Albumin (human)

Uses and Indications

This drug is indicated for the restoration and maintenance of circulating blood volume in various clinical conditions, including:

Hypovolemia and Hypoalbuminemia

• This drug is indicated for the treatment of hypovolemia and hypoalbuminemia, which may occur in conditions such as burns, major surgery, sepsis, and intensive care scenarios.

Specific Conditions

• Ovarian Hyperstimulation Syndrome (OHSS): This drug is indicated for the management of OHSS.

• Adult Respiratory Distress Syndrome (ARDS): It is indicated for use in ARDS, particularly when accompanied by hypoproteinemia and fluid volume overload.

• Acute Nephrosis: This drug may be beneficial in managing acute nephrosis, especially in patients who do not respond to standard therapies.

• Hemolytic Disease of the Newborn (HDN): It is indicated for use in HDN, particularly prior to exchange transfusion to bind free bilirubin.

• Acute Liver Failure: This drug may support colloid osmotic pressure and bind excess plasma bilirubin in cases of rapid liver function loss.

• Sequestration of Protein-Rich Fluids: It is indicated for conditions such as acute peritonitis, pancreatitis, mediastinitis, and extensive cellulitis, where there is a need to treat reduced volume or oncotic activity.

• Erythrocyte Resuspension: This drug may be required to prevent excessive hypoproteinemia during certain types of exchange transfusion or with large volumes of previously frozen or washed red cells.

Emergency Treatment

• Hypovolemic Shock: This drug is indicated for the emergency treatment of hypovolemic shock, expanding plasma volume significantly when administered intravenously.

• Burn Therapy: It is indicated for use in burn therapy, particularly beyond the first 24 hours post-injury to maintain plasma colloid osmotic pressure.

Cardiopulmonary Bypass

• This drug is indicated for use in cardiopulmonary bypass procedures, where it is used for preoperative dilution of blood.

Renal Dialysis

• It may be of value in treating shock or hypotension in patients undergoing renal dialysis.

Limitations of Use

• This drug is not indicated as an intravenous nutrient.

No teratogenic or nonteratogenic effects have been mentioned in the provided data.

Dosage and Administration

Albumin (human) is indicated for intravenous use only. The daily dose should not exceed 2 g per kg body weight.

For hypovolemia, the recommended dosage is as follows:

• Adults: 25 g

• Children (less than 13 years): 2.5 to 1.25 g

For hypoalbuminemia, adults may receive a dosage of 50 to 75 g.

In the prevention of volume depletion after paracentesis, adults should be administered 8 g for every 1,000 mL of ascitic fluid removed.

For ovarian hyperstimulation syndrome, adults may receive 50 to 100 g over 4 hours, with the option to repeat at 4-12 hour intervals as necessary.

In cases of adult respiratory distress syndrome (ARDS), adults may be given 25 g over 30 minutes, with the possibility of repeating the dose at 8 hours for up to 3 days if necessary.

For acute nephrosis, adults should receive 25 g together with a diuretic once daily for 7-10 days.

In the case of hemolytic disease of the newborn, the recommended dosage is 1 g per kilogram body weight prior to or during exchange transfusion.

For hypovolemic shock, the volume administered and the speed of infusion should be adapted to the individual patient's response. In infants and young children, the recommended dosage is 12 to 20 mL per kg body weight, while older children and adults may receive an initial dose of 250 to 500 mL, with the option to repeat after 15 to 30 minutes if the response is inadequate.

When administering large volumes (greater than 1500 mL), the product should be warmed to room temperature before use. It is important to note that bottles are for single use only, and the solution should not be diluted with sterile water for injection, as this may cause hemolysis in recipients.

The rate of administration should not exceed 2 mL per minute, as more rapid injection may precipitate circulatory embarrassment and pulmonary edema. The venipuncture site should be prepared with standard aseptic technique, and the solution is compatible with whole blood or packed red cells, as well as the usual electrolyte and carbohydrate solutions intended for intravenous use.

Contraindications

The use of albumin preparations is contraindicated in individuals with a known hypersensitivity to albumin or any of the excipients in the formulation. Patients with a history of allergic reactions to albumin are specifically advised against its use. Additionally, certain patients, particularly those with a history of congestive cardiac failure, renal insufficiency, or stabilized chronic anemia, are at an increased risk of developing circulatory overload and should not receive albumin preparations. Severe anemia or cardiac failure in the presence of normal or increased intravascular volume also contraindicates the use of these products.

