Flexbumin

Description

FLEXBUMIN 25% is a sterile, nonpyrogenic preparation of albumin intended for intravenous administration. Each 100 mL of the solution contains 25 g of albumin, adjusted to physiological pH using sodium bicarbonate and/or sodium hydroxide. The formulation is stabilized with N-acetyltryptophan (0.02M) and sodium caprylate (0.02M), with a sodium content of 145 ± 15 mEq/L. FLEXBUMIN 25% is free from preservatives and does not contain any coagulation factors typically found in fresh whole blood or plasma.

The solution appears as a transparent or slightly opalescent liquid, which may exhibit a greenish tint and can range in color from pale straw to amber, while remaining clear of particulate matter. FLEXBUMIN 25% is produced from human plasma through the modified Cohn-Oncley cold ethanol fractionation process, which involves a series of cold-ethanol precipitation, centrifugation, and/or filtration steps, followed by pasteurization of the final product at 60 ± 0.5°C for 10 to 11 hours. This manufacturing process ensures both the purification of albumin and the reduction of viruses.

Uses and Indications

FLEXBUMIN 25%, Albumin (Human) Solution is indicated for the treatment of hypovolemia and hypoalbuminemia associated with conditions such as burns, adult respiratory distress syndrome (ARDS), and nephrosis. This product is also indicated for use during cardiopulmonary bypass surgery and in the management of hemolytic disease of the newborn (HDN).

Limitations of use: FLEXBUMIN 25% is not indicated as an intravenous nutrient.

Dosage and Administration

For intravenous use only. The dose and rate of infusion should be adjusted based on the patient's clinical status. The daily dose must not exceed 2 g of albumin per kg of body weight. For patients with normal blood volume, the infusion rate should not exceed 1 mL/min. It is important to note that dilution with Sterile Water for Injection is not recommended.

Dosage by Indication:

Hypovolemic Shock:

• In infants and young children, the recommended dosage is 2.5 to 5 mL per kg of body weight.

• In older children and adults, an initial dose of 100 to 200 mL is advised, with the option to repeat the dose after 15 to 30 minutes if the response is inadequate.

Hypoalbuminemia:

• The body albumin compartment should be calculated to be 80 to 100 mL per kg of body weight. The daily dose must not exceed 2 g of albumin per kg of body weight.

Burns:

• The dosage should be determined based on the patient's condition and response to treatment after the first 24 hours.

Hemolytic Disease of the Newborn:

• A dosage of 1 g per kg of body weight is recommended prior to or during exchange transfusion.

Contraindications

Use is contraindicated in patients with a history of hypersensitivity reactions to albumin preparations or to any of the excipients, including N-acetyltryptophan and sodium caprylate, due to the risk of severe allergic reactions.

Additionally, the product is contraindicated in individuals with severe anemia or cardiac failure when intravascular volume is normal or increased, as this may exacerbate the patient's condition.

Warnings and Precautions

Hypersensitivity reactions, including anaphylactic reactions, have been reported in patients receiving this product. If a hypersensitivity reaction is suspected, it is imperative to discontinue use immediately and initiate appropriate standard medical treatment.

In situations where hypervolemia and/or hemodilution may occur, it is essential to adjust the dose and rate of infusion according to the patient's volume status. When administering large volumes, healthcare professionals should closely monitor hemodynamic parameters and ensure that adequate substitution of other blood constituents, such as coagulation factors, platelets, and erythrocytes, is available. Additionally, monitoring of electrolyte balance is recommended to prevent complications.

Post-administration, healthcare providers must closely monitor hemodynamic parameters for signs of cardiac or respiratory failure, renal failure, or increasing intracranial pressure. In trauma and postoperative surgery patients, it is particularly important to monitor blood pressure to detect any re-bleeding that may occur due to clot disruption.

It is critical to avoid diluting this product with Sterile Water for Injection, as this can lead to hemolysis in recipients. This product is derived from human plasma and may contain infectious agents, including viruses, and theoretically, the variant Creutzfeldt-Jakob disease agent.

