KEDBUMIN- albumin (human) injection, solution
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use KEDBUMIN™ safely and effectively. See full prescribing information for KEDBUMIN™ [Albumin (Human) U.S.P.] sterile, aqueous solution for single dose intravenous administration
Initial U.S. Approval: June, 2011.
RECENT MAJOR CHANGES
Dosage forms and strenghts (3) 08/2012
INDICATIONS AND USAGE
KEDBUMIN™ is a 25% albumin solution indicated for:
DOSAGE AND ADMINISTRATION
Intravenous Administration Only. KEDBUMIN™ may be diluted with 5% glucose or 0.9% sodium chloride. Concentration, dosage, and infusion-rate should be adjusted to the patient’s individual requirements and indication (2.1). Daily dosage should not exceed 2g per kg body weight.
DOSAGE FORMS AND STRENGTHS
WARNINGS AND PRECAUTIONS
The most common adverse reactions include fever, chills, rash, nausea, vomiting, tachycardia, and hypotension (6).
To report SUSPECTED ADVERSE REACTIONS, contact KEDRION at 1-855-427-6378 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION.
FULL PRESCRIBING INFORMATION: CONTENTS*
For restoration and maintenance of circulating blood volume where volume deficiency is demonstrated and colloid use is appropriate.
KEDBUMIN™ is indicated for severe albumin deficiency caused by illness or active bleeding. When albumin deficiency results from excessive protein loss, the effect of albumin administration will be temporary unless the underlying disorder is reversed.
KEDBUMIN™ is indicated for maintenance of cardiovascular function following the removal of large volumes of ascitic fluid due to cirrhosis [1, 2].
KEDBUMIN™ is indicated as a plasma expander in the fluid management in of severe forms of ovarian hyperstimulation syndrome (OHSS) [3, 4].
KEDBUMIN™ is indicated in conjunction with diuretics to correct fluid volume overload associated with ARDS .
KEDBUMIN™ is indicated after > 24 hours post burn in patients experiencing severe albumin depletion in order to favor edema re-absorption .
KEDBUMIN™ is indicated in patients undergoing long term dialysis or for those patients who are fluid-overloaded and cannot tolerate substantial volumes of salt solution for therapy of shock or hypotension .
KEDBUMIN™ is indicated in cardiopulmonary bypass procedures as part of the priming fluids [8, 9].
Intravenous Administration Only.
The concentration of the albumin preparation, dosage, and infusion-rate should be adjusted to the patient’s individual requirements and indication.
|Hypovolemia||Adults: Initial dose of 25 g is suggested. Pediatric dosage should be adjusted based upon on age, weight and clinical conditions|
|Prevention of Central Volume Depletion after
Paracentesis due to Cirrhotic Ascites
|Adults: 6-8 g for every 1000 mL of ascitic fluid removed|
|OHSS||Adults:50-100 g over 4 hours and repeated at 4-12 hour intervals as necessary. 10-50 g: single infusion|
|ARDS||Adults: 25 g over 30 minutes and repeated at 8 hours for 3 days if necessary|
|Burns||The amount of albumin required to achieve adequate plasma volume and protein content should be determined by direct observation of vital signs or measurement of either plasma oncotic pressure or protein content|
|Cardiopulmonary Bypass||Required dose can be estimated from the difference between the desired and actual total serum protein concentration multiplied by the estimated plasma volume (approximately 40mL per kg) times 2 (to account for extravascular deficit, which absorbs about half of the administered dose)|
Intravenous administration only.
Inspect visually for particulate matter and discoloration prior to administration, whenever the solution and container permit.
Do not dilute with sterile water for injection as hemolysis may occur (5.3).
KEDBUMIN™ may be diluted with 5% glucose or 0.9% sodium chloride.
Adjust the infusion rate to the rate of removal in plasma exchange.
Warm the product to room temperature if large volumes are to be administered.
Do not begin administration > 4 hours after the container has been entered. Discard unused material.
Record the batch number every time KEDBUMIN™ is administered to a patient.
KEDBUMIN™ is a sterile, aqueous solution for single dose administration intravenously. The product contains 0.25 g per mL human albumin and is available in the following presentation :
KEDBUMIN™ is contraindicated in patients with a history of hypersensitivity to albumin, excipients used in its formulation, or components of the container .
KEDBUMIN™ is also contraindicated in severely anemic patients and in patients with heart failure.
Hypersensitivity or allergic reactions have been observed, and may in some cases progress to severe anaphylaxis. Epinephrine should be available immediately to treat any acute hypersensitivity reaction.
KEDBUMIN™ should be used with caution in conditions where hypervolemia and its consequences or hemodilution could represent a special risk (10). Examples of such conditions may include but are not limited to:
Do not dilute KEDBUMIN™ with Sterile Water for Injection, as this may cause hemolysis in recipients. There is a risk of potentially fatal hemolysis and acute renal failure from the use of Sterile Water for Injection as a diluent for 25% albumin12. Suitable solutions for dilution include 5% glucose and 0.9% sodium chloride (2.2).
