Bioven solution for infusions 10% bottle 100 ml No. 1

Instructions Bioven solution for infusions 10% bottle 100 ml No. 1

Composition

active substance: Human normal immunoglobulin for intravenous administration;

1 ml of the drug contains 0.1 g of immunologically active protein fraction of immunoglobulin G;

Excipients: glycine (aminoacetic acid); water for injections.

Dosage form

Solution for infusion.

Main physicochemical properties: transparent or slightly opalescent, colorless or slightly yellowish liquid.

Pharmacotherapeutic group

Human immunoglobulin normal for intravenous administration. ATX code J06B A02.

Pharmacological properties

Pharmacodynamics

The drug is an immunologically active protein fraction (distribution of immunoglobulin G subclasses in the drug: IgG1: 65.6%, IgG2: 22.1%, IgG3: 10.8%, IgG4: 1.5%), the maximum content of immunoglobulin A in the drug is 400 μg/ml.

The active component of the drug is antibodies that have specific activity against various pathogens - viruses and bacteria, including hepatitis A and B, cytomegalovirus, human herpes virus type 1, type 2 and type 6, Epstein-Barr virus, chickenpox, influenza, measles, mumps, polio, rubella, whooping cough, staphylococcus, Escherichia coli, pneumococcus, tetanus and diphtheria toxin. It also has non-specific activity, which is manifested in increasing the body's resistance.

The drug has low spontaneous anticomplementary activity.

The drug is a native immunoglobulin G, retaining all biological properties: complement activation, effector and opson-phagocytic functions.

The drug is an immunologically active protein fraction isolated from human serum or plasma, tested for the absence of antibodies to HIV-1, HIV-2, hepatitis C virus and hepatitis B virus surface antigen, purified and concentrated by fractionation with alcohol-water precipitants, which has undergone the stage of viral inactivation by the solvent-detergent method.

Data on the effectiveness of inactivation of model viruses are presented in Table 1.

Table 1

Virus inactivation/removal efficiency

n/a – no data.

Clinical trials

In an open international multicenter phase III study, in accordance with the Guideline on the clinical investigation of human normal immunoglobulin for intravenous administration (IVIg) 28 June 2018 EMA/CHMP/BPWP/94033/2007 rev.3 Committee for Medicinal Products for Human Use (CHMP), the efficacy, safety and some pharmacokinetic parameters of the drug were studied.

Bioven in patients with primary immunodeficiencies (PID). Patients received Bioven for 1 year 1 time in 4 weeks in an average dose of 0.5 g/kg of body weight. Patients were assessed for immunoglobulin levels, number of infections, clinical and biochemical blood test parameters. Also, the most important indicators of heart function, respiration, body temperature were determined, and all cases of possible adverse reactions were recorded.

During 1 year of treatment, 1 case of serious infectious diseases was recorded (2.3%, or 0.023 cases per 1 patient per year). The median trough concentration of immunoglobulin in blood plasma was significantly higher than the minimum target level of 5 g/l and after 6 months of treatment was 8.6 g/l, and after 1 year – 8.8 g/l.

In the group of 49 patients receiving Bioven, 20 cases of mild (2%) and moderate (0.5%) adverse events were recorded, which totaled 2.5% of the injection episodes. No cases of clinically significant deviation of laboratory parameters that were associated with the administration of the drug or required discontinuation of treatment were recorded. 18 patients (adults and children) were administered Bioven with increasing infusion rates. In the first stage of the study, the infusion rate increased to 5.0 ml/kg/h (0.08 ml/kg/min); in the second stage - to 7.0 ml/kg/h (0.11 ml/kg/min). The maximum infusion rate in the third stage was 8.5 ml/kg/h (0.14 ml/kg/min). The incidence of adverse events was low (2 cases per 35 separate injections), they were mild in nature, and did not correlate with the infusion rate. Based on the prevalence of adverse events and assessment of the dynamics of key vital signs, the tolerability of Bioven at a maximum administration rate of 8.5 ml/kg/h (0.14 ml/kg/min) was assessed as good in 94.0% of patients and satisfactory in 6.0%.

The presence of clinical efficacy was confirmed within the framework of the clinical study "Open multicenter randomized study to evaluate the efficacy of the drug Bioven, manufactured by Biopharma Plasma LLC, in the complex therapy of patients with pneumonia caused by COVID-19 / SARS-CoV-2 coronavirus infection" (study code - 2020-BV-BP).
The study included 76 patients with a confirmed diagnosis according to all criteria. 66 patients who passed the screening and did not have exclusion criteria were randomized into 2 groups (study group - Bioven + basic therapy and control group - only basic therapy).