Side Effects

Serious adverse reactions associated with the use of this product include hypersensitivity reactions, which may manifest as anaphylactic reactions. In cases where a hypersensitivity reaction is suspected, it is imperative to discontinue use and implement appropriate standard medical treatment. Additionally, pulmonary edema has been reported as a serious adverse reaction.

Patients with a history of hypersensitivity reactions to albumin preparations or to any of the excipients, such as N-acetyltryptophan and sodium caprylate, should be closely monitored. Other notable adverse reactions include severe anemia or cardiac failure, which may occur despite normal or increased intravascular volume. Furthermore, hypervolemia may arise if the dosage and rate of infusion exceed recommended levels.

Drug Interactions

Hypersensitivity reactions, including anaphylactic reactions, have been reported. If a hypersensitivity reaction is suspected, it is advised to discontinue use immediately and implement appropriate standard medical treatment.

In situations where hypervolemia and/or hemodilution may occur, it is essential to adjust the dose and rate of infusion according to the patient's volume status. Continuous monitoring of coagulation and hematology parameters is recommended when large volumes are replaced. Additionally, ensure adequate substitution of other blood constituents, including coagulation factors, platelets, and erythrocytes. Monitoring of electrolyte status is also necessary to maintain electrolyte balance.

Administration should be discontinued at the first clinical signs of cardiovascular overload, which may include symptoms such as headache, dyspnea, jugular venous distention, rales, and abnormal elevations in systemic or central venous blood pressure.

For drug and laboratory test interactions, it is crucial to monitor hemodynamic parameters after administering FLEXBUMIN 25% to detect any evidence of cardiac or respiratory failure, renal failure, or increasing intracranial pressure. In trauma and postoperative surgery patients resuscitated with FLEXBUMIN 25%, blood pressure should be closely monitored to identify potential re-bleeding secondary to clot disruption.

It is important to note that FLEXBUMIN 25% should not be diluted with Sterile Water for Injection, as this can lead to hemolysis in recipients. The use of Sterile Water for Injection as a diluent for Albumin (Human) in concentrations of 20% or higher poses a risk of potentially fatal hemolysis and acute renal failure.

Biosimilarity

Flexbumin is the FDA‑licensed reference product against which biosimilar and interchangeable products are compared.

Packaging & NDC

The table below lists all NDC Code configurations of Flexbumin (albumin human) originator presentations. Columns show Packaging, Form, and Strength.

Pediatric Use

The safety of albumin solutions has been established in pediatric patients when dosed appropriately according to body weight. However, the safety of FLEXBUMIN 25% specifically has not been evaluated in studies conducted by the sponsor involving pediatric populations. Caution is advised when considering the use of FLEXBUMIN 25% in children, as the absence of dedicated pediatric studies limits the understanding of its safety profile in this demographic.

Geriatric Use

Elderly patients may not have sufficient data available to assess the safety and efficacy of the medication, as there are no human or animal studies specifically addressing this population. Therefore, healthcare providers should exercise caution when prescribing this medication to geriatric patients.

Due to the lack of clinical findings, it is recommended that healthcare providers closely monitor elderly patients for any adverse effects and consider potential dose adjustments based on individual patient needs and responses.

Pregnancy

There are no available human or animal data to indicate the presence or absence of drug-associated risk with FLEXBUMIN 25% during pregnancy. Consequently, it is not known whether FLEXBUMIN 25% can cause fetal harm when administered to a pregnant patient or if it can affect reproductive capacity. Healthcare professionals should weigh the potential benefits against the unknown risks when considering the use of FLEXBUMIN 25% in pregnant patients.

Lactation

There are no human or animal data available to indicate the presence or absence of drug-associated risk for lactating mothers using FLEXBUMIN 25%. Additionally, it is not known whether FLEXBUMIN 25% is excreted in human milk. Therefore, the effects on breastfed infants remain unclear. Healthcare professionals should consider the potential benefits and risks when prescribing this medication to lactating mothers.

Renal Impairment

Patients with renal impairment should be closely monitored for hemodynamic parameters following administration. This monitoring is essential to detect any evidence of cardiac or respiratory failure, renal failure, or increasing intracranial pressure. Adjustments to dosing may be necessary based on the patient's renal function, and healthcare professionals should remain vigilant in assessing these parameters to ensure patient safety.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In cases of overdosage, hypervolemia may occur as a result of excessive dosage or an accelerated rate of infusion. Healthcare professionals should be vigilant in monitoring patients for signs and symptoms associated with fluid overload.

