Alfacalcidol - instructions for use, dose, side effects, contraindications

Alfacalcidol (1α-hydroxyvitamin D₃) is rapidly converted into the liver into 1,25-dihydroxyvitamin D₃, an active metabolite of vitamin D (calcitriol), which acts as a regulator of calcium and phosphorus metabolism. Increases the absorption of calcium and phosphorus in the intestine, increases their reabsorption in the kidneys, restores the positive calcium balance in the treatment of calcium malabsorption syndrome and reduces the concentration of parathyroid hormone in the blood.

Influencing both parts of the bone remodeling process (resorption and synthesis), alfacalcidol not only increases the mineralization of bone tissue, but also increases its elasticity by stimulating the synthesis of bone matrix proteins, bone morphogenetic proteins, bone growth factors, thereby reducing the incidence of fractures.

In elderly patients, against the background of endocrine-immune dysfunction, including a deficit in the production of D-hormone (calcitriol), there is a decrease in total muscle mass (sarcopenia) and the appearance of a muscle weakness syndrome (due to disruption of the normal functioning of the neuromuscular system), which is accompanied by an increase risk of falls and the resulting injuries and fractures. A number of studies have shown a significant reduction in the incidence of falls in elderly patients with the use of alfacalcidol.

Alfacalcidol stimulates the regeneration of muscle fibers, which restores the lost muscle tone.

Pharmacokinetics:

The onset of action (hypercalcemic) - after 6 hours, duration - up to 48 hours. After oral administration, it is completely absorbed from the digestive tract. C max in plasma is achieved 8-12 hours after a single dose. In the blood it binds to specific alpha globulins and is transported to the liver,where it turns into an active metabolite - calcitriol (1,25-dihydroxycolecalciferol). The smaller part is metabolized in bone tissue. It is not metabolized in the kidneys (unlike natural vitamin D), which allows it to be prescribed for vitamin D deficiency in patients with renal insufficiency (the effect does not depend on the hydroxylation in the kidneys). Products of biotransformation are excreted by the kidneys and with bile (approximately in the same ratio). Half-life of blood - 3 h.

Indications:Osteodystrophy (including chronic renal failure), hypoparathyroidism and pseudohypopathyrheitis, rickets and osteomalacia of various genesis, osteoporosis (including postmenopausal, senile, steroid), renal acidosis, Fanconi syndrome (hereditary renal acidosis with nephrocalcinosis, late rickets and adipozogenitalth dystrophy).

ICD-10

IV.E20-E35.E20.8 Other forms of hypoparathyroidism

IV.E20-E35.E20.0 Idiopathic hypoparathyroidism

IV.E50-E64.E55.0 Rickets active

IV.E70-E90.E72.0 Disruption of amino acid transport

IV.E70-E90.E83.3 Disorders of phosphorus metabolism

XIII.M80-M85.M82.8 * Osteoporosis in other diseases classified elsewhere

XIII.M80-M85.M81.8 Other osteoporosis

XIII.M80-M85.M81.5 Idiopathic osteoporosis

XIII.M80-M85.M81.4 Medicinal osteoporosis

XIII.M80-M85.M81.2 Osteoporosis caused by immobility

XIII.M80-M85.M81.1 Osteoporosis after removal of ovaries

XIII.M80-M85.M81.0 Postmenopausal osteoporosis

XIV.N25-N29.N25.0 Renal osteodystrophy

XIII.M80-M85.M83 Osteomalacia in adults

XIV.N25-N29.N25.8 Other disorders due to renal tubular dysfunction

Contraindications:Hypersensitivity, hypercalcemia, hyperphosphatemia (except for hyperphosphatemia in hyperparathyroidism), hypermagnes, hypervitaminosis D, renal osteodystrophy with hyperphosphatemia, intoxication with vitamin D, hypersensitivity to alfacalcidol, pregnancy, breastfeeding, children under 3 years.

Carefully:Atherosclerosis, sarcoidosis or other granulomatosis, chronic heart failure, history of nephrolithiasis, hyperphosphatemia, chronic renal failure, pulmonary tuberculosis (active form), risk of hypercalcemia (especially with urolithiasis, children over 3 years old.

