Enclave (Nplate)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceRomiplostimRomiplostim
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  • Enclave
    powder PC 
    Amgen Europe BV     Netherlands
    • Dosage form: & nbsp
    Powder for the preparation of a solution for subcutaneous administration

    Composition:

    Each vial contains 250 micrograms of Romiplostim.

    After dilution, the final volume of 0.5 ml of the solution contains 250 μg of Romiplostim (500 μg / ml). Each vial contains the amount of Romiplostima providing the concentration of the active substance in the prepared solution of 250 μg / 0.5 ml.

    Excipients: Mannitol (E421) - 30 mg, sucrose - 15 mg, L-histidine-1.2 mg, polysorbate 20-0.03 mg, hydrochloric acid (for pH adjustment) to pH 5.0.

    Each vial contains 500 μg of Romiplostime. After dilution, the final volume of 1 ml of the solution contains 500 μg of Romiplostim (500 μg / ml). Each vial contains the amount of Romiplostim that provides the concentration of the active substance in the prepared solution of 500 μg / ml.

    Excipients: Mannitol (E421) - 50 mg, sucrose - 25 mg, L-gystidine-1.9 mg, polysorbate 20-0.05 mg, Hydrochloric acid (for pH adjustment) to pH 5.0.

    Description:
    Liofilizate white.

    Reconstituted drug: a clear, colorless liquid, practically free of inclusions.
    Pharmacotherapeutic group:Antihemorrhagic means.
    ATX: & nbsp

    B.03.X.A   Other stimulators of hemopoiesis

    B.02.B.X.04   Romiplostim

    Pharmacodynamics:
    Romiplostim is produced by recombinant DNA technology using the strain Escherichia coli (E. Coli).
    Pharmacodynamics
    Romiplostim is an Fc-peptidylated protein (peptide antibody) involved in signaling and activating intracellular transcription by binding to the receptors of thrombopoietin (TPO) (also known as cMpl) and inducing an increase in platelet formation. The peptide antibody molecule consists of an Fc fragment of the human IgGl immunoglobulin in which each single-stranded subunit is linked by a covalent bond at the C-terminus to a peptide chain containing 2 TPO receptor-binding fragments. The amino acid sequence of the romiplostym is not homologous to the amino acid sequence of the endogenous TPO. In preclinical and clinical studies there was no cross-reacting antibodies to romiplostimu with endogenous TPO.

    Clinical efficacy

    Efficiency and safety Romiplostima was evaluated with a treatment duration of up to 5 years. In clinical trials, the treatment with Romiplostim resulted in dose-dependent increase in the number of platelets.The time to reach the maximum effect relative to the number of platelets was about 10-14 days and did not depend on the dose. After a single subcutaneous injection of Romiplostim at a dose of 1 to 10 μg / kg in patients with idiopathic (immune) thrombocytopenic purpura (ITP), the peak of the platelet count was 1.3-14.9 times the initial platelet count for 2-3 weeks. The response to treatment in all patients was different. Most patients with ITP who received within 6 weeks Romiplastim in the range of doses from 1 to 3 μg / kg, the number of platelets varied from 50 to 450 x 10%. Of the 271 patients with ITP who received Romiplastim in clinical trials, 55 (20%) were 65 years of age or older and 27 (10%) were aged 75 years and older. In placebo-controlled studies, no differences in safety and effectiveness between elderly and young patients were identified.

    Results of fundamental placebo-controlled studies

    Safety and efficiency Romiplostima was evaluated in two placebo-controlled double-blind studies in adult patients with ITP who received,at least one course of treatment before participating in the study, and representing the full spectrum of the group of patients with ITP. Both studies were conducted in a similar design. Patients (over 18 years of age) were randomized to ratio of 2: 1 and received a starting dose of Romiblastim 1 μg / kg or placebo, respectively. For 24 weeks, a single injection was administered weekly.

