Alfacalcidol

When ATH:
A11CC03

Characteristic

Vitamin D analogues₃.

Colourless crystals or a white crystalline powder. Practically insoluble in water, slightly soluble in ethanol, small and slowly soluble in sunflower oil and other vegetable oils. Not resistant to the action of atmospheric oxygen and light. Molecular weight 400,64.

Pharmacological action

Regulatory calcium-phosphorus metabolism.

Application

Hypo- and vitamin deficiency of vitamin D (Prevention and treatment), and the state of increased demand for vitamin D: osteomalacia, osteoporosis, osteopathy (incl. after kidney transplantation, in patients with renal insufficiency), inadequate and unbalanced nutrition (incl. parenteral, vegetarian diet), malabsorption, insufficient insolation, hypocalcemia on the background of hypoparathyroidism, familial hypophosphatemia (vitamin D-rezistentnыy rickets), alcoholism, hepatic failure, cirrhosis of the liver; Fanconi's anemia (hereditary renal acidosis with nephrocalcinosis, late rickets and hypophyseal syndrome); obstructive jaundice, gastrointestinal diseases (gluten enteropathy, persistent diarrhea, tropical sprue, Crohn's disease), rapid weight loss, pregnancy (particularly when the nicotine and drug dependence, polycyesis), lactation; newborns, are breastfed, when there is insufficient insolation.

Contraindications

Hypersensitivity, hypercalcemia, гипервитаминоз D, renal osteodystrophy with hyperphosphatemia (the risk of metastatic calcification; However, vitamin D therapy can begin, as soon as the serum phosphate level is stabilized).

Restrictions apply

Atherosclerosis, pulmonary tuberculosis (active form), sarcoidosis or other granulomatosis, heart failure, chronic renal failure, nefrourolitiaz history, giperfosfatemiя, advanced age (can promote atherosclerosis), childhood.

Pregnancy and breast-feeding

In animal experiments show, at doses that calcitriol, at 4-15 times the recommended human dose, teratogenic.

During pregnancy and lactation is possible, if the expected benefit to the mother outweighs the potential risk to the fetus and child. Hypercalcemia in the mother (associated with prolonged overdose of vitamin D during pregnancy) can cause fetal increased sensitivity to vitamin D, suppression of parathyroid, specific syndrome elfopodobnoy appearance, mental retardation, aortalnыy stenosis.

Category actions result in FDA - C. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)

Small amounts into breast milk. During the period of breastfeeding with caution systemically in high doses, tk. possible hypercalcemia in infants.

Newborns, are breastfed, especially born to women with dark skin and / or not getting enough sun exposure, have a high risk of vitamin D deficiency.

Side effects

Metabolism: hypercalcemia, a slight increase in HDL cholesterol in the plasma, giperfosfatemiя (when severe impaired renal function).

From the digestive tract: constipation (most often in children and adolescents), diarrhea, dryness of the oral mucosa, thirst, decreased appetite, metallic taste in mouth, nausea or vomiting (most often in children and adolescents), discomfort in epigastric, a slight increase in ALT, AST in the plasma, pancreatitis.

From the nervous system and sensory organs: fatigue, generalized weakness, drowsiness, headache, psychosis, conjunctivitis (red eyes, century, discharge from the eyes), increased sensitivity to light, eye or eye irritation, rhinorrhea.

Cardio-vascular system and blood (hematopoiesis, hemostasis): increased blood pressure, heart rhythm disturbance.

With the genitourinary system: clouding of urine, impairment of renal function, thamuria / nocturia, polyuria, decreased libido.

Allergic reactions: itch, skin rash.

Other: myalgia, arthralgia, ectopic calcification, fever, weight loss.

Cooperation

While the use of digitalis drugs increases the risk of cardiac arrhythmias. Inductors of microsomal liver enzymes (anticonvulsants, incl. phenytoin, barbiturates, and others.) promote metabolism alphacalcidol, inhibitors - reduce (you can change its effectiveness). Cholestyramine, colestipol, sucralfate, antacids, Albumin, Mineral oil - reduce the absorption of alfacalcidol. When used together with antacids or laxatives, containing magnesium, It increases the risk of giperalyuminemii and / or gipermagniemii; when used with thiazide diuretics, calcium supplementation, PM, containing vitamin D and its derivatives - the risk of hypercalcemia. Perhaps the combined use of estrogen and antiresorptive drugs of different groups in the treatment of osteoporosis.

