Etafa - instructions for use, doses, side effects, contraindications

Auxiliary components: acids of citric monohydrate-0.14 mg; ethanol-113 mg; macrogolglycerol hydroxy stearate-22.6 mg; methylparahydroxybenzoate-1.5 mg; sodium citrate 9.4 mg; sorbitol-452 mg; vitamin E (α-tocopherol) -0.02 mg; water purified to 1 ml.

Description:Colorless, clear or slightly opalescent solution.

Pharmacotherapeutic group:Vitamin - calcium-phosphorus exchange regulator

ATX: & nbsp

A.11.C.C.03 Alfacalcidol

Pharmacodynamics:

Alfacalcidol (1α-hydroxyvitamin D3) fast turns into a liver in 1,25-dihydroxycholecalciferol - a metabolite of the vitamin D, which acts as a regulator of calcium and phosphorus metabolism. Inadequate endogenous synthesis in the kidneys of 1,25-dihydroxycholecalciferol leads to disturbances in the metabolism of mineral salts. The drug increases the absorption of calcium and phosphorus in the intestine, increases their reabsorption in the kidneys, increases the mineralization of bone tissue, reduces the concentration of parathyroid hormone in the blood. The main advantages of alfacalcidol in comparison with vitamin-D - rapid action and the possibility of more precise dose adjustment, which reduces the risk of hypercalcemia.

Pharmacokinetics:Alfacalcidol is metabolized mainly in the liver to form an active metabolite of dihydroxycholecalciferol by hydroxylation isoenzymes CYP27A1 and CYP3A4. Studies have shown that neither alfacalcidol, nor 1,25-dihydroxycholecalciferol does not inhibit the cytochrome P450 system.

Indications:

Prophylaxis and treatment of renal osteodystrophy, treatment of secondary hyperparathyroidism in patients with chronic renal insufficiency 3-5 stages.

Contraindications:

Hypersensitivity to the drug components

Hypercalcemia

Hyperphosphatemia

Hypermagnia

Hypervitaminosis D

The period of pregnancy and breastfeeding

Long-term immobilization

Tuberculosis of the lungs (active form)

Deficiency of sugar / isomaltase, intolerance to fructose, glucose-galactose malabsorption.

Carefully:

Carefully prescribe the drug for organic heart lesions; atherosclerosis; acute and chronic diseases of the liver and kidneys; nephrolithiasis in the anamnesis; diseases of the gastrointestinal tract (including gastric ulcer and duodenal ulcer); hypothyroidism; sarcoidosis, inactive forms of tuberculosis or other granulomatosis, as these conditions have a predisposition to increase the sensitivity to vitamin D.

Dosing and Administration:

The drug is taken internally during meals. The dose of Ethal should be determined for each individual patient under the control of parathyroid hormone concentration, calcium concentration, phosphate, calcium phosphate compounds, and serum alkaline phosphatase activity.

Doses from half the drop should be rounded to the next whole number.

Patients in the pre-stage stages of chronic renal failure (CRF) stage 3 and stage 4

It is recommended to start treatment with Ethal's drug, when the concentration of 25-hydroxycholecalciferol in the blood serum is less than 30 ng / ml (75 nmol / L) and the concentration of intact parathyroid hormone (PTH) in the blood plasma is above the permissible level for chronic renal failure (intact PTH more than 70 ng / ml for stage 3, intact PTH more than 110 ng / ml for stage 4).

Adults

The recommended initial dose is 0.3 μg per day. The maintenance dose is 0.5 mcg.

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

Elderly

When applying the drug in the elderly in the pre-dialysis stages of chronic renal failure at the age of 65 or more years, dose adjustments are not required.

Children

In clinical practice, it is used in children at pre-stage stages of CRF at the age of 18 years at doses from 0.2-39 ng / kg / day (equivalent to 0.0002-0.039 μg / kg / day), in an average dose of 10-12 ng / kg / day (equivalent to 0.010-0.012 μg / kg / day).

Patients on dialysis with chronic renal failure of stage 5

In patients who are on hemodialysis or peritoneal dialysis, it is recommended to begin treatment with Etagol,when the concentration of intact parathyroid hormone in the blood serum is more than 300 ng / ml (33.0 pmol / L) to reduce it in the serum to a value of 150-300 ng / ml (16.5-33.0 nmol / l).

