Ergocalciferol

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ERGOCALCIFEROL (ERGOCALCIFEROL)

Composition:

Active substance: ergocalciferol;

1 ml of solution contains ergocalciferol (vitamin D2) 1.25 mg (50000 IU);

Excipient: sunflower oil.

Pharmaceutical form. Oil-based oral solution.

Main physicochemical properties: clear oily liquid ranging from light yellow to dark yellow, without rancid taste. A specific odor may be present. Ergocalciferol activity is expressed in international units (IU): 0.025 μg of chemically pure vitamin D2 corresponds to 1 IU.

Pharmatherapeutic group.

Vitamin D and its analogues. ATC code A11CC01.

Pharmacological Properties.

Ergocalciferol (vitamin D2) regulates phosphorus and calcium metabolism in the body, promoting their absorption from the intestine by increasing the permeability of its mucous membrane and ensuring adequate deposition in bone tissue. The action of ergocalciferol is enhanced when calcium and phosphorus compounds are simultaneously supplied.

Pharmacodynamics.

Vitamin D2 belongs to the group of fat-soluble vitamins and is one of the regulators of calcium and phosphorus metabolism. It promotes the intestinal absorption of these minerals, as well as their distribution and deposition in bones during bone growth. The specific effect of the vitamin is particularly evident in rickets (antirachitic vitamin).

Pharmacokinetics.

Orally administered vitamin D is absorbed into the blood in the small intestine, particularly well in its proximal segment. From the blood, the vitamin reaches liver cells, where it undergoes hydroxylation with the participation of 25-hydroxylase to form its transport form, which is then delivered by blood to the mitochondria of the kidneys. In the kidneys, further hydroxylation occurs via 1α-hydroxylase, resulting in the formation of the hormonal form of vitamin D. This active form of vitamin D is then transported by blood to target tissues, such as the intestinal mucosa, where it initiates Ca²⁺ absorption.

Clinical characteristics.

Indications.

For the prevention and treatment of vitamin D deficiency, rickets, as well as bone diseases caused by disturbances in calcium metabolism (various forms of osteoporosis, osteomalacia), disorders of parathyroid gland function (tetany), cutaneous and osseous tuberculosis, psoriasis, and cutaneous and mucosal systemic lupus erythematosus (SLE).

Contraindications.

• Hypersensitivity to the components of the drug;
• vitamin D hypervitaminosis;
• active pulmonary tuberculosis;
• peptic ulcer of the stomach and duodenum;
• acute and chronic liver and kidney diseases;
• organic heart and vascular diseases in the decompensation stage;
• elevated levels of calcium and phosphorus in blood and urine;
• sarcoidosis;
• urolithiasis.

Interaction with other medicinal products and other types of interactions.

Concomitant use with calcium salts increases the toxicity of vitamin D2. When administered with iodine-containing preparations, oxidation of the vitamin occurs. When used simultaneously with antibiotics (tetracycline, neomycin), impaired absorption of ergocalciferol is observed. Combination of the drug with mineral acids leads to its destruction and inactivation.

Thiazide diuretics and medicinal products containing Ca2+ increase the risk of hypercalcemia, which reduces tolerance to cardiac glycosides, resulting in slowed elimination of the drug and its accumulation in the body.

Under the influence of barbiturates (including phenobarbital), phenytoin, and primidone, the requirement for vitamin D may significantly increase, manifested by the intensification of osteomalacia or severity of rickets (due to accelerated metabolism of ergocalciferol into inactive metabolites as a result of induction of microsomal enzymes).

Prolonged therapy with concomitant use of antacids containing Al3+ and Mg2+ increases their concentration in blood and the risk of intoxication (especially in the presence of chronic renal failure). Calcitonin, derivatives of etidronic and pamidronic acids, plikamycin, gallium nitrate, and glucocorticosteroids reduce the effect. Cholestyramine, colestipol, and mineral oils reduce the absorption of fat-soluble vitamins in the gastrointestinal tract and require an increase in their dosage.

Rifampicin, isoniazid, antiepileptic drugs, and cholestyramine reduce the efficacy of ergocalciferol.

Use with caution with ketoconazole and cytochrome P450 inhibitors.

Increases the absorption of phosphorus-containing drugs and the risk of developing hyperphosphatemia.