    Doses were adjusted to maintain the amount platelets (from 50 to 200 x 10%). In both studies efficacy was determined by the increase in the number of patients in whom a sustained increase in the number of platelets was achieved. The average weekly dose in patients with splenectomy was 3 μg / kg, and 2 μg / kg in patients with preserved spleen. In both studies, a significantly larger proportion of patients who received Romiplastim, demonstrated a persistent response in the form of an increase in the number of platelets compared to patients receiving a placebo. In placebo-controlled studies after the first 4 weeks of romiplostim, the platelet count was maintained at> 50 x 10% in 50-70% of patients during the 6-month treatment period.In the placebo group during the 6-month treatment period, only 0-7% of patients had an increase in the number of platelets. In both studies, patients already receiving therapy for ITP in accordance with the established scheme continued to use these drugs throughout the study period (corticosteroids, danazol and / or azathioprine). At the beginning of the study, 21 patients with preserved spleen and 18 patients with splenectomy received therapy for the treatment of ITP (mainly corticosteroids). In all patients (100%) after splenectomy, who received Romiplastim, it became possible to reduce the dose of corticosteroids by more than 25%, or even to abolish standard therapy for treatment of ITP at the end of treatment, compared with 17% of patients receiving placebo. In 73% of patients with preserved spleen, ratio of 2: 1 and received a starting dose of Romiblastim 1 μg / kg or placebo, respectively. For 24 weeks, a single injection was administered weekly.

    Doses corrected to maintain the number of platelets (from 50 to 200 x 10%).

    In both research effectiveness was determined by the increase in the number of patients in whom a sustained increase in the number of platelets was achieved. The average weekly dose in patients with splenectomy was 3 μg / kg, and 2 μg / kg in patients with preserved spleen. In both studies, a significantly larger proportion of patients who received Romiplastim, demonstrated resistant response in the form of an increase in the number of platelets compared to patients receiving a placebo. In placebo-controlled studies after the first 4 weeks of romiplostim, the platelet count was maintained at> 50 x 10% in 50-70% of patients during the 6-month treatment period. In the placebo group during the 6-month treatment period, only 0-7% of patients had an increase in the number of platelets. In both studies, patients already receiving therapy for ITP in accordance with the established scheme continued to use these drugs throughout the study period (corticosteroids, danazol and / or azathioprine). At the beginning of the study, 21 patients with preserved spleen and 18 patients with splenectomy received therapy for the treatment of ITP (mainly corticosteroids). In all patients (100%) after splenectomy, who received Romiplastim, it became possible to reduce the dose of corticosteroids by more than 25%, or even to abolish standard therapy for treatment of ITP at the end of treatment, compared with 17% of patients receiving placebo. In 73% of patients with preserved spleen who received Romiplastim, it was possible to reduce the dose by more than 25%, or even abolish the standard therapy for treatment of ITP at the end of treatment, compared with 50% of patients receiving placebo.

    The use of Romiplostim for the treatment of ITP in patients with preserved spleen in comparison with standard therapy

    In a randomized study comparing the use of Romiplostim and standard therapy in patients with preserved spleen,

    duration 52 weeks, the efficacy of romiplostim was significantly higher than in standard therapy, i.e. In the group of romiplostima, the patients had fewer indications for splenectomy and ineffective treatment. The overall percentage of indications for splenectomy was significantly lower in the group of rhyplostim compared to the group receiving standard therapy: 8.9% (14 of 157 patients) in the romiplostym group compared with 36.4% (28 of 77 patients) in the standard group therapy.

    The overall percentage of patients with ineffective treatment was significantly lower in the romiplostym group than in the standard therapy group: 11.5% (18 of 157 patients) of the romiplostim group, compared with 29.9% (23 of 77 patients) in the standard therapy group.

    In this study, 157 patients randomized to the group

    Romiplostim, the total average exposure to romiplostim for 154 patients was 52 weeks, ranging from 2 to 53 weeks. The most frequently used weekly dose in the range of 3-5 μg / kg (25% - 75%, respectively, the average value of 3 μg / kg).

