ALBUTEIN Dailymed

Recent Major Changes Section

1 Indications And Usage

ALBUTEIN 25% is an albumin solution indicated for:x

• Hypovolemia. (1.1)
• Cardiopulmonary bypass procedures. (1.2)
• Acute nephrosis. (1.3)
• Hypoalbuminemia. (1.4)
• Ovarian hyperstimulation syndrome. (1.5)
• Neonatal hyperbilirubinemia. (1.6)
• Adult respiratory distress syndrome (ARDS). (1.7)
• Prevention of central volume depletion after paracentesis due to cirrhotic ascites. (1.8)

1.1 Hypovolemia

For restoration and maintenance of circulating blood volume where hypovolemia is demonstrated and colloid use is appropriate. When hypovolemia is long standing and hypoalbuminemia exists accompanied by adequate hydration or edema, 20-25% albumin solutions should be used.^1,2,3

Acute liver failure is a special situation in which both hypovolemia and hypoalbuminemia can be present. ALBUTEIN 25% can be used in such cases.¹

ALBUTEIN 25% may be of value in the treatment of shock or hypotension in renal dialysis patients.¹

1.2 Cardiopulmonary Bypass Procedures (Treatment Adjunct)

Preoperative dilution of blood using albumin and crystalloid can be used in cardiopulmonary bypass procedures. Albumin also may be used in the priming fluid.^4,5,6

1.3 Acute Nephrosis (Treatment Adjunct)

ALBUTEIN 25% may be used to treat peripheral edema in patients with acute nephrosis who are refractory to cyclophosphamide, corticosteroid therapy or diuretics.^1,2,7

1.4 Hypoalbuminemia

ALBUTEIN 25% may be indicated for subjects with hypoalbuminemia who are critically ill and/or actively bleeding. When albumin deficit is the result of excessive protein loss, the effect of ALBUTEIN 25% administration will be temporary unless the underlying disorder is reversed.^8,9,10 Septic patients and patients undergoing major surgery may lose more than half of their circulating plasma volume.^1,11 Treatment with ALBUTEIN 25% may be of value in such cases, especially when plasma colloid oncotic pressure is abnormally low.¹

In the first 24 hours after thermal injury, large volumes of crystalloids are infused to restore the depleted extracellular fluid volume. Beyond 24 hours, ALBUTEIN 25% can be used to maintain plasma colloid osmotic pressure.^2,12,13 Protein loss from the third space due to infection (acute peritonitis, pancreatitis, mediastinitis or extensive cellulitis) may require treatment with an infusion of albumin.^14,15

1.5 Ovarian Hyperstimulation Syndrome

ALBUTEIN 25% may be used as a plasma volume expander in fluid management relating to severe forms of ovarian hyperstimulation syndrome.^16,17

1.6 Neonatal Hyperbilirubinemia

ALBUTEIN 25% is indicated for the treatment of neonatal hyperbilirubinemia. It may be used prior to or during an exchange procedure in an attempt to bind free bilirubin and enhance its excretion.^18,19,20

1.7 Adult Respiratory Distress Syndrome (ARDS) (Treatment Adjunct)

ALBUTEIN 25% infusions may be indicated in conjunction with diuretics to correct fluid overload and hypoproteinemia associated with ARDS.^6,21

1.8 Prevention of Central Volume Depletion after Paracentesis due to Cirrhotic Ascites (Treatment Adjunct)

ALBUTEIN 25% may be used to maintain cardiovascular function following removal of large volumes of ascitic fluid after paracentesis due to cirrhotic ascites.^2,22,23,24

2 Dosage And Administration

For Intravenous Use Only


For Intravenous Use Only

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)
Cardiopulmonary bypass procedures	Adults: Initial dose of 25 g. (2.1)
Acute nephrosis	Adults: 25 g together with diuretic once a day for 7 - 10 days. (2.1)
Hypoalbuminemia	Adults: 50 to 75 gFor 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 100mL.Third space protein loss due to infection: initial dose of 50 to 100 g. (2.1)
Ovarian hyperstimulation syndrome	Adults: 50 g to 100 g over 4 hours and repeated at 4-12 hour intervals as necessary. (2.1)
Neonatal hyperbilirubinemia	1 g per kilogram body weight prior to or during exchange transfusion. (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)
Prevention of central volume depletion after paracentesis due to cirrhotic ascites	Adults: 8 g for every 1000 mL of ascitic fluid removed. (2.1)

Do not dilute with sterile water for injection as this may cause hemolysis in recipients. (5.7)

2.1 Dosage

Adjust the concentration, dosage and infusion rate of the albumin preparation to the patient's individual requirements

The dose required depends on the patient's body weight, severity of injury/illness and on continuing fluid and protein losses. Use adequacy of circulating blood volume, not plasma albumin levels, to determine the dose required.

