PRINCIPAL DISPLAY PANEL - 250 mL Vial Carton

NDC 64208-2510-1

Albumin (Human) - kjda
ALBUMINEX® 5%

12.5 g

solution for infusion

For intravenous use only

Rx only

1 vial

250 mL

Bio Products Laboratory

6 ADVERSE REACTIONS

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 USE IN SPECIFIC POPULATIONS

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.

8.2 Lactation

Risk Summary

There is no information regarding the presence of ALBUMINEX 5% in human milk, the effects on the breast-fed infant, or the effects on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for ALBUMINEX 5% and any potential adverse effects on the breast-fed infant from ALBUMINEX 5% or from the underlying maternal condition.

8.4 Pediatric Use

No human or animal data. Use only if clearly needed.

8.5 Geriatric Use

No human or animal data. Use only if clearly needed.

11 DESCRIPTION

ALBUMINEX 5% is a sterile, ready-for-use, clear, slightly viscous, almost colorless, yellow, amber or slightly green aqueous solution of human albumin for single dose intravenous infusion. It is prepared from the pooled plasma of US donors in FDA-licensed facilities in the US. The product also contains 130-160 mmol/L of sodium, less than 200 micrograms/L of aluminum and is stabilized with caprylate (0.08 mmol/g albumin) and acetyltryptophanate (0.08 mmol/g albumin) but does not contain any preservative.

12.5 g (250 mL) of ALBUMINEX 5% is oncotically equivalent to 250 mL plasma.

25 g (500 mL) of ALBUMINEX 5% is oncotically equivalent to 500 mL plasma.

The vials are closed with a synthetic rubber stopper. The stopper is not made with natural rubber latex.

The viral risk from human plasma is minimized by the fractionation process and pasteurization of the albumin solution for 10 hours at 60**°C (140°**F) in its final container. These processes are effective for both enveloped and non- enveloped viruses. There have been no reports of virus transmission with products manufactured using this combination of processes.

Typical reductions of experimental viral loads are shown in Table 1.

Table 1: Virus Reduction for Albumin (Human) 5%

Mean Reduction Factors (log10)
	Enveloped Virus	Enveloped Virus	Enveloped Virus	Enveloped Virus	Non-Enveloped Virus	Non-Enveloped Virus
nd: not determined
HIV-1: Human Immunodeficiency Virus Type 1
BVDV: Bovine Viral Diarrhoea Virus
IBR: Infectious Bovine Rhinotracheitis
HAV: Hepatitis A Virus
CPV: Canine Parvovirus
Manufacturing Step	HIV-1	Sindbis	BVDV	IBR	HAV	CPV
A+1 Precipitation	nd	4.1	3.4	3.4	3.4	3.7
Fraction IV Precipitation	4.6	7.1	4.2	5.7	4.2	6.0
Pasteurization	6.7	6.4	4.2	5.4	4.0	4.0
Overall	>11.3	>13.5	>8.4	>11.1	8.2	10.0

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Human albumin accounts for more than half of the total protein in the plasma and represents about 10% of protein synthesis activity by the liver.

The primary physiological function of albumin results from its contribution to plasma colloid oncotic pressure and transport function. Albumin stabilizes circulating blood volume and is a carrier of hormones, enzymes, medicinal products and toxins. Other physiological functions include antioxidant properties, free radical scavenging, and capillary membrane integrity.

12.3 Pharmacokinetics

Albumin is distributed throughout the extracellular space and more than 60% of the body albumin pool is located in the extravascular fluid compartment. Albumin has a circulating life span of 15-20 days, with a turnover of approximately 15 g per day. The balance between synthesis and breakdown is normally achieved by feedback regulation. Elimination is predominantly intracellular and due to lysosome proteases.

In healthy subjects, less than 10% of infused albumin leaves the intravascular compartment during the first 2 hours following infusion. There is considerable individual variation in the effect of albumin on plasma volume.

In some patients, the plasma volume can remain elevated for several hours. In critically ill patients, however, albumin can leak out of the vascular space in substantial amounts at an unpredictable rate.

16 HOW SUPPLIED/STORAGE AND HANDLING

How ALBUMINEX 5% is supplied

ALBUMINEX 5%, 5 g/dL in clear Type II glass vials.

Strength	Grams and fill size	NDC carton number	NDC vial number
5%	12.5 g in 250 mL	64208-2510-1	64208-2510-2
5%	25 g in 500 mL	64208-2510-5	64208-2510-6

Not all pack sizes may be marketed.

Storage and handling

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.

Do not use ALBUMINEX 5% 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.

ALBUMINEX 5% should be inspected visually for particulate matter and discoloration prior to administration.

U.S. federal law prohibits dispensing without prescription.

17 PATIENT COUNSELING INFORMATION

Ensure that patients to be treated with ALBUMINEX 5% are informed of the potential risks and benefits of its use for their clinical condition [see Warnings and Precautions (5)].

Check that they are not known to be allergic to the product or its excipients [see Contraindications (4) and Description (11)].

Make them aware of the symptoms of anaphylaxis [see Hypersensitivity (5.1)].

Make them aware of the symptoms of potential circulatory overload [see Hypervolemia (5.2)].

Inform patients that because ALBUMINEX 5% is derived from human blood plasma it may contain infectious agents that cause disease (e.g. viruses and, theoretically CJD agent) although the risk of infection from ALBUMINEX 5% has been reduced by the procedures used in donor selection and during manufacture [see Infectious Diseases (5.6) and Description (11)].

2 DOSAGE AND ADMINISTRATION

For intravenous administration only.

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.