    Open long-term effectiveness study

    Patients who completed preliminary studies with Romiplostim (including Phase 3 studies) were allowed to participate in a long-term open-label advanced study. In 292 adult patients who were subsequently included in the extended study, the platelet count was increased and, subsequently, was maintained at a stable level regardless of whether the patients were receiving Romiplastim or placebo in preliminary placebo-controlled studies. In most patients, after taking one of the three doses of romiplostime, an average platelet count of 50 x 109/ l and this level was maintained throughout the study with an average duration of use

    Romiplostima 78 weeks and a maximum duration of 277 weeks.

    Cases of bleeding

    During the whole clinical program of treatment of ITP, an inverse relationship was observed between the cases bleeding and the number of platelets. All clinically significant cases of bleeding (> 3 degrees) occurred at a platelet level <30 x 109/ l. All cases of bleeding > 2 degrees occurred at a platelet level <50x10%. There were no statistically significant differences between all observed cases of bleeding among patients who received the Enplet or placebo. In two placebo-controlled trials, 9 patients experienced bleeding, which was regarded as serious, (5 [6.0%] Romiplastim, 4 [9.8%] placebo; relative risk [Romiploplasm / placebo] = 0.59; 95% confidence interval = (0.15, 2.31)). Cases of bleeding of grade 2 or higher were noted in 15% of patients who received Romiplastim, and 34% of patients who received placebo (relative risk; [Romiplostim / placebo] = 0.35; 95% confidence interval = (0.14, 0.85)).

    Pharmacokinetics:

    The pharmacokinetics of Romiplostima is based on a target-mediated

    distribution of the drug, which is probably due to TPO receptors located on the surface of platelets and other platelet cells, such as megakaryocytes.

    Suction

    After subcutaneous administration of 3 to 15 μg / kg of Romiplostima, the maximum concentration of Romiplostima in plasma in patients with ITP was noted after 7-50 hours (on average, after 14 hours). The concentrations of the drug in the blood plasma varied in different patients and did not correlate with the prescribed dose. Concentrations of Romiplostima in blood plasma, probably, have feedback with the number of platelets.

    Distribution

    The volume of distribution of Romiplostima in healthy volunteers after intravenous injection decreases nonlinearly from 122; 78.8 to 48.2 ml / kg for intravenous doses of 0.3; 1.0 and 10 μg / kg, respectively. Such a nonlinear decrease in the volume of the distribution corresponds to a target-mediated binding of Romiplostim (receptors for megakaryocytes and platelets), which can be saturated at higher doses.

    Excretion

    The half-life period of Romiplostima in patients with ITP varies from 1 to 34 days (on average, 3.5 days). Removal of Romiplostima from the blood plasma is partially dependent on the expression of TPO receptors on platelets.As a consequence of the dose received, patients with a high platelet count exhibit low plasma concentrations and vice versa. In another study involving patients with ITP, no cumulation was observed after 6 weeks of weekly use of Romiplostim (3 μg / kg).

    Special patient groups

    There were no studies pharmacokinetics of Romiplostima in patients with renal and hepatic insufficiency. Presumably, the pharmacokinetics of Romiplostima does not depend on age, body weight and sex in a clinically significant degree.

    Indications:
    Chronic idiopathic (immune) thrombocytopenic purpura in adult patients after splenectomy, resistant to other types of treatment (eg, glucocorticosteroids, immunoglobulins).
    The therapist can be used as second-line therapy in patients with preserved spleen with contraindications to splenectomy.
    Contraindications:Hypersensitivity to the active substance of the drug, to any of the excipients or to E. coli proteins.
    Pregnancy and lactation:
    Clinical data on the use of Romiplostima during pregnancy are absent.In animal experiments, reproductive toxicity was noted, in particular, the transplacental passage and an increased number of platelets in the rat fetus. The potential risk to humans is unknown. Romiplostim should not be used during pregnancy, except for a severe need. There is no data on the penetration of Romiplostim into breast milk. Nevertheless, this is possible, and the risk for an infant can not be ruled out.
    The decision to continue / stop breastfeeding or continue / stop therapy with romiplothym should be taken, given the benefits of breastfeeding for the baby and the benefit of Romiplostim treatment for the mother.
    Dosing and Administration:

    Treatment should be carried out under the supervision of a doctor who has experience in the treatment of hematological patients. The therapist should be administered once a week as a subcutaneous injection.

