Parsabiv (Parsabiv)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceEthylcalcytideEthylcalcytide
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  • Parsabiv
    solution in / in 
    Amgen Europe BV     Netherlands
    • Dosage form: & nbspsolution for intravenous administration
    Composition:

    One 0.5 ml bottle contains:

    Active substance:

    3.1 mg etalkalcetidide hydrochloride (2.5 mg in terms of etalkalcetide) in 0.5 ml solution (5 mg / ml);

    Excipients: sodium chloride - 4.3 mg, succinic acid - 0.6 mg, hydrochloric acid - to pH 3.3, sodium hydroxide - to pH 3.3, water for injection - to a volume of 0.5 ml.

    One 1.0 ml bottle contains:

    Active substance:

    6.2 mg of etalkalcetidide hydrochloride (5 mg in terms of etalkalcetide) in 1 ml of the solution (5 mg / ml);

    Excipients: sodium chloride - 8.5 mg, succinic acid - 1.2 mg, hydrochloric acid - to pH 3.3, sodium hydroxide - to pH 3.3, water for injection - to a volume of 1.0 ml.

    One 2.0 ml bottle contains:

    Active substance:

    12.3 mg etalkalcetidide hydrochloride (10 mg in terms of etalkalcetide) in 2 ml solution (5 mg / ml);

    Excipients: sodium chloride - 17.0 mg, succinic acid - 2.4 mg, hydrochloric acid - to pH 3.3, sodium hydroxide - to pH 3.3, water for injection - up to a volume of 2.0 ml.

    Description:

    Transparent, colorless liquid, free from mechanical inclusions.

    Pharmacotherapeutic group:Anti-parathyroid agent
    ATX: & nbsp

    H.05.B.X.04   Ethylcalcytide

    Pharmacodynamics:

    Mechanism of action

    Ethylcetcide is a synthetic peptide, calcimimetic. Ethylcalcytide specifically binds to calcium-sensitive receptors (CaSR) and causes their activation, which leads to a decrease in the secretion of parathyroid hormone (PTH) by the main cells of the parathyroid gland.

    In patients on hemodialysis, the decrease in PTH concentration correlates with the concentration of etalkalcetide in the blood plasma. Reduction in the concentration of PTH is associated with concomitant decrease in the concentrations of calcium and phosphate in the blood serum.

    After a single intravenous (iv) bolus administration of ethalkylcetide, a rapid (within 30 minutes) decrease in PTH concentration occurs.

    The severity and duration of PTH decrease are enhanced with increasing dose. Reduction of PTH concentration leads to a decrease in calcium concentration and limits the increase in phosphate concentration after dialysis. With IV bolus administration of ethalkalcetide 3 times a week, the decrease in PTH concentration persisted for 6 months.

    Clinical Trials Data

    Evaluation of the drug Parsabiv was carried out in three 6-month, multicenter, randomized, double-blind, controlledclinical trials in patients with secondary hyperparathyroidism (GPT) in chronic renal failure (CRF) on hemodialysis. The study of Parsabiv was also conducted in one multicenter, uncontrolled study to assess the safety of the transfer of patients with secondary GPT, who were on hemodialysis, from oral administration of zincalcite to the IV injection of Parsabiv.

    Efficacy and safety of Parsabiv in patients with secondary GPT with CRF. who were on hemodialysis 3 times a week, were evaluated in two 6-month, multicenter, randomized, double-blind, placebo-controlled studies. In each of the studies, the primary endpoint was represented by the proportion of patients who had achieved a decrease in PTH concentration by more than 30% over the initial value during the EAP (EAP) period. Secondary endpoints were represented by the proportion of patients with an average PTH level ≤ 300 pg / ml during the efficacy period, a percentage change from the baseline during the period of efficacy assessment of indicators such as the concentration of PTH, albumin-corrected calcium in the blood serum, and the product of calcium phosphorus (Ca x P).