Pregnancy and lactation:

The action category for fetus by FDA is C.

Adequate and well-controlled studies on humans and animals have not been conducted. The application is possible if the expected benefit for the mother exceeds the potential risk to the fetus.

Hypercalcemia in the mother (associated with prolonged vitamin D overdose during pregnancy) can cause the fetus to increase sensitivity to vitamin D, parathyroid function suppression, specific elf-like appearance syndrome, mental retardation, aortic stenosis.

Small amounts of the drug penetrate into breast milk. During breastfeeding, use with caution systemically in large doses, since hypercalcemia is possible in infants.

Newborns who are breastfed, especially those born to women with dark skin and / or who have insufficient insolation, have a high risk of vitamin D deficiency.

Dosing and Administration:

Individually. The daily dose for adults varies from 0.07 μg to 20 μg, for children 0.01-0.08 μg / kg.

Inside. The recommended daily dose of the drug can be taken immediately for 1 reception, you can divide the dose into 2 divided doses. Therapy can last from 2-3 months to 1 year or more. The duration of treatment is determined by the doctor for each patient individually.

Adults

When osteomalacia associated with malnutrition or suction: from 1 to 3 mcg per day for a minimum of 2-3 months.

When hypoparathyroidism: from 1 to 4 mcg per day.

When osteodystrophy in chronic renal failure: from 0.5 to 2 mcg per day for 2-3 months 2-3 times a year.

When Fanconi syndrome and renal acidosis: from 2 to 6 mcg per day.

When hypophosphatemic osteomalacia: Therapy is started with a dose of 4 μg per day. The maximum daily dose can reach 20 mcg.

When osteoporosis (including postmenopausal, senile, steroid): from 0.5 to 1 mcg per day. It is recommended to start treatment with a minimal dose, controlling the content of calcium and phosphorus in blood plasma once a week. The dose can be increased by 0.5 mcg per day until the biochemical parameters stabilize.

Parenterally, intravenously. Begin the treatment with minimal doses, controlling once a week the level of calcium and phosphorus in the blood. Inside, adults: the initial dose of 1 mcg per day, can be increased by 0.25-0.5 mcg per day to stabilize biochemical indicators.

Intravenously, with hemodialysis at the end of each session in the form of a bolus (within 30 s). The injection should be carried out in the return line of the device (as close as possible to the patient - to eliminate the risk of absorption of alfacalcidol by plastic).The initial dose is 1 μg, the maximum dose is 6 μg for dialysis, but not more than 12 μg for 1 week.

Children over 3 years old

When rachitis and osteomalacia, associated with malnutrition or absorption: from 1 to 3 mcg per day for a minimum of 2-3 months.

When osteodystrophy in chronic renal failure: from 0.5 to 1 mcg per day for 2-3 months 2-3 times a year.

When Fanconi syndrome and renal acidosis: from 2 to 6 mcg per day.

When hypophosphatemic rickets and osteomalacia: Therapy starts with a dose of 1 mcg per day.

Parenterally, intravenously. Hypophosphatemic rickets, persistent hypocalcemia in connection with hypo- and pseudohypoparathyroidism. 1 month-12 years: intravenously at a dose of 25-50 ng / kg per day (maximum dose of 1 μg). 12-18 years: 1 mcg per day.

Persistent neonatal hypocalcemia. Newborns are administered intravenously at a dose of 50-100 ng / kg per day (up to 2 μg / kg in resistant cases).

Prevention of vitamin D deficiency in patients with kidney disease or cholestatic liver disease. The newborn is administered intravenously at a dose of 20 ng / kg per day. 1 month-12 years with a body weight of up to 20 kg 15-30 ng / kg per day (maximum dose - up to 500 ng), with a mass exceeding 20 kg - at a dose of 250-500 ng per day; children 12-18 years: in a dose of 250-500 ng per day.

Side effects:

From the digestive system: anorexia, nausea, vomiting, dry mouth, discomfort in the epigastric region, constipation; rarely - a slight increase in the activity of alanine aminotransferase, aspartate aminotransferase.

