BUMINATE- albumin human injection, solution
Baxalta US Inc.
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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use BUMINATE 25% safely and effectively. See full prescribing information for BUMINATE 25%.
BUMINATE 25% Albumin (Human), USP, 25% Solution For intravenous use Initial U.S. Approval: 1954 INDICATIONS AND USAGEBUMINATE 25%, Albumin (Human) Solution is indicated for:
Limitations of Use: Albumin is not indicated as an intravenous nutrient.(1.5) DOSAGE AND ADMINISTRATIONFor intravenous use only
DOSAGE FORMS AND STRENGTHSBUMINATE 25% is a solution containing 25 g of albumin per each 100 mL. (3) CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
ADVERSE REACTIONSThe most serious adverse reactions are hypersensitivity reaction (including anaphylactic reaction) and pulmonary edema. (6) To report SUSPECTED ADVERSE REACTIONS, contact Baxalta US Inc., customer service at 1-800-999-1785 or contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See 17 for PATIENT COUNSELING INFORMATION. Revised: 7/2017 |
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
BUMINATE 25% [Albumin (Human)] is indicated for hypovolemia, hypoalbuminemia, cardiopulmonary bypass surgery, and hemolytic disease of the newborn (HDN).
1.1 Hypovolemia
BUMINATE 25% [Albumin (Human)] is indicated for reversing hypovolemia. When hypovolemia is long standing and hypoalbuminemia exists accompanied by adequate hydration or edema, 25% albumin should be used.4,6
1.2 Hypoalbuminemia
BUMINATE 25% is indicated for patients with hypoalbuminemia resulting from one or more of the following:5
(1) Inadequate production (e.g., malnutrition, burns, major injury, infections)
(2) Excessive catabolism (e.g., burns, major injury, pancreatitis)
(3) Loss from the body (e.g., hemorrhage, excessive renal excretion, burn exudates)
(4) Redistribution within the body (e.g., major surgery, various inflammatory conditions)
BUMINATE 25% is indicated for patients with hypoalbuminemia accompanying severe injuries, infections or severe pancreatitis that cannot be quickly reversed and nutritional supplements fail to restore serum albumin levels.
Burns
After the first 24 hours, BUMINATE 25% is indicated, in conjunction with appropriate crystalloid therapy, for the treatment of oncotic deficits following extensive burns and to replace the protein loss which accompanies any severe burn.4,6
1.3 Cardiopulmonary Bypass Surgery
Preoperative dilution of blood using albumin and crystalloid can be used in cardiopulmonary bypass surgery. BUMINATE 25% is indicated as a component of the pump priming during cardiopulmonary bypass procedures.4,6,12
2 DOSAGE AND ADMINISTRATION
For intravenous use only.
2.1 Dose
The dose required depends on the patient's body weight, severity of injury/illness and on continuing fluid and protein losses. Adjust the concentration, dosage and infusion rate to the patient's individual requirements. Use adequacy of circulating blood volume, not plasma albumin levels, to determine the dose required. Refer to Table 1 for recommended doses.
Do not exceed 2 g of albumin per kg of body weight for the daily dose. Do not exceed 1 mL/min for patients with normal blood volume. More rapid administration can cause circulatory overload and pulmonary edema.14 [See Warnings and Precautions (5.2)]
| Indication | Dose |
|---|---|
| Hypovolemic Shock | Infants and young children: 2.5 to 5 mL per kg body weight. Older children and adults: initial dose 100 to 200 mL. Repeat after 15 to 30 minutes if response is not adequate. |
| Hypoalbuminemia | Calculate the body albumin compartment to be 80 to 100 mL per kg body weight. Do not exceed a daily dose of 2 g of albumin per kg of body weight. |
| Burns | The dosage should be determined according to the patient's condition and response to treatment after the first 24 hours. |
| Hemolytic disease in newborn | 1 g per kilogram body weight prior to or during exchange transfusion.15 |
2.2 Administration
- Visually inspect parenteral drug product for particulate matter and discoloration prior to administration. BUMINATE 25% is a transparent or slightly opalescent solution, which may have a greenish tint or may vary from a pale straw to an amber color. Do not use unless solution is clear of particulate matter or if the solution is turbid.
