9c45986e-4e62-4f7d-971c-bec74dc4d234 — v1

6. ADVERSE REACTIONS The most common adverse reactions include fever and chills, rash, nausea, vomiting, tachycardia and hypotension. Should an adverse reaction occur, slow or stop the infusion for a period of time which may result in the disappearance of the symptoms. If administration has been stopped and the patient requires additional Albutein ® 5%, material from a different lot should be used. Albutein ® 5%, particularly if administered rapidly, may result in vascular overload with resultant pulmonary edema. To report SUSPECTED ADVERSE REACTIONS, contact Grifols Biologicals Inc. at 1-888-GRIFOLS (1-888-474-3657) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . The most common adverse reactions include fever and chills, rash, nausea, vomiting, tachycardia and hypotension ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Grifols Biologicals Inc. at 1-888-GRIFOLS (1-888-474-3657) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

12. CLINICAL PHARMACOLOGY 12.1 Mechanism of Action There are no known cases of viral hepatitis which have resulted from the administration of Albutein ® 5%. Albumin is a highly soluble, globular protein (MW 66,500), accounting for 70-80% of the colloid osmotic pressure of plasma. Therefore, it is important in regulating the osmotic pressure of plasma. 1,3 Albutein ® 5% supplies the oncotic equivalent of approximately its volume of human plasma. It will increase the circulating plasma volume by an amount approximately equal to the volume infused. This extra fluid reduces hemoconcentration and decreases blood viscosity. 4 The degree and duration of volume expansion depend upon the initial blood volume. When treating patients with diminished blood volume, the effect of infused albumin may persist for many hours. The hemodilution lasts for a shorter time when albumin is administered to individuals with normal blood volume. Albumin is also a transport protein and binds naturally occurring, therapeutic, and toxic materials in the circulation. 1 The binding properties of albumin may, in special circumstances, provide an indication for its clinical use. For such purposes, however, the 25% solution should be used. Albumin is distributed throughout the extracellular water and more than 60% of the body albumin pool is located in the extravascular fluid compartment. The total body albumin in a 70 kg man is approximately 320 g. Albumin has a circulating life span of 15-20 days, with a turnover of approximately 15 g per day. 3

4. CONTRAINDICATIONS Albutein ® 5% is contraindicated in patients with severe anemia or cardiac failure in the presence of normal or increased intravascular volume. The use of Albutein ® 5% is contraindicated in patients with a history of allergic reactions to albumin. Patients with severe anemia or cardiac failure in the presence of normal or increased intravascular volume ( 4 ) Patients with a history of allergic reactions to albumin ( 4 )

11. DESCRIPTION Albutein ® 5% is a sterile, aqueous solution for single dose intravenous administration containing 5% human albumin (weight/volume). Albutein ® 5% is prepared by a cold alcohol fractionation method from pooled human plasma obtained from venous blood. The product is stabilized with 0.08 millimole sodium caprylate and 0.08 millimole sodium acetyltryptophanate per gram of albumin. Albutein ® 5% is osmotically and isotonically equivalent to an equal volume of normal human plasma. Albutein ® 5% contains 130-160 milliequivalents of sodium ion per liter and has a pH of 7.0 ± 0.3. The aluminum content of the solution is not more than 200 micrograms per liter during the shelf life of the product. The product contains no preservatives. Albutein ® 5% is heated at 60 °C for ten hours. No positive assertion can be made, however, that this heat treatment completely destroys the causative agents of viral hepatitis.