The patients were assessed for respiratory function, general condition, duration of intensive care, need for mechanical ventilation (MV), total duration of treatment. Survival during the 28-day observation period, laboratory blood parameters (complete blood count and biochemical), as well as levels of cytokines, inflammatory factors, and other indicators of the immune system were also assessed.

The results of the study proved the predominant effectiveness of the main variable.

Improvement of the condition occurs significantly faster: the study group - on day 5 (interquartile range - 3.50–7.25 days), the control group - on day 9 (interquartile range - 6.00–14.75 days), p = 0.0073. The probability of achieving stabilization of the condition in patients in the study group is significantly higher by 2.27 times (95% confidence interval (CI) - 1.26–4.11, p = 0.006) than in patients from the control group.

The predominant effectiveness is also confirmed by secondary variables. When using Bioven in the treatment regimen, the mortality rate from COVID-19 is significantly lower: in the study group - 6.25% (2 cases out of 32 participants), in the control group - 23.63% (8 cases out of 34 participants), p=0.039.

The duration of lymphopenia is also significantly reduced. The median of reaching the lymphocyte level of 1000 cells/mm3 and above in the study group was on day 4 (interquartile range: 3.00–5.00 days), in the control group on day 7 (interquartile range: 3.00–7.50 days), p = 0.0097.

Pharmacokinetics

The high effectiveness of the drug is ensured by the rapid and 100% entry of antibodies into the bloodstream and a normal half-life from the body.

After intravenous administration, the bioavailability of human normal immunoglobulin in the recipient's circulation is immediate and complete. It is rapidly distributed between plasma and extravascular fluid, reaching equilibrium between the intra- and extravascular spaces after approximately 3-5 days.

Normal human immunoglobulin has a half-life of approximately 40 days. This half-life may vary from patient to patient, especially in primary immunodeficiency. IgG and IgG complexes are degraded in the cells of the reticuloendothelial system.

A clinical study of individual pharmacokinetic parameters of Bioven was conducted in 22 patients. Cmax was 19.94±4.73 g/l, Tmax was 0.63 hours, AUC (0-t) was 8309.60±2631.49 g/h/l. Plasma immunoglobulin levels were consistently above the minimum target level of 5 g/l for at least 28 days after a single administration of Bioven.

Indication

The drug is used in adult patients for replacement immunotherapy in the treatment of primary and secondary immunodeficiency states and related diseases:

primary immunodeficiency syndromes: congenital agammaglobulinemia or hypogammaglobulinemia, severe combined immunodeficiency, unclassified variable immunodeficiency, Wiskott-Aldrich syndrome; secondary antibody deficiency syndrome: cytopenias of various genesis (acute and chronic leukemia, aplastic anemia, condition after cytostatic therapy), severe forms of bacteriotoxic and viral infections (including surgical complications accompanied by bacteremia and septicopyemic conditions, and complications during the preparation of surgical patients for surgery); autoimmune diseases: idiopathic thrombocytopenic purpura with a high risk of bleeding or before surgery - to correct the platelet count; Guillain-Barré syndrome, chronic inflammatory neuropathy (demyelinating), inflammatory myopathy, Wegener's granulomatosis, dermatomyositis, systemic connective tissue diseases (rheumatoid arthritis), Kawasaki syndrome; bone marrow transplants.

Replacement therapy in children and adolescents (0-18 years) for:

primary immunodeficiency syndromes (PID) with impaired antibody production; secondary immunodeficiencies (SID) in patients suffering from severe or recurrent infections, ineffective antimicrobial treatment, or if there is proven insufficiency of specific antibodies (DNSA*) or serum IgG levels <4 g/l.

*DNSA – failure to achieve at least a two-fold increase in IgG titer against pneumococcal polysaccharide and polypeptide antigen vaccines.

Use as part of complex therapy for adult patients with severe pneumonia caused by COVID-19 / SARS-CoV-2 coronavirus infection.

