Calcefenit (Drops) Instructions for Use

Marketing Authorization Holder

Usolye-Sibirskiy Chemical and Pharmaceutical Plant, JSC (Russia)

Manufactured By

Usolye-Sibirskiy Chemical and Pharmaceutical Plant, JSC (Russia)

ATC Code

A11CC05 (Colecalciferol)

Active Substance

Colecalciferol (Rec.INN registered by WHO)

Dosage Form

Calcefenit

Oral drops 15000 IU/1 ml: 10 ml, 15 ml, 20 ml, 25 ml or 30 ml bottle

Dosage Form, Packaging, and Composition

Oral drops in the form of a transparent or slightly opalescent, colorless or weakly colored liquid with an aniseed odor.

Excipients: macrogol glycerol ricinoleate – 75 mg, sucrose – 250 mg, disodium hydrogen phosphate dodecahydrate – 7 mg, citric acid monohydrate – 0.43 mg, anise flavor – 16.2 mg, benzyl alcohol – 15 mg, purified water – up to 1 ml.

10 ml – dark glass bottles (1) – cardboard packs.
15 ml – dark glass bottles (1) – cardboard packs.
20 ml – dark glass bottles (1) – cardboard packs.
25 ml – dark glass bottles (1) – cardboard packs.
30 ml – dark glass bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Drug regulating calcium and phosphorus metabolism

Pharmacotherapeutic Group

Calcium-phosphorus metabolism regulator

Pharmacological Action

Vitamin D₃, an anti-rachitic agent. It participates in the regulation of calcium-phosphorus metabolism, enhances calcium absorption in the intestines and phosphate reabsorption in the kidneys, promotes bone mineralization, and is necessary for the normal functioning of the parathyroid glands. It participates in the synthesis of lymphokines and ATP.

Calcium and/or vitamin D₃ deficiency causes hypersecretion of parathyroid hormone. As a result of this secondary hyperparathyroidism, bone tissue remodeling increases, leading to bone fragility and fractures. The use of calcium and vitamin D₃ in the recommended dose range causes a decrease in parathyroid hormone secretion.

Pharmacokinetics

After oral administration, Colecalciferol is absorbed from the small intestine. C_max in tissues is reached after 4-5 hours, after which the concentration decreases somewhat, remaining at a constant level for a long time. Colecalciferol in blood plasma binds to the Colecalciferol-binding protein and is transported to the liver, where microsomal hydroxylation occurs to form the inactive metabolite 25-hydroxycholecalciferol (calcifediol). The concentration of circulating calcifediol in the blood is an indicator of the level of vitamin D₃ in the body. Then calcifediol enters the kidneys, where it undergoes repeated hydroxylation to form the active metabolite 1,25-dihydroxycholecalciferol (calcitriol). Vitamin D₃ and its metabolites can accumulate in muscle and adipose tissues, where their concentration can persist for several months. After taking high doses of vitamin D₃, the concentration of calcifediol in the blood serum can remain elevated for several months. Hypercalcemia due to vitamin D₃ overdose can persist for several weeks. Calcitriol undergoes further hydroxylation before being excreted from the body. The main route of excretion of vitamin D₃, as well as its hydroxylated and sulfate derivatives, is bile (feces), and at least 2% of these substances are excreted in the urine. Colecalciferol crosses the placental barrier. It is excreted in breast milk.

Indications

Prevention of rickets and osteomalacia in children and adults; prevention of diseases associated with vitamin D₃ insufficiency (deficiency) in healthy children and adults without malabsorption; prevention of rickets in full-term and premature newborns; prevention of diseases associated with vitamin D₃ insufficiency (deficiency) in children and adults with malabsorption syndrome (chronic diseases of the small intestine, biliary cirrhosis of the liver, conditions after resection of the stomach and/or small intestine).

Treatment of rickets and osteomalacia in newborns, children and adults (against the background of mineral metabolism disorders in patients over 45 years of age, long-term immobilization in case of injuries, adherence to diets with the refusal of milk and dairy products).

Maintenance therapy for osteoporosis in adults.

Treatment of hypoparathyroidism in adults.

ICD codes

Dosage Regimen

Determine the dosage individually based on the clinical indication, patient age, and baseline vitamin D status.

For oral administration. Administer the drops directly into the mouth or mix with a small amount of infant formula, milk, or other liquid immediately before use.

For prevention of rickets in full-term newborns from 4 weeks of age: administer 1 drop (approximately 500 IU) daily. For premature newborns from 4 weeks of age: administer 2 drops (approximately 1000 IU) daily. Continue throughout the autumn-winter period.