Adults

The recommended initial dose is 0.5 mcg per day. The dose is increased by 0.25 or 0.5 μg with an interval of not less than 1 week until the controlled levels of laboratory indicators are within the normal range.

The maintenance dose is 1 μg.

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

Elderly

When using the drug in elderly people on hemodialysis, at the age of 65 or more years, dose adjustment is not required.

Children

In clinical practice alfacalcidol is administered orally to infants, children and adolescents up to the age of 17 years on hemodialysis or continuous outpatient peritoneal dialysis at doses of 10-20 ng / kg / day (equivalent to 0.010-0.020 mkg / kg / day).

Each drop of the drug contains 0.1 μg of alfacalcidol.

The drug can not be used for children with a body weight of less than 10 kg.

Patients with hepatic insufficiency

The effectiveness of alfacalcidol is generally maintained in patients with reduced liver function.In severe hepatic insufficiency, the concentration of active metabolite 1,25-dihydroxycholecalciferol may decrease by decreasing the hydroxylation process or by reducing intestinal hepatic recirculation. In this case, it may be necessary to administer the drug at higher doses.

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

Side effects:

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

The following are data on adverse adverse reactions, depending on the frequency of their occurrence. Adverse adverse reactions other than signs of hypercalcemia, obtained as separate reports, are also included.

Very often> 1/10

Often> 1/100 and <1/10
Infrequently> 1/1000 and <1/100
Rarely> 1/10000 and <1/1000
Very rarely <1/10000, including individual messages
Frequency is unknown (can not be estimated based on available data)

Disorders from the metabolism and nutrition

Often:
Hypercalcemia
Infrequently:
Metastatic calcification, hyperphosphataemia, high content of calcium-phosphate compounds, anorexia
Frequency unknown:
Hypermagnesemia, decreased appetite

Immune system disorders:

Frequency unknown:

Hypersensitivity reactions with symptoms such as fever, chills, hives and swelling of the tongue.

Impaired nervous system:
Infrequently:
Headache, dysesthesia, dysgeusia

Disorders from the cardiovascular system:

Rarely:
Tachycardia, high blood pressure
Disorders from the gastrointestinal tract:
Infrequently:
Nausea, vomiting, abdominal pain, constipation, diarrhea, indigestion
Frequency unknown:
Ulceration of the tongue, ulceration of the gums

Disturbances from the skin

Often:
Itchy skin
Frequency unknown:
Rash (erythematous, maculopapular, pusteleznaya), exfoliative dermatitis Disorders from the urinary system:
Often:
Hypercalciuria
Frequency unknown:
Renal failure, nephrocalcinosis

General disorders:

Rarely:
Calcification, asthenia and fatigue

Overdose:

Early symptoms of hypervitaminosis D (caused by 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: pain in the bones, clouding of urine (appearance of hyaline cylinders in the urine); increased blood pressure, itchy skin; photophobia; hyperemia conjunctiva, arrhythmia; drowsiness; myalgia; nausea; vomiting; decreased body weight; rarely - a change in the psyche and mood; confusion of consciousness.

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

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

Hypercalcemia is treated with a temporary discontinuation of alfacalcidol, the introduction of a diet with a low calcium content, and discontinuation of calcium supplements.

In severe cases of acute accidental overdose and persistent hypercalcemia, general supportive measures should be taken.

In case of an overdose, the drug should be discontinued.In severe cases (the concentration of calcium in the blood serum, more than 3 mmol / L), it may be necessary to carry out supportive medical measures - hydration with the introduction of infusion saline solutions (for the purpose of forced diuresis), in some cases - the appointment of glucocorticosteroid drugs, loop diuretics, bisphosphonates , calcitonin, peritoneal dialysis or hemodialysis using calcium-free dialysate. It is mandatory to monitor the content of electrolytes in the blood serum (especially calcium), kidney function and heart condition (according to the electrocardiogram) especially in patients taking digoxin (or other cardiac glycosides).

