FDA Label for Albuminex

1.1 Hypovolemia

ALBUMINEX 25% 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 25% 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 25% infusion plus administration of vasoactive drugs is indicated in the treatment of type I hepatorenal syndrome. ⁶

For patients with spontaneous bacterial peritonitis, ALBUMINEX 25% is indicated as adjuvant treatment to antibiotic therapy.

1.3 Hypoalbuminemia Including From Burns

ALBUMINEX 25% 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 25% 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 25% 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 25% is indicated in conjunction with diuretics to correct fluid volume overload associated with ARDS. ^{17, 18, 19}

1.6 Cardiopulmonary Bypass

ALBUMINEX 25% 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.

2.1 Dosage

The concentration of ALBUMINEX 25% used, its dosage, and infusion rate should be adjusted to the patient's individual requirements and clinical indication.

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 25% 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.

3 Dosage Forms And Strengths

ALBUMINEX 25% is a sterile, aqueous solution of human albumin (25% w/v i.e. 25 g/dL) for intravenous administration available as:

• 50 mL (12.5 g) single dose vial
• 100 mL (25 g) single dose vial

4 Contraindications

ALBUMINEX 25% 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

5.1 Hypersensitivity Reactions

Suspicion of allergic or anaphylactic reactions requires 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

20% - 25% human albumin solutions are relatively low in electrolytes compared to 4% - 5% human albumin solutions so if comparatively large volumes are to be replaced, care must be taken to ensure adequate substitution of other blood constituents (coagulation factors, electrolytes, platelets and erythrocytes).

5.4 Clinical Hemodynamics Parameters

Colloid-osmotic effect of human albumin 25% is approximately five times that of blood plasma. Therefore, when concentrated albumin is administered, care must be taken to assure adequate hydration of the patient. Patients should be monitored carefully to guard against circulatory overload and hyperhydration. Patients with marked dehydration require administration of additional fluids.

The following parameters should be assessed during administration of ALBUMINEX 25%:

• Arterial blood pressure and pulse rate
• Central venous pressure
• Pulmonary artery occlusion pressure
• Urine output
• Electrolytes
• Hematocrit/hemoglobin

5.5 Pre-Infusion Preparation

ALBUMINEX 25% 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 25%.

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 25%.

7 Drug Interactions

Do not mix ALBUMINEX 25% with blood, blood components, protein hydrolysates, alcoholic solutions or other medicinal products except 0.9% saline or 5% dextrose. However, it can be administered, via a separate IV line, concomitantly with other parenterals.

Other

Risk Summary

There are no data with ALBUMINEX 25% use in pregnant women to inform on drug-associated risk. Animal reproduction studies have not been conducted using ALBUMINEX 25%. It is not known whether ALBUMINEX 25% can cause fetal harm when administered to a pregnant woman or can affect fertility. ALBUMINEX 25% 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.

Risk Summary

There is no information regarding the presence of ALBUMINEX 25% 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 25% and any potential adverse effects on the breast-fed infant from ALBUMINEX 25% or from the underlying maternal condition.

How ALBUMINEX 25% is supplied

ALBUMINEX 25%, 25 g/dL in clear Type II glass vials.

Not all pack sizes may be marketed.

Manufactured by:
Bio Products Laboratory Ltd.,
Elstree,
WD6 3BX.
United Kingdom

U.S. Distributor:
Bio Products Laboratory USA Inc.,
302 East Pettigrew Street,
Suite C-190,
Durham, NC 27701
USA

U.S. Licence No:1811

ALBUMINEX^® is a registered trademark of Bio Products Laboratory Ltd.

AAUSPI1

Version 1

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 25% 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 (50 mL) of ALBUMINEX 25% is oncotically equivalent to 250 mL plasma.
25 g (100 mL) of ALBUMINEX 25% 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.

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. Human Albumin 25% has a corresponding hyperoncotic effect.

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.

