The mechanism of action Stimulator B lymphocytes (BLyS, also known as BAFF and TNFSF13), belonging to the family ligands of tumor necrosis factor (TNF), suppresses apoptosis in lymphocytes and stimulates differentiation of B lymphocytes into plasma cells that produce immunoglobulin.In patients with systemic lupus erythematosus (SLE) is observed overexpression BlyS. There is a strong correlation between the degree of activity of SLE (on the basis of a national assessment of estrogen safety in lupus erythematosus (the Safety of Estrogen in Lupus Erythematosus National Assessment) – the index of the activity of systemic lupus erythematosus [SELENA-SLEDAI]). And BlyS plasma level of deca durabolin results is a fully human monoclonal antibody class IgGIA, which specifically binds to human soluble BLyS and inhibits its biological activity. deca durabolin results binds to B cells not directly, but by binding to BlyS deca durabolin results inhibits viability of B-lymphocytes in the Risley autoreactive clones, and reduces the differentiation of B lymphocytes into plasma cells that produce immunoglobulin.Pharmacodynamics Reducing elevated serum levels of IgG and antibodies to double-stranded DNA (anti-dsDNA) was observed starting at 8 weeks and continued until 52 weeks of treatment. Patients with hypergammaglobulinemia before the study who received the placebo and deca durabolin results, IgG level normalization to week 52 was observed in 49% and 20%, respectively. In deca durabolin results group among patients with baseline presence of anti-dsDNA observed reduction in the number of patients with anti-dsDNA compared to baseline; a decrease in their number has become apparent since the 8th week and 52-week anti-the dsDNA ceased to be determined in 16% of patients treated with deca durabolin results and in 7% of patients receiving placebo. In patients with low baseline complement therapy drug Benlista accompanied by an increase in its level since the 4th week and throughout the subsequent period. By the 52 th week of the SOC levels and C4 normalized respectively 38% and 44% of patients receiving deca durabolin results compared to 17% and 19% of patients receiving placebo. The target of deca durabolin results is a BLyS, a cytokine critical to the survival of B-lymphocytes, their differentiation and proliferation. deca durabolin results significantly reduced the number of circulating B cells, native and active form, plasma cells, and a subpopulation of lupus B lymphocytes at the 52 th week. Reducing the number of untrained shapes short plasma and plasma cells, and a subpopulation of B lymphocytes lupus observed starting from the 8th week. The number of memory cells initially increased and then slowly decreased to baseline to 52 weeks. Immunogenicity Two phase III studies in 4 out of 563 (0.7%) patients treated at 10 mg / kg, and 27 of 559 (4.8%) patients treated at a dose of 1 mg / kg, there was persistent formation of antibodies to deca durabolin results. The frequency of this phenomenon in the group of patients treated with a dose of 10 mg / kg, may be lower due to a decrease in the sensitivity of methods for determining the presence of high concentrations of the drug. Neutralizing antibodies were detected in 3 patients receiving deca durabolin results 1 mg / kg. However, the formation of antibodies to deca durabolin results are relatively rare, however due to the small number of patients with the presence of antibodies can not be made any definitive conclusions regarding the impact of immunogenicity on the pharmacokinetics of deca durabolin results.
Pharmacokinetics Absorption deca durabolin results administered as an intravenous infusion. The maximum concentration in serum deca durabolin results usually observed at the end of infusion, or immediately after its completion. According to the results of modeling the curve of drug concentration against time using the typical values of the parameter in a population pharmacokinetic model in a maximum serum concentration was 313 ug / ml. Distribution eelimumab distributed in tissues with a total volume of distribution equal to 5.29 liters. Metabolism deca durabolin results is a protein It alleged that metabolic pathway consists in the cleavage into small peptides and amino acids via specific common proteolytic enzymes. Classical biotransformation studies have not been conducted of the drug. Excretion Reduced serum concentrations of deca durabolin results was biexponential with a period of 1.75 days poluraspredeleniya and a terminal half-life equal to 19.4 days. Systemic clearance was 215 ml / day. Drug interactions Concomitant use of mycophenolate mofetil, azathioprine, hydroxychloroquine, and has no significant effect on the pharmacokinetics of deca durabolin results, as evidenced by the results of a population pharmacokinetic analysis. A wide range of other drugs (NSAIDs, acetyl salicylic acid, HMG-CoA reductase) also has no significant effect on the pharmacokinetics of deca durabolin results. Concomitant administration of ACE inhibitors and steroids during the population pharmacokinetic analysis resulted in a statistically significant increase in systemic clearance. However, these effects did not have clinical significance, since the magnitude of the deviations is in the range of natural variability in clearance.