Interaction:

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

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

Absorption of alfacalcidol decreases when it is used together with colestramine, colestipol, mineral oil, sucralfate, antacids.To reduce the probability of interaction alfacalcidol should be used, 1 hour before or 4-6 hours after taking the above drugs.

Calcitonin, etidronic and pamidronic acid derivatives, plikamycin, gallium nitrate and glucocorticosteroids reduce the effect of alfacalcidol.

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

Simultaneous use of alfacalcidol with calcium preparations, thiazide diuretics can cause hypercalcemia, by increasing the absorption of calcium in the intestine, increasing its reabsorption in the kidneys.

Combined therapy with magnesium-containing antacids and vitamin D can cause an increase in the concentration of magnesium in the blood, and aluminum-containing antacids - aluminum in the blood, especially in chronic kidney failure.

Simultaneous application of various vitamin analogues D is accompanied by an additive effect with the development of hypercalcemia. The drug Etagaz should not be administered concomitantly with other preparations of the vitamin D and its derivatives.

Special instructions:

The drug Ethal contains 14% vol.ethanol, which corresponds to 340 mg of ethanol in a single dose of alfacalcidol. This should be taken into account in patients with alcoholism.

Pay attention 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, since such patients may increase the risk of developing hypercalcemia.

The drug can promote the development of hypercalcemia, so patients should be informed about the clinical symptoms of this condition (see the section "Overdose").

During the use of the preparation of Ethal, it is necessary to regularly monitor the concentration of calcium, phosphate, calcium-phosphate compounds, activity of alkaline phosphatase and the concentration of parathyroid hormone in the blood serum.

The concentration of calcium should be determined once a week or a month, depending on the clinical situation. More frequent measurement of calcium is required at the beginning of treatment, especially in conditions without significant bone damage, for example, hypoparathyroidism, and if the calcium content in the plasma is already increased, as well as at later stages of treatment with signs of bone structure restoration.The risk of developing hypercalcemia is determined by such factors as the degree of bone demineralization, the functional ability of the kidneys and the dose of Ethal's preparation. The appearance of hypercalcemia may be due to the fact that the dose of the drug does not decrease in a timely manner and adequately in the presence of biochemical signs of restoration of the structure of bone tissue (normalization of the activity of alkaline phosphatase in the blood). It is necessary to prevent the development of prolonged hypercalcemia, especially in chronic renal failure, focusing on such factors as concentration in the serum calcium, activity of alkaline phosphatase, parathyroid hormone, the amount of calcium excreted in the urine, radiologic and biochemical data.

With the development of hypercalcemia or a persistent increase in the level of calcium phosphate compounds that go beyond the clinical norm, the drug should be immediately discontinued, at least until these parameters are normalized (usually within one week), then the drug can be prescribed again in a dose of half of the previous one.

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

It is necessary to avoid excessive suppression of parathyroid hormone. For patients on dialysis, the concentration of parathyroid hormone in the serum should not be less than 2-3 times the upper limit of the norm.

In order to prevent the development of hyperphosphataemia in patients with bone lesions of renal genesis, Etagol's preparation can be administered together with phosphate binding agents.

Effect on the ability to drive transp. cf. and fur:

Ethalph has little or no effect on the ability to drive and complex machinery.

Form release / dosage:Drops for oral administration.

Packaging:

To 20 ml of the drug in a bottle of brown light-protective glass, sealed with a stopper-dropper from polyethylene and a screw cap made of polypropylene,allowing to control the first autopsy.

One bottle with instructions for use is placed in a cardboard box.

Storage conditions:

At a temperature of 2 to 8 ° C.

The vial is stored for 28 days at a temperature of 2 to 8 ° C. Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012029 / 02

Date of registration:03.12.2011

Date of cancellation:2017-11-27

The owner of the registration certificate:Leo Pharmaceutical Products Co., Ltd. A / S (Leo Pharma A / S) Leo Pharmaceutical Products Co., Ltd. A / S (Leo Pharma A / S) Denmark

Manufacturer: & nbsp

LEO Pharmaceutical Products Ltd. A / S (LEO Pharma A / S) Denmark

Representation: & nbspNycomed Distribution Ltd.Nycomed Distribution Ltd.

Information update date: & nbsp27.11.2017

Illustrated instructions

Instructions

Ethal® (Etalpha®)