ALBUMINEX

1 INDICATIONS AND USAGE ALBUMINEX 5% is a 5% albumin solution indicated for adults and children: Hypovolemia ( 1.1 ) Ascites ( 1.2 ) Hypoalbuminemia including from burns ( 1.3 ) Acute Nephrosis ( 1.4 ) Acute Respiratory Distress Syndrome (ARDS) ( 1.5 ) Cardiopulmonary Bypass ( 1.6 ) 1.1 Hypovolemia ALBUMINEX 5% is indicated for restoration and maintenance of circulating blood volume where volume deficiency has been demonstrated, and use of a colloid is appropriate e.g. hypovolemia following shock due to trauma or sepsis, in surgical patients and in other similar conditions with volume deficiency when restoration and maintenance of circulating blood volume is required in both adult and pediatric patients. In pediatric patients to reverse hypovolemia and achieve normal capillary refill time. 1, 2, 3, 4, 5, 6, 7, 8 1.2 Ascites ALBUMINEX 5% is indicated for prevention of central volume depletion and maintenance of cardiovascular function after large volume parencentesis in patients with liver cirrhosis or other chronic liver disease in adults and children. 9, 10, 11, 12 ALBUMINEX 5% infusion plus administration of vasoactive drugs is indicated in the treatment of type I hepatorenal syndrome. 6 For patients with spontaneous bacterial peritonitis ALBUMINEX 5% is indicated as adjuvant treatment to antibiotic therapy. 9, 10, 13 1.3 Hypoalbuminemia including from burns ALBUMINEX 5% is indicated in patients with severe burn injury (> 20% total body surface area), but not until at least 12 to 24 hours after the burn, in order to correct protein loss, decrease overall fluid requirements, decrease systemic edema and stabilize cardiovascular hemodynamics without fluid overload (initial resuscitation should be with crystalloids). 8, 14 ALBUMINEX 5% is also indicated in patients with pre- or post-operative hypoproteinemia and for third space protein loss due to infection or burns. 1.4 Acute Nephrosis ALBUMINEX 5% is indicated in patients with acute nephrosis in combination with loop diuretics to reinforce the diuretic therapeutic effect, which is reduced by hypoalbuminemia, and for the correction of reduced oncotic pressure. 15, 16 1.5 Acute Respiratory Distress Syndrome (ARDS) ALBUMINEX 5% is indicated in conjunction with diuretics to correct fluid volume overload associated with ARDS. 17, 18, 19 1.6 Cardiopulmonary Bypass ALBUMINEX 5% is indicated in cardiopulmonary bypass procedures as part of the priming fluids to passivate the synthetic surfaces of the extracorporeal circuit and maintain the patient's colloid oncotic pressure. 20, 21, 22, 23, 24, 25

2 DOSAGE AND ADMINISTRATION For intravenous administration only. For intravenous use only. ALBUMINEX 5% may be diluted with 0.9% saline or 5% dextrose (glucose). Dosage and infusion rate should be adjusted to the patient's individual requirements. Indication Dose Hypovolemia Adults: Initial dose of 25 g (including renal dialysis). For acute liver failure: initial dose of 12 to 25 g. ( 2.1 ) Prevention of central volume depletion after paracentesis due to cirrhotic ascites Adults: 8 g for every 1000 mL of ascitic fluid removed. ( 2.1 ) Hypoalbuminemia including from burns Adults: 50 to 75 g For pre- and post-operative hypoproteinemia: 50 to 75 g. For burn therapy after the first 24 h: initial dose of 25 g and dose adjustment to maintain plasma protein concentration of 2.5 g per 100 mL. Third space protein loss due to infection: initial dose of 50 to 100 g. ( 2.1 ) Acute nephrosis Adults: 25 g together with diuretic once a day for 7-10 days. ( 2.1 ) Adult respiratory distress syndrome (ARDS) Adults: 25 g over 30 minutes and repeated at 8 hours for 3 days, if necessary. ( 2.1 ) Cardiopulmonary bypass procedures Adults: Initial dose of 25 g. ( 2.1 ) 2.1 Dosage The concentration of ALBUMINEX 5% used, its dosage, and infusion rate should be adjusted to the patient's individual requirements and clinical indication. Indication Dose Hypovolemia Hypovolemia Adults: Initial dose of 25 g. If hemodynamic stability is not achieved within 15 to 30 minutes, an additional dose may be given. For acute liver failure: initial dose of 12 to 25 g. An infusion rate of 1-2 mL per minute is usually indicated. For renal dialysis; the initial dose should not exceed 25 g and patients should be carefully observed for signs of fluid overload. Prevention of central volume depletion after paracentesis due to cirrhotic ascites Adults: 8 g for every 1000 mL of ascitic fluid removed. Hypoalbuminemia including from burns Adults: 50 to 75 g For pre- and post-operative hypoproteinemia: 50 to 75 g. In burns, therapy usually starts with administration of large volumes of crystalloid solution to maintain plasma volume. After 24 hours: initial dose of 25 g and dose adjustment to maintain plasma protein concentration of 2.5 g per 100 mL or a serum protein concentration of 5.2 g per 100 mL. Third space protein loss due to infection or burns: initial dose of 50 to 100 g. An infusion rate of 1-2 mL per minute is usually indicated in the absence of shock. Treatment should always be guided by hemodynamic response. Acute nephrosis Adults: 25 g together with diuretic once a day for 7-10 days. Adult respiratory distress syndrome (ARDS) Adults: 25 g over 30 minutes and repeated at 8 hours for 3 days, if necessary. Cardiopulmonary bypass procedures Adults: Initial dose of 25 g. Additional amounts may be administered as clinically indicated. 2.3 Administration Visually inspect the solution for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if there are any particulates seen or if the solution is discolored. If a large volume is infused, ensure that the vial is at room temperature before infusion. Do not dilute with Sterile Water for Injection as hemolysis may occur. ALBUMINEX 5% may be diluted with 0.9% saline or 5% dextrose. Begin the infusion within 4 hours of piercing the vial stopper (the product does not contain any preservative). Adjust the rate of infusion according to the individual patient's hemodynamic and other physiological responses, using appropriate clinical monitoring.

