Zems

Active material: Parikalьcitol
When ATH: A11CC07
CCF: Preparation, regulates the exchange of calcium and phosphorus
ICD-10 codes (testimony): E21
When CSF: 16.04.01.01
Manufacturer: ABBOTT LABORATORIES Ltd. (Great Britain)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

The solution for the on / in the colorless, clear, not containing extraneous particles visible to the naked eye.

Excipients: ethanol 95%, propylene glycol, water d / and.

1 ml – colorless glass vials (5) – packs cardboard.
1 ml – colorless glass vials (5) – trays, plastic (1) – packs cardboard.

The solution for the on / in the colorless, clear, not containing extraneous particles visible to the naked eye.

Excipients: ethanol 95%, propylene glycol, water d / and.

2 ml – colorless glass vials (5) – packs cardboard.
2 ml – colorless glass vials (5) – trays, plastic (1) – packs cardboard.

Pharmacological action

Preparation, regulates the exchange of calcium and phosphorus. Parikalьcitol – synthetic analogue of biologically active vitamin D (calcitriol). Paricalcitol has a biological effect by interacting with vitamin D receptors, which leads to selective activation response, mediated in this vitamin. Vitamin D and paricalcitol reduce parathyroid hormone levels by inhibiting its synthesis and secretion. In the early stages of chronic kidney disease is observed reduction of calcitriol.

Secondary hyperparathyroidism is characterized by an increase in the content of parathyroid hormone (PTG), It is associated with inadequate levels of active vitamin D. This vitamin is synthesized in the skin and enters the body with food. Vitamin D is sequentially hydroxylated in the liver and kidneys and is converted to the active form, which interacts with the vitamin D receptor.

Calcitriol [1,25(IT)2 D₃] – This is an endogenous hormone, which activates vitamin D receptors in the parathyroid glands, intestine, kidney and bone (thanks to this feature it supports the parathyroid glands and calcium and phosphorus homeostasis), as well as in many other tissues, including prostate, endothelium and immune cells. Receptor activation is necessary for normal bone formation. When kidney disease inhibits the activation of vitamin D, resulting in increased levels of PTH, the development of secondary hyperparathyroidism and disturbance of homeostasis of calcium and phosphorus. Reduced levels of calcitriol and elevated PTH, which often precede changes in plasma levels of calcium and phosphorus, cause changes in bone turnover rate, and may lead to the development of renal osteodystrophy. In patients with chronic kidney diseases, a decrease in the level of PTG has a beneficial effect on the activity of the bone SCF, metabolism in bone and bone fibrosis. The active vitamin D therapy not only reduces the PTH level and improves metabolic processes in bone, but also helps to prevent or eliminate other consequences of vitamin D deficiency.

Pharmacokinetics

Within two hours after V/in the Boleus Introduction of the Paricalcitol in Doses from 0.04 ug / kg to 0.24 mcg/kg concentration of the drug quickly decreases; However, subsequently the concentration of the drug decreases linearly, with average t_1/2 about 15 no. Repeated use of paricalcitol signs of accumulation were observed.

Distribution

Paricalcitol is actively associated with plasma proteins (more 99%). In healthy people v_d at steady state is about 23.8 l. In patients with chronic kidney diseases 5 stage, received treatment with hemodialysis or peritoneal dialysis, V_d Paricalcitol in a dose 0.24 ug / kg averages 31-35 l. Parmacokinetics of fruit -based fruit was studied in patients with chronic renal failure, received treatment with hemodialysis.

Metabolism

Several metabolites of the drug are determined in the urine and feces. In urine, unchanged paricalcitol was not found. Paricalcitol is metabolized under the influence of liver and nonsense enzymes, including mitochondrial CYP24, as well as CYP3A4 and UGT1A4. Identified metabolites include products 24(R)-hydroxylation (plasma is in low concentrations), and 24,26- and 24,28-dihydroxylation and direct glyukuronirovaniya. Paricalcitol has no inhibitory effect on CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A in concentrations before 50 nM (21 ng / ml). At similar concentrations of paricalcitol Activity CYP2B6, CYP2C9 and CYP3A4 increases less than 2 times.