Concomitant use with other vitamin D analogs (especially calcifediol) increases the risk of hypervitaminosis (not recommended).

Special precautions for use.

Vitamin D2 preparations should be stored under conditions that exclude exposure to light and air, which can inactivate them: oxygen oxidizes vitamin D2, while light converts it into toxic toxisterine.

It should be noted that vitamin D2 has cumulative properties.

During prolonged use, calcium (Ca2+) concentrations in blood and urine should be monitored.

Excessively high doses of vitamin D2 administered over a long period or in bolus doses may lead to chronic vitamin D2 hypervitaminosis.

In cases of hypervitaminosis caused by ergocalciferol, an enhanced effect of cardiac glycosides and an increased risk of arrhythmias may occur due to the development of hypercalcemia (adjustment of cardiac glycoside dosage may be necessary).

Use with caution in patients with long-term hypothyroidism and in elderly individuals, as vitamin D2 may promote calcium deposition in the lungs, kidneys, and blood vessels, thereby contributing to the development and worsening of atherosclerosis.

In elderly patients, the requirement for vitamin D2 may increase due to reduced absorption of vitamin D, decreased capacity of the skin to synthesize provitamin D3, reduced exposure to sunlight, and increased incidence of renal insufficiency.

When used in high doses, vitamin A (10,000–15,000 IU daily), ascorbic acid, and B-complex vitamins should be co-administered to reduce systemic toxicity. Concomitant use of vitamin D2 and exposure to ultraviolet lamp irradiation should be avoided. Calcium preparations should not be used simultaneously with high-dose vitamin D. During treatment, monitoring of calcium and phosphorus levels in blood and urine is recommended.

Use with caution in patients with diabetes mellitus and in immobilized patients.

The drug should be used under medical supervision. Individual requirements should take into account all possible sources of this vitamin.

Use during pregnancy or breastfeeding.

Ergocalciferol may be used starting from the 30th–32nd week of pregnancy. Caution is required when prescribing ergocalciferol to pregnant women over 35 years of age. Maternal hypercalcemia (associated with prolonged intake of vitamin D2 during pregnancy) may cause increased fetal sensitivity to vitamin D, suppression of parathyroid gland function, elfin-like facial features syndrome, delayed mental development, and aortic stenosis. During treatment of pregnant women, vitamin D2 overdose may lead to hypercalcemia, which could result in impaired fetal parathyroid gland function.

High-dose vitamin D2 (over 2000 IU/day) should not be taken during pregnancy due to the potential teratogenic effects in case of overdose.

Vitamin D2 should be prescribed with caution during breastfeeding, as high-dose maternal intake may cause symptoms of overdose in the infant.

Ability to affect reaction rate while driving or operating machinery.

Caution is recommended when driving or operating machinery, due to the potential for adverse reactions affecting the nervous system.

Method of Administration and Dosage

Ergocalciferol should be taken orally during meals. 1 ml of the preparation contains 50000 IU. The preparation is administered as drops; 1 drop from an eye dropper or dosing device contains approximately 1400 IU.

For the treatment of rickets, taking into account its severity and clinical course, Ergocalciferol (vitamin D2) is prescribed at a dose of 1400–5600 IU daily for 30–45 days. After achieving the therapeutic effect within the specified period, switch to prophylactic administration of vitamin D at a dose of 500 IU* daily until the child reaches three years of age. During summer months, discontinue the drug.

For the prevention of rickets (in newborns and infants), Ergocalciferol should be prescribed to pregnant women and breastfeeding mothers. During pregnancy, the drug should be taken from week 30–32 at a dose of 1400 IU daily for 6–8 weeks. Breastfeeding mothers should take Ergocalciferol at a daily dose of 500–1000 IU* from the first days of lactation until vitamin D supplementation is initiated in the infant.

For prophylaxis, the preparation should be administered to full-term infants starting from the 3rd week of life. For preterm infants, infants on artificial feeding, twins, and children living in unfavorable environmental (including domestic) conditions, the preparation should be started from the 2nd week of life.

For rickets prophylaxis, Ergocalciferol can be administered using different methods:

• Physiological method – daily administration to full-term infants, for 3 years, excluding summer months, at a dose of 500 IU* daily (annual course dose – 180000 IU);
• Course method – daily administration of Ergocalciferol at 1400 IU for 30 days at the 2nd, 6th, and 10th months of life; thereafter, 2–3 courses per year until age 3, with intervals of 3 months between courses (annual course dose – 180000 IU).