Special patient groups Elderly patients The use of deca durabolin results has been studied in a limited number of elderly patients. In the population pharmacokinetic analysis of the general population of patients with SLE receiving the drug intravenously in studies, age did not affect deca durabolin results exposure. However, given the small number of patients aged 65 years and older, the influence of age can not be definitively ruled out. Children and adolescents Information about the pharmacokinetics of the drug in pediatric missing patients. Patients with impaired renal function Official studies of renal failure effect on the pharmacokinetics of deca durabolin results is not conducted. During clinical trials studied deca durabolin results a limited number of patients with SLE and renal impairment (creatinine clearance <60 mL / min, including the small number of patients with a creatinine clearance <30 mL / min). Although proteinuria (> 2 g / day) resulted in an increase and a decrease in creatinine clearance – a reduction deca durabolin results clearance, these changes were within the expected range of variability. Therefore, dose adjustments in patients with renal impairment is not required. Patients with hepatic impairment No official research on the effect of hepatic impairment on the pharmacokinetics of deca durabolin results is not carried out. The molecules of IgGl, such as deca durabolin results, widespread cleaved by proteolytic enzymes, which are present not only in the liver tissue; so changing the function of the liver, it is not likely to have any effect on deca durabolin results removal from the body. Other patient characteristics sex, race or ethnicity of patients had no significant effect on the pharmacokinetics of deca durabolin results. Change deca durabolin results actions depending on the size of the body is corrected by calculating the dose based on body weight.
use of the drug Benlista shown to reduce disease activity in adult patients receiving standard therapy with active systemic lupus erythematosus (SLE) and the presence of autoantibodies.
Contraindications for use
- deca durabolin results hypersensitivity to the drug or one of the components;
- Children up to age 18;
- pregnancy and lactation;
- active forms of infectious and neoplastic diseases of immunodeficiency.Precautions
severe active CNS lupus, kidney; HIV infection; hypogammaglobulinemia (IgG <400 mg / ml); IgA deficiency (IgA <10 mg / ml); transplanting large body of hematopoietic stem cells, bone marrow or kidney (in history). The simultaneous use of drugs aimed at suppressing the activity of B-lymphocytes, and cyclophosphamide Concomitant use of deca durabolin results with other drugs directed suppressive activity of B-lymphocytes, or intravenous cyclophosphamide It has not been studied. Caution should be exercised when treating both deca durabolin results and other drugs aimed at suppressing the activity of B-lymphocytes, or cyclophosphamide. The risk of infection As is the case with other immunomodulating agents, the mechanism of action of deca durabolin results could increase the potential risk of infection. You should carefully monitor patients who during treatment with deca durabolin results has developed an infectious disease. Physicians should exercise caution in the appointment of deca durabolin results in patients with chronic infections. Patients receiving treatment for chronic infection should not begin therapy deca durabolin results. The risk of cancer As is the case with other immunomodulating agents, the mechanism of action of deca durabolin results could increase the potential risk of development of malignant tumors. In clinical studies, there were no differences in the degree of malignant tumors in the groups treated with deca durabolin results and placebo groups, immunizationshould not be vaccinated with live vaccines within 30 days prior to or during treatment with deca durabolin results, as clinical safety of this combination has not been established . There are no data on the secondary transmission of infection from persons who have received the vaccine, patients receiving deca durabolin results. Due to its mechanism of action of deca durabolin results could disrupt response to immunization. The efficacy of vaccination in patients receiving deca durabolin results unknown. The few data suggest that deca durabolin results has little effect on the ability to maintain a protective immune response upon immunization, carried out before the appointment of deca durabolin results.Pregnancy and lactation
Data on the use of deca durabolin results in pregnant women is limited; formal studies have been conducted. Antibodies are immunoglobulin G (IgG), including deca durabolin results, may pass through the placental barrier.deca durabolin results should not be used during pregnancy.
