract).

Treatment milk or calcium-containing antacids to bind the drug. Due to the risk of esophageal irritation, vomiting should not be induced; the patient should be placed in an upright position (standing or sitting).

Colecalciferol + Calcium carbonate

Symptoms hypervitaminosis D, hypercalcemia, which is manifested by anorexia, thirst, nausea, vomiting, constipation, abdominal pain, muscle weakness, fatigue, polyuria, bone pain, hypercreatininemia, hypercalciuria, arrhythmia. With long-term use – calcification of blood vessels and tissues.

Drug Interactions

Concomitant use of calcium preparations, antacids and other drugs reduces the absorption of alendronic acid. The interval between taking the drugs should be at least 1 hour.

Ranitidine increases the bioavailability of alendronic acid by 2 times (clinical significance not determined).

NSAIDs enhance the side effects of alendronic acid from the gastrointestinal tract.

Thiazide diuretics reduce the excretion of calcium. Due to the increased risk of hypercalcemia, serum calcium levels should be regularly monitored throughout the course of treatment with thiazide diuretics.

Glucocorticoids reduce the absorption of calcium. During a course of glucocorticoid treatment, it may be necessary to increase the dose of the combination of colecalciferol + calcium carbonate.

Concomitant use with ion-exchange resins such as cholestyramine or laxatives may reduce the absorption of vitamin D.

Use of the combination Colecalciferol + Calcium carbonate simultaneously with tetracycline is possible either 2 hours before taking tetracycline or 4-6 hours after.

The combination Colecalciferol + Calcium carbonate may enhance the toxicity of cardiac glycosides. Patients need to have their calcium concentration and ECG examined.

When sodium fluoride and the combination Colecalciferol + Calcium carbonate are prescribed simultaneously, the interval between taking the drugs should be at least 3 hours.

Oxalic acid interferes with the absorption of calcium because it forms insoluble complexes with calcium ions. The patient should not take tablets containing the combination Colecalciferol + Calcium carbonate within 2 hours after consuming foods high in oxalic acid (rhubarb, spinach).

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 – 2 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by 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.