Contraindication

Hypersensitivity to any of the components of the drug. Hypersensitivity to homologous immunoglobulins, especially in very rare cases of IgA deficiency, when the patient has antibodies to IgA. The administration of immunoglobulin is contraindicated in persons with a history of severe allergic reactions to the administration of human blood protein preparations. Patients suffering from allergic diseases or prone to allergic reactions are recommended to take antihistamines during the administration of immunoglobulin and for the next 8 days. Persons suffering from immunopathological systemic diseases (immune blood diseases, collagenosis, nephritis) should be prescribed the drug after consultation with an appropriate specialist. During the period of exacerbation of the allergic process, the drug should be administered after the conclusion of an allergist according to vital indications.

Special safety precautions

Some serious adverse reactions may be related to the rate of administration of the drug. Patients receiving immunoglobulin for the first time usually experience mild adverse reactions with a higher frequency than those on regular immunoglobulin therapy. The following infusion rate parameters should be followed and patients should be closely observed both during the infusion and for 1 hour after the end of the first infusion. In the event of adverse reactions, the infusion rate should be reduced or the infusion itself stopped until the undesirable symptoms disappear. If symptoms persist after discontinuation of the administration, symptomatic therapy is appropriate. In the event of shock, the instructions for anti-shock therapy should be followed. For patients with diabetes mellitus and risk of renal failure, as well as for patients with systemic lupus erythematosus with renal damage, creatinine levels should be measured within 3 days after the administration of the drug. For subsequent infusions, patients should be closely observed for 20 minutes after the end of the administration of the drug.

The drug Bioven should be used only in a hospital setting, observing the rules of asepsis. Before administration, the drug should be kept at a temperature of (20±2) °C for at least 2 hours. The solution should be transparent or slightly opalescent, colorless or slightly yellowish. Do not use cloudy solutions or those with sediment. A separate infusion system must be used to administer the drug.

Interaction with other medicinal products and other types of interactions

Treatment with the drug can be combined with the use of any medications.

Live attenuated virus vaccines

The administration of immunoglobulins may reduce the efficacy of live attenuated (attenuated) virus vaccines against measles, rubella, mumps and varicella for a period of 6 weeks to 3 months. After administration of this product, 3 months should elapse before vaccination with live attenuated virus vaccines. In the case of measles vaccination, this reduction in vaccine efficacy may last up to 1 year. Therefore, antibody status should be checked in patients receiving measles vaccine.

After vaccination against these infections, the drug should be administered no earlier than 2 weeks later; if Bioven is needed before this period, vaccination against measles or mumps should be given.
Mumps vaccination should be repeated. Vaccinations against other infections can be carried out at any time before or after the administration of the drug.

Impact on serological test results

Following immunoglobulin injection, a temporary increase in the blood levels of various passively transmitted antibodies may lead to false-positive serological tests. Passive transmission of antibodies to red cell antigens, such as A, B or D, may interfere with some serological tests for red cell alloantibodies (e.g. Coombs test), reticulocyte count and haptoglobin.

Application features

Precautions for drug administration

Some serious adverse reactions may be related to the rate of infusion. The recommended infusion rate should be strictly adhered to. The patient should be closely monitored and closely observed for any symptoms throughout the infusion period.

Some side effects may occur more often:

in the case of high infusion rates; in patients receiving human normal immunoglobulin for the first time, or, in rare cases, when switching to human normal immunoglobulin, or when a long time has passed since the previous infusion.

Potential complications can be avoided by making sure that:

In the event of an adverse reaction, either the rate of administration should be reduced or the infusion should be stopped. The necessary treatment depends on the nature and severity of the adverse reaction. In the event of shock, treatment should be carried out in accordance with approved recommendations for anti-shock therapy.

For all patients, when administering IgG, the following is required:

Ensure adequate hydration before starting IgG infusion; Monitor urine output; Monitor serum creatinine levels; Avoid concomitant use of loop diuretics.

Hypersensitivity

Serious allergic reactions may occur. Therefore, persons who have received the drug should be under medical supervision for 30 minutes. In the event of such reactions, the administration of Bioven by infusion should be stopped immediately and appropriate treatment should be administered. Patients with immunoglobulin A deficiency and existing antibodies to immunoglobulin A are at significant risk of developing serious allergic and anaphylactoid reactions that may occur in connection with the administration of Bioven.
In rare cases, human normal immunoglobulin may cause a decrease in blood pressure with anaphylactic reaction, even in patients who have received previous treatment with human normal immunoglobulin.

