Etalpha^® (Capsules, Solution, Drops) Instructions for Use

ATC Code

A11CC03 (Alfacalcidol)

Active Substance

Alfacalcidol (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Drug regulating calcium and phosphorus metabolism

Pharmacotherapeutic Group

Vitamin – calcium-phosphorus metabolism regulator

Pharmacological Action

Alfacalcidol (1α-hydroxyvitamin D₃) is rapidly converted in the liver to 1,25-dihydroxyvitamin D₃ – a metabolite of vitamin D, which acts as a regulator of calcium and phosphorus metabolism. Insufficient endogenous synthesis of 1,25-dihydroxyvitamin D₃ in the kidneys leads to disturbances in mineral salt metabolism.

The drug increases the absorption of calcium and phosphorus in the intestine, increases their reabsorption in the kidneys, enhances bone mineralization, and reduces the concentration of parathyroid hormone in the blood.

The main advantages of Etalpha^® compared to vitamin D are its rapid action and the possibility of more precise dose regulation, which reduces the risk of hypercalcemia.

Pharmacokinetics

Absorption and Metabolism

Alfacalcidol is fat-soluble, its bioavailability after oral administration is about 100%.

After absorption, Alfacalcidol is metabolized in the liver to form the active metabolite 1,25-dihydroxyvitamin D₃. C_max of 1,25-dihydroxyvitamin D₃ in blood plasma is reached 8-12 hours after a single dose of alfacalcidol.

Elimination

T_1/2 of 1,25-dihydroxyvitamin D₃ is about 35 hours. It is excreted by the kidneys and with bile in approximately equal amounts.

Indications

• Prevention and treatment of renal osteodystrophy;
• Treatment of secondary hyperparathyroidism in patients with chronic renal failure stages 3-5 (for oral drops).

ICD codes

Dosage Regimen

Capsules

The drug is prescribed orally (regardless of meals) once a day. The duration of the treatment course is determined by the doctor individually in each specific case and depends on the nature of the disease and the effectiveness of therapy. Capsules are taken without chewing and with a sufficient amount of water.

Adults and children with body weight over 20 kg

Initial dose – 1 mcg/day; maintenance dose – 0.25-2 mcg/day.

For rickets and osteomalacia – 1-3 mcg/day; for hypoparathyroidism – 1-4 mcg/day; for osteodystrophy in chronic renal failure – 0.5-2 mcg/day; for osteoporosis (including postmenopausal, senile, steroid-induced) – 0.5-1 mcg/day.

It is recommended to start treatment with minimal doses, controlling the concentration of calcium and phosphorus in blood plasma once a week. The drug dose can be increased by 0.25 or 0.5 mcg/day until biochemical parameters stabilize.

After achieving the minimum effective dose, it is recommended to control the concentration of calcium in blood plasma every 3-5 weeks.

Drops

The drug Etalpha^® is taken orally during meals. The dose should be determined for each individual patient under the control of parathyroid hormone concentration, calcium, phosphate, calcium-phosphate product concentrations, and alkaline phosphatase activity in blood serum.

Doses with half a drop should be rounded up to the next whole number.

Patients at pre-dialysis stages of chronic renal failure (CRF) stages 3 and 4

It is recommended to start treatment with Etalpha^® when the serum 25-hydroxycholecalciferol concentration is less than 30 ng/ml (75 nmol/l) and the plasma intact parathyroid hormone (PTH) concentration is above the acceptable level for CRF (intact PTH more than 70 pg/ml for stage 3; intact PTH more than 110 pg/ml for stage 4).

For adults, the recommended initial dose is 0.3 mcg/day. Maintenance dose is 0.5 mcg.

The maximum recommended dose is no more than 12 mcg per week.

When using the drug in elderly people at pre-dialysis stages of CRF aged 65 years and older, no dose adjustment is required.

In clinical practice, it is used in children at pre-dialysis stages of CRF under the age of 18 years in doses from 0.2-39 ng/kg/day (equivalent to 0.0002-0.039 mcg/kg/day), in an average dose from 10-12 ng/kg/day (equivalent to 0.01-0.012 mcg/kg/day).