    Initial dose

    The initial dose of Romiplostima is 1 μg / kg of actual body weight.

    Calculation of dose

    Initial or subsequent weekly dose

    Volume of administration

    Body weight * in kg x dose in μg / kg = individual dose of patient in μg

    The dose in μg x 1 ml / 500 μg = the amount for administration in ml

    Example:

    Patient with body weight of ug / kg

    75 kg is prescribed romiplostime. Individual dose of the patient = 75 kg x 1 μg / kg = 75 μg Accordingly, the amount of solution of the drug Enplet for injection = 75 μg x 1 ml / 500 μg = 0.15 ml

    * When calculating the dose of Romiplostim at the beginning of treatment, the calculation should always be based on body weight. With subsequent correction of the dose should be based exclusively on changes in the number of platelets, and increase the dosage by 1 μg / kg (see table below).

    Dose selection

    The weekly dose of romiplostime should be increased in 1 μg / kg body weight until the patient's platelet count reaches >50 x 10%. The number of platelets should be assessed weekly until a stable amount is achieved (> 50 x 109/ l for at least 4 weeks without dose adjustment). In the future, the number of platelets should be assessed on a monthly basis. Do not exceed the maximum weekly dose of 10 mcg / kg.

    The dose should be adjusted as follows:

    Colic

    thrombocytes

    (X 109/ l)

    Correction of dose

    <50

    Increase the weekly dose by 1 mcg / kg

    >200 2

    weeks in a row

    Reduce the weekly dose by 1 mcg / kg

    >400

    Do not prescribe a drug, continue to evaluate the number of platelets weekly. After the platelet count drops to <200 x 109/ l, continue treatment with a weekly dose reduced by 1 μg / kg

    If the response to treatment fails or if it is impossible to maintain a stable amount of platelets when treated with rhyplostimom in the recommended doses, it is necessary to establish the cause of the loss of response.

    Discontinuation of treatment

    Treatment with romiplostim should be discontinued if the platelet count does not increase to a level sufficient to prevent clinically significant bleeding after 4 weeks of romiplostim therapy at a maximum dose of 10 μg / kg.

    Periodic clinical examination of the patient is necessary, and on an individual basis the doctor must decide on continuing treatment. After the withdrawal of treatment, a relapse of thrombocytopenia is possible.

    Mode of application

    After diluting the powder, the injection solution should be administered subcutaneously. The injection volume can be very small. You should use a syringe with 0.01 ml divisions.

    Precautions for preparation of solution

    Care should be taken when calculating the dose and dilution of the drug Enplet with the correct volume of sterile water for injection. It should be ensured that the required amount of Enplet preparation is selected for the syringe (see "Special instructions" and "Overdose") for subcutaneous injection.

    Patients of advanced age (> 65 years)

    In general, there was no difference in efficacy and safety in the groups of patients younger than 65 and over 65 years of age. Despite the fact that no dose adjustment for elderly patients is required based on these data, care must be taken when treating them. This is due to the fact that at the present time a small number of elderly patients have participated in clinical trials.

    Children and adolescents (<18 years old)

    The drug is not recommended for use in children younger than 18 years due to insufficient data on safety and efficacy. In this group, the lack of data does not allow us to formulate recommendations for dosing.

    In a 1/2-phase study of dose selection in 22 pediatric patients, the profile of the Enplet preparation was similar to that in adult studies.

    Hepatic and renal insufficiency

    In this group of patients there were no controlled clinical trials. It should be used with care in such patients.