    In these placebo-controlled studies, a total of 1,023 patients participated (509 received Parsabiv, 514-placebo).

    The demographic and baseline characteristics of both groups in both studies were comparable. In studies, similar results were obtained: during the period of the efficacy assessment of the drug, Parsabiv compared with placebo significantly increased the proportion of patients who experienced a decrease in the average PTH concentration by more than 30% from the baseline, increased the proportion of patients with an average PTH concentration ≤ 300 pg / ml (secondary efficacy evaluation), and also caused a statistically significant decrease in the concentration of PTH, albumin-corrected calcium, phosphate and calcium phosphorus (Ca x P).

    Reduction in the concentration of PTH, albumin-corrected calcium, phosphate and Ca x P in the serum was maintained for 78 weeks of treatment.

    Parsabiv caused a decrease in the concentration of PTH, regardless of its initial value, the duration of dialysis, previous treatment with cinacalcet, and the use of sterol forms of vitamin D.

    The efficacy and safety of Parsabiv was also evaluated in a 6-month, randomized, cinakalcet-controlled, double-blind study involving 683 patients with secondary GPT and CRF who were on hemodialysis. Parsabiv did not concede to zincalcetes according to the proportion of patients who experienced a decrease in mean PTH concentration> 30% relative to the baseline value during the efficacy evaluation period. Parsabiv was also superior to cinacalcet at the secondary endpoint: among patients randomly assigned to the Parsabiv group, the proportion of patients who experienced a decrease in mean PTH concentration> 50% during the efficacy evaluation period was higher than in the zincalcet group. Statistically significant differences between the two groups were absent with respect to the secondary endpoint, which estimated the average number of days per week with episodes of vomiting or nausea during the first 8 weeks of treatment.

    Estimation of changes in the concentration of albumin-corrected calcium in the serum of blood during the transfer of patients from the zincalcetus to Parsabiv was performed in 147 patients.The results showed that treatment with Parsabiv in the initial dose of 5 mg is safe to start 7 days after the abolition of the zincalcet at a concentration of albumin-corrected calcium in the blood serum ≥ 8.3 mg / dL at the time of transfer.

    Pharmacokinetics:

    Suction

    In patients with CRF and secondary GPT who require hemodialysis, the pharmacokinetics of ethalkylcetide were linear and did not change over time, either after iv injection of a single dose (5-60 mg) or after iv repeated doses (2, 5-20 mg). After iv introduction, the kinetics of ethalkylcetide exhibited a tri-exponential decline. Against the backdrop of iv administration 3 times a week at the end of 3-4 hours of hemodialysis, the concentrations of etalkalcetide in blood plasma reached a near equilibrium state in patients with CRF 4 weeks after initiation of treatment, with the observed cumulation increasing by 2-3 times, and the effective half-life was 3-5 days. In patients with normal renal function, there is a rapid elimination of etalkalcetide, while in patients with CRF. which require hemodialysis, hemodialysis becomes the main way of eliminating the drug.

    Distribution

    In the population pharmacokinetic model, the volume of distribution in the equilibrium state (Vss) was approximately 796 liters. Ethylcalcytide predominantly binds to blood serum albumin by reversible covalent binding. The ability for non-covalent binding in etalkalcetide is low, and the unbound fraction is 0.53. The relationship between the concentrations [14C] -ethylcalcetide in the blood and in the blood plasma is approximately 0.6.

    Metabolism

    Ethylcalcetide is not metabolized by isoenzymes of the cytochrome system CYP450. In the blood ethecalcetide undergoes biotransformation by reversible disulfide exchange with endogenous thiols with the predominant formation of conjugates with serum albumin.