Warnings and Precautions

Hypersensitivity or allergic reactions, including severe anaphylaxis, have been observed with the use of albumin products. Epinephrine should be readily available to treat any acute hypersensitivity reaction.

Risk of Infectious Agents

Albumin products are derived from human plasma and may contain infectious agents, such as viruses, and theoretically, the Creutzfeldt-Jakob Disease (CJD) agent. The risk of transmission of CJD is considered extremely remote, and no cases of transmission of viral diseases or CJD have been identified for albumin. Despite rigorous screening and inactivation processes, there remains a potential risk for disease transmission, including unknown infectious agents. All suspected infections thought to be transmitted by this product should be reported to the appropriate health authorities.

Hypervolemia and Hemodilution

Caution is advised when administering albumin to patients at risk of hypervolemia or hemodilution. Infusion should be stopped if signs of cardiovascular overload occur. In cases of hemorrhage, the administration of albumin should be supplemented with whole blood transfusions to address relative anemia associated with hemodilution.

Monitoring Requirements

Patients receiving albumin should be closely monitored for:

• Electrolyte imbalances

• Coagulation status and hematocrit

• Hemodynamic performance, including blood pressure, to detect hypotension or signs of cardiac or respiratory failure

• Evidence of renal failure or increasing intracranial pressure

Administration Precautions

• Do not dilute albumin solutions with sterile water for injection, as this can lead to hemolysis.

• Ensure adequate hydration when administering concentrated albumin.

• Turbid solutions must not be used, and administration should not begin more than 4 hours after the introduction of the administration set. Partially used vials should be discarded.

General Precautions

Patients should be monitored carefully to guard against circulatory overload. In the presence of dehydration, albumin must be administered with or followed by additional fluids. The rapid rise in blood pressure following administration necessitates careful observation to detect and manage any potential complications.

Physician-Patient Discussion

Healthcare providers should discuss the risks and benefits of albumin therapy with patients prior to administration.

Side Effects

Adverse reactions associated with albumin (human) solutions are primarily categorized by their seriousness and frequency of occurrence.

Common Adverse Reactions

• Anaphylactoid type reactions: Observed in ≥5% of patients. These reactions may progress to severe anaphylaxis, necessitating immediate availability of epinephrine for treatment.

• Hypersensitivity or allergic reactions: Manifestations may include urticaria, chills, fever, and changes in respiration, pulse, and blood pressure. Severe allergic reactions, including anaphylactic shock, have been reported.

Cardiovascular Reactions

• Hypotension: Has been observed; monitoring of hemodynamic performance is recommended.

• Hypervolemia: Use with caution in patients at risk of hypervolemia or hemodilution. Infusion should be stopped if signs of cardiovascular overload occur, such as headache, dyspnea, or pulmonary edema.

Electrolyte and Coagulation Abnormalities

• Electrolyte imbalances: Monitoring of electrolyte status is advised.

• Coagulation abnormalities: Ensure adequate substitution of other blood constituents and monitor coagulation status and hematocrit.

Rare Adverse Reactions

• Non-septic incompatibility reactions: Very rare instances of nausea, chills, fever, urticaria, headache, and hypotension have been reported.

• Severe hemolysis and acute renal failure: May occur from inappropriate use of diluents, such as sterile water for injection. Acceptable diluents include 0.9% sodium chloride or 5% dextrose in water.

Infection Risk

• Products made from human plasma may contain infectious agents, including viruses and the theoretical risk of Creutzfeldt-Jakob disease (CJD). The risk of transmission of viral diseases or CJD is considered extremely remote due to rigorous screening and inactivation processes, but unknown infectious agents may still be present.

Contraindications

• Albumin should not be used in individuals with a known hypersensitivity to albumin preparations or any components of the formulation. Special caution is warranted in patients with a history of congestive cardiac failure, renal insufficiency, or stabilized chronic anemia, as they are at increased risk for circulatory overload.

Patients receiving albumin should be monitored closely for any signs of adverse reactions, particularly during the initial stages of infusion.

Drug Interactions

No drug interaction studies have been conducted for Albumin (human) in any of its formulations, including solutions. This lack of data extends to other products such as Kedbumin, which also does not provide any information regarding drug interactions or interactions with laboratory tests.

In terms of specific formulations, Albutein, available in 5%, 20%, and 25% concentrations, must not be mixed with other medicinal products. Similarly, Human Albumin Grifols 20% is contraindicated for mixing with other medicinal products. This caution is critical to ensure the safety and efficacy of the treatment.