    Preparation of the solution

    The product is a sterile preparation, does not contain preservatives or stabilizers and is intended for use immediately after the preparation of the solution. The therapist should be planted in accordance with proper asepsis rules.

    An 250 mcg envelope, a powder for the preparation of a solution for subcutaneous administration, should be diluted in 0.72 ml of sterile water for injection to give a volume of 0.5 ml. Each vial contains a sufficient amount of Romiplostim to ensure a solution with a concentration of 250 μg / 0.5 ml. The 500 mcg, powder for the preparation of a solution for subcutaneous administration, should be diluted in 1.2 ml of sterile water for injection to obtain a volume of 1 ml. Each vial contains a sufficient amount of Romiplostim to ensure a solution with a concentration of 500 μg / ml. Do not use sodium chloride or bacteriostatic water for dilution of the preparation.

    Water for injection should be injected into the vial. The bottle must be turned gently to dissolve the contents.

    The bottle should not be shaken or energetically stirred with its contents.

    Usually dissolution of the drug Enplet takes less than 2 minutes. The finished solution should be clear and colorless. Before use, you should visually verify that there are no foreign particles and a color violation of the solution. Do not use a colored solution or solution containing foreign particles.

    Unused preparation or waste must be disposed of in accordance with the requirements. In the absence of studies on pharmaceutical compatibility, this preparation should not be diluted with other solvents, except as noted above.

    Side effects:

    Based on an analysis of data for all adult patients with ITP who received Romiplastim in 4 controlled and 5 uncontrolled clinical

    studies, the total number of cases of undesirable reactions in patients in the romiplostim group was 91.5% (248/271). The average exposure time for romiplostim in these studies was 50 weeks.

    The frequency of occurrence is defined as follows: very often (> 1/10), often (>1/100, <1/10) and rarely (> 1/1000, <1/100). Undesirable reactions are presented in order of decreasing incidence in each class of organ system in terms of the Medical Dictionary of Regulatory Activity (MedDRA).

    Class of organ system MedDRA

    Often

    Often

    Rarely

    Infections and invasions

    Flu

    Local

    infection

    Nasopharyngitis

    Benign neoplasms, malignant neoplasms and unspecified neoplasms (including cysts and polyps)

    Multiple myeloma

    Myelofibrosis

    Violations of the blood and lymphatic system

    Disturbances from the bone marrow*

    Thrombocytopenia *

    Anemia

    Aplastic anemia

    Malignant neoplasm of bone marrow

    Leukocytosis

    Splenomegaly

    Thrombocythemia

    Increase in the number of platelets

    Abnormal amount of platelets

    Immune system disorders

    Hypersensitivity**

    Angioedema

    Disorders from the metabolism and nutrition

    Intolerance to alcohol

    Anorexia

    Decreased appetite

    Dehydration

    Gout

    Disruption from the psyche

    Insomnia

    Depression

    Unusual dreams

    Disturbances from the nervous system

    Headache

    Dizziness

    Migraine

    Paresthesia

    Clonic convulsions

    Dysgeusia

    Hypesesia

    Hypoguezia

    Peripheral Neuropathy

    Thrombosis of transverse sinus

    Disturbances on the part of the organ of sight

    Subconjunctival hemorrhage

    Violation of accommodation

    Blindness

    Visual disturbances

    Itching of the eyes

    Increased lacrimation

    Edema of the optic disc

    Visual impairment

    Disorders from the vestibular apparatus

    Dizziness

    Disorders from the cardiovascular system

    Myocardial infarction

    Increase heart rate

    Vascular disorders

    The rush of blood

    Deep vein thrombosis

    Hypotension

    Embolism of peripheral vessels

    Ischemia of peripheral vessels

    Phlebitis

    Surface thrombophlebitis

    Thrombosis

    Disturbances from the respiratory system, chest and mediastinal organs

    Embolism of the pulmonary artery *

    Cough

    Rhinorrhea

    Feeling

    dryness in

    throat

    Dyspnea

    Stagnation

    nose

    Pain when breathing

    Disorders from the gastrointestinal tract

    Nausea

    Diarrhea

    Pain in

    abdomen

    Constipation

    Dyspepsia

    Vomiting

    Bleeding

    from the direct

    intestines

    Unpleasant

    smell from the mouth

    Dysphagia

    Reflux-

    esophagitis

    Hematocheia

    (emergence

    unchanged

    blood in

    feces

    masses)