Women of childbearing age care should be taken to prevent pregnancy during treatment with deca durabolin results. During the application of deca durabolin results and for at least 4 months after the last administration of the drug should use effective methods of contraception.
In animal studies there was no evidence of direct or indirect harmful effects of the drug for toxicity to the mother’s body, pregnancy or fetal development. Associated with the introduction of the drug changes in body infant monkeys limited reversible decrease in the number of B-lymphocytes. Lactation data concerning allocation deca durabolin results milk women or suction deca durabolin results into the systemic circulation from the child intestine after feeding absent. However, the presence of deca durabolin results defined in breastmilk cynomolgus macaques. The safety of deca durabolin results during lactation has not been established.
Dosing and Administration
The recommended dose is 10 mg / kg treatment days 0, 14 and 28 and thereafter once every 1 to 4 weeks. The drug should be administered indefinitely.
The infusion of deca durabolin results should be carried out for 1 hour.
The product should not Benlista administered intravenously.
In the event of patient infusion reactions injection speed can be reduced or the administration of the drug may be suspended. The infusion should be immediately interrupted if a patient develops a life-threatening adverse reactions.
Before infusion of deca durabolin results can be carried out with the use of blockers premedication H 1 histamine receptors, together with the use of antipyretic or without it.
The drug is administered intravenously Benlista before administering it must be restored ( dissolve) and dissolve.
preparation Benlista does not contain preservatives and therefore subsequent dissolution of the drug dilution should be carried out under aseptic conditions.
Allow the vial to warm to room temperature for 10-15 min. 120 mg of deca durabolin results single use vial should be dissolved in 1.5 ml of sterile water for injection deca durabolin results achieve a final concentration of 80 mg / ml. 400 mg of deca durabolin results single use vial should be dissolved in 4.8 ml of sterile water for injection deca durabolin results achieve a final concentration of 80 mg / ml.
A stream of water for injection should be directed to the bottle wall to minimize foaming. The contents of the vial at room temperature should be mix gently in a circular motion for 60 seconds. Thereafter, the vial should be allowed to stand on a table for 5 minutes, and then again the vial contents should be mixed for 60 seconds and leaving it to stand for 5 minutes. The described mixing and settling procedure is repeated until the contents of the vial until the lyophilizate is dissolved completely. Do not shake the bottle.
The dissolution process generally takes 10 to 15 minutes after the addition of sterile water, but it can last up to 30 minutes. Protect the resulting solution from sunlight.
When dissolution deca durabolin results used a mechanical device, the speed should not exceed 500 rev / min and the vial rotation time should not exceed 30 minutes.
The reconstituted solution should be opalescent colorless to pale yellow, free of visible particles. However, the intrusion of small air bubbles solution.
The resulting solution was diluted to 250 ml 0.9% physiological sodium chloride solution for intravenous infusion. 5% dextrose for intravenous injection deca durabolin results compatible with and therefore should not be used. From the fluid container containing 250 ml physiological sodium chloride solution, extract volume equal deca durabolin results solution required for introduction of the dose calculated for a given patient.Then add the required volume of the resulting solution deca durabolin results in this capacity for infusion. Gently invert the container to mix the solution. Remains of deca durabolin results unused solution in the vials must be disposed of. Before use, visually check for the solution of undissolved particles and discoloration. Discard the solution if it contains undissolved particles or solution color change is observed. If the drug solution is not used immediately, it should be protected from direct sunlight and stored in a refrigerator at 2 ° C to 8 ° C. Diluted in less than 8 hours of sodium chloride saline formulation may be stored at 2 ° C to 8 ° C or at room temperature. Special groups of patients Children Application deca durabolin results in patients younger than 18 years have not been studied. Safety and efficacy of deca durabolin results data in patients in this age group are not available. Elderly patients Despite the fact that the data on the use of the drug in elderly patients are limited, to conduct correction dose is not recommended. Patients with impaired renal function formal studies deca durabolin results use for the treatment of patients with systemic lupus erythematosus with renal impairment have been conducted. The study of deca durabolin results actions conducted in a limited number of patients with SLE and renal events. Dose adjustment in patients with renal impairment is not required. Patients with hepatic impairment official trials of deca durabolin results in patients with systemic lupus erythematosus with hepatic impairment have been conducted. However, according to the results of clinical trials of the functional state of the liver had no significant effect on the pharmacokinetics of deca durabolin results. Given these results and the fact that, in general, the liver is not directly involved in the clearance of the antibody, it can be assumed that the need for dose adjustment in patients with hepatic failure is virtually absent.