Overall, the absence of interaction studies and the specific mixing instructions highlight the importance of careful administration and monitoring when using these albumin products.

Pediatric Use

The use of albumin solutions in pediatric patients varies by product and age.

Efficacy and Safety:

• KEDBUMIN® has not been clinically evaluated in children under 12 years of age. For children aged 12-16 years, the adult dose may be administered, typically at one-fourth to one-half the adult dose. The rate of administration in children should be one-fourth the adult rate. Physicians should carefully weigh the risks and benefits when considering KEDBUMIN® for pediatric use.

• The safety of FLEXBUMIN 5% and FLEXBUMIN 25% has not been evaluated in sponsor-conducted pediatric studies. However, the safety of albumin solutions in children has been demonstrated when the dose is appropriate for body weight.

• No human or animal data are available for Albutein and Human Albumin Grifols, and these products should only be used in pediatric patients if clearly needed.

Dosing Considerations:

• For KEDBUMIN®, dosage will vary based on the clinical state and body weight of the individual child.

In summary, while some albumin solutions may be used in pediatric patients, careful consideration of dosing and safety is essential, particularly in younger children.

Geriatric Use

Elderly patients may not have specific geriatric use information available for the products reviewed, including Kedbumin, Flexbumin, and Albutein. There are no recommended age considerations, dosage adjustments, or safety concerns explicitly mentioned for this population. Additionally, the absence of human or animal data across these products suggests that they should be used only if clearly needed in geriatric patients. Healthcare professionals should exercise caution and consider individual patient circumstances when administering these treatments to elderly patients. Regular monitoring for efficacy and safety is advised.

Pregnancy

Animal reproduction studies have not been conducted with ALBURX® 5, ALBURX® 25, KEDBUMIN®, FLEXBUMIN 5%, FLEXBUMIN 25%, ALBUTEIN 5%, ALBUTEIN 20%, and ALBUTEIN 25%. There is no available data to indicate the presence or absence of drug-associated risk for these products. It is not known whether these products can cause fetal harm when administered to pregnant patients or affect reproductive capacity.

ALBURX® 5, ALBURX® 25, ALBUTEIN 5%, ALBUTEIN 20%, and ALBUTEIN 25% should be administered to pregnant patients only if clearly needed. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

KEDBUMIN® and FLEXBUMIN do not have any known contraindications specifically associated with reproduction, pregnancy, or the fetus, but caution is advised due to the lack of data.

Healthcare professionals should weigh the potential benefits against the unknown risks when considering the use of these products in pregnant patients.

Lactation

It is not known whether ALBURX® 5, ALBURX® 25, KEDBUMIN®, FLEXBUMIN 5%, FLEXBUMIN 25%, or ALBUTEIN (in any concentration) are excreted in human milk. There is a lack of human or animal data to indicate the presence or absence of drug-associated risks for these products when administered to lactating mothers.

Caution should be exercised when administering ALBUTEIN 25% and ALBUTEIN 20% to nursing mothers, as there is no information regarding their effects on breastfed infants or milk production. The developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for these products and any potential adverse effects on the breastfed infant.

Given the absence of specific data on excretion in breast milk and effects on infants, healthcare providers should consider the necessity of treatment with these products in lactating mothers and discuss potential risks with them.

Renal Impairment

Patients with renal impairment may require careful consideration when receiving albumin solutions. While most labels do not provide specific information regarding dosage adjustments or monitoring for patients with reduced kidney function, there are important precautions to note.

The use of hyperoncotic protein solutions, such as Albumin (Human), can lead to severe hemolysis and acute renal failure if inappropriate diluents are used. It is critical to avoid using Sterile Water for Injection as a diluent; instead, acceptable alternatives include 0.9% Sodium Chloride or 5% Dextrose in Water. This caution applies to various formulations, including Plasbumin and Albuked, which emphasize the risks associated with improper diluent selection.

Additionally, for products like Flexbumin, it is advised to closely monitor hemodynamic parameters after administration. This monitoring is essential to detect any signs of cardiac or respiratory failure, renal failure, or increasing intracranial pressure, particularly in patients with compromised renal function.

Overall, while specific dosing adjustments for renal impairment are not detailed across the labels, the potential risks associated with the administration of albumin solutions necessitate vigilant monitoring and adherence to recommended diluents to ensure patient safety.