    Bleeding

    of oral

    cavities

    Discomfort

    in area

    belly

    Stomatitis

    Change

    tooth color

    Disorders from the liver and biliary tract

    Thrombosis

    gate

    veins

    Increase in the level of liver transaminases

    Violations

    from

    skin and

    subcutaneous-

    fatty

    cellulose

    Itching

    Ecchymoses

    Rash

    Alopecia

    Reactions

    photosensitivity

    the

    Acne

    Contact

    dermatitis

    Dryness

    leather

    Eczema

    Erythema

    Exfoliative

    rash

    Violation

    hair growth

    Prurigo

    Hemorrhages

    rash

    Papular

    rash

    Itchy

    rash

    Nodal

    thickening

    on the skin

    Change

    smell of the skin

    Hives

    Violations

    from

    skeletal-

    muscular

    and

    connector

    fabric

    Arthralgia

    Myalgia

    Muscular

    the

    spasm

    Pain in

    course

    that

    Pain in

    back

    Pain in

    bones

    Muscular

    voltage

    Muscular

    weakness

    Pain in the shoulder

    Muscular

    twitching

    Violations

    from

    kidney and

    urinary-

    pathways

    Availability

    protein in the urine

    Violations

    from

    reproductions

    vain

    systems and

    dairy

    glands

    Bleeding

    from the vagina

    General disorders

    and

    disorders at the injection site

    Fatigability

    Peripheral edema

    Flu-like

    state

    Pain

    Asthenia

    Fever

    Chills

    Reactions in

    place

    injections

    Hemorrhages at the injection site Pain in the chest Irritability Mischief Swelling of the face Feeling of heat

    Feeling of anxiety

    Research

    Increased blood pressure

    pressures

    Increase

    concentrations

    lactate-

    rogenase

    blood

    Increase

    temperatures

    bodies

    Weight loss Body weight gain

    Injuries, poisonings and procedural complications

    Injury

    * see section "Special instructions"

    ** Hypersensitivity reactions include rash, hives and angioedema. In addition, the undesirable reactions listed below were also linked by the investigating physicians with the treatment being administered.

    Thrombocytosis

    Based on an analysis of data for all adult patients with ITP who received Romiplastim in 4 controlled and 5 uncontrolled clinical trials, there were 3 cases of thrombocytosis, n = 271. All three patients had no clinical consequences due to an increase in the number of platelets.

    Thrombocytopenia after discontinuation of treatment

    Based on an analysis of data for all adult patients with ITP who received Romiplastim in 4 controlled and 5 uncontrolled clinical trials, there were 4 cases of thrombocytopenia after discontinuation of treatment, n = 271.

    Increased concentration of reticulin in the bone marrow

    In clinical trials, the treatment with romiplostim was discontinued in 4 of the 271 patients due to the deposition of reticulin in the bone marrow. In 6 patients, reticulin was detected with bone marrow biopsy.

    Immunogenicity

    In clinical studies, antibodies to romiplostim were determined. In clinical trials of ITP, with the participation of 537 adult patients, 5.8% and 3.9% of the cases were identified with antibodies to romiplostim and TPO, respectively, and only 2 studies (0.4%) were positive for neutralizing antibodies to Romiplot, but cross-over reactivity with endogenous TPO was not observed. Both studies gave a negative result for the neutralization of antibodies to romiplostym 4 months after the end of the drug. The level of previously existing antibodies to romiplostimu and TPO was 8.0% and 5.4%, respectively. Like all therapeutic proteins, Romiplastim has potential immunogenicity. In case of suspicion of the formation of neutralizing antibodies, you should contact the official representative of the company in the Russian Federation to conduct an antibody test.