When replacing comparatively large volumes of albumin, control of coagulation and hematocrit is essential. Ensure adequate substitution of other blood constituents as coagulation factors, electrolytes, platelets, and erythrocytes.
The colloid osmotic effect of KEDBUMIN™ 25% is approximately four times that of human blood. Therefore, when concentrated albumin is administered, ensure adequate hydration of the patient. Carefully monitor to guard against circulatory overload (10).
Hemodynamic performance should be monitored regularly. This may include arterial blood pressure and pulse rate, central venous pressure, pulmonary artery occlusion pressure, urine output, electrolyte levels, and hematocrit/hemoglobin.
Because KEDBUMIN™ is derived from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. No cases of transmission of viral diseases or CJD have ever been identified for KEDBUMIN.
ALL infections suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Kedrion at 1-855-427-6378.
See also PATIENT COUNSELING INFORMATION(17).
The most common adverse reactions include flushing, urticaria, fever, chills, nausea, vomiting, tachycardia and hypotension. These reactions normally disappear when the infusion rate is slowed or stopped.
If a severe reaction such as shock or anaphylaxis occurs, the infusion should be stopped and appropriate treatment initiated.
KEDBUMIN™ should not be mixed with other medicinal products including blood and blood components, but can be administered concomitantly with other parenterals such as whole blood, plasma, saline, glucose or sodium lactate when medically necessary.
KEDBUMIN™ should not be mixed with protein hydrolysates or solutions containing alcohol since these combinations may cause protein precipitation.
Pregnancy Category C. Animal reproductive studies using KEDBUMIN™ have not been conducted. It is also not known whether KEDBUMIN™ can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. KEDBUMIN™ should be given to a pregnant woman only if necessary.
The adult dose may be given in children 12-16 years of age. Use of KEDBUMIN™ in children less than 12 years of age has not been clinically evaluated. If administered to children the dosage will vary with the clinical state and body weight of the individual. Typically, a dose one-fourth to one-half the adult dose may be administered. The usual rate of administration in children should be one-fourth the adult rate. Physicians should weigh the risks and benefits of KEDBUMIN™ in the pediatric population.
Hypervolemia may occur if the dosage and rate of infusion are too high. At the first clinical sign of circulatory overload, e.g. headache, dyspnea, jugular venous congestion, increased blood pressure, raised central venous pressure, or pulmonary edema, the infusion should be stopped and hemodynamic parameters carefully monitored. Additionally, diuresis or cardiac output should be increased in accordance with the severity of the clinical situation (5.2).
KEDBUMIN™ is a sterile, aqueous solution for single dose intravenous administration. The product contains 0.25 g per mL human albumin and is prepared by cold ethanol fractionation from pooled human plasma obtained from venous blood at FDA-licensed facilities located in the USA. Intermediate source material (albumin paste) is obtained from a U.S. licensed manufacturer. The colloid osmotic effect of KEDBUMIN™ is approximately four times that of blood plasma.
KEDBUMIN™ is a clear, slightly viscous liquid, with a yellow, amber, or green tint. The productis stabilized by the addition of 0.08 mmol sodium caprylate and 0.08 mmol sodium acetyltryptophan per gram of albumin. Additionally, each liter of material contains 130-160 mEq of sodium ion and ≤ 200 µg of aluminum. The product contains no preservatives.
KEDBUMIN™ is heated for ten hours at 60°C. The KEDBUMIN manufacturing process results in viral reduction in in vitro studies (see table below). These reductions are achieved through a combination of process steps including Cohn fractionation and final container heat treatment.
|HIV-1: Human Immunodeficiency Virus Type 1
BVDV: Bovine Viral Diarrhoea Virus
PRV: Pseudorabies Virus
REO: Reovirus Type 3
PPV: Porcine Parvovirus
HAV: Hepatitis A Virus
EMCV: Encephalomyocarditis virus
|Mean Reduction Factor (log10)|
|Enveloped viruses||Non enveloped viruses|
|Fractionation of Effluent I to Effluent II
|Fractionation of Effluent IV-1 to Effluent
|Ethanol inactication during fraction
|Depth Filtration of Fraction V suspension||3.4||≥3.4||4.9||4.2||2.0|
|Generation of Albumin paste||1.5|
|Overall Reduction Factor||≥16.57||>10.17||≥15.75||11.62||5.2||>8.4||3.7|
Human albumin is not a glycoprotein. It has the lowest molecular weight (66,241 Daltons) of all plasma proteins. Because of its three dimensional structure, solutions of albumin have a lower viscosity than solutions of other plasma proteins. This is important since work performed by the heart depends in part on the viscosity of blood. Human albumin accounts quantitatively for more than half of the total proteins in the circulation (by weight) and represents approximately 10 % of the protein synthesized in the liver.