Toxic effects of impaired vitamin A, tocopherol, vitamin C, pantothenic acid, thiamine, riboflavin. Calcitonin, derived etidronovoy and Pamidronic acids, reduce the effect of glucocorticoid. Alfacalcidol increases the absorption of phosphorus-containing drugs and the risk of hyperphosphataemia.

Overdose

Symptoms of hypervitaminosis vitamin D: early, due to hypercalcemia, - Bone pain, constipation, diarrhea, drowsiness, dry mouth, headache, polydipsia, thamuria / nocturia, polyuria, irregular heartbeat, decreased appetite, metallic taste in mouth, myalgia, nausea or vomiting, itch, unusual tiredness or weakness. Late symptoms of hypervitaminosis D, due to hypercalcemia: bone pain, clouding of urine (appearance in the urine hyaline cylinders, proteinuria, leucocyturia), conjunctivitis, decreased libido, ectopic calcification, fever, pressurization, increased sensitivity to light, eye or eye irritation, itchy skin, drowsiness, decreased appetite, myalgia, nausea or vomiting and pancreatitis (severe pain in the stomach), psychosis (mental changes and mood), rhinorrhea, weight loss. Symptoms of chronic vitamin D intoxication: calcification of soft tissues, kidney, light, blood vessels, arterial hypertension, kidney and cardiovascular failure or death (These effects are more likely to occur when connecting to hypercalcemia hyperphosphatemia), dysplasia in children.

Treatment: removal of the drug. In the early stages of an acute overdose - washing stomach, reception of mineral oil (reduces absorption and increases excretion with feces); in severe cases may require supporting medical measures - the introduction of intravenous hydration with saline solution (forced diuresis), loop diuretics, glюkokortikoidov, ʙifosfonatov, calcitonin and dialysis using solutions with low calcium.

Dosing and Administration

Inside, I /. Treatment should begin with minimal doses, controlling 1 weekly blood calcium and phosphorus in the blood. Inside, adult: the initial dose 1 mg / day, may rise to 0.25-0.5 mg / day to stabilize the biochemical parameters. Children - depending on age and body weight. Duration of treatment is determined individually and depends on the nature of the disease and the effectiveness of therapy. In some cases, the drug is used for life.

B /, at the end of each dialysis session bolus (during 30 from). The injection should be carried out in the return line unit (as close as possible to the patient - to eliminate the risk of absorption of alfacalcidol plastic). The initial dose - 1 g, maximum - 6 na ug dialysis, but not more 12 xg for 1 Sun.

Precautions

During treatment requires constant monitoring of the concentration of Ca²⁺ and phosphate in blood (at the beginning of the treatment - 1-2 times per week, when the optimal effective dose is recommended to control the content of Ca²⁺ plasma every 3-5 weeks, the concentration of Ca²⁺ in urine - every 1-3 months), as well as the activity of alkaline phosphatase (in chronic renal failure - weekly). In chronic renal failure requires the preliminary correction of hyperphosphatemia. With the normalization of alkaline phosphatase in the plasma must be an appropriate reduction in dose (to avoid the development of hypercalcemia).

The risk of hypercalcaemia depends on such factors, the degree of demineralization, renal function and dose. Hypercalcemia develops in case, If the dose of alfacalcidol do not reduce the appearance of biochemical evidence of normalization of bone structure (such as normalization of serum alkaline phosphatase). Avoid prolonged hypercalcemia, especially in chronic renal failure. Patients with renal osteodystrophy alfacalcidol can be administered in combination with means, svyazıvayuşçïmï phosphate, to prevent hyperphosphatemia.

The solution for injection should be used with caution in preterm infants.

In the case of the drug is stopped hypercalciuria, then appointed in small doses. It should not be administered concurrently with other drugs, containing vitamin D or its derivatives. It will be appreciated, sensitivity to vitamin D in various individual patients and even some patients receiving therapeutic doses may cause phenomena of hypervitaminosis. The sensitivity of infants to vitamin D may be different, some of them can be sensitive even to very low doses. Children, receiving vitamin D for a long period of time, and increased risk of growth retardation. To prevent vitamin D deficiency, most preferably a balanced diet. In old age, the need for vitamin D may increase due to reduced absorption of vitamin D, reducing the time insolation, increase in the incidence of renal failure.

Cooperation