Patients on dialysis with chronic renal failure stage 5

In patients on hemodialysis or peritoneal dialysis, it is recommended to start treatment with Etalpha^® when the serum intact parathyroid hormone concentration is more than 300 pg/ml (33 pmol/l) to reduce it in the blood serum to a value of 150-300 pg/ml (16.5-33 pmol/l).

The recommended initial dose for adults is 0.5 mcg/day. The dose is increased by 0.25 or 0.5 mcg at intervals of at least 1 week as long as the controlled laboratory parameters are within normal limits. Maintenance dose is 1 mcg.

The maximum recommended dose is 6 mcg per 1 dialysis session, but not more than 12 mcg per week.

When using the drug in elderly people on hemodialysis aged 65 years and older, no dose correction is required.

In clinical practice, Alfacalcidol is used orally in infants, children and adolescents up to the age of 17 years, on hemodialysis or continuous ambulatory peritoneal dialysis, in doses of 10-20 ng/kg/day (equivalent to 0.010-0.020 mcg/kg/day).

Each drop of the drug contains 0.1 mcg of alfacalcidol.

The drug cannot be used for children with body weight less than 10 kg.

Patients with hepatic impairment

The efficacy of alfacalcidol is generally preserved in patients with reduced liver function. In severe hepatic impairment, the concentration of the active metabolite 1,25-dihydroxycholecalciferol may decrease due to impaired hydroxylation or due to reduced enterohepatic recirculation. In this case, it may be necessary to prescribe the drug in higher doses.

If a dose was missed – do not take a double dose of the drug. Continue to adhere to the proposed dosing regimen.

Solution

Ampoules must be shaken for 5 seconds before use. The drug should be used immediately after opening.

The drug Etalpha^® is administered intravenously 3 times a week at the end of each hemodialysis session, as a bolus, for approximately 30 seconds into the return line of the apparatus as close as possible to the patient, since absorption of alfacalcidol by plastic can lead to an undesirable reduction in the drug dose.

In patients on hemodialysis or peritoneal dialysis, it is recommended to start treatment when the serum intact parathyroid hormone concentration is more than 300 pg/ml (33 pmol/l) to reduce it in the blood serum to a value of 150-300 pg/ml (16.5-33 pmol/l).

The dose of the drug Etalpha^® should be determined for each individual patient under the control of parathyroid hormone concentration, calcium, phosphate, calcium-phosphate product concentrations, and alkaline phosphatase activity in blood serum.

The recommended initial dose for adults is 1 mcg per 1 dialysis session. The dose can be increased at intervals of at least 1 week as long as the controlled laboratory parameters are within normal limits.

The maximum recommended dose is 6 mcg per 1 dialysis session, but not more than 12 mcg per week.

In clinical practice, for children on hemodialysis or continuous ambulatory peritoneal dialysis, Alfacalcidol in oral dosage forms is used.

When using the drug in elderly people on hemodialysis aged 65 years and older, no dose correction is required.

The efficacy of alfacalcidol is generally preserved in patients with reduced liver function. In severe hepatic impairment, the concentration of the active metabolite 1,25-dihydroxycholecalciferol may decrease due to impaired hydroxylation or due to reduced enterohepatic recirculation. In this case, it may be necessary to prescribe the drug in higher doses.

If a dose administration was missed – do not administer a double dose of the drug. Continue to adhere to the proposed dosing regimen.

Adverse Reactions

The most common undesirable effects of the drug Etalpha^® are hypercalcemia, hypercalciuria and vitamin D-dependent toxicity.

Below are data on adverse reactions, depending on the frequency of their occurrence. Adverse reactions other than signs of hypercalcemia, received as individual reports, are also included: very common (≥ 1/10); common (≥ 1/100 and < 1/10); uncommon (≥ 1/1000 and < 1/100); rare (≥ 1/10,000 and < 1/1000); very rare (< 1/10,000, including individual reports); frequency unknown (cannot be estimated from the available data).

Metabolism and nutrition disorders very common – hypercalcemia; uncommon – metastatic calcification, hyperphosphatemia, high calcium-phosphate product, anorexia; frequency unknown – hypermagnesemia, decreased appetite.