Kidney failure

Cases of acute renal failure have been reported in patients receiving IgG therapy. These include acute renal failure, acute tubular necrosis, proximal tubular nephropathy, and osmotic nephrosis. In most cases, risk factors such as pre-existing renal failure, diabetes mellitus, hypovolemia, overweight, concomitant nephrotoxic medications, age ≥65 years, sepsis, or paraproteinemia have been identified. Since these reports of renal dysfunction and acute renal failure have been associated with the use of many licensed IgG products, those containing a stabilizer have accounted for a disproportionate share of the total incidence of such cases. In patients at increased risk, the use of IgG products that do not contain sucrose/sucrose/maltose may be considered.

Before starting the administration of Bioven by infusion, it should be ensured that the patient has
there are no signs of dehydration.

In patients with a potential risk of developing acute renal failure, periodic monitoring of renal function and diuresis should be carried out. Renal function indicators, including blood urea nitrogen (BUN)/serum creatinine, should be assessed before the first administration of Bioven and at regular intervals thereafter. If renal function deteriorates, the drug should be discontinued.

For patients with a potential risk of developing impaired renal function and/or thrombotic complications, the amount of Bioven administered per unit time should be carefully reduced.

Hyperproteinemia

Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving immunoglobulin therapy. Hyponatremia may manifest as pseudohyponatremia, manifested by decreased calculated plasma osmolality or increased osmolar interval. It is clinically important to distinguish true hyponatremia from pseudohyponatremia because, when serum free water is reduced, targeted treatment of patients with pseudohyponatremia may result in dehydration, which increases serum viscosity and may lead to thromboembolic complications.

Thromboembolic complications

Thrombosis may occur as a result of treatment with immunoglobulins. Risk factors: obesity, history of atherosclerosis, cardiac output disorders, hypertension, diabetes mellitus with a history of vascular disease and thrombosis, patients with acquired or hereditary thrombophilia, patients with severe hypovolemia, patients with diseases that increase blood viscosity, old age, prolonged immobilization, hypercoagulable states, history of venous or arterial thrombosis, estrogen use, use of indwelling central vascular catheters, increased blood viscosity and risk of cardiovascular disease. Thrombosis may also occur even in the absence of known risk factors.

A general assessment of blood viscosity should be performed in patients at risk for increased viscosity, including cryoglobulin-related, fasting chylomicronemia/markedly high levels
triglycerides (triglycerides) or monoclonal gammopathy. For patients at risk of thrombosis, it is practiced to administer immunoglobulin preparations in minimal doses and with
minimum infusion rate. Before using the drug, ensure that the patient is adequately hydrated. In patients at risk of increased viscosity, monitoring for symptoms of thrombosis and assessment of blood viscosity should be performed.

Aseptic meningitis syndrome (AMS) has been reported to occur rarely in association with immunoglobulin therapy. Discontinuation of the therapy has been associated with a resolution of the AMS within a few days without complications. The syndrome usually occurs within a few hours to two days of immunoglobulin therapy and rapid administration. It is characterized by symptoms including severe headache, neck stiffness, drowsiness, fever, photophobia, pain on eye movement, nausea, and vomiting. Cerebrospinal fluid (CSF) studies are often positive for pleocytosis with several thousand cells per mm3, predominantly granulocytic, and elevated protein levels to several hundred mg/dL. Patients presenting with these symptoms should undergo a neurological evaluation, including a CSF study, to exclude other causes.
Meningitis. Patients with a history of migraine are more prone to it. Meningitis sepsis syndrome may occur more frequently with high-dose IgG treatment.

Hemolysis

Immunoglobulin preparations may contain blood group antibodies that can act as hemolysins and promote in vivo coating of erythrocytes with immunoglobulin, resulting in a positive direct immunoglobulin reaction and occasionally hemolysis. Hemolytic anemia may occur in association with immunoglobulin treatment due to increased red blood cell sequestration. Patients,
Patients receiving immunoglobulin therapy should be monitored for clinical signs of hemolysis. If such signs occur after immunoglobulin infusion, laboratory tests should be performed to confirm hemolysis.

Acute post-transfusion lung injury syndrome

Non-cardiogenic pulmonary edema (acute post-transfusion lung injury syndrome (ATPIS)) has been reported in patients receiving immunoglobulin. ATPIS is characterized by
severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever, which usually occurs within 1-6 hours after transfusion. Patients with SGUL can be treated with oxygen therapy with appropriate supplemental ventilation.

Patients receiving immunoglobulin should be monitored for respiratory adverse reactions. If SGLT is suspected, appropriate tests for antineutrophil antibodies should be performed both in the product and in the patient's serum.