From the side of the central nervous system: weakness, fatigue, dizziness, drowsiness.

From the cardiovascular system: tachycardia.

Allergic reactions: skin rash, itching.

From the side of metabolism: rarely - increase high-density lipoproteins in plasma; with severe renal dysfunction, hyperphosphataemia.

Overdose:

Early symptoms of hypervitaminosis D due to hypercalcemia: bone pain, constipation, diarrhea, drowsiness, dry mouth, headache, polydipsia, pollakiuria / nocturia, polyuria, irregular heartbeat, decreased appetite, metallic taste in the mouth, muscle pain, nausea or vomiting , itching, unusual fatigue or weakness.

The late symptoms of hypervitaminosis D, caused by hypercalcemia: bone pain, clouding of urine (appearance in the urine of hyaline cylinders, proteinuria, leukocyturia), conjunctivitis, decreased libido, ectopic calcification, fever,increased sensitivity, eye sensitivity to light or eye irritation, skin itching, drowsiness, decreased appetite, muscle pain, nausea or vomiting and pancreatitis (severe pain in the stomach), psychosis (changes in the psyche and mood), rhinorrhea, weight loss.

Symptoms of chronic intoxication with vitamin D: calcification of soft tissues, kidneys, lungs, blood vessels, arterial hypertension, renal and cardiovascular insufficiency up to the lethal outcome (these effects occur more often when hypercalcemia of hyperphosphataemia is attached), growth disorders in children.

Treatment: cancellation of the drug. In the early periods of acute overdosage - gastric lavage, the intake of mineral oil (helps to reduce absorption and increase excretion with feces); in severe cases, it may be necessary to carry out supportive medical measures - hydration with the introduction of infusion salt solutions (forced diuresis), loop diuretics, glucocorticoids, bisphosphonates, calcitonin and hemodialysis using solutions with low calcium content.

Interaction:

Danazol: an increase in the effect of alfacalcidol, possibly the development of hypercalcemia.

Calcitonin: decreased effect of alfacalcidol.

Kolestyramin: a decrease in the effect of alfacalcidol.

Pamidronic acid: a decrease in the effect of alfacalcidol.

Ethidronic acid: a decrease in the effect of alfacalcidol.

Phenytoin: increasing the metabolism of alfacalcidol, reducing the concentration of alfacalcidol in the blood plasma (possibly changing its effectiveness).

Phenobarbital: a decrease in the concentration of alfacalcidol in the blood plasma (it is possible to change its effectiveness).

Special instructions:

During the treatment, constant monitoring of the concentration of Ca2 + and phosphates in the blood (at the beginning of treatment - 1-2 times a week, when the optimal effective dose is achieved, it is recommended to monitor the Ca2 + content in the plasma every 3-5 weeks, the concentration of Ca2 + in the urine - every 1-3 month), as well as the activity of alkaline phosphatase (with chronic renal failure - weekly). In chronic renal failure, a preliminary correction of hyperphosphataemia is required. When the alkaline phosphatase content in the plasma is normalized, an appropriate dose reduction is necessary (to avoid the development ofhypercalcemia).

Alfacalcidol is comparable in effectiveness to calcium in patients with new compression fractures of the vertebrae.

Exceeds the effectiveness of the additionally taken vitamin D in osteoporosis (vertebrae) in the elderly, calcitonin and alendronate in the prevention of hyperparathyroidism in patients after kidney transplantation; inferior to the falecalcidol in the suppression of the level parathyroid hormone with secondary hyperthyroidism and calcitriol in osteopenia caused by cirrhosis of the liver.

After the alkaline phosphatase content in the plasma is normalized, it is necessary to lower the dose accordingly (to avoid the development of hypercalcemia). Hypercalcemia and hypercalciuria are corrected, canceling treatment and decreasing Ca2 + intake (usually after 1 week). After normalization, treatment is continued, appointing half of the last dose applied.

Solution for injection should be used with caution in preterm infants.

Instructions

Alfacalcidol (Alphacalcidolum)