Immune system disorders frequency unknown – hypersensitivity reactions with symptoms such as fever, chills, urticaria and tongue swelling.

Nervous system disorders uncommon – headache, dysesthesia, dysgeusia.

Cardiac disorders rare – tachycardia, increased blood pressure.

Gastrointestinal disorders uncommon – nausea, vomiting, abdominal pain, constipation, diarrhea, dyspepsia; frequency unknown – ulceration of the tongue, gums.

Skin and subcutaneous tissue disorders common – pruritus; frequency unknown – rash (erythematous, maculopapular, pustular), exfoliative dermatitis.

Renal and urinary disorders common – hypercalciuria; frequency unknown – renal failure, nephrocalcinosis.

General disorders and administration site conditions rare – calcinosis, asthenia and increased fatigue.

Contraindications

• Hypercalcemia;
• Hyperphosphatemia;
• Hypermagnesemia;
• Hypervitaminosis D;
• Pulmonary tuberculosis (active form);
• Prolonged immobilization;
• Children under 12 years of age;
• Pregnancy;
• Breastfeeding period;
• Sucrase/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption;
• Hypersensitivity to the components of the drug.

With caution, the drug is prescribed for organic heart lesions; atherosclerosis; acute and chronic diseases of the liver and kidneys; history of nephrolithiasis; gastrointestinal diseases (including gastric and duodenal ulcers); hypothyroidism; sarcoidosis, inactive forms of tuberculosis or other granulomatous diseases, since these conditions predispose to increased sensitivity to vitamin D.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

With caution, the drug is prescribed for acute and chronic liver diseases.

Use in Renal Impairment

The drug should be used with caution in renal failure.

Pediatric Use

For young children, it is recommended to prescribe Etalpha^® in the form of drops (dosing and administration of the drug in capsule form is difficult).

For body weight <20 kg, the drug is prescribed at a rate of 0.01-0.05 mcg/kg/day.

For body weight ≥20 kg – 1 mcg/day (except for cases of renal osteodystrophy).

For renal osteodystrophy in children, the dose is 0.04-0.08 mcg/kg/day. The dose is determined according to the dynamics of biochemical parameters in order to prevent hypercalcemia.

Special Precautions

The drug Etalpha^® in the form of oral drops contains 14% vol. ethanol, which corresponds to 340 mg of ethanol in one dose of alfacalcidol. This should be taken into account when using in patients with alcoholism.

Attention should be paid to patients taking cardiac glycosides, as hypercalcemia can lead to the development of arrhythmia in such patients.

Attention should be paid to patients taking thiazide diuretics, as such patients may have an increased risk of developing hypercalcemia.

The drug may contribute to the development of hypercalcemia, so patients should be informed about the clinical symptoms of this condition.

During the use of the drug Etalpha^®, it is necessary to regularly monitor the concentration of calcium, phosphates, calcium-phosphate product, alkaline phosphatase activity and parathyroid hormone concentration in blood serum.

The calcium concentration should be determined once a week or once a month depending on the clinical situation. More frequent measurement of calcium content is required at the beginning of treatment, especially in conditions without significant bone damage, for example, hypoparathyroidism and if the plasma calcium level is already elevated, as well as at later stages of treatment in the presence of signs of restoration of bone structure. The risk of developing hypercalcemia is determined by factors such as the degree of bone demineralization, renal functional capacity and the dose of Etalpha^®. The appearance of hypercalcemia may be due to the fact that the drug dose is not reduced timely and adequately in the presence of biochemical signs of restoration of bone structure (normalization of alkaline phosphatase activity in the blood). The development of prolonged hypercalcemia should be prevented, especially in chronic renal failure, focusing on such indicators as serum calcium concentration, alkaline phosphatase activity, parathyroid hormone, the amount of calcium excreted in the urine, radiological and biochemical data.

If hypercalcemia develops or there is a persistent increase in the calcium-phosphate product beyond the clinical norm, the drug should be discontinued immediately, at least until these indicators normalize (usually within one week), then the drug can be prescribed again at a dose that is half the previous one.