Deduction

Paricalcitol derived by biliary excretion. In healthy people, about 63% the drug is excreted through the intestines and 19% kidney. T_1/2 Paricalcitol when used in doses from 0.04 to 0.16 ICG/kg in healthy volunteers is on average 5-7 no.

Pharmacokinetics in special clinical situations

Pharmacokinetics of parcalcitol in people older 65 years has not been studied.

Pharmacokinetics of parcalcitol in children and adolescents aging younger 18 years has not been studied.

Pharmacokinetics of the parcalcitol does not depend on the gender.

Pharmacokinetics of the parcalcitol (0.24 mg / kg) compared in patients with a mild and moderate impaired liver function (classification Child-Pugh) And healthy people. The pharmacokinetics of unrelated parcalcitol was similar in these groups of patients. Dose correction in patients with a mild or moderate impaired liver function is not required. Pharmacokinetics of the parcalcitol in patients with severe impaired liver function was not studied.

Farmacokinetics of fruit -based carcalcitol were studied in patients with chronic kidney diseases 5 stage, received treatment with hemodialysis or peritoneal dialysis. Hemodialysis did not have a significant impact on the excretion of parcalcitol. However, in patients with chronic kidney diseases 5 the stage revealed a decrease in the clearance and an increase in t_1/2 Compared to healthy people.

Testimony

- Prevention and treatment of secondary hyperparatysis, developing chronic renal failure (Chronic kidney diseases 5 stage).

Dosage regimen

The drug zyakplar is usually administered through a catheter for hemodialysis. If the patient does not have a hemodiaalis catheter, then the drug can be administered slowly in/in for at least 30 sec, to minimize pain on infusion. Like other solutions for parenteral use, The ampoule with the drug Zyakplaus before administration should be examined for the presence of extraneous particles and changes in color. Unused residues of the solution should be poured.

Adult

The initial dose

There are two methods of choosing the initial dose. In clinical studies, the maximum safe dose has reached 40 g.

Choosing the initial dose by body weight

The recommended initial dose of the fruit is 0.04-0.1 mg / kg (2.8-7 g). It is introduced in the form of a bolus no more often, than a day every other day during dialysis.

The choice of the initial dose, taking into account the initial level of PTG

In patients with chronic renal failure (chronic kidney disease 5 stage) To analyze the level of biological active intact PTG, the second generation method is used. The initial dose is calculated by the formula, following, and introduce in/into the form of a bolus no more often, than a day every other day during dialysis:

The initial dose (g) = Initial PTG level (pg / ml)/80

Dose titration

Generally accepted target levels of PTG in patients with terminal renal failure, receiving treatment with dialysis, exceed WHN in patients without uremia (150-300 pg / ml) not more than 1.5-3 times. To achieve these levels, thorough monitoring of the level of PTG and individual dose titration is necessary.

In case of any dose changes, it is often necessary to determine the serum levels of calcium (amended by hypoalbuminum) and phosphorus. With an increase in the adjusted level of calcium (>11.2 mg / dL) or a persistent increase in phosphorus concentration (>6.5 mg / dL) It is necessary to reduce the dose of the drug, until these indicators are normalized. In the presence of hypercalcemia or a persistent increase in the work CA × p (more 75) reduce the dose of the drug or take a break in treatment, the indicated parameters have not been normalized yet. Then you can resume therapy with a parcalcitol in a smaller dose. If the patient receives calcium -containing drug, Binding phosphates, it is advisable to reduce its dose, Dit the drug for a while or transfer the patient to the drug, not containing calcium. As the levels of PTH decrease in response to treatment, it may take a decrease in the dose of fruits of fruit. Thus, the dose should be adjusted individually.

If you achieve an adequate answer, it is not possible, then the dose can be increased by 2-4 mcg every 2-4 of the week. With a decrease in the level of PTG <150 pg/ml dose of the drug should be reduced.