- Do not dilute with Sterile Water for Injection. Acceptable diluents include 0.9% Sodium Chloride or 5% Dextrose in Water. [See Warnings and Precautions (5.5)]
- Do not mix or add with other medicinal products including blood and blood components, protein hydrolysates or solutions containing alcohol. Do not add supplementary medication.
- Administer within 4 hours after the container has been entered.
- Monitor hemodynamic parameters in patients receiving BUMINATE 25% and check for the risk of hypervolemia and cardiovascular overload. [See Warnings and Precautions (5.2)]
- Record the name and batch number of the product to maintain a link between the patient and the product.
- Discard unused portion.
4 CONTRAINDICATIONS
- Patients with a history of hypersensitivity reaction to albumin preparations or to any of the excipients (N-acetyltryptophan and sodium caprylate). Reactions have included anaphylactic shock, anaphylactic reaction, or hypersensitivity/allergic reactions. [See Warnings and Precautions (5.1) and Adverse Reactions (6.2)]
- Patients with severe anemia or cardiac failure with normal or increased intravascular volume. [See Warnings and Precautions (5.2)]
- Do not administer to patients with chronic renal insufficiencies due to the potential for accumulations of aluminum. Accumulations of aluminum in patients with chronic renal insufficiencies have led to toxic manifestations such as hypercalcemia, vitamin D-refractory osteodystrophy, anemia, and severe progressive encephalopathy.11,12,13
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions
Hypersensitivity reactions (including anaphylactic reactions) have been observed. Discontinue administration immediately if a hypersensitivity reaction (including anaphylactic type reactions) is suspected. In case of shock, implement standard medical treatment for shock.
5.2 Hypervolemia/Hemodilution
Under conditions where hypervolemia and/or hemodilution may occur, adjust dose and rate of infusion to the patient's volume status. Monitor coagulation and hematology parameters when comparatively large volumes are replaced. Ensure adequate substitution of other blood constituents (coagulation factors, platelets, and erythrocytes). Monitor electrolyte status to maintain the electrolyte balance.
Discontinue administration at the first clinical signs of cardiovascular overload (e.g., headache, dyspnea, jugular venous distention, rales and abnormal elevations in systemic or central venous blood pressure).
Conditions that pose increased risk of hypervolemia and/or hemodilution include but are not limited to:
- Heart failure
- Hypertension
- Esophageal varices
- Pulmonary edema
- Hemorrhagic diathesis
- Severe anemia
- Renal failure
5.3 Hemodynamics
Closely monitor hemodynamic parameters after administering BUMINATE 25% for evidence of cardiac or respiratory failure, renal failure, or increasing intracranial pressure.
5.4 Blood Pressure
Monitor blood pressure in trauma patients and postoperative surgery patients resuscitated with BUMINATE 25% in order to detect re-bleeding secondary to clot disruption.
5.5 Hemolysis
Do not dilute BUMINATE 25% with Sterile Water for Injection as this can cause hemolysis in recipients. There exists a risk of potentially fatal hemolysis and acute renal failure from the use of Sterile Water for Injection as a diluent for Albumin (Human) in concentrations of 20% or higher. [See Dosage and Administration (2.2)]
5.6 Transmission of Infectious Agents
BUMINATE 25% is a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases and variant Creutzfeldt-Jakob disease (vCJD). There is a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD), but if that risk actually exists, the risk of transmission would also be considered extremely remote. No cases of transmission of viral diseases, CJD or vCJD, have ever been identified for licensed albumin.
All infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Baxalta US Inc. at 1-800-423-2090. The physician should discuss the risks and benefits of this product with the patient.
6 ADVERSE REACTIONS
The most serious adverse reactions are hypersensitivity reaction (including anaphylactic reaction) and pulmonary edema.
6.1 Clinical Trials Experience
No sponsor initiated clinical studies have been conducted with BUMINATE 25%.