    Exposure of biotransformation products in blood plasma was approximately 5 times higher than the exposure of ethalkalcetide, and the concentration-time profile of biotransformation products was comparable to the profile of ethalkylcetide. Excretion

    In patients with CRF. which required hemodialysis, hemodialysis became the main way of elimination of etalkalcetide. Effective removal of etalkalcetid occurred at a clearance of hemodialysis of 7.66 l / h.After the administration of a single dose of radiolabeled etalkalcetide to patients with CRF and secondary GPT who required hemodialysis, approximately 60% of the dialysate was found [14C] -ethylcalcetide, and in total urine and feces - 7% for 175 days of collection period.

    Pharmacokinetics in specific patient groups

    Liver failure

    Formal pharmacokinetic studies on the use of ethalkalcetide in patients with hepatic insufficiency have not been conducted. Research in vitro showed that ethecalcetide is not a substrate, inhibitor or inducer of enzymes CYP450.

    Renal insufficiency

    Formal pharmacokinetic studies on the use of etalkalcetide in patients with mild to severe renal insufficiency have not been conducted. Characteristics of the pharmacokinetics of ethalkylcetide were compiled for patients with CRF on hemodialysis. Ethylcalcytide is intended for use in patients with chronic renal failure who are on hemodialysis.

    Body mass, gender, race and age

    The results of population pharmacokinetic analysis indicate that body weight (from 29 to 163 kg), sex,race and age (from 20 to 93 years) do not affect the pharmacokinetics of ethalkylcetide.

    Elderly patients

    The pharmacokinetics of ethecalcetid in patients 65 years of age and older is similar to that of patients younger than 65 years of age.

    Patients of childhood

    Among patients under 18 years of age, studies of the pharmacokinetics of ethalkylcetide have not been conducted.

    Indications:LSecondary HTT in patients with HFH, who are on hemodialysis.
    Contraindications:

    Hypocalcemia

    Do not start treatment with Parsabiv with a concentration of albumin-corrected calcium in the serum below the lower limit of normal values ​​(see section "Special instructions").

    Hypersensitivity

    Parsabian is contraindicated in patients with established hypersensitivity to the active substance or any of the excipients.

    Pregnancy and the period of breastfeeding.

    Children under 18 years.

    Pregnancy and lactation:

    Pregnancy

    Controlled studies of ethalkylcetide with the participation of pregnant women have not been conducted. Pre-clinical studies showed no effect on embryo-fetal development in rats and rabbits with intravenous administrationethalkalcytide in the period of organogenesis at an exposure of 1.8-4.3 times higher than the exposure achieved in patients who received ethecalcetide when administered at a dose of 15 mg 3 times a week. At a higher exposure (2.7-7 times higher than the exposure in patients), the fetal growth was slowed, which was associated with such toxic manifestations in the mother as hypocalcemia, tremor, weight loss and food intake. In studies on rats during the period of prenatal and postnatal development, the effect on puberty, neurobehavioral and reproductive functions in the offspring was not revealed at an exposure 1.8 times higher than in patients who received ethecalcetide in a dose of 15 mg 3 times a week. At an exposure similar to that in patients, a minimal increase in the mortality of the offspring was observed, a delay in the timing of delivery and a temporary decrease in the rate of postnatal growth, which was associated with such toxic manifestations in the mother as hypocalcemia, tremor, weight loss and food intake. Studies on animals do not always allow you to predict the response to a drug in humans. Therefore, it is not known whether ethecalcetide to have a negative effect on the fetus during its appointment during pregnancy, and therefore the use of Parsabiv during pregnancy is contraindicated.

    Breast-feeding

    It is not known whether the ethecalcetide in breast milk. Studies in rats have been shown. [14C] -ethylcalcetid is excreted into milk in concentrations similar to those in blood plasma. Many drugs penetrate into human milk in humans, so, given the unwanted reactions that can cause ethecalcetide in newborns, it is necessary to decide whether to cancel the Parsabiv drug or stop breastfeeding, assessing the estimated benefit of continued Parsabiv therapy for the mother and the possible risk of a negative impact on the newborn.

    Reproductive function

    There are no data on the effect of Parsabiv on human reproductive function. In rats, the effect on reproductive function was not observed.

