Instructions for Bioven Mono solution for infusions bottle 100 ml No. 1
Composition
active substance: Human normal immunoglobulin for intravenous administration;
1 ml of the drug contains 0.05 g of normal human immunoglobulin (including at least 95% immunoglobulin G (IgG);
excipients: glycine, water for injection.
Dosage form
Solution for infusion 5%.
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 of immunoglobulin G isolated from human blood 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 ethyl alcohol, which has undergone the stage of viral inactivation by the solvent-detergent method and nanofiltration method. Distribution of immunoglobulin G (IgG) subclasses: IgG1 - approx. 65.6%, IgG2 - approx. 22.1%, IgG3 - approx. 10.8%, IgG4 - approx. 1.5%); the limiting content of immunoglobulin A in the drug is 25 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, herpes, chickenpox, influenza, measles, mumps, polio, rubella, whooping cough, staphylococcus, Escherichia coli, pneumococcus. It also has non-specific activity - it increases the body's resistance.
There are no anti-complementary properties, since the isolated immunoglobulins are purified from aggregated proteins and impurities.
Pharmacokinetics.
After intravenous administration, human normal immunoglobulin is immediately and completely bioavailable in the recipient's circulation. 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.
Indication
Replacement therapy
Primary immunodeficiency syndromes, such as:
congenital agammaglobulinemia and hypogammaglobulinemia;
common variable immunodeficiency;
severe combined immunodeficiency;
Wiskott-Aldrich syndrome;
Transient hypogammaglobulinemia in children.
Secondary immunodeficiency syndromes, such as:
severe recurrent bacterial infections in children with HIV/AIDS;
cytopenias of various genesis (acute and chronic leukemia, aplastic anemia, condition after cytostatic therapy);
severe forms of bacterial-toxic and viral infections in adults and children (including surgical complications accompanied by bacteremia and septicopyemic conditions, and during the preparation of surgical patients for surgery);
prevention and treatment of infections in premature infants with low birth weight;
Hypogammaglobulinemia in patients after allogeneic bone marrow transplantation.
Immunomodulatory therapy:
idiopathic thrombocytopenic purpura;
Guillain-Barré syndrome;
Kawasaki syndrome;
chronic inflammatory neuropathy (demyelinating);
general myopathy;
Wegener's granulomatosis;
dermatomyositis;
systemic connective tissue diseases (rheumatoid arthritis).
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), the drug should be prescribed after consultation with an appropriate specialist. During the period of exacerbation of the allergic process, the drug is administered after the conclusion of an allergist according to vital indications.
Special safety precautions
Bioven mono® should only be used in a hospital setting, observing aseptic precautions. Before administration, the drug should be kept at a temperature of (20±2) °C for at least 2 hours.
The solution should be clear or slightly opalescent, colorless or slightly yellowish. Do not use cloudy solutions or those with a precipitate.
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 other medications.
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 the above-mentioned infections (measles, rubella, mumps and chickenpox), the drug should be administered no earlier than 2 weeks later; if Bioven mono® is needed before this period, the measles or mumps vaccination should be repeated. Vaccinations against other infections can be carried out at any time before or after the drug is administered.
Impact on serological test results
After immunoglobulin injection, a temporary increase in the blood level of various passively transmitted antibodies may lead to false positive results in serological tests.
Passive transfer of antibodies to red cell antigens, such as A, B, or D, may affect 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 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:
patients are insensitive to human normal immunoglobulin when first administered slowly by infusion;
Patients should be closely monitored for any symptoms throughout the infusion period. In particular, patients who have not previously received immunoglobulin products, who have been treated with an alternative product, or who have had a long interval since the last immunoglobulin administration should be monitored during the first infusion and for the first hour after the first infusion to detect signs of potential adverse effects. Such patients should be monitored throughout the first infusion period and for 1 hour after the end of the administration. All other patients should be monitored for the first 30 minutes after the administration.
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;
control diuresis;
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 mono® by infusion should be stopped immediately and appropriate treatment should be applied. 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 mono®. The drug is contraindicated in patients with selective IgA deficiency (see section "Contraindications").
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 or older, sepsis, or paraproteinemia have been identified.
Reports of renal dysfunction and acute renal failure have been associated with the use of many licensed IgG products containing various excipients such as sucrose, glucose and maltose, and products containing sucrose as a stabilizer. For patients at increased risk, the use of IgG products that do not contain these excipients may be considered.
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 mono® 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 mono® 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, acquired or hereditary thrombophilia, severe hypovolemia, 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.
Due to the potential increased risk of thrombosis, blood viscosity should be assessed in patients at risk of increased viscosity, including cryoglobulins, fasting chylomicronemia/markedly high triglycerides (triglycerides), or monoclonal gammopathy. For patients at risk of thrombosis, immunoglobulin preparations should be administered in minimal doses and at minimal infusion rates. Before using the drug, ensure that the patient is adequately hydrated. Patients at risk of increased viscosity should be monitored for symptoms of thrombosis and blood viscosity should be assessed.