6.2 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of BUMINATE 25%. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following adverse reactions have been reported in the post approval use of BUMINATE 25%:
- Immune System Disorders: Anaphylactic shock, anaphylactic reaction, hypersensitivity/allergic reactions
- Nervous System Disorders: Headache, dysgeusia
- Cardiac Disorders: Myocardial infarction, atrial fibrillation, tachycardia
- Vascular Disorders: Hypotension, flushing
- Respiratory, Thoracic, and Mediastinal Disorders: Pulmonary edema, dyspnea
- Gastrointestinal Disorders: Vomiting, nausea
- Skin and Subcutaneous Tissue Disorders: Urticaria, rash, pruritus
- General Disorders and Administration Site Conditions: Pyrexia, chills
8 USE IN SPECIFIC POPULATIONS
10 OVERDOSAGE
Hypervolemia may occur if the dosage and rate of infusion are too high. [See Warnings and Precautions (5.2)]
11 DESCRIPTION
BUMINATE 25% is a sterile, nonpyrogenic preparation of albumin in a single dosage form for intravenous administration. Each 100 mL contains 25 g of albumin. It has been adjusted to physiological pH with sodium bicarbonate and/or sodium hydroxide and stabilized with N-acetyltryptophan (0.02M) and sodium caprylate (0.02M). The sodium content is 145 ± 15 mEq/L. BUMINATE 25% contains no preservative and none of the coagulation factors found in fresh whole blood or plasma. BUMINATE 25% is a transparent or slightly opalescent solution which may have a greenish tint or may vary from a pale straw to an amber color and is clear of particulate matter.
BUMINATE 25% is manufactured from human plasma by the modified Cohn-Oncley cold ethanol fractionation process, which includes 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 - 11 hours. This process accomplishes both purification of albumin and reduction of viruses.
In vitro studies demonstrate that the manufacturing process for BUMINATE 25% provides for effective viral reduction. These viral reduction studies, summarized in Table 2, demonstrate viral clearance during the manufacturing process for BUMINATE 25%.
These studies indicate that specific steps in the manufacturing of BUMINATE 25% are capable of eliminating/inactivating a wide range of relevant and model viruses. Since the mechanism of virus elimination/inactivation by fractionation and by heating steps is different, the overall manufacturing process of BUMINATE 25% is effective in reducing viral load.
| Process Step | Viral Reduction Factor (log10) | |||||
|---|---|---|---|---|---|---|
| Lipid Enveloped | Non-Enveloped | |||||
| HIV-1 | Flaviviridae | PRV | HAV | Parvoviridae | ||
| BVDV | WNV | MMV | ||||
|
||||||
| Processing of Fraction I+II+III/II +III supernatant to Fraction IV4 Cuno 70C filtrate† | >4.9 | >4.8 | >5.7 | >5.5 | >4.5 | 3.0 |
| Pasteurization | >7.8 | >6.5 | n.d.‡ | >7.4 | 3.2 | 1.6§ |
| Mean Cumulative Reduction Factor, log10 | >12.7 | >11.3 | >5.7 | >12.9 | >7.7 | 4.6 |
The likelihood of the presence of viable hepatitis viruses has been minimized by testing the plasma at three stages for the presence of hepatitis viruses, by fractionation steps with demonstrated virus removal capacity and by heating the product for 10 hours at 60°C. This procedure has been shown to be an effective method of inactivating hepatitis virus in albumin solutions even when those solutions were prepared from plasma known to be infective. 1,2,3
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Albumin is responsible for 70-80% of the colloid osmotic pressure of normal plasma, thus making it useful in regulating the volume of circulating blood.4,5,6 Albumin is also a transport protein and binds naturally occurring, therapeutic and toxic materials in the circulation.5,6
12.2 Pharmacodynamics
BUMINATE 25% is osmotically equivalent to approximately five times its volume of human plasma. When injected intravenously, 25% albumin will draw about 3.5 times its volume of additional fluid into the circulation within 15 minutes, except when the patient is markedly dehydrated. This extra fluid reduces hemoconcentration and blood viscosity. The degree and duration of volume expansion depends upon the initial blood volume. In patients with decreased blood volume, the effect of infused albumin can persist for many hours; however, in patients with normal blood volume, the duration will be shorter.7,8,9
12.3 Pharmacokinetics
Total body albumin is estimated to be 350 g for a 70 kg patient, with more than 60% located in the extravascular fluid compartment. The half-life of albumin is 15 to 20 days with a turnover of approximately 15 g per day.5
The minimum plasma albumin level necessary to prevent or reverse peripheral edema is unknown. It is recommended that plasma albumin levels be maintained at approximately 2.5 g/dL. This concentration provides a plasma oncotic pressure value of 20 mmHg.4
15 REFERENCES
- Cai K, Gierman T, Hotta J, et al: Ensuring the Biologic Safety of Plasma-Derived Therapeutic Proteins. Biodrugs 2005; 19 (2): 79-96.