For preterm infants, the daily prophylactic dose of vitamin D may be increased to 1000 IU*, prescribed daily by a physician during the first six months of life. Thereafter, administer 1400–2800 IU daily for one month, 2–3 times per year, with intervals of 3–4 months between courses.

In regions with long winters, prophylaxis should continue until the child reaches 3–5 years of age.

Treatment with the drug should be conducted under monitoring of calcium (Ca++) levels in urine.

In rachitic-like disorders, pathological processes in bone tissue caused by impaired calcium metabolism, certain forms of tuberculosis, and psoriasis, the drug should be prescribed according to comprehensive treatment regimens for these conditions.

The daily dose for the treatment of lupus vulgaris in adults is 100000 IU. In this condition, children under 16 years of age are prescribed Ergocalciferol after meals at daily doses ranging from 25000 to 75000 IU (the daily dose is divided into two administrations), depending on age. The treatment course lasts 5–6 months.

* - provided such dosing is feasible.

Children.

The physician individually determines the child's daily requirement for vitamin D and the method of administration, adjusting it during periodic examinations, especially during the first months of life.

Newborns may exhibit variable sensitivity to vitamin D2; some may be sensitive even to very low doses.

When prescribing vitamin D2 to preterm infants, it is advisable to simultaneously administer phosphates.

Overdose.

Symptoms of vitamin D hypervitaminosis:

Early symptoms (due to hypercalcemia) – constipation or diarrhea, dryness of oral mucosa, headache, thirst, polydipsia, nocturia, polyuria, anorexia, metallic taste in the mouth, nausea, vomiting, increased fatigue, asthenia, hypercalcemia, hypercalciuria;

Late symptoms – bone pain, cloudy urine (appearance of hyaline cylinders in urine, proteinuria, leukocyturia), elevated arterial pressure, itching, photophobia, conjunctival hyperemia, arrhythmia, drowsiness, myalgia, nausea, vomiting, pancreatitis, gastralgia, weight loss, rarely – mood and mental changes (up to the development of psychosis).

Symptoms of chronic vitamin D intoxication (after intake over several weeks or months: in adults at doses of 20000–60000 IU/day, in children at 2000–4000 IU/day): calcification of soft tissues, kidneys, lungs, blood vessels; arterial hypertension; renal and cardiovascular insufficiency, up to fatal outcome (these effects most commonly occur when hypercalcemia and hyperphosphatemia are present); impaired growth in children (prolonged intake at a maintenance dose of 1800 IU/day).

Treatment: discontinue the drug, strictly limit intake of vitamin D2 with food, induce vomiting or perform gastric lavage with activated charcoal, administer saline laxatives, correct water-electrolyte balance. In cases of hypercalcemia, administer edetates. Hemodialysis and peritoneal dialysis are effective.

The toxic effects of high doses of the drug are reduced when vitamin A is taken simultaneously.

Side effects.

With prolonged use of high doses, the following adverse reactions may occur:

• Immune system: hypersensitivity reactions, including rash, urticaria, itching;
• Central nervous system: headache, vertigo, sleep disturbances, irritability, depression;
• Metabolic disorders: hyperphosphatemia, increased urinary calcium levels (risk of internal organ calcification);
• Gastrointestinal tract: anorexia, loss of appetite, diarrhea, nausea, vomiting;
• Musculoskeletal system: bone pain;
• Urinary system: proteinuria, cylinduria, leukocyturia;
• General disorders: general weakness, chills.

If the described effects occur, discontinue the drug and strictly limit calcium intake into the body, including dietary sources.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging in a refrigerator (at a temperature of +2 °C to +8 °C).

Keep out of reach of children.

Packaging.

10 ml in glass bottles, placed in a carton; 10 ml in polymer bottles, placed in a carton; 10 ml in polymer bottles with a dosing device, placed in a carton.

Prescription status. Prescription only.

Manufacturer.

JSC "VITAMINS".

Manufacturer's address and place of business.

20300, Uman, Usypenska St., 31, Cherkasy region, Ukraine.

Marketing Authorization Holder.

JSC "VITAMINS".

Address of the Marketing Authorization Holder and/or its representative.

20300, Uman, Usypenska St., 31, Cherkasy region, Ukraine.