2. DOSAGE AND ADMINISTRATION Albutein ® 5% is administered intravenously. The total dosage will vary with the individual. In adults, an initial infusion of 500 mL is suggested. Additional amounts may be administered as clinically indicated. In the treatment of the patient in shock with greatly reduced blood volume, Albutein ® 5% may be administered as rapidly as necessary in order to improve the clinical condition and restore normal blood volume. This may be repeated in 15-30 minutes if the initial dose fails to prove adequate. In the patient with a slightly low or normal blood volume, the rate of administration should be 1-2 mL per minute. DIRECTIONS FOR USE: (250 mL and 500 mL) Albutein ® 5% is administered intravenously. The total dosage will vary with the individual. In adults, an initial infusion of 500 mL is suggested. Additional amounts may be administered as clinically indicated. When an administration set is used ( 2.1 ) When an administration set is not used ( 2.2 ) 2.1 When an Administration Set is Used Flip off plastic cap on top of the vial and expose rubber stopper. Cleanse exposed rubber stopper with suitable germicidal solution, being sure to remove any excess. Observe aseptic technique and prepare sterile intravenous equipment as follows: Close clamp on administration set. With bottle upright, squeeze drip chamber, thrust piercing pin straight through stopper center. Do not twist or angle. Immediately invert bottle, release drip chamber to automatically establish proper fluid level in drip chamber (half full). Attach infusion set to administration set, open clamp and allow solution to expel air from tubing and needle, then close clamp. Make venipuncture and adjust flow. Discard all administration equipment after use. Discard any unused contents. 2.2 When an Administration Set is Not Used Flip off plastic cap on top of the vial and expose rubber stopper. Cleanse exposed rubber stopper with suitable germicidal solution, being sure to remove any excess. Observe aseptic technique and prepare sterile intravenous equipment as follows: Using aseptic technique, attach filter needle to a sterile disposable plastic syringe. Insert filter needle into Albutein ® 5%. Aspirate Albutein ® 5% from the vial into the syringe. Remove and discard the filter needle from the syringe. Attach desired size needle to syringe. Discard all administration equipment after use. Discard any unused contents.

3. DOSAGE FORMS AND STRENGTHS Albutein ® 5% is a sterile, aqueous solution for single dose intravenous administration containing 5% human albumin (weight/volume). It is available in the following presentations: 12.5 g albumin/250 mL single dose vial. 25 g albumin/500 mL single dose vial. Albutein ® 5% is a sterile, aqueous solution for single dose intravenous administration containing 5% human albumin (weight/volume), provided in the following presentations: ( 3 ) 12.5 g albumin/250 mL single dose 25 g albumin/500 mL single dose

16. HOW SUPPLIED/STORAGE AND HANDLING Albutein ® 5% is supplied as a sterile, aqueous solution for single dose intravenous administration containing 5% human albumin (weight/volume). It is available in the following vial sizes: 250 mL vial Albutein ® 5% (NDC 68516-5214-1). 500 mL vial Albutein ® 5% (NDC 68516-5214-2). Storage Albutein ® 5% is stable for three years provided that storage temperature does not exceed 30 °C. Protect from freezing.

1. INDICATIONS AND USAGE Albumin (Human) U.S.P., Albutein ® 5% Solution is indicated: For treatment of hypovolemic shock. 1,2 In conditions in which there is severe hypoalbuminemia. However, unless the pathologic condition responsible for the hypoalbuminemia can be corrected, administration of albumin can afford only symptomatic or supportive relief. As an adjunct in hemodialysis and in cardiopulmonary bypass procedures. In those conditions in which the colloid requirement is high and there is less need for fluid, albumin should be administered as a 25% solution. Albumin (Human) U.S.P., Albutein ® 5% Solution is indicated ( 1 ): For treatment of hypovolemic shock. In conditions in which there is severe hypoalbuminemia. However, unless the pathologic condition responsible for the hypoalbuminemia can be corrected, administration of albumin can afford only symptomatic or supportive relief. As an adjunct in hemodialysis and in cardiopulmonary bypass procedures. In those conditions in which the colloid requirement is high and there is less need for fluid, albumin should be administered as a 25% solution.

