1.1 Hypovolemia

For restoration and maintenance of circulating blood volume where volume deficiency is demonstrated and colloid use is appropriate.

1.2 Hypoalbuminemia

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.

1.3 Prevention of Central Volume Depletion after Paracentesis due to Cirrhotic Ascites

KEDBUMIN® is indicated for maintenance of cardiovascular function following the removal of large volumes of ascitic fluid due to cirrhosis [1, 2].

1.4 Ovarian Hyperstimulation Syndrome (OHSS)

KEDBUMIN® is indicated as a plasma expander in the fluid management of severe forms of ovarian hyperstimulation syndrome (OHSS) [3, 4].

1.5 Adult Respiratory Distress Syndrome (ARDS)

KEDBUMIN® is indicated in conjunction with diuretics to correct fluid volume overload associated with ARDS [5].

1.6 Burns

KEDBUMIN® is indicated after > 24 hours post burn in patients experiencing severe albumin depletion in order to favor edema re-absorption [6].

1.7 Hemodialysis

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 [7].

1.8 Cardiopulmonary Bypass

KEDBUMIN® is indicated in cardiopulmonary bypass procedures as part of the priming fluids [8, 9].

2.1 Dosage

The concentration of the albumin preparation, dosage, and infusion-rate should be adjusted to the patient's individual requirements and indication.

2.2 Administration

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.

5.1 Hypersensitivity

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.

5.2 Hypervolemia

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:

• Heart failure
• Arterial hypertension
• Esophageal varices
• Pulmonary edema
• Hemorrhagic diathesis
• Severe anemia
• Renal and post-renal anuria

5.3 Hemolysis

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% albumin 12. Suitable solutions for dilution include 5% glucose and 0.9% sodium chloride (2.2).

5.4 Large Volumes

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.

5.5 Hydration

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.

5.6 Infectious Diseases

Albumin 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 suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Kedrion Biopharma, Inc. at 1-855-3KDRION (1-855-353-7466).

See also PATIENT COUNSELING INFORMATION (17).

6.1 General

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.

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

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.

12.1 Mechanism of Action

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 [14].

12.3 Pharmacokinetics

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.

Storage

Do not use KEDBUMIN® after the expiration date which is stated on the carton and label after "EXP." The expiration date refers to the last day of that month.

Do not store above 30°C (86° F).

Keep the vial stored in the outer carton in order to protect from light.

Do not freeze.