Flexbumin

INSTRUCTION for medical use of the medicinal product FLEKSBUMIN

Composition:

Active substance: human albumin;

1 l of solution contains 200 g of human albumin (the albumin content must constitute not less than 95 % of total protein content);

Excipients: sodium caprylate, N-acetyltryptophan, sodium chloride, water for injections.

Total sodium ion content is 130–160 mmol/l (3.33 g).

Pharmaceutical form. Infusion solution.

Main physicochemical properties: clear, slightly viscous solution; almost colorless, ranging from yellow to brown or green in color.

Pharmacotherapeutic group.

Blood and related agents. Plasma substitutes and plasma protein fractions. Albumin.

ATC code B05A A01.

Immunological and biological properties.

Pharmacodynamics.

Human albumin quantitatively constitutes more than half of total plasma protein and about 10 % of total protein synthesized by the liver.

Human albumin 200 g/l exerts a hyperoncotic effect. The most important physiological function of albumin is participation in maintaining blood oncotic pressure and transport functions. Albumin stabilizes the circulating blood volume and acts as a carrier for hormones, enzymes, medicinal products, and toxins.

Children

Specific data on pharmacodynamic properties of the drug in the pediatric population are lacking.

Pharmacokinetics.

Under normal conditions, the total volume of albumin distribution is 4–5 g/kg body weight, of which 40–45 % is intravascular and 55–60 % is extravascular. Increased capillary permeability alters albumin kinetics. In conditions such as severe burns or septic shock, abnormal distribution may occur.

Under normal conditions, the mean half-life of albumin is approximately 19 days. The balance between synthesis and degradation is usually maintained via feedback regulation. Elimination occurs predominantly intracellularly with the participation of lysosomal proteases.

In healthy volunteers, less than 10 % of administered albumin leaves the intravascular space within the first 2 hours after administration. There is considerable individual variability in the effect on plasma volume. In some patients, plasma volume may be increased for several hours. However, in critically ill patients, albumin may be lost from the vascular space in significant amounts at an unpredictable rate.

Children

Specific data on pharmacokinetic properties of the drug in the pediatric population are lacking.

Clinical characteristics.

Indications.

Restoration and maintenance of circulating blood volume in conditions associated with volume deficiency and when colloids are indicated.

The choice of albumin over synthetic colloids depends on the individual clinical situation for each patient, based on official recommendations.

Contraindications.

Hypersensitivity to albumin or to any of the excipients of the medicinal product.

Special precautions.

The solution may be administered directly intravenously using a single-use, sterile, pyrogen-free infusion set. Before inserting the infusion set into the stopper of the bag's port, it should be disinfected with an appropriate antiseptic. After the infusion set has been connected to the bag, the contents of the bag should be administered immediately.

Albumin solution must not be diluted with water for injections, as this may cause hemolysis in the patient.

When large volumes are administered, the product should be warmed to room temperature or body temperature prior to administration.

Do not use if the solution is cloudy or contains a precipitate. This may indicate protein instability or contamination of the solution.

Do not use the bag if the port protector is damaged, detached, or missing.

Do not use if the packaging is damaged. Destroy if leakage is detected.

After opening the bag, the product should be used immediately. Any unused solution must be destroyed according to local regulations.

Interaction with other medicinal products and other forms of interaction.

Specific interactions of human albumin with other medicinal products are unknown. Human albumin should not be mixed with other medicinal products (except for recommended diluents), whole blood, or packed red blood cells. Human albumin should also not be mixed with protein hydrolysates (e.g., parenteral nutrition) or with alcohol-containing solutions, as such combinations may result in protein precipitation.

Special precautions for use.

Suspicion of allergic or anaphylactic reactions requires immediate discontinuation of the drug administration. In case of shock development, standard treatment should be initiated.

Albumin should be used with caution in cases of hypervolemia and its consequences or hemodilution, as well as in other conditions that may pose a particular risk to the patient, for example:

• decompensated heart failure;
• arterial hypertension;
• esophageal varices;
• pulmonary edema;
• hemorrhagic diathesis;
• severe anemia;
• renal and post-renal anuria.

The colloid-osmotic effect of 200 g/L human albumin is approximately equivalent to four times that of blood plasma. Therefore, when administering concentrated albumin, caution must be exercised to ensure adequate hydration of the patient. The patient's condition must be carefully monitored to prevent circulatory overload and hyperhydration.

The 200 g/L human albumin solution has a relatively low electrolyte content compared to 40–50 g/L human albumin solutions. During albumin administration, the patient's electrolyte status should be regularly monitored, and appropriate measures should be taken to restore and maintain electrolyte balance.

Flexbumin 200 g/L contains sodium.

50 ml pack: the medicinal product Flexbumin contains 149.5–184 mg of sodium per pack, which corresponds to 7.5–9.2% of the WHO recommended maximum daily sodium intake of 2 g for adults.

100 ml pack: the medicinal product Flexbumin contains 299–368 mg of sodium per pack, which corresponds to 15–18.4% of the WHO recommended maximum daily sodium intake of 2 g for adults.

When relatively large volumes of blood need to be replaced, coagulation and hematocrit should be monitored. Care should be taken to ensure appropriate replacement of other blood components (coagulation factors, electrolytes, platelets, and erythrocytes).

If dosage and infusion rate do not match the patient's circulatory status, hypervolemia may develop. At the first clinical signs of cardiovascular overload (headache, dyspnea, jugular vein distension) or increased arterial pressure, elevated central venous pressure, and pulmonary edema, administration of the drug should be immediately discontinued.