    Dosing and Administration:

    The recommended initial dose of Parsabiv in adults is 5 mg in the form of a bolus injection 3 times a week.

    The Parsabiev drug is administered through the venous catheter of the dialysis system during the flushing period at the end of the hemodialysis procedure, or intravenously after the catheter is washed. Before the administration of the first dose of Parsabiev, an increase in the dose of Parsabiev or the re-administration of Parsabiv after a temporary cessation of treatment, the concentration of albumin-corrected calcium in serum should be> 8.3 mg / dl.

    The dose should be selected individually in the range of 2.5 to 15 mg. The drug Parsabiv should not be administered more often than 3 times a week. Measurement of PTH concentration should be performed 4 weeks after the start of Parsabi drug or dose changes to determine the need for additional dose adjustment. To achieve the target concentration of PTH, the dose of Parsabiv can be increased to a maximum dose of 15 mg 3 times a week in 2.5 or 5 mg increments, but not more often than every 4 weeks. If the PTH concentration drops below the target values, the dose of Parsabiv should be reduced or temporarily discontinued. To achieve the target concentrations of PTH after the temporary discontinuation of Parsabiv, treatment should be resumed using lower doses.

    Measurement of serum calcium concentration should be carried out within 1 week after starting the use of Parsabiv, or changing the dose. After determining the maintenance dose, the measurement of albumin-corrected calcium in serum should be performed approximately every 4 weeks. In the case of a clinically significant decrease in the concentration of albumin-corrected calcium in the serum below 8.3 mg / dL and / or the appearance of symptoms of hypocalcemia, the following tactics are recommended:

    Concentration of albumin-corrected calcium in serum or clinical symptoms of hypocalcemia

    Recommendations

    <8.3 mg / dl (2.07 mmol / L) and ≥ 7.5 mg / dL (1.88 mmol / L)

    - In the presence of clinical indications:

    • start taking or increase the dose of calcium supplements, phosphate-binding drugs containing calcium, and / or sterol forms of vitamin D;
    • increase the concentration of calcium in dialysate.

    <7.5 mg / dL (1.88 mmol / L) or the appearance of symptoms of hypocalcemia

    - Discontinue Parsabiv until the albumin-corrected calcium concentration in the blood serum reaches ≥ 8.3 mg / dl (2.07 mmol / L), and the hypocalcemia symptoms (if any) will not be stopped.

    - In the presence of clinical indications:

    • start taking or increase the dose of calcium supplements, phosphate-binding drugs containing calcium, and / or sterol forms of vitamin D;
    • increase the concentration of calcium in dialysate.

    - Re-designate Parsabiv in a dose of 5 mg below the last dose administered. If the last administered dose of Parsabiev was 2.5 mg or 5 mg, treatment should be resumed after the restoration of albumin-corrected serum calcium to a concentration of> 8.3 mg / dl (2.07 mmol / L) and resolution of symptoms of hypocalcemia ( if any) with a dose of 2.5 mg.

    If you miss the planned procedure for hemodialysis The administration of Parsabiv should be carried out during the next procedure in a similar dose. Do not administer the missed dose. If the administration of Parsabiev has been missed for more than 2 weeks, then therapy should be resumed from a dose of 5 mg (or 2.5 mg if the last dose administered was) and titrate the dose to achieve the target PTH concentration.

    The Parsabiv preparation can be used alone or in combination with sterol forms of vitamin D and / or phosphate binders.

    Transfer from the zincalcite to the preparation Parsabiv

    Therapy with Parsabiv should not be started earlier than 7 days after the last dose of zincalcet and at a concentration of albumin-corrected calcium ≥ 8.3 mg / dl.

    Side effects:

    Security Profile Summary

    Taking into account the data on the use of Parsabiv in patients in placebo-controlled studies and in a study with active control, the most common undesirable reactions against the background of treatment with Parsabiv are reduction of calcium concentration in the blood, muscle spasms, diarrhea, nausea and vomiting. In most patients, these events were mild or moderate in severity and were of a temporary nature. The termination of treatment due to adverse reactions occurred mainly due to a decrease in the concentration of calcium in the blood, nausea and vomiting.