    Unwanted reactions from spontaneous Reporting (not reported in clinical research)

    The frequency of adverse reactions from spontaneous reporting can not be estimated (frequency, unknown). Adverse reactions from spontaneous reporting include: Disorders from the vascular system: erythromelalgia.

    Overdose:In rats receiving a single dose of 1000 mcg / kg or in monkeys, after repeated appointment of Romiplostim at a dose of 500 mcg / kg (exceeding the maximum clinical dose of 10 mcg / kg - 100 or 50 times, respectively), no undesirable reactions were observed. In case of an overdose, the number of platelets may increase and lead to thromboembolic complications. If the number of platelets increases rapidly, you should stop taking the drug Enplet and then carefully monitor the level of platelets. Renewal of the drug is possible only according to the recommendations on the method of application and dosage (see the sections "Dosing and Administration" and "Special instructions").
    Interaction:
    There have been no studies on interactions with other drugs.

    Possible interactions of rhyomplostim with concomitantly taken drugs that arise when binding to plasma proteins are unknown.

    Drugs used to treat ITP in combination with Romiplostim during clinical trials included glucocorticosteroids, danazol and / or azathioprine, intravenous immunoglobulin (BBIT), and anti-D immunoglobulin. It is necessary to control the number of platelets with simultaneous appointment of romiplostim with other drugs for the treatment of ITP, in order to prevent an increase in the number of platelets beyond the recommended range.

    The use of glucocorticosteroids, danazol and azathioprine can be reduced or stopped with the simultaneous use of these drugs with romiplostimom. It is necessary to control the number of platelets with the reduction or elimination of other drugs to treat ITP, in order to prevent a decrease in the number of platelets below the recommended level.
    Special instructions:
    The following special instructions and precautions are based on events that have been observed, or can occur as a result of the pharmacological action of receptor stimulants tothrombopoietin (TPO).
    Recurrent thrombocytopenia and bleeding after withdrawal of treatment
    After the abolition of Romiplostima, a relapse of thrombocytopenia is possible. In the event that the abolition of romiplostime occurs against the background of anticoagulants or antiplatelet agents, the risk of bleeding increases. Patients should be closely monitored for the timely detection of a decrease in the number of platelets and to prevent bleeding after the abolition of Romiplostima. Upon termination therapy with romipliplasm it is recommended to begin again the therapy of ITP in accordance with the current guidelines for treatment. Additional medical purposes may include the abolition of anticoagulants and / or antiaggregants or transfusion of thrombomass.

    Increased reticulin in the bone marrow

    An increase in the concentration of reticulins in the bone marrow is thought to be a consequence of stimulation of TPO receptors, which leads to an increase in the number of megakaryocytes in the bone marrow, which may subsequently contribute to the release of cytokines. An increase in the concentration of reticulin can be suspected by the morphological changes in peripheral blood cells, and determined by bone marrow biopsy.Thus, before and during treatment with Romiplotome, it is recommended that a study of the smear of peripheral blood and counting the number of blood cells is recommended. In case of loss of efficacy, or detection of pathology in the smear of peripheral blood in a patient, it is necessary to cancel Romiplastim, conduct a physical examination, and consider conducting a bone marrow biopsy with staining on the reticulin. If possible, biopsy results should be compared with previous results. If the efficacy persists and pathology in the peripheral blood smear is observed, the physician should conduct an adequate clinical evaluation, including the decision to conduct bone marrow biopsy. It is also necessary to determine the benefit-risk ratio for romiplostima, and revise the possibility of prescribing an alternative therapy for ITP.

    Thrombotic / thromboembolic complications

    The number of platelets exceeding the norm is a theoretical risk factor for the development of thrombotic / thromboembolic complications. In clinical studies, the frequency of thrombotic / thromboembolic complications observed in control groups,was similar to the Enplet. The relationship between these complications and the increase in the number of platelets has not been established. Follow the guidance on dose adjustment (see section "Dosage and Administration"). When used in routine practice, thrombotic / thromboembolic complications were observed.