Recommended dose titration scheme

Side effect

The frequency is undesirable, in clinical studies for the 2 and 3 phase

The table lists the undesirable phenomena of any genesis, whose frequency in the Paricalcitol group was 2% or more (patients, in which the same reaction was reconnected, Considered 1 time).

Changes in the average calcium levels, Phosphorus, The works of CA × P in an open 13-month study confirm the safety of prolonged therapy with parcalcitol in this group of patients.

Undesirable phenomena in clinical research 4 phase

In one study 4 phases often noted headache (2%) And a perversion of taste (2%).

Adverse reactions, registered during post -marketing observations

In clinical practice, the following undesirable reactions were rarely recorded during the use of injection bargcytol:

Allergic reactions: hives, angioedema, laryngeal edema.

On the part of the peripheral nervous system: dysgeusia (metallic taste).

Dermatological reactions: rash, itch.

Contraindications

- hypervitaminosis D;

- joint reception with phosphates or derivatives of vitamin D;

- Hypercalcemia;

- Children up to age 18 years (clinical studies have not been conducted);

- Breastfeeding;

- Hypersensitivity to the drug.

FROM caution The drug should be prescribed simultaneously with heart glycosides.

Pregnancy and lactation

Studies in pregnant women have not been conducted. Information about the removal of a parlzitol with breast milk does not have women. Paricalcitol can be used during pregnancy only when, If the potential benefit for the mother justifies the possible risk to the fetus. If necessary, use during lactation, Breastfeeding should be discontinued.

Cautions

During dose titration paricalcitol may require more frequent laboratory tests. When the dose is chosen, serum levels of calcium and phosphorus to be measured, at least, 1 once a month. PTH levels in serum or plasma is recommended to control every 3 Months. For reliable analysis of biologically active PTH in patients with chronic kidney disease 5 stage it is recommended to use the method of the second or subsequent generation.

There were no differences in efficacy or safety of the drug in patients under the age of 65 and older 65 years.

Use in Pediatrics

Experience in the use of parcalcitol for injection in Children and adolescents aging younger 18 years limited.

Overdose

Simtom: An overdose of the fruit -ctionitol can lead to the development of hypercalcemia, hypercalciuria, hyperphosphatemia and suppression of PTG secretion.

Acute overdose of the fruit -based fruit can lead to the development of hypercalcemia and requires emergency assistance. During the dose selection, it is necessary to regularly control the serum levels of calcium and phosphorus. Long -term carcalcitol therapy can be complicated by hypercalcemia, increasing the work CA × P and calcification of soft tissues (Metastatic calcinosis).

Treatment: In case of clinically significant hypercalcemia, it is necessary to immediately reduce the dose of the paralkitol or interrupt treatment. Recommended measures include a hypocalcium diet, The cancellation of calcium preparations, Control of the water-electrolyte balance, Ecg-change assessment (is critical for patients, receiving cardiac glycosides) and hemodialysis or peritoneal dialysis using dialysis, not containing calcium. Calcium serum levels must be regularly monitored before they are normalized. When suppressing the level of PTG below the norm, the development of adynamic bone disease is possible – pathological condition with low bone exchange.

Drug Interactions

In accordance with the in vitro research data, the parcalcitol should not inhibit the clearance of drugs, which are metabolized by icopers CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A, or inducing the clearance of substances, biotrans forming under the influence of CYP2B6, CYP2C9 или Cyp3a.

The interaction of the parcalcitol for injection with other drugs was not specifically studied.

When studying the interaction of ketoconazole and parcalcitol in the capsules, it was shown, that ketoconazole causes an increase in aucaricalcitol in approximately 2 times. Paricalcitol is partially metabolized by the action of isoenzyme CYP3A, Ketoconazole is a potent inhibitor of isozyme, Therefore, caution should be observed with combined use of fruit -zitol with ketoconazole and other powerful inhibitors of the CYP3A isoenzyme.

Hypercalcemia of any origin enhances intoxication cardiac glycosides, Therefore, caution must be observed with their combined use with parcalcitol.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at temperature from 15 ° to 25 ° C; Do not freeze. Shelf life – 2 year.