- Gerety R, Aronson D: Plasma derivatives and viral hepatitis. Transfusion 1982; 22 (5): 347- 351.
- Burnouf T, Padilla A: Current strategies to prevent transmission of prions by human plasma derivatives. Transfusion Clinique et Biologique 2006; 13: 320-328.
- Tullis J: Albumin 1. Background and use, Albumin 2. Guidelines for clinical use. JAMA 1977; 237 (4): 355-360, 460-463.
- Peters T Jr: Serum albumin. The Plasma Proteins, 2nd Edition, Vol 1. Putnam FW (ed). New York, Academic Press, 1975, pp 133-181.
- Finlayson J: Albumin products. Seminars in Thrombosis and Hemostasis 1980; 6 (2): 85-120.
- Haynes G, Navickis R, Wilkes M: Albumin administration – what is the evidence of clinical benefit? A systematic review of randomized controlled trials. European Journal of Anesthesiology 2003; 20: 771-793.
- Mendez C, McClain C, Marsano L, et al: Albumin Therapy in Clinical Practice. Nutrition in Clinical Practice 2005; 20: 314-320.
- Quinlan G, Martin G, Evans T: Albumin: Biochemical Properties and Therapeutic Potential. Hepatology 2005; 41 (6):1211-1219.
- Blümel J, Schmidt I, Willkommen H, et al: Inactivation of parvovirus B19 during pasteurization of human serum albumin. Transfusion 2002; 42: 1011-1018.
- Milliner D, Shenaberger J, Shuman P, et al: Inadvertent aluminum administration during plasma exchange due to aluminum contamination of albumin-replacement solutions. N Engl J Med 1985; 312: 165-7.
- Ott S, Maloney N, Klein G, et al: Aluminum is associated with low bone formation in patients receiving chronic parenteral nutrition. Ann Intern Med 1983; 98: 910-914.
- Wills M, Savory J: Aluminum poisoning: dialysis encephalopathy, osteomalacia, and anaemia. Lancet 1983; 2: 29-34.
- Grocott M, Mythen M, Gan T: Perioperative Fluid Management and Clinical Outcomes in Adults. Anesth Analg 2005; 100: 1093-1106.
- Tsao Y, Yu V: Albumin in management of neonatal hyperbilirubinaemia. Archives of Disease in Childhood 1972; 47: 250.
16 HOW SUPPLIED/STORAGE AND HANDLING
BUMINATE 25% is supplied in a single-dose glass bottle:
| NDC Number | Fill Size | Grams Protein |
|---|---|---|
| NDC 0944-0490-01 | 20 mL | 5 g |
| NDC 0944-0490-02 | 50 mL | 12.5 g |
| NDC 0944-0490-03 | 100 mL | 25 g |
Storage
Room temperature: not exceed 30°C (86°F). Protect from freezing.
Stability testing for BUMINATE 25% showed that aluminum concentration increased over time reaching levels that could exceed 1000 ppb over the shelf life of the product. [see Contraindications (4)].
17 PATIENT COUNSELING INFORMATION
- Inform patients of the early signs of hypersensitivity reactions, including hives, generalized urticaria, chest tightness, dyspnea, wheezing, faintness, hypotension, and anaphylaxis. [See Warnings and Precautions (5.1)]
- Inform patients that BUMINATE 25% is made from human plasma and may contain infectious agents that can cause disease (e.g., viruses and, theoretically, the CJD agent). Explain that the risk of BUMINATE 25% transmitting an infectious agent has been reduced by screening the plasma donors, by testing the donated plasma for certain virus infections, and by a process demonstrated to inactivate and/or remove certain viruses during manufacturing. Symptoms of a possible virus infection include headache, fever, nausea, vomiting, weakness, malaise, diarrhea, or, in the case of hepatitis, jaundice. [See Warnings and Precautions (5.6)].