Recommended Actions Upon suspicion of overdosage, it is imperative to assess the patient's clinical status promptly. Monitoring vital signs and fluid balance is essential. If hypervolemia is confirmed, appropriate management strategies should be implemented, which may include the adjustment of fluid intake, diuretics administration, and close observation of the patient's response to treatment.

Potential Symptoms Symptoms of hypervolemia may include, but are not limited to, hypertension, edema, and respiratory distress. Early recognition of these symptoms is crucial for effective management and to prevent further complications.

In summary, careful monitoring and prompt intervention are key components in the management of overdosage to mitigate the risks associated with hypervolemia.

Nonclinical Toxicology

No human or animal data are available to indicate the presence or absence of drug-associated risk regarding teratogenic effects. It is not known whether FLEXBUMIN 25% can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity.

Similarly, there are no human or animal data available to assess the presence or absence of drug-associated risk concerning non-teratogenic effects. It remains unclear whether FLEXBUMIN 25% is excreted in human milk.

No specific nonclinical toxicology data or animal pharmacology and toxicology data have been provided.

Postmarketing Experience

FLEXBUMIN 25% is derived from human plasma, which may contain infectious agents capable of causing disease, including viruses and, theoretically, the agent responsible for Creutzfeldt-Jakob disease (CJD). The risk of transmitting infectious agents through FLEXBUMIN 25% has been mitigated through several measures. These include the screening of plasma donors, testing of donated plasma for specific viral infections, and the implementation of manufacturing processes that have been shown to inactivate and/or remove certain viruses.

Patients should be informed that symptoms indicative of a potential viral infection may include headache, fever, nausea, vomiting, weakness, malaise, diarrhea, and, in cases of hepatitis, jaundice.

Patient Counseling

Healthcare providers should inform patients about the early signs of hypersensitivity reactions associated with FLEXBUMIN 25%. Patients should be made aware of symptoms such as hives, generalized urticaria, chest tightness, dyspnea, wheezing, faintness, hypotension, and anaphylaxis.

It is essential to communicate that FLEXBUMIN 25% is derived from human plasma and may contain infectious agents that can lead to disease, including viruses and, theoretically, the agent responsible for Creutzfeldt-Jakob disease (CJD). Providers should explain that the risk of transmitting infectious agents through FLEXBUMIN 25% has been mitigated through several measures. These include screening plasma donors, testing donated plasma for specific viral infections, and employing a manufacturing process that has been shown to inactivate and/or remove certain viruses.

Patients should also be educated about the potential symptoms of a viral infection, which may include headache, fever, nausea, vomiting, weakness, malaise, diarrhea, or jaundice, particularly in the case of hepatitis.

Finally, it is crucial for the patient and physician to engage in a thorough discussion regarding the risks and benefits associated with the use of FLEXBUMIN 25%. This dialogue will help ensure that patients are fully informed and can make educated decisions about their treatment options.

Storage and Handling

FLEXBUMIN 25% is supplied in a single-dose plastic container. It is essential to store this product at room temperature, ensuring that the temperature does not exceed 25°C (77°F). Additionally, the product must be protected from freezing to maintain its integrity and efficacy.

Additional Clinical Information

Clinicians should monitor coagulation and hematology parameters when administering comparatively large volumes of FLEXBUMIN 25%. It is essential to assess electrolyte status to maintain balance and closely observe hemodynamic parameters for signs of cardiac or respiratory failure, renal failure, or increasing intracranial pressure. In trauma and postoperative surgery patients resuscitated with FLEXBUMIN 25%, monitoring blood pressure is crucial to detect potential re-bleeding due to clot disruption.

Patient counseling should include a discussion of the risks and benefits associated with FLEXBUMIN 25%. Any infections suspected to be transmitted by this product must be reported by healthcare providers to Takeda Pharmaceuticals U.S.A., Inc. at 1-877-TAKEDA-7 (1-877-825-3327).

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Flexbumin as submitted by Takeda Pharmaceuticals America, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)