    The list of undesirable reactions in the tables

    Undesirable reactions that have been identified as at least possibly associated with the treatment of ethecalcetid based on evidentiary data and the evaluation of the cause-effect relationship are listed below according to the following classification: very often (≥ 1/10); often (≥ 1/100 to <1/10); infrequently (≥ 1 / 1,000 to <1/100); rarely (≥ 1 / 10,000 to <1 / 1,000); very rarely (<1 / 10,000).

    Class of organ system (MedDRA)

    Often (> 1/10)

    Often (from ≥ 1/100 to <1/10)

    Disorders from the metabolism and nutrition

    Reducing the concentration of calcium in the blood1

    Hypocalcemia1 Hyperkalemia2 Hypophosphatemia

    Disturbances from the nervous system

    Paresthesia Headache3

    Heart Disease

    Decompensation of chronic heart failure1

    Vascular disorders

    Arterial hypotension

    Disorders from the gastrointestinal system

    Nausea

    Vomiting

    Diarrhea

    Disturbances from musculoskeletal system and connective tissue

    Muscle spasms

    Myalgia

    1 see section "Description of individual adverse reactions".

    2 The term "hyperkalemia" included such preferable terms as hyperkalemia and an increase in the potassium concentration in the blood.

    3 The term "paresthesia" included such preferred terms as paresthesia and hypoesthesia.

    Description of individual adverse reactions

    Hypocalcemia

    In the clinical study program of Parsabiv, an asymptomatic decrease in calcium concentration below 7.5 mg / dL, or an asymptomatic decrease in the albumin-corrected calcium concentration in the range of 7.5 to 8.3 mg / dL, which required treatment, or which the investigator determined to be clinically significant, was recorded as "a decrease in the concentration of calcium in the blood."

    A decrease in the albumin-corrected calcium concentration below 8.3 mg / dl, accompanied by clinical manifestations, was recorded as "hypocalcemia," indicating appropriate objective and subjective symptoms. Most of the events presented by the asymptomatic decrease in calcium concentration in the blood and hypocalcemia with clinical manifestations were mild or moderate in severity. In the pooled data of placebo-controlled studies, the proportion of patients in whom the albumin-corrected serum albumin concentration was <7.0 mg / dL (7.6 mg / dL) was recorded at least once in the Parsabiv group compared to the placebo group % in the treatment group, 3.1% in the placebo group), <7.5 mg / dl (27.1% in the treatment group, 5.5% in the placebo group) and <8.3 mg / dl (78.6% in the treatment group, 19.4% in the placebo group). In these studies, 1% of patients in the Parsabiv treatment group and 0% of patients in the placebo group discontinued treatment because of the undesirable "low serum calcium concentration".

    Interval lengthening QTc, caused by hypocalcemia

    In the pooled data of placebo-controlledstudies in the treatment group of Parsabiv compared with the placebo group had a higher proportion of patients with a maximum interval elongation QTcF more than 60 msec relative to the baseline (1.2% in the Parsabiv treatment group, 0% in the placebo group). The proportion of patients who had a maximum value after the initial survey QTcF > 500 msec (measured prior to dialysis), was 4.8% in the treatment group and 1.9% in the placebo group.

    Decompensation of chronic heart failure

    In a combination of placebo-controlled studies, the proportion of patients who had decompensated chronic heart failure requiring hospitalization was 2.2% in the Parsabiv group and 1.2% in the placebo group.