Laboratory studies

If symptoms of hemolysis occur after immunoglobulin infusion, appropriate laboratory tests should be performed to confirm the diagnosis.

If there is suspicion of SGPT, appropriate tests should be performed for the presence of antineutrophil antibodies in both the product and the patient's serum.

Due to the potential increased risk of thrombosis, blood viscosity should be assessed in patients at risk for increased viscosity, including cryoglobulins, fasting chylomicronemia/markedly high triglycerides (triglycerides), or monoclonal gammopathy.

General information

The product is prepared from human plasma. Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of donated blood samples and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/destruction of viruses. Despite these, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infections cannot be totally excluded. This also applies to unknown and emerging viruses and other pathogens.

The measures taken are considered effective against enveloped viruses such as HIV, hepatitis B virus and hepatitis C virus. For non-enveloped viruses such as hepatitis A virus and
parvovirus B19, these measures may be of limited effectiveness. Clinical experience has convincingly demonstrated the absence of transmission of hepatitis A virus and parvovirus B19 with the use of human immunoglobulin preparations. In addition, it is assumed that antibody content is of great importance in increasing viral safety.

The drug does not contain preservatives and antibiotics.

Ability to influence reaction speed when driving vehicles or other mechanisms

No effect on the ability to drive or use machines was observed.

Use during pregnancy or breastfeeding

The safety of this drug in pregnant women has not been established in controlled clinical studies, so it should be administered with caution to pregnant women and mothers during breastfeeding. Studies of the administration of IgG to mothers have shown that it crosses the placenta, especially in the third trimester. Clinical experience with the use of immunoglobulins indicates that no harmful effects on the course of pregnancy, the fetus or the infant should be expected.

Immunoglobulins pass into breast milk and may contribute to the transfer of protective antibodies to the newborn.

Clinical experience with the use of immunoglobulins has shown that there is no effect on fertility.

Method of administration and doses

Bioven should be administered intravenously by drip, with an initial rate of 0.5 - 1.0 ml/kg body weight/hour for 30 minutes. Provided that there are no undesirable side effects, the rate of administration can be gradually increased (recommended increase by 0.5 - 1.5 ml/kg body weight/hour every 10 minutes). According to clinical studies, the maximum rate of administration is 8.5 ml/kg body weight/hour.

In congenital agammaglobulinemia or hypogammaglobulinemia, severe combined immunodeficiency, Wiskott-Aldrich syndrome, unclassified variable immunodeficiency - 4 - 5 ml (0.4 - 0.5 g) / kg (minimum dose - 2 ml (0.2 g) / kg, maximum - 8 ml (0.8 g) / kg) every 3 - 4 weeks, the dose is selected individually, depending on the severity of the infectious syndrome (the optimal level is considered to be achieving a serum IgG level of 5 g / l, but not less than 3 - 4 g / l).

In replacement therapy for secondary immunodeficiency, as a rule, 2–4 ml (0.2–0.4 g)/kg every 3–4 weeks.

For cytopenias of various genesis (acute and chronic leukemia, aplastic anemia, condition after cytostatic therapy) - 2 - 4 ml (0.2 - 0.4 g) / kg / day for 4 - 5 days or 10 ml (1 g) / kg / day for 2 days.

In severe forms of bacterial-toxic and viral infections (including surgical complications accompanied by bacteremia and septicopyemic conditions and during preparation of surgical patients for surgery) - 4 ml (0.4 g)/kg/day for 1-4 days.

In idiopathic thrombocytopenic purpura - 2-4 ml (0.2-0.4 g)/kg/day for 2-5 days or 8-10 ml (0.8-1 g)/kg/day on the first day and, if necessary, on the third day.

For Guillain-Barré syndrome, chronic inflammatory neuropathy (demyelizing), inflammatory myopathy, Wegener's granulomatosis - 2 - 4 ml (0.2 - 0.4 g) / kg / day for 3 - 7 days, if necessary - repeat 5-day courses of treatment at intervals of 4 weeks.

For dermatomyositis – 10 ml (1 g) kg/day for 3–5 days.

For systemic connective tissue diseases (rheumatoid arthritis, etc.) - 2 - 5 ml (0.2 - 0.5 g) / kg / day for 5 days.

For Kawasaki syndrome – 10–20 ml (1–2 g)/kg in equal doses for 2–5 days or 20 ml (2 g)/kg once (adjunct to acetylsalicylic acid therapy).