For treatment of rickets: administer 2 to 10 drops (approximately 1000 to 5000 IU) daily for 1 year. The exact dosage and duration are determined by the physician based on disease severity.

For prevention of vitamin D deficiency in children and adults without malabsorption: administer 1 to 2 drops (approximately 500 to 1000 IU) daily.

For prevention in children and adults with malabsorption syndrome: administer 6 to 14 drops (approximately 3000 to 7000 IU) daily.

For treatment of osteomalacia and as part of maintenance therapy for osteoporosis: administer 2 to 4 drops (approximately 1000 to 2000 IU) daily.

For treatment of hypoparathyroidism in adults: administer 20 to 40 drops (approximately 10,000 to 20,000 IU) daily. Adjust the dose based on plasma calcium levels.

During long-term therapy at doses exceeding 1000 IU daily, monitor plasma calcium levels periodically. Adjust the dose for children during periods of increased sunlight exposure.

Adverse Reactions

Symptoms caused by hypercalcemia and/or hypercalciuria are most likely with hypersensitivity to colecalciferol and overdose: anorexia, nausea, vomiting, headache, heart disorders, muscle and joint pain, weakness, irritability, depression, weight loss, severe thirst, polyuria, kidney stone formation, nephrocalcinosis, calcification of soft tissues.

Contraindications

Hypersensitivity to colecalciferol, hypervitaminosis D, hypercalcemia, hypercalciuria, urolithiasis with calcium stones, pseudohypoparathyroidism, acute and chronic diseases of the liver and kidneys; depending on the dosage form used – sarcoidosis, active form of pulmonary tuberculosis.

With caution

Patients on immobilization; taking cardiac glycosides; taking additional amounts of vitamin D₃ and calcium (for example, as part of other drugs), with impaired excretion of calcium and phosphates in the urine, when treated with benzothiadiazine derivatives and in immobilized patients (risk of developing hypercalcemia and hypercalciuria); in infants with a predisposition to early closure of fontanelles; with atherosclerosis, heart failure, organic heart lesions; with granulomatosis; hyperphosphatemia, phosphate nephrourolithiasis; with gastrointestinal diseases, gastric and duodenal ulcers; with hypothyroidism.

Use in Pregnancy and Lactation

Should not be used in high doses during pregnancy.

When used in a high dose in a nursing mother, symptoms of overdose may develop in the child.

During pregnancy and breastfeeding, the dose is set individually by the doctor.

Use in Hepatic Impairment

Acute and chronic liver diseases.

Use in Renal Impairment

Acute and chronic kidney diseases.

Pediatric Use

In children and adolescents under 18 years of age, use in dosage forms intended for this category of patients.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

May be used in combination with calcium carbonate.

Use with caution in elderly patients, as well as in patients with long-term immobilization.

When used concomitantly with thiazide diuretics, the level of calcium in the blood and urine should be monitored every 3-6 months.

During long-term treatment with vitamin D₃ in a daily dose exceeding 1000 IU, the level of calcium in the blood should be monitored.

Use in pediatrics

In children and adolescents under 18 years of age, use in dosage forms intended for this category of patients.

For children in conditions of increased insolation, the single and, accordingly, course dose should be reduced.

Drug Interactions

Phenytoin, primidone and drugs of the barbiturate group increase the need for vitamin D₃ due to an increase in the rate of biotransformation of colecalciferol into inactive metabolites, due to a decrease in the level of calcifediol in blood plasma.

Concomitant therapy with corticosteroids may reduce the effectiveness of vitamin D₃.

Concomitant therapy with cardiac glycosides (digitalis) may increase their toxic potential due to the development of hypercalcemia (risk of cardiac arrhythmia). In such patients, it is necessary to monitor ECG parameters and the level of calcium in blood plasma and urine, and adjust the doses of cardiac glycosides. It is also necessary to monitor the levels of digoxin and digitoxin in blood plasma if indicated.

Vitamin D₃ can be combined with metabolites or analogues of vitamin D₃ only in exceptional cases and under the control of the level of calcium in the blood serum.

Thiazide diuretics can reduce the excretion of calcium in the urine and, accordingly, increase the risk of developing hypercalcemia. In such patients, constant monitoring of the level of calcium in the blood and urine is necessary with long-term use of the drug.

Rifampicin and isoniazid may reduce the effectiveness of the drug due to an increase in the rate of biotransformation of vitamin D₃.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

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.