    Progression of the present myelodysplastic syndrome (MDS)

    TPO receptor stimulators are growth factors that lead to growth of hematopoietic progenitor cells, differentiation and platelet production. The TPO receptor is predominantly located on the surface of myeloid cells; the expression of TPO receptors on solid tumor cells is not confirmed. There is a theoretical risk that TPO receptor stimulants can stimulate the progression of an existing MDS.

    In clinical studies in the treatment of patients with MDS romiplostimom, there were cases of progression of the disease to acute myeloid leukemia (OML) - the expected outcome of the MDS. In addition, there have been cases of transient growth of blast cells, without progression to OML. The benefit-risk relationship for romiplostime is not established for patients with MDS or other diseases (except ITP).

    Lack of response to romiplostim therapy

    If you lose a response to treatment or can not maintain a stable amount of platelets in the treatment with Romiplostim at recommended doses, you need to establish the causative factors, including immunogenicity and an increase in the concentration of reticulin in the bone marrow.

    Errors in the use of the drug

    Patients receiving the Encelete were informed of medical errors involving overdose and the introduction of an inadequate dose. Overdose can lead to an increase in the number of platelets, and, as a consequence, the development of thrombotic / thromboembolic complications. With an excessive increase in the number of platelets, it is necessary to stop treatment with Enplet and monitor the number of platelets. Renewal of the treatment is necessary according to the recommendations for dosing and the way of use. The introduction of an insufficient dose may lead to the formation of less than expected platelet counts and the likelihood of bleeding.Patients receiving the Encelete need to control the platelet count (see the section "Dosing and Administration", "Special instructions" and "Overdose").

    The effect of Romiplostim on red and white blood cells

    Changes in the number of red (decrease) and white (increase) in blood cells were observed during preclinical studies of drug toxicity (in rats and monkeys), but not in patients with ITP. It should be determined whether these parameters should be monitored in patients receiving rhyplostimic treatment.

    Effect on the ability to drive transp. cf. and fur:There was no research on the impact on the ability to drive vehicles and research mechanisms.
    During clinical trials, some patients experienced transient dizziness attacks, which may affect the ability to drive vehicles and mechanisms.
    Form release / dosage:
    Powder for the preparation of a solution for subcutaneous administration is 250 μg, 500 μg (500 μg / ml).
    Packaging:Bottle of 5 ml of hydrolytic class I glass with 13 mm elastomeric plug, aluminum cap and breakable polypropylene cap.One vial containing 250 μg or 500 μg of Romiplostime is placed in a contiguous cell package. One contour mesh package is placed in a cardboard pack together with an instruction for use.
    Storage conditions:
    Store at 2 - 8 ° C. Do not freeze. Keep in original packaging to protect from light. Keep out of the reach of children!

    Special instructions on the condition of storage

    After dilution: the chemical and physical stability of the diluted preparation is maintained for 24 hours at a temperature of 25 ° C and for 24 hours at a temperature of 2-8 ° C, in a dark place and in the original packaging. From the microbiological point of view, the drug should be used immediately. If no immediate application has been made, the terms and conditions for keeping the diluted product before use remain the responsibility of the consumer. Shelf life of the diluted product should not exceed 24 hours at a temperature of 25 ° C, or 24 hours in a refrigerator (at a temperature of 2 - 8 ° C). The drug should be stored in a place protected from light.
    Shelf life:
    5 years.

    Do not use after the expiration date.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-007739/09
    Date of registration:01.10.2009/18.05.2012
    Expiration Date:unlimited
    The owner of the registration certificate:Amgen Europe BVAmgen Europe BV Netherlands
    Manufacturer: & nbsp
    Representation: & nbspAMDZHEN LLC AMDZHEN LLC Russia
    Information update date: & nbsp01.07.2016
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