In bone marrow transplantation, 5 ml (0.5 g)/kg once 7 days before transplantation, then once a week for 3 months after transplantation.

For use as part of complex therapy in adult patients with severe pneumonia caused by COVID-19 / SARS-CoV-2 coronavirus infection (see section "Indications"), the recommended dose is 0.8–1.0 g/kg body weight per day for 2 days (course dose 1.6–2.0 g/kg body weight). The frequency of infusions and the rate of administration are determined by the doctor depending on the patient's condition. The daily dose may be adjusted to avoid exceeding the maximum permissible daily volume of infusion therapy. Monitoring of the state of the blood coagulation system and diuresis is mandatory, especially in patients with excess body weight.

Pediatric patients: Doses for children (aged 0 to 18 years) are the same as for adults, as the dose for each indication is based on body weight and adjusted based on clinical response.

Children

The drug can be used in pediatric practice (see the "Indications" section).

Overdose

Overdose may lead to hypervolemia and increased blood viscosity, especially in patients at risk, including elderly patients or patients with impaired renal function.

Adverse reactions

From the blood and lymphatic system: anemia, lymphadenopathy, hemolysis, leukopenia, hemolytic anemia.

Immune system disorders: hypersensitivity, anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, angioedema, facial edema.

On the part of the endocrine system: thyroid dysfunction.

Nervous system: headache, cerebrovascular accident, aseptic meningitis, migraine, dizziness, paresthesia, hypoesthesia, amnesia, burning sensation, dysarthria, dysgeusia, balance disorder, transient ischemic attack, tremor.

Mental disorders: agitation, anxiety, insomnia;

Cardiac: myocardial infarction, tachycardia, palpitations, cyanosis.

Vascular disorders: peripheral vascular insufficiency, hypotension, hypertension, peripheral coldness, phlebitis, deep vein thrombosis.

Respiratory, thoracic and mediastinal disorders: respiratory failure, pulmonary embolism, pulmonary edema, bronchospasm, dyspnea, cough, increased respiratory rate, rhinorrhea, asthma, nasal congestion, oropharyngeal edema, pharyngolaryngeal pain.

Gastrointestinal: nausea, vomiting, diarrhea, abdominal pain.

Skin and subcutaneous tissue disorders: eczema, urticaria, rash, erythematous rash,
dermatitis, itching, alopecia, cold sweat, photosensitivity reactions, night sweats.

Musculoskeletal and connective tissue disorders: back pain, pain in extremities, arthralgia, muscle spasms, muscle twitching, myalgia.

Renal and urinary disorders: acute renal failure, proteinuria.

From the organs of vision: conjunctivitis, eye pain, eye swelling.

General disorders and administration site conditions: fever, influenza-like symptoms, weakness, chest discomfort, pain, chest tightness, asthenia, malaise, peripheral edema, feeling of heat, fatigue, chills, flushing, hyperemia, hyperhidrosis; injection site reactions including pain, hypersensitivity, hyperemia, edema, phlebitis, pruritus.

Laboratory tests: increased liver enzymes, false positive blood glucose, increased blood creatinine, increased blood cholesterol, increased urea, decreased hematocrit, decreased red blood cell count, positive direct Coombs test, decreased oxygen saturation.

Infections and infestations: bronchitis, nasopharyngitis, chronic sinusitis, mycosis, infection, kidney infection, sinusitis, upper respiratory tract infection, urinary tract infection, bacterial urinary tract infection.

Injury, poisoning and general procedural complications: contusion, transfusion-associated acute lung injury.

Children: In clinical studies with Bioven, most adverse reactions in children were assessed as mild, resolving rapidly on their own or in response to simple measures (reducing the rate of intravenous administration or temporarily stopping it).

Expiration date

3 years.

Shelf life when stored at a temperature not exceeding 25°C is 6 months.

Storage conditions

Store in the original packaging to protect from light at a temperature of 2°C to 8°C. Do not freeze. When stored at a temperature not exceeding 25°C, the shelf life is 6 months.

After this period, the drug cannot be placed in the refrigerator and must be disposed of.

Packaging

100 ml in a bottle or vial. 1 bottle or vial in a box.

Vacation category

According to the recipe.

Producer

LLC "BIOPHARMA PLASMA", Ukraine.

Location of the manufacturer and its business address

Ukraine, 03680, Kyiv, M. Amosova St., 9;

Ukraine, 09100, Kyiv region, Bila Tserkva, Kyivska st., 37-V