17. PATIENT COUNSELING INFORMATION The most common adverse reactions include fever and chills, rash, nausea, vomiting, tachycardia and hypotension. Depending on the severity of the reaction, patients should be advised to discontinue use of the product and contact their physician and/or seek immediate emergency care. Albutein ® 5% should be administered with caution to patients with low cardiac reserve. Rapid infusion may cause vascular overload with resultant pulmonary edema. Patients should be closely monitored for signs of increased venous pressure. A rapid rise in blood pressure following infusion necessitates careful observation of injured or postoperative patients to detect and treat severed blood vessels that may not have bled at a lower pressure. Patients with marked dehydration require administration of additional fluids. Albutein ® 5% may be administered with the usual dextrose and saline intravenous solutions. However, solutions containing protein hydrolysates or alcohol must not be infused through the same administration set in conjunction with Albutein ® 5% since these combinations may cause the proteins to precipitate. See also WARNINGS AND PRECAUTIONS ( 5.2 ). Manufactured and Distributed by: Grifols Biologicals Inc. Los Angeles, CA 90032, U.S.A. U. S. License No. 1694 DATE OF REVISION: 07/2008 3028183

12.1 Mechanism of Action There are no known cases of viral hepatitis which have resulted from the administration of Albutein ® 5%. Albumin is a highly soluble, globular protein (MW 66,500), accounting for 70-80% of the colloid osmotic pressure of plasma. Therefore, it is important in regulating the osmotic pressure of plasma. 1,3 Albutein ® 5% supplies the oncotic equivalent of approximately its volume of human plasma. It will increase the circulating plasma volume by an amount approximately equal to the volume infused. This extra fluid reduces hemoconcentration and decreases blood viscosity. 4 The degree and duration of volume expansion depend upon the initial blood volume. When treating patients with diminished blood volume, the effect of infused albumin may persist for many hours. The hemodilution lasts for a shorter time when albumin is administered to individuals with normal blood volume. Albumin is also a transport protein and binds naturally occurring, therapeutic, and toxic materials in the circulation. 1 The binding properties of albumin may, in special circumstances, provide an indication for its clinical use. For such purposes, however, the 25% solution should be used. Albumin is distributed throughout the extracellular water and more than 60% of the body albumin pool is located in the extravascular fluid compartment. The total body albumin in a 70 kg man is approximately 320 g. Albumin has a circulating life span of 15-20 days, with a turnover of approximately 15 g per day. 3

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 250 ML VIAL GRIFOLS NDC 68516-5214-1 Albumin (Human) U.S.P. Albutein ® 5% 5% 12.5 g 250 mL 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. PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 250 ML VIAL

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 500 ML VIAL GRIFOLS NDC 68516-5214-2 Albumin (Human) U.S.P. Albutein ® 5% 5% 25 g 500 mL 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. PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 500 ML VIAL

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 250 ML CARTON GRIFOLS NDC 68516-5214-1 Albumin (Human) U.S.P. Albutein ® 5% Solution 12.5 g 250 mL 5% Store at temperatures not exceeding 30 °C. PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 250 ML CARTON

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 500 ML CARTON GRIFOLS NDC 68516-5214-2 Albumin (Human) U.S.P. Albutein ® 5% Solution 25 g 500 mL 5% Store at temperatures not exceeding 30 °C. PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 500 ML CARTON

8.4 Pediatric Use The pediatric use of Albutein ® 5% has not been clinically evaluated. The dosage will vary with the clinical state and body weight of the individual. Typically, a dose one-quarter to one-half the adult dose may be administered, or dosage may be calculated on the basis of 0.6 to 1.0 gram per kilogram of body weight (12 to 20 mL of Albutein ® 5%). The usual rate of administration in children should be one-quarter the adult rate. Therefore, physicians should weigh the risks and benefits of the use of Albutein ® 5% in the pediatric population. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

5.2 Precautions Albutein ® 5% should be administered with caution to patients with low cardiac reserve. Rapid infusion may cause vascular overload with resultant pulmonary edema. Patients should be closely monitored for signs of increased venous pressure. A rapid rise in blood pressure following infusion necessitates careful observation of injured or postoperative patients to detect and treat severed blood vessels that may not have bled at a lower pressure. Patients with marked dehydration require administration of additional fluids. Albutein ® 5% may be administered with the usual dextrose and saline intravenous solutions. However, solutions containing protein hydrolysates or alcohol must not be infused through the same administration set in conjunction with Albutein ® 5% since these combinations may cause the proteins to precipitate. See also PATIENT COUNSELING INFORMATION ( 17 ).