Standard measures to prevent transmission of infections with medicinal products derived from human blood or plasma include donor selection, testing of individual plasma donations and plasma pools for specific infectious markers, and implementation of effective viral inactivation/removal steps during manufacturing. Nevertheless, when administering medicinal products derived from human blood or plasma, transmission of infectious agents cannot be completely ruled out. This also applies to unknown or emerging viruses and other pathogens.

There are no data confirming transmission of viruses with albumin properly manufactured according to the specifications of the European Pharmacopoeia.

It is recommended to record the name and batch number of the product each time Flexbumin is administered to a patient, in order to establish a traceable link between the patient and the product batch.

Children

Data on the use of Flexbumin 200 g/L in children are limited. General precautions for use also apply to this patient group.

Use during pregnancy or breastfeeding.

Pregnancy

The safety of using the drug in pregnant women has not been established in controlled clinical trials. However, clinical experience with albumin administration has not revealed any harmful effects on pregnancy, the fetus, or the newborn. Nevertheless, healthcare professionals should weigh the potential risks and prescribe Flexbumin only if clearly needed.

Breastfeeding

A decision should be made whether to discontinue breastfeeding or to withhold Flexbumin therapy, taking into account the benefits of breastfeeding for the child and the therapeutic benefit for the mother.

Fertility

The effects of albumin on fertility have not been studied.

Studies on the influence of the drug on reproductive function in animals have not been conducted. Experimental animal studies are insufficient to evaluate the safety of reproductive function, embryonic or fetal development, course of pregnancy, and pre- and postnatal development. However, human albumin is a normal constituent of human blood.

Ability to affect reaction speed when driving or operating machinery.

No effect on the ability to drive or operate machinery has been observed.

Administration and Dosage

The albumin concentration, dosage, and infusion rate must be adjusted according to the individual patient's needs.

A 100 ml container contains 20 g of human albumin.

A 50 ml container contains 10 g of human albumin.

Dosage

The required dose depends on the patient's body weight, severity of injury or illness, duration of fluid and protein loss. To determine the appropriate dose, it is necessary to assess circulating blood volume and plasma albumin levels.

During administration of human albumin, hemodynamic parameters should be monitored regularly, including:

• arterial blood pressure and pulse rate;
• central venous pressure;
• pulmonary artery wedge pressure;
• urine output (diuresis);
• electrolyte concentrations;
• hematocrit/hemoglobin;
• clinical signs of cardiac/respiratory insufficiency (e.g., dyspnea);
• clinical signs of increased intracranial pressure (e.g., headache).

Route of Administration

Flexbumin may be administered intravenously either undiluted or after dilution with an isotonic solution (e.g., 5% glucose solution or 0.9% sodium chloride solution). Instructions for dilution of the medicinal product prior to administration are provided in the section “Special precautions for safety”.

The infusion rate should be adjusted according to individual circumstances and indications. During plasmapheresis, the infusion rate should correspond to the plasma removal rate.

Children

Clinical studies on the safety and efficacy of Flexbumin in pediatric patients have not been conducted.

Data on the use of Flexbumin 200 g/L in children are limited; therefore, dosage recommendations cannot be provided. Generally, the product should be administered to this patient group only if the benefits clearly outweigh the potential risks.

Overdose

If the dosage or infusion rate is too high, hypervolemia may occur. At the first clinical signs of cardiovascular overload (headache, dyspnea, jugular vein distension), increased arterial pressure, elevated central venous pressure, or pulmonary edema, administration must be stopped immediately and the patient's hemodynamic parameters should be closely monitored.

Adverse reactions.

Summary of safety profile

Mild reactions to human albumin solution, such as flushing, urticaria, fever, and nausea, occur rarely. These reactions usually resolve quickly when the infusion rate is slowed or the infusion is stopped. Very rarely, severe reactions such as shock may occur. In such cases, the infusion should be discontinued and appropriate treatment initiated.

Criteria for assessing the frequency of adverse drug reactions: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000); frequency not known (frequency cannot be estimated from the available data).

During post-marketing surveillance, the following adverse reactions have been reported, classified according to the MedDRA system organ classification, followed by the preferred term in order of severity:

• Immune system disorders: anaphylactic reactions, hypersensitivity/allergic reactions;
• Nervous system disorders: headache, dysgeusia;
• Cardiac disorders: myocardial infarction, atrial fibrillation, tachycardia;
• Vascular disorders: arterial hypotension;
• Respiratory, thoracic and mediastinal disorders: pulmonary edema, dyspnea;
• Gastrointestinal disorders: vomiting;
• Skin and subcutaneous tissue disorders: urticaria, pruritus;
• General disorders and administration site conditions: chills.

Data on adverse reactions from clinical trials of Flexbumin (human) are not available.

Safety information regarding the prevention of transmission of infectious agents with the use of the medicinal product is provided in the section "Use in specific populations".

Children

Specific data in the pediatric population are lacking.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

Shelf life.

3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C. Keep out of the reach of children!

Incompatibilities.

Human albumin must not be mixed with other medicinal products (except as specified in the section "Dosage and method of administration"), whole blood or packed red blood cells. In addition, human albumin should not be mixed with protein hydrolysates (e.g., parenteral nutrition) or solutions containing alcohol, as such combinations may cause protein precipitation.

Packaging.

50 ml in a polyethylene bag; 1 or 24 bags with the package leaflet in a cardboard box.

100 ml in a polyethylene bag; 1 or 12 bags with the package leaflet in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Takeda Manufacturing Austria AG, Austria / Takeda Manufacturing Austria AG, Austria.

Manufacturer's address and location of operation.

Industriestrasse 67, 1221 Vienna, Austria / Industriestrasse 67, 1221 Vienna, Austria.