Adverse events reported below are listed according to the anatomical and physiological classification and frequency of occurrence. The frequency is defined as follows: very common (≥1 / 10), commonly (≥1 / 100 and <1/10), uncommon (≥1 / 1000 and <1/100), rare (≥1 / 10,000 and <1/1 000), very rare (<1/10 000, including isolated cases). Frequency categories were formed on the basis of clinical trials of the drug. The incidence of adverse events Immune system Common: hypersensitivity reaction. Uncommon: anaphylaxis, angioedema. Skin and subcutaneous tissue Common: rash. Common reactions and injection site reactions Often:. fever, infusion reactions, urticaria also observed in patients following adverse events: nausea, diarrhea, pyrexia, infection, bronchitis, cystitis, nasopharyngitis, pharyngitis, depression, insomnia, migraine, leukopenia, pain in the limbs. The causal relationship of data of adverse events with the use of the drug has not been established. In 0.4% of patients have been reported clinically significant hypersensitivity reactions associated with the introduction of deca durabolin results and demanded the full withdrawal of the drug. Typically, such reactions have been observed during the first infusion.
In clinical cases, deca durabolin results was no overdose. Patients receiving two doses of 20 mg / kg body weight as an intravenous infusion at intervals of 21 days, no increase in the frequency or severity of adverse reactions compared to patients receiving the drug in doses of 1, 4 or 10 mg / kg body weight .
Interaction with other drugs
Research deca durabolin results drug interactions with other drugs has not been.
| In clinical trials in patients with SLE co-administration of mycophenolate mofetil, azathioprine, hydroxychloroquine, methotrexate, non-steroidal anti-inflammatory drugs, aspirin and inhibitors GMG CoA reductase inhibitors had no significant effect the action of deca durabolin results.
The product is incompatible with dextrose.
Special instructions and precautions for use
Infusion reactions and hypersensitivity reactions
Introduction deca durabolin results can lead to reactions associated with the administration of the drug, and hypersensitivity reactions. In case of severe reaction deca durabolin results administration must be interrupted and assign the appropriate medication therapy.
Before deca durabolin results infusion can be performed using premedication blockers H 1 histamine receptors, together with antipyretic or without it. According to clinical studies, serious reactions associated with administration of the drug, and hypersensitivity reactions have developed less than 1% of patients, and included anaphylactic reaction, bradycardia, hypotension, angioedema, and dyspnea. Infusion reactions occurred more frequently during the first two infusions, with each subsequent infusion tended to reduce the number of reactions.
Effects on ability to drive and moving machinery
Research influence deca durabolin results on the ability to drive or control mechanical means are not carried out. The pharmacological characteristics of deca durabolin results give reason to believe that it has no adverse effect on the ability to perform such activities.
In considering the patient’s ability to perform tasks requiring high concentration, complex motor and cognitive skills necessary to consider the clinical condition of the patient and the deca durabolin results safety profile.
Valium for concentrate for solution for infusion, 120 mg, 400 mg.
, 120 mg deca durabolin results or deca durabolin results 400 mg vial of clear, colorless glass (type I, Evr.F.), rubber stoppers of butyl rubber and break in | aluminum cap. 1 bottle with instruction on use in carton box.