Baxalta US Inc.
Westlake Village, CA 91362
U.S. License No. 2020
BAXALTA® and BUMINATE® are trademarks of Baxalta Incorporated, a wholly-owned, indirect subsidiary of Shire plc.
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
Buminate 25% 20 mL Unit Carton
20 mL (5 g protein)
NDC 0944-0490-01
Albumin (Human), USP, 25% Solution
BUMINATE 25%
For Intravenous Administration Only.
See enclosed directions for use.
Do not use if turbid. Do not begin
administration more than 4 hours
after the container has been entered.
Certain components used in the packaging of this product contain
natural rubber latex.
Caution: In patients with marked dehydration, additional fluids must
accompany or follow administration of this product.
The patient and physician should discuss the risks and benefits of this product.
Rx Only
Baxalta US Inc.
Westlake Village, CA 91362 USA
U.S. License No. 2020
Buminate 25% 20 mL Booklet Label
20 mL (5 g protein)
NDC 0944-0490-01
Albumin (Human), USP, 25% Solution
Buminate 25%
Baxalta
Osmotically equivalent to 100 mL of normal human plasma.
Sodium Content is 145 ± 15 mEq/L. Contains no preservative.
See accompanying directions for use. Caution: In patients
with marked dehydration, additional fluids must accompany
or follow administration of this product. Do not use if turbid.
Do not begin administration more than 4 hours after
The container has been entered. Single dose container.
Discard partially used bottle. The patient and physician
should discuss the riska and benefits of this product.
Rx Only
Baxalta US Inc.
Westlake Village, CA 91362 USA
U.S. License No. 2020
Buminate 25% 50 mL Booklet Label
50 mL (12.5 g protein)
NDC 0944-0490-02
Albumin (Human), USP, 25% Solution
Buminate 25%
Baxalta
This bottle contains 12.5 g albumin from venous plasma in buffered diluent and is osmotically
equivalent to 205 mL of normal human plasma. It has been stabilized with sodium caprylate and N-acetyltrptophan and heated for 10 hours at 60°C. The sodium content is 145 ± 15 mEq/L. Contains no preservative. Store at room temperature, not to exceet 30°C (86°F). Avoid freezing to prevent damage to the bottle. See accompanying directions for use. Caution: In patients with marked dehydration additional fluids must accompany or follow administration of this product. Do not use if turbid. Do not begin administration more than 4 hours after the container has been entered. Single dose container. Discard partially used bottle. The patient and physician should discuss the risks and benefits of this product.
Rx Only
Baxalta US Inc.
Westlake Village, CA 91362 USA
U.S. License No. 2020
Buminate 25% 100 mL Booklet Label
100 mL (25 g protein)
NDC 0944-0490-03
Albumin (Human), USP, 25% Solution
Buminate 25%
Baxalta
This bottle contains 25 g albumin from venous plasma in buffered diluent and is osmotically
equivalent to 500 mL of normal human plasma. It has been stabilized with sodium caprylate and N-acetyltrptophan and heated for 10 hours at 60°C. The sodium content is 145 ± 15 mEq/L. Contains no preservative. Store at room temperature, not to exceet 30°C (86°F). Avoid freezing to prevent damage to the bottle. See accompanying directions for use.
Caution: In patients with marked dehydration additional fluids must accompany or follow administration of this product. Do not use if turbid. Do not begin administration more than 4 hours after the container has been entered. Single dose container. Discard partially used bottle. The patient and physician should discuss the risks and benefits of this product.
Rx Only
Baxalta US Inc.
Westlake Village, CA 91362 USA
U.S. License No. 2020
| BUMINATE
albumin human injection, solution |
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| Labeler - Baxalta US Inc. (079887619) |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| BAXALTA INCORPORATED | 085206634 | MANUFACTURE(0944-0490) | |