    Overdose:

    There are no clinical data on the overdose of the drug Parsabiv. Patients who received dialysis were given a single dose of 60 mg or a multiple dose of up to 22.5 mg 3 times a week at the end of the dialysis procedure. An overdose of Parsabiv may lead to hypocalcemia with or without clinical manifestations and may require treatment. Although

    Parsabiev is excreted in dialysis, hemodialysis was not studied as an overdose therapy for Parsabiv. In order to timely conduct appropriate interventions, in case of overdose, it is necessary to monitor the serum calcium concentration and observe the patient to identify symptoms of hypocalcemia (see the section "Dosing and Administration").

    Interaction:

    There are no data on the pharmacokinetic drug interactions of ethalkylcetide.

    In vitro ethecalcetide did not inhibit or induce the activity of cytochrome system isoenzymes CYP450, and was not their substrate.

    In vitro ethecalcetid was not a substrate for efflux transport proteins and capture proteins (P-glycoprotein (Pgp), breast cancer resistance protein (BCRP), a carrier of organic anions (OAT) 1 and 3, an organic anion (AAPP) 1B1 and 1B3 transporter, an organic cation transport (OCT) 2 transporter, and a peptide transporter (PERT) 1 and 2).

    In vitro ethecalcetide also showed no ability to inhibit common protein transporters (Pgp, BCRP, ОАТ1, ОАТ3, ОАТР1В1, ОАТР1В3, ОСТ2 or exporting a pump of salts of bile acids (EPZhK)).

    Other drugs that reduce the concentration of calcium

    The simultaneous use of other drugs that reduce the concentration of calcium in the blood serum and the drug Parsabiv may lead to an increased risk of hypocalcemia (see section "Special instructions").

    Special instructions:

    Hypocalcemia

    Parsabiv drug reduces the serum calcium concentration and can lead to the development of hypocalcemia (see the section "Side effect"). Treatment with Parsabiv should not be started in patients with chronic renal failure who are on hemodialysis, at a concentration of albumin-corrected calcium in the serum below the lower limit of normal values ​​(see the section "Contraindications").

    Follow the patient to identify hypocalcemia. Control of serum calcium concentration should be performed before the start of therapy, within one week after initiation of therapy or dose adjustment, and every 4 weeks of treatment with Parsabiv (see Dosage and Administration section). Possible clinical manifestations of hypocalcemia include paresthesia, myalgia, muscle spasms and convulsions. The patient should be advised to consult a doctor in case of symptoms of hypocalcemia.With a clinically significant decrease in the concentration of albumin-corrected calcium in blood serum, it is necessary to carry out measures aimed at increasing the concentration of calcium in the serum (see section "Method of administration and dose").

    Ventricular arrhythmia and lengthening of the interval QT, hypocalcemia

    Reducing the concentration of calcium in the blood serum can lead to lengthening of the interval QT, which, in turn, may be accompanied by the development of ventricular arrhythmia. In patients with congenital syndrome of lengthening the interval QT, lengthening the interval QT in the anamnesis, lengthening of the interval QT or sudden cardiac death in a family history, as well as other predictive states of lengthening the interval QT and the development of ventricular arrhythmia, it is necessary to ensure a careful control of the concentration of calcium in the serum during treatment with Parsabiv.

    Convulsions

    The threshold of convulsive readiness can be reduced with a significant decrease in the concentration of calcium in the blood serum. In patients with convulsive disorders in history, careful monitoring of serum calcium in the course of treatmentpreparation Parsabiv.

    Decompensation of chronic heart failure

    Decreased myocardial function. hypotension and chronic heart failure may be associated with a significant decrease in serum calcium concentration. Patients with chronic heart failure history (which may be associated with a decrease in serum calcium concentration) is necessary to provide careful control of the calcium concentration in serum during treatment with Parsabiv.

    Simultaneous use with other drugs

    Patients receiving the drug Parsabiv. Do not administer cinacalcetone (see section "Method of administration and dose"). Their simultaneous application can lead to the development of severe hypocalcemia.

    The drug Parsabiv should be administered with caution to patients receiving any other drugs that reduce the concentration of calcium in the blood serum. Patients receiving other medicines that reduce the concentration of calcium in the blood serum should be carefully monitored.