Approximately 40% of albumin is contained in the circulation. The remainder is located in the extravascular space of tissues, principally muscle, skin, and intestine.
KEDBUMIN 25% has a hyperoncotic effect.
A major function of albumin is its role in osmotic regulation. Albumin is responsible for 75% of normal oncotic pressure within the intravascular space [13, 14]. Other physiological functions include binding and transport of molecules (hormones, enzymes, drugs and toxins); free radical scavenging; hemostatic effects (platelet function inhibition and antithrombotic effects); and capillary membrane permeability .
Under normal conditions, the total exchangeable albumin pool is 4-5 g per kg body weight, of which 40-45% is present intravascularly and 55-60% is in the extravascular space. Increased capillary permeability will alter albumin kinetics and abnormal distribution may occur in conditions such as severe burns or septic shock.
Under normal conditions, the half-life of albumin is approximately 19 days. The balance between synthesis and breakdown is normally achieved by feed-back regulation. Elimination is predominantly intracellular and due to lysosomal proteases. In healthy subjects, less than 10% of infused albumin leaves the intravascular compartment during the first two hours following infusion. There is considerable individual variation in the effect on plasma volume. In some patients plasma volume can remain elevated for several hours. However, in critically ill patients, albumin can leak out of the vascular space in substantial amounts at an unpredictable rate.
KEDBUMIN™ is supplied as a sterile, aqueous solution for single dose intravenous administration containing 0.25 g per mL human albumin. It is available in the following glass vial size:
50 mL vial 25% (NDC 76179-025-01) is packaged in one carton (NDC 76179-025-02)
100 mL vial 25% (NDC 76179-025-03) is packaged in one carton (NDC 76179-025-04)
Inform patients being treated with KEDBUMIN about the potential risks and benefits with its use (6). Discontinue immediately if allergic symptoms or cardiocirculatory overload occur (e.g. skin rashes, hives, itching, breathing difficulties, coughing, nausea, vomiting, fall in blood pressure, increased heart rate).
Inform patients that KEDBUMIN is a derivative of human plasma and may contain infectious agents that cause disease (e.g., viruses, and theoretically, CJD agent). Inform patients that the risk that KEDBUMIN may transmit an infectionious agent has been reduced by screening plasma donors for prior exposure for certain viruses, by testing the donated plasma for certain virus infections, and by inactivating and/or removing certain viruses during manufacturing (5).
Kedrion Biopharma, Inc.
Parker Plaza, 400 Kelby Street
Fort Lee, NJ 07024
Via Provinciale Loc. Bolognana
55027 Gallicano (Lucca)
Phone: +39 0583 1969 1
Fax: +39 0583 1969 981
U.S. License No. 1851
KEDBUMIN 25% 12.5 g 50 mL
Precautions: Do not freeze.
Instructions: The patient and physician should discuss the risks and benefits before using this product. For information on directions of administration, see the enclosed insert.
Each 50 mL contains 12.5 g of Albumin (Human) in aqueous diluent. The solution is hyperoncotic. Sodium range 130-160 milliequivalents per liter.
Contains no preservative.
Heat treated at 60° C for 10 hours.
Kedrion Biopharma, Inc. Parker Plaza,
400 Kelby Street Fort Lee, NJ 07024
U.S. License No.1851
Keep the vial in the outer carton in order to protect from light. Store at temperatures not exceeding 30° C.
DO NOT USE IF TURBID. DO NOT BEGIN ADMINISTRATION MORE THAN 4 HOURS AFTER THE CONTAINER HAS BEEN ENTERED.
8096036 - Rev. 02 03/12
Albumin (Human) U.S.P.
Solution 12.5 g 50 mL
Store at temperatures not exceeding 30° C
Do not use KEDBUMIN 25% after the expiration date which is stated on the carton and label after “EXP.” The expiration date refers to the last date of that month.
Do not store above 30°C.
Keep the vial stored in the outer carton in order to protect from light.
Do not freeze.
The patient and physician should discuss the risks and benefits before using this product. For information on directions of administration, see the enclosed insert.
DO NOT USE IF TURBID.
DO NOT BEING ADMINISTRATION 4 HOURS AFTER THE CONTAINER HAS BEEN ENTERED.
One 50 mL vial containing Albumin (Human) U.S.P. KEDBUMIN 25%
Each 50 mL contains 12.5 g of Albumin (Human) in aqueous diluent.
The solution is hyperoncotic.
Sodium range 130 – 160 milliequivalents per liter.
Stabilized with 0.08 millimole sodium caprylate and 0.08 millimole acetyltryptophan per gram of albumin
Contains no preservative
Heat treated at 60°C for 10 hours for viral inactivation
Kedrion Biopharma, Inc.
Parker Plaza, 400 Kelby Street
Fort Lee, NJ 07024
Bolognana, Gallicano (Lucca) Italy
U.S. License No. 1851
Rev. 04 08/13
albumin (human) injection, solution
|Labeler - Kedrion S.p.A (339096023)|