Aseptic meningitis syndrome
Aseptic meningitis syndrome (AMS) has been reported to occur rarely in association with immunoglobulin therapy. Discontinuation of the therapy results in uncomplicated remission of the AMS within a few days. 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 examination, including CSF studies, to exclude other causes of meningitis. Patients with a history of migraine are more likely to develop this syndrome. 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 immunoglobulin coating of red blood cells, resulting in a positive direct immunoglobulin reaction and occasionally hemolysis. Hemolytic anemia may occur in association with immunoglobulin therapy due to increased red blood cell sequestration. 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
Noncardiogenic pulmonary edema (transfusion-associated lung injury (TALES)) has been reported in patients receiving immunoglobulin. TALES is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever, usually occurring within 1 to 6 hours after transfusion. Patients with TALES may benefit from 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 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, 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 that there are no cases of transmission of hepatitis A virus and parvovirus B19 with the use of human immunoglobulin preparations. In addition, the antibody content is assumed to be of great importance for increasing viral safety. The preparation does not contain a preservative or antibiotics.
Children
Children may be more susceptible to volume overload.
Elderly patients
Patients aged 65 years and older may be at increased risk of developing certain adverse reactions, such as thromboembolic complications and acute renal failure.
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 and breastfeeding women. Studies of IgG administration to pregnant women have shown that it crosses the placenta, especially in the third trimester. Clinical experience with immunoglobulins suggests 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 immunoglobulins has shown no effect on fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
No effect on the ability to drive or use machines was observed.
Method of administration and doses
The drug is administered intravenously by drip. The rate of administration for children should be from 0.08 to 0.5 ml/min depending on body weight, for adults - 1–1.5 ml/min. Faster administration may cause the development of a collaptoid reaction.
In congenital agammaglobulinemia or hypogammaglobulinemia, other primary deficiency syndromes, including severe combined immunodeficiency, Wiskott-Aldrich syndrome, common variable immunodeficiency, transient hypogammaglobulinemia in children - 8–10 ml (0.4–0.5 g)/kg (minimum dose - 4 ml (0.2 g)/kg, maximum - 16 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 – 4–8 ml (0.2–0.4 g)/kg every 3–4 weeks.
For severe recurrent bacterial infections in children with HIV/AIDS – 8 ml (0.4 g)/kg every 3–4 weeks.
For cytopenias of various genesis (acute and chronic leukemia, aplastic anemia, condition after cytostatic therapy) - 4–8 ml (0.2–0.4 g)/kg/day for 4–5 days or 20 ml (1 g)/kg/day for 2 days.
For severe forms of bacterial-toxic and viral infections in adults and children (including surgical complications accompanied by bacteremia and septicopyemic conditions and during preparation of surgical patients for surgery) - 8 ml (0.4 g)/kg/day for 1–4 days.
In allogeneic bone marrow transplantation, 4–8 ml (0.2–0.4 g)/kg every 3–4 weeks until target IgG levels are achieved. If necessary, the dose can be increased to 10 ml (0.5 g)/kg.
In idiopathic thrombocytopenic purpura – 4–8 ml (0.2–0.4 g)/kg/day for 2–5 days or 16–20 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 (demyelinating), general myopathy, Wegener's granulomatosis - 8 ml (0.4 g)/kg/day for 3–7 days, if necessary, 5-day courses of treatment are repeated at intervals of 4 weeks.
For dermatomyositis – 20 ml (1 g) kg/day for 3–5 days.
For systemic connective tissue diseases (rheumatoid arthritis) - 4–10 ml (0.2–0.5 g)/kg/day for 5 days.
In Kawasaki syndrome - 20–40 ml (1–2 g)/kg in equal doses for 2–5 days or 40 ml (2 g)/kg once (adjunct to acetylsalicylic acid therapy).
For the prevention and treatment of infections in premature infants with low birth weight, 3–8 ml (0.15–0.4 g)/kg on the second to third day of life (in the first stage) and on the second to third week of life (in the second stage).
The drug can be used in pediatric practice (see section "Method of administration and dosage").
Overdose
Overdose may lead to fluid overload and increased fluid viscosity, especially in patients at risk, including the elderly or patients with impaired renal function.
Side effects
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, tachypnea, 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, pruritus, alopecia, cold sweat, photosensitivity, 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.
On the part of the auditory organs: vertigo, fluid in the inner ear.
General disorders and administration site conditions: fever, flu-like symptoms, weakness, chest discomfort, pain, chest tightness, asthenia, malaise, peripheral edema, feeling hot, fatigue, chills, flushing, hyperemia, hyperhidrosis; injection site reactions including pain, hypersensitivity, hyperemia, edema, phlebitis, pruritus.
Laboratory tests: increased liver enzymes, 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.
Pediatric population: The frequency, type and severity of adverse reactions in children are the same as in adults.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature of 2 to 8 ºС.
Keep out of reach of children.
Incompatibility
The drug should not be mixed with other drugs in the same infusion system.
Packaging
25 ml or 50 ml or 100 ml in a bottle. 1 bottle in a pack.
Vacation category
According to the recipe.
Producer
LLC "BIOPHARMA PLASMA", Ukraine.
Location of the manufacturer and its business address
Legal address
Ukraine, 09100, Kyiv region, Bila Tserkva, Kyivska st., 37-V.
Address of place of business
Ukraine, 09100, Kyiv region, Bila Tserkva, Kyivska st., 37-V.