Hepatic Impairment

Patients with hepatic impairment do not have specific dosage adjustments, special monitoring requirements, or precautions outlined for the use of albumin products, including Albumin (human), Plasbumin, Albuked, Alburx, Kedbumin, Flexbumin, and Albutein. The available information across multiple labels indicates that there are no defined recommendations or restrictions for this patient population. Therefore, healthcare providers should exercise clinical judgment when considering the use of these products in patients with liver problems, as no specific guidance is provided in the product inserts.

Overdosage

In the event of an overdose of albumin solutions, specific information regarding overdosage is generally lacking across various formulations. However, it is important to note that hypervolemia may occur if the dosage and rate of infusion are excessively high, particularly with products such as Flexbumin and Albuked.

Management of potential overdose should include careful monitoring of the patient for signs of hypervolemia, which may manifest as increased blood pressure, pulmonary edema, or other symptoms related to fluid overload. In cases where severe hemolysis or acute renal failure is suspected due to inappropriate diluent use, such as Sterile Water for Injection, immediate medical intervention is warranted. Acceptable diluents include 0.9% Sodium Chloride or 5% Dextrose in Water, and it is crucial to ensure that solutions have not been frozen, are not turbid, and that partially used vials are discarded appropriately.

Healthcare professionals should be vigilant in assessing the patient's condition and implementing supportive measures as necessary, including the potential need for diuretics or other interventions to manage fluid overload.

Nonclinical Toxicology

Human Albumin is a normal constituent of human plasma and functions similarly to physiological albumin. No nonclinical toxicology studies have been conducted for various concentrations of human albumin, including 5%, 20%, and 25%.

Teratogenicity

For Kedbumin, there is no available human or animal data to assess the potential teratogenic effects. It remains unknown whether Kedbumin can cause fetal harm when administered to a pregnant woman or if it can affect reproductive capacity.

Non-Teratogenic Effects

Similarly, there is no data available regarding the non-teratogenic effects of Kedbumin, including whether it is excreted in milk.

Nonclinical Toxicology

No specific nonclinical toxicology information has been provided for either human albumin or Kedbumin in the respective inserts.

Animal Pharmacology and Toxicology

There is a lack of specific information regarding animal pharmacology and toxicology for Kedbumin as well.

Storage and Handling

Albumin (human) solutions are available in various concentrations and packaging configurations.

How Supplied:

• ALBUMIN (HUMAN) 5%: Supplied in single-use, individually laser etched vials. Stable for 36 months when stored at +2°C to +25°C (36°F to 77°F).

• ALBUMIN (HUMAN) 20%: Supplied in single-use, individually laser etched vials. Stable for 36 months when stored at +2°C to +25°C (36°F to 77°F).

• ALBUMIN (HUMAN) 25%: Supplied in single-use, individually laser etched vials. Stable for 36 months when stored at +2°C to +25°C (36°F to 77°F).

• ALBURX® 5%: Supplied in single-use containers. Store at a temperature not exceeding 30°C (86°F).

• ALBURX® 25%: Supplied in single-use containers. Store at a temperature not exceeding 30°C (86°F).

• ALBUTEIN 5%: Supplied in single-use, individually laser etched vials. Stable for three years when stored at a temperature not exceeding 30°C (86°F).

• ALBUTEIN 20%: Supplied in single-use, individually laser etched vials. Stable for three years when stored at a temperature not exceeding 30°C (86°F).

• ALBUTEIN 25%: Supplied in single-use, individually laser etched vials. Stable for three years when stored at a temperature not exceeding 30°C (86°F).

• ALBUTEIN FlexBag 5%: Supplied in flexible containers. Stable for three years when stored at a temperature not exceeding 30°C (86°F).

• ALBUTEIN FlexBag 20%: Supplied in flexible containers. Stable for two years when stored at a temperature not exceeding 30°C (86°F).

• ALBUTEIN FlexBag 25%: Supplied in flexible containers. Stable for two years when stored at a temperature not exceeding 30°C (86°F).

• PLASBUMIN: Available in 50 mL, 250 mL, and 500 mL rubber-stoppered vials. Store at room temperature not exceeding 30°C (86°F).

• KEDBUMIN®: Available in vials. Store at room temperature not exceeding 30°C (86°F).

• FLEXBUMIN 5%: Supplied in a single-dose plastic container. Store at room temperature not to exceed 25°C (77°F).

• FLEXBUMIN 25%: Supplied in a single-dose plastic container. Store at room temperature not to exceed 25°C (77°F).

Storage and Handling:

• All products should be stored protected from light.

• Do not freeze any of the solutions.

• Do not use after the expiration date printed on the label.

• Solutions should not be used if turbid.