4 CONTRAINDICATIONS ALBUMINEX 5% is contraindicated in patients with: Hypersensitivity to human albumin or any of the excipients Severe anemia or cardiac failure with normal or increased intravascular volume Hypersensitivity to human albumin or the excipients Severe anemia or cardiac failure with normal or increased intravascular volume

5 WARNINGS AND PRECAUTIONS Suspicion of allergic or anaphylactic reactions requires immediate discontinuation of the injection and implementation of appropriate medical treatment ( 5.1 ) Hypervolemia may occur if the dosage and rate of infusion are not adjusted to the patient's volume status. Use with caution in conditions where hypervolemia and its consequences or hemodilution could represent a special risk to the patient. ( 5.2 ) Assess electrolytes, coagulation and hematology parameters, and hemodynamic status when albumin is administered ( 5.4 ) Do not dilute with sterile water for injection ( 2.3 , 5.5 , 7.0 ) This product is made from human plasma and may contain infectious agents, e.g. viruses and, theoretically, the Creutzfeldt-Jakob disease agent. ( 5.5 ) 5.1 Hypersensitivity Reactions Suspicion of allergic or anaphylactic reactions, require immediate discontinuation of the infusion and implementation of appropriate medical treatment. 5.2 Hypervolemia Hypervolemia may occur if the dosage and rate of infusion are not adjusted to the patient's volume status. At the first clinical signs of cardiovascular overload (headache, dyspnea, jugular venous distention, increased blood pressure), the infusion must be slowed or stopped immediately. Use albumin with caution in conditions where hypervolemia and its consequences or hemodilution could represent a special risk to the patient. Examples of such conditions are: Decompensated heart failure Hypertension Esophageal varices Pulmonary edema Hemorrhagic diathesis Severe anemia Renal and post-renal anuria 5.3 Laboratory Parameters When large volumes of albumin are being infused, control of coagulation parameters and hematocrit value is essential. Also, ensure adequate substitution of other blood constituents such as coagulation factors, electrolytes, platelets, and erythrocytes, as appropriate. 5.4 Clinical Hemodynamic Parameters The colloid osmotic pressure of ALBUMINEX 5% is about the same as plasma. The following parameters should be assessed during administration of ALBUMINEX 5%: Arterial blood pressure and pulse rate Central venous pressure Pulmonary artery occlusion pressure Urine output Electrolytes Hematocrit/hemoglobin 5.5 Pre-infusion preparation ALBUMINEX 5% must not be diluted with sterile water for injection as this may cause hemolysis in recipients. The product can be diluted in an isotonic solution (e.g., 5% dextrose in water or 0.9% sodium chloride) [see Dosage and Administration (2.2) ]. 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. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) is also considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for ALBUMINEX 5%.

7 DRUG INTERACTIONS Do not mix ALBUMINEX 5% with blood, blood components, protein hydrolysates, alcoholic solutions or other medicinal products. Although it is not usually necessary to dilute Albuminex 5%, if it should be necessary, it may be diluted with 0.9% saline or 5% dextrose. However, it can be administered, via a separate IV line, concomitantly with other parenterals.

6 ADVERSE REACTIONS The most common adverse reactions are rigors, hypotension/decreased BP, tachycardia/increased heart rate, pyrexia, feeling cold (chills), nausea, vomiting, dyspnea/bronchospasm, rash/pruritus. Stop the infusion if anaphylaxis, with or without shock is observed. To report SUSPECTED ADVERSE REACTIONS, contact Kedrion Biopharma, Inc. at 1-855-3KDRION (1-855-353-7466) or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 General In general, human albumin solutions are well-tolerated and no specific, clinically relevant alterations in organ function or coagulopathy have been substantiated. 26 The most common adverse reactions associated with infusion of human albumin solutions are rigors, hypotension/decreased BP, tachycardia/increased heart rate, pyrexia, feeling cold (chills), nausea, vomiting, dyspnea/bronchospasm, rash/pruritus. Reactions usually resolve when the infusion is slowed or stopped. Anaphylaxis, with or without shock, may occur and in this situation, stop the infusion. 6.2 Clinical Trials Experience No clinical studies were done using ALBUMINEX 5%.

8.1 Pregnancy Risk Summary There are no data with ALBUMINEX 5% use in pregnant women to inform on drug-associated risk. Animal reproduction studies have not been conducted using ALBUMINEX 5%. It is not known whether ALBUMINEX 5% can cause fetal harm when administered to a pregnant woman or can affect fertility. ALBUMINEX 5% should be given to a pregnant woman 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.