8.1 Pregnancy Pregnancy Category C. Animal reproduction studies have not been conducted with Albutein ® 5%. It is also not known whether Albutein ® 5% can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Albutein ® 5% should be given to a pregnant woman only if clearly needed.

15. REFERENCES Finlayson, J.S., Albumin Products Semin Thromb Hemo, 6:85-120, 1980. Hauser, C.J., et. al., Oxygen Transport Responses to Colloids and Crystalloids in Critically Ill Surgical Patients, Surg Gyn Obs, 150:811-816, June 1980. Tullis, J.L., Albumin: 1. Background and Use. 2. Guidelines for Clinical Use. JAMA 237:355-360, 460-463, 1977. Janeway, C.A., Human Serum Albumin: Historical Review in Proceedings of the Workshop on Albumin, Sgouris, J.T. and Rene A. (eds), DHEW Publication No. (NIH) 76-925, Washington, D.C., U.S. Government Printing Office, 1976, pp. 3-21.

Albutein Albumin (Human) Albumin Human Albumin Human Sodium Chloride Sodium Caprylate Sodium Acetyltryptophanate Water

Storage Albutein ® 5% is stable for three years provided that storage temperature does not exceed 30 °C. Protect from freezing.

8. USE IN SPECIFIC POPULATIONS Unknown whether can cause fetal harm or affect reproduction capacity ( 8.1 ) The pediatric use has not been clinically evaluated ( 8.4 ) 8.1 Pregnancy Pregnancy Category C. Animal reproduction studies have not been conducted with Albutein ® 5%. It is also not known whether Albutein ® 5% can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Albutein ® 5% should be given to a pregnant woman only if clearly needed. 8.4 Pediatric Use The pediatric use of Albutein ® 5% has not been clinically evaluated. The dosage will vary with the clinical state and body weight of the individual. Typically, a dose one-quarter to one-half the adult dose may be administered, or dosage may be calculated on the basis of 0.6 to 1.0 gram per kilogram of body weight (12 to 20 mL of Albutein ® 5%). The usual rate of administration in children should be one-quarter the adult rate. Therefore, physicians should weigh the risks and benefits of the use of Albutein ® 5% in the pediatric population. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

5.1 Warnings Albutein ® 5% is made from pooled human plasma. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases, including a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD). Although no cases of transmission of viral diseases or CJD have ever been identified for albumin, the risk of infectious agents cannot be totally eliminated. The physician should weigh the risks and benefits of the use of this product and should discuss these with the patient. Solutions of Albutein ® 5% should not be used if they appear turbid or if there is sediment in the bottle. Do not begin administration more than 4 hours after the container has been entered. Discard unused portion.

5. WARNINGS AND PRECAUTIONS Risk of infectious agents ( 5.1 ) Patients with low cardiac reserve ( 5.2 ) 5.1 Warnings Albutein ® 5% is made from pooled human plasma. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases, including a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD). Although no cases of transmission of viral diseases or CJD have ever been identified for albumin, the risk of infectious agents cannot be totally eliminated. The physician should weigh the risks and benefits of the use of this product and should discuss these with the patient. Solutions of Albutein ® 5% should not be used if they appear turbid or if there is sediment in the bottle. Do not begin administration more than 4 hours after the container has been entered. Discard unused portion. 5.2 Precautions Albutein ® 5% should be administered with caution to patients with low cardiac reserve. Rapid infusion may cause vascular overload with resultant pulmonary edema. Patients should be closely monitored for signs of increased venous pressure. A rapid rise in blood pressure following infusion necessitates careful observation of injured or postoperative patients to detect and treat severed blood vessels that may not have bled at a lower pressure. Patients with marked dehydration require administration of additional fluids. Albutein ® 5% may be administered with the usual dextrose and saline intravenous solutions. However, solutions containing protein hydrolysates or alcohol must not be infused through the same administration set in conjunction with Albutein ® 5% since these combinations may cause the proteins to precipitate. See also PATIENT COUNSELING INFORMATION ( 17 ).