15 References

• Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004;3650:2247-2256
• Bunn F, Trivedi D, Ashraf S. Colloid solutions for fluid resuscitation. Cochrane Database of Systematic Reviews 2011, Issue 3. Art. No.: CD001319. DOI: 10.1002/14651858.CD001319.pub3
• Powell-Tuck J, Gosling P, Lobo DN, et al. British Consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical Patients. BAPEN; 2011. Available from: http://www.bapen.org.uk/pdfs/bapen_pubs/giftasup.pdf (Guideline Ref ID GIFTASUP2011)
• Rochwerg B, Alhazzani W, Sindi A, et al. Fluid resuscitation in sepsis: a systematic review and network meta-analysis. Ann Intern Med 2014;161(5):347-355
• Wiedermann CJ, Joannidis M. Albumin replacement in severe sepsis or septic shock. N Engl J Med 2014;371:83-84
• Akech S, Gwer S, Idro R, et al. Volume expansion with albumin compared to gelofusine in children with severe malaria: results of a controlled trial. PLoS Clin Trials 2006; 5:0001-0011
• Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Critical Care Medicine, 2013; 41(2):580–637
• Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database of Systemic Reviews 2013, Issue 2.Art. No.CD000567. DOI:10.1002/14651858.CD000567.pub6.
• Runyon BA. Management of Adult Patients with Ascites Due to Cirrhosis: Update 2012. The American Association for the Study of Liver Diseases 2012. http://www.aasld.org/publications/practice-guidelines-0 [accessed 15 April 2016]
• EASL clinical practise guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol 2010; 53: 397–417
• Bernardi M, Carceni P, Navickis RJ, et al. Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials. Hepatology 2012;55:1172-1181
• Sarma MS, Yachha SK, Bhatia V, et al. Safety, complications and outcome of large volume paracentesis with or without albumin therapy in children with severe ascites due to liver disease. J Hepatol 2015:63;1126-1132
• Wiest R, Krag A, Gerbes A. Spontaneous Bacterial Peritonitis. Recent Guidelines and Beyond. Gut 2012; 61(2):297-310
• Pham TN, Cancio LC, Gibran NS. American Burn Association Practice Guidelines Burn Shock Resuscitation. J Burn Care Res 2008; 29(1): 257-266
• Bircan Z, Kervancioglu M. Does albumin and furosemide therapy affect plasma volume in nephrotic children? Pediatr Nephrol 2001;16:497-499
• Dharmaraj R, Hari P, Bagga A, Randomized cross-over trial comparing albumin and frusemide infusions in nephrotic syndrome. Pediatr Nephrol 2009; 24(4):775-782
• Martin GS, Moss M, Wheeler AP, et al. A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury. Crit Care Med 2005;33(8):1681-1687
• Uhlig C, Pedro L, Silva PL, et al. Albumin versus crystalloid solutions in patients with the acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care 2014, 18:R10 http://ccforum.com/content/18/1/R10 [accessed 02 November 2016]
• Quinlan GJ, Mumby S, Martin GS, et al. Albumin influences total plasma antioxidant capacity favorably in patients with acute lung injury. Crit Care Med 2004;32:755–759
• Wilkes MM, Navickis RJ, Sibbald WJ. Albumin versus hydroxyethyl starch in cardiopulmonary bypass surgery: a metaanalysis of postoperative bleeding. Ann Thorac Surg 2001;72(2):527-534
• Golab HD, Scohy TV, de Jong PL, et al. Relevance of colloid oncotic pressure regulation during neonatal and infant cardiopulmonary bypass: a prospective randomized study. Eur J Cardio-Thor Surg 2011; 39(6):886-891
• Hanart C, Khalife M, De Villé A, et al. Perioperative volume replacement in children undergoing cardiac surgery: Albumin versus hydroxyethyl starch 130/0.4. Crit Care Med 2009;37 (2): 696-701 DOI: 10.1097/CCM.0b013e3181958c81
• Loeffelbein F, Zirell U, Benk C, et al. High colloid oncotic pressure priming of cardiopulmonary bypass in neonates and infants: implications on haemofiltration, weight gain and renal function. Eur J Cardio-Thor Surg 2008; 34(3):648-652
• Oliver WC Jr, Beynen FM, Nuttall GA, et al. Blood loss in infants and children for open heart operations: albumin 5% versus fresh-frozen plasma in the prime. Ann Thor Surg 2003;75(5):1506-1512
• Yu K, Liu Y, Hei F, et al. Effect of different albumin concentrations in extracorporeal circuit prime on perioperative fluid status in young children. ASAIO Journal 2008; 54(5):463-466
• German Medical Association. Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivatives. 4th revised and updated edition 2014. http://www.bundesaerztekammer.de/aerzte/medizin-ethik/wissenschaftlicher-beirat/veroeffentlichungen/haemotherapie-transfusionsmedizin/english/ [accessed 15 April 2016]

Storage And Handling

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 25% 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 25% 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 25% 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 25% 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 25% has been reduced by the procedures used in donor selection and during manufacture [see Infectious Diseases (5.6) and Description (11)].

Principal Display Panel - 100 Ml Vial Label

NDC 64208-2512-8

Albumin (Human) - kjda

ALBUMINEX^® 25%

solution for infusion
For intravenous use only

Distributor: BPL USA, Inc., 302 E. Pettigrew Street,
Suite C-190, Durham, NC 27701 USA

PRINCIPAL DISPLAY PANEL - 100 mL Vial Label - albuminex 01

Principal Display Panel - 100 Ml Vial Carton

NDC 64208-2512-7

Albumin (Human) - kjda

ALBUMINEX^® 25%

25 g

solution for infusion

For intravenous use only

Rx only

1 vial

100 mL

Bio Products Laboratory

PRINCIPAL DISPLAY PANEL - 100 mL Vial Carton - albuminex 02

Principal Display Panel - 50 Ml Vial Label

NDC 64208-2512-4

Albumin (Human) - kjda

ALBUMINEX^® 25%

solution for infusion
For intravenous use only

Distributor: BPL USA, Inc., 302 E. Pettigrew Street,
Suite C-190, Durham, NC 27701 USA

PRINCIPAL DISPLAY PANEL - 50 mL Vial Label - albuminex 03

Principal Display Panel - 50 Ml Vial Carton

NDC 64208-2512-3

Albumin (Human) - kjda

ALBUMINEX^® 25%

12.5 g

solution for infusion

For intravenous use only

Rx only

1 vial

50 mL

Bio Products Laboratory

PRINCIPAL DISPLAY PANEL - 50 mL Vial Carton - albuminex 04