Patients with severe bone damage (unlike patients with renal failure) may tolerate higher doses of the drug without signs of hypercalcemia. The absence of a rapid increase in serum calcium in patients with osteomalacia does not necessarily mean that the drug dose should be increased, as calcium can penetrate into the demineralized bone due to its increased absorption in the intestine.

Excessive suppression of parathyroid hormone should be avoided. For patients on dialysis, the serum parathyroid hormone concentration should be no lower than 2-3 times the upper limit of normal.

In order to prevent the development of hyperphosphatemia in patients with bone lesions of renal origin, the drug Etalpha^® can be prescribed together with phosphate-binding agents.

Effect on ability to drive vehicles and operate machinery

Etalpha^® does not affect or insignificantly affects the ability to drive a car and operate complex machinery.

Overdose

Early symptoms of hypervitaminosis D (due to hypercalcemia): constipation or diarrhea, dryness of the oral mucosa, headache, thirst, pollakiuria, nocturia, polyuria, anorexia, metallic taste in the mouth, nausea, vomiting, general weakness, hypercalciuria.

Late symptoms of hypervitaminosis D: bone pain, cloudy urine (appearance of hyaline casts in the urine); increased blood pressure, skin itching; photophobia, conjunctival hyperemia, arrhythmia, drowsiness, myalgia, nausea, vomiting, weight loss; rarely – changes in psyche and mood; confusion.

Symptoms of chronic intoxication with vitamin D: calcification of soft tissues, blood vessels and internal organs (kidneys, lungs), renal and cardiovascular failure, growth impairment in children.

The concentration of calcium in the blood serum normalizes within 2-7 days after discontinuation of the drug.

Treatment: hypercalcemia is treated by temporarily discontinuing alfacalcidol, introducing a low-calcium diet and discontinuing calcium supplements. In severe cases of acute accidental overdose and persistent hypercalcemia, general supportive measures should be taken. In case of overdose, the drug should be discontinued. In severe cases (serum calcium concentration more than 3 mmol/l), supportive therapeutic measures may be required – hydration with infusion of saline solutions (for forced diuresis), in some cases – prescription of corticosteroids, “loop” diuretics, bisphosphonates, calcitonin, peritoneal dialysis or hemodialysis using a dialysate that does not contain calcium. Control of serum electrolyte levels (especially calcium), renal function and heart condition (according to ECG) is mandatory, especially in patients taking digoxin (or other cardiac glycosides).

Drug Interactions

Inducers of liver microsomal enzymes (including phenytoin and phenobarbital) reduce, and inhibitors increase the concentration of alfacalcidol in plasma (a change in its effectiveness is possible).

With simultaneous use of alfacalcidol with cardiac glycosides, the risk of arrhythmia increases.

The absorption of alfacalcidol decreases when used concomitantly with cholestyramine, colestipol, mineral oil, sucralfate, antacids. To reduce the likelihood of interaction, Alfacalcidol should be taken 1 hour before or 4-6 hours after taking the above drugs.

Calcitonin, derivatives of etidronic and pamidronic acids, plicamycin, gallium nitrate and corticosteroids reduce the effect of alfacalcidol.

Alfacalcidol increases the absorption of phosphorus-containing drugs and the risk of hyperphosphatemia.

Concomitant use of alfacalcidol with calcium preparations and thiazide diuretics may cause hypercalcemia due to increased calcium absorption in the intestine and increased its reabsorption in the kidneys.

Combination therapy with magnesium-containing antacids and vitamin D may cause an increase in blood magnesium concentration, and with aluminum-containing antacids – an increase in blood aluminum concentration, especially in chronic renal failure.

Concomitant use of various vitamin D analogues is accompanied by an additive effect with the development of hypercalcemia. Etalpha^® should not be prescribed simultaneously with other vitamin D preparations and its derivatives.

Storage Conditions

The drug should be stored out of the reach of children at a temperature between 2°C (35.6°F) and 8°C (46.4°F).

Shelf Life

The shelf life is 3 years.

The opened bottle with oral drops should be stored for 28 days at a temperature between 2°C (35.6°F) and 8°C (46.4°F).

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.