    Adynamic bone disease

    With prolonged suppression of the concentration of PTH below 100 pg / ml, development of adynamic bone disease is possible. If the PTH concentration falls below the recommended target range, it is necessary to reduce doses or cancel therapy with sterol forms of vitamin D and / or Parsabiv. After withdrawal, therapy is resumed at lower doses to maintain PTH concentration 'within the range of the target values ​​(see section "Dosage and Administration").

    Special patient groups

    Children

    In children, the safety and efficacy of Parsabiv has not been established.

    Elderly patients

    There were no clinically significant differences in safety and efficacy between patients 65 years of age and older and younger patients (≥ 18 and <65 years). There were no differences in the plasma concentrations of etalkalcetide between patients 65 years of age and older and younger patients (≥ 18 and <65 years). Of the 503 patients who received the Parsabiv drug in placebo-controlled trials, 177 patients (35.2%) were 65 years of age or older.

    Liver failure

    Ethylcetcide does not undergo hepatic metabolism; so it is expected that liver failure will not have a significant effect on the excretion of ethecalcetide.Influence of hepatic insufficiency on pharmacokinetics ethecalcetide was not studied (see the section "Pharmacokinetics").

    Renal insufficiency

    Parsabium is indicated for patients on hemodialysis. The effect of the degree of severity of renal insufficiency on the pharmacokinetics of Parsabiv has not been studied (see the section "Pharmacokinetics").

    Immunogenicity

    Evaluation of the immunogenicity of ethalkylcetide was carried out by means of an immunological study based on surface plasmon resonance, which allowed detecting binding antibodies to ethalkylcetide. In clinical trials, in 7,1% (71 of 995) patients with secondary hyperparathyroidism (GPT) treated with etalkalcetide for up to 6 months, binding antibodies were found (80.3% of them had [57 of 71] antibodies were detected at the initial examination).

    There was no change in the pharmacokinetic profile, clinical response, or safety profile due to the presence of antibodies to ethylcalcetide initially present or developed during treatment. If there is a suspicion of the formation of antibodies to etalkalcetide, which is accompanied by clinically significant effects,contact the company "Amgen" to decide whether to conduct a laboratory test to detect antibodies.

    Special instructions for use and precautions

    Parsabiv does not require mixing or dilution before use. The solution is clear and colorless. Before using the drugs for parenteral administration, a visual inspection must be carried out beforehand to detect foreign particles and discoloration. The solution can not be used in case of turbidity or discoloration, the content of turbid or colored inclusions.

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

    Studies of the effect of the Parsabiv drug on the ability to drive vehicles and mechanisms have not been carried out.

    Form release / dosage:RAsterol for intravenous administration, 5.0 mg / ml.

    Packaging:

    0.5 ml, 1.0 ml or 2.0 ml solution in a 3 ml bottle of hydrolytic class I glass with an elastomeric plug, laminated fluoropolymer, an aluminum cap and a breakable polypropylene cap.

    6 bottles placed in a pack of cardboard along with instructions for use.

    For each pack, glued protective labels - control the first opening, having a longitudinal color strip.

    Storage conditions:

    Store at temperatures between 2 ° C and 8 ° C. Do not freeze.

    Keep in original packaging to protect from light.

    Do not shake.

    Keep out of the reach of children!

    If you take it out of the cold store, it is possible to store the medicinal product at a temperature of no higher than 25 ° C for 7 days in the original package (cardboard bundle), in case of storing the vial without a cardboard bundle - for 4 hours, avoiding direct sunlight.

    Shelf life:

    2 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003993
    Date of registration:05.12.2016
    Expiration Date:05.12.2021
    The owner of the registration certificate:Amgen Europe BVAmgen Europe BV Netherlands
    Manufacturer: & nbsp
    Representation: & nbspAMDZHEN LLC AMDZHEN LLC Russia
    Information update date: & nbsp14.01.2017
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