Indication	Dose
Hypovolemia	Adults: Initial dose of 25 g.If hemodynamic stability is not achieved within 15 to 30 minutes, an additional dose may be given.Hemodilution may follow administration of ALBUTEIN 25%. Anemia resulting from hemorrhage should be corrected by administration of compatible red blood cells or compatible whole blood.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.
Cardiopulmonary bypass procedures	Adults: Initial dose of 25 g. Additional amounts may be administered as clinically indicated.
Acute nephrosis	Adults: 25 g together with diuretic once a day for 7 - 10 days.
Hypoalbuminemia	Adults: 50 to 75 gFor 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: 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.
Ovarian hyperstimulation syndrome	Adults: 50 g to 100 g over 4 hours and repeated at 4-12 hour intervals as necessary, when infusion of normal saline fails to achieve or maintain hemodynamic stability and urine output.
Neonatal hyperbilirubinemia	1 g per kilogram body weight prior to or during exchange transfusion.
Adult respiratory distress syndrome (ARDS)	Adults: 25 g over 30 minutes and repeated at 8 hours for 3 days, if necessary.
Prevention of central volume depletion after paracentesis due to cirrhotic ascites	Adults: 8 g for every 1000 mL of ascitic fluid removed.

2.2 Administration

Intravenous use only

• Some moisture or condensation may be observed in the protective overwrap. This is normal and does not affect the quality or safety of the albumin solution.
• Check the inner bag for any leaks prior to use by squeezing it firmly. If leaks are detected, discard the solution.
• ALBUTEIN 25% is a clear and slightly viscous solution. Visually inspect for particulate matter and discoloration prior to administration. Do not use if the solution is turbid, if there is sediment in the container, or if the seal is broken.
• Warm product to room temperature before use if large volumes are administered.
• Do not add supplementary medication.
• Do not dilute with sterile water for injection.  Acceptable diluents include 0.9% Sodium Chloride or 5% Dextrose in Water [see Warnings and Precautions (5.7)].
• ALBUTEIN 25% contains no preservatives. Once open, the product should be used within four hours. Discard unused portion.
• For single use. Any unused solution must be discarded.

CAUTION: Do not use bags in series connections. Such use could result in air embolism due to residual air being drawn from the primary bag before the administra­tion of the fluid from the secondary bag is complete.

• After checking that protective overwrap is not damaged, remove it by tearing the slots at either end (refer to Figure 1).
• Suspend the inner bag from the eyelet support (refer to Figure 2).
• Holding the protective safety shield at the infusion port of the inner bag with one hand, use the free hand to exert light force to turn the twist-off opening about 90 degrees until it leaves the port (refer to Figure 3).
• Attach either a non-vented or vented administration set (refer to Figure 4).  Adjust the infusion rate to the individual circumstances and the indication. Refer to the complete directions of administration set used.

3 Dosage Forms And Strengths

ALBUTEIN 25% is a solution containing 250 g per L of total protein of which at least 95% is human albumin.


Albutein 25% is a solution containing 250 g per L of total protein of which at least 95% is human albumin.

4 Contraindications

• Hypersensitivity to albumin preparations or to any of the excipients.
• Severe anemia or cardiac failure with normal or increased intravascular volume.X

• Hypersensitivity to albumin preparations or to any of the excipients.
• Severe anemia or cardiac failure with normal or increased intravascular volume. (4)

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)
• When concentrated albumin is administered, care must be taken to assure adequate hydration of the patient. (5.3)
• Monitor electrolytes, coagulation and hematology parameters and hemodynamic status when albumin is administered. (5.4, 5.5, 5.6)
• Do not dilute with sterile water for injection. (5.7)
• Albumin is a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk of 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 ALBUTEIN 25%. (5.8)

5.1 Hypersensitivity

Suspicion of allergic or anaphylactic reactions requires immediate discontinuation of the infusion and implementation of appropriate medical treatment.

5.2 Hypervolemia/Hemodilution

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 Dehydration

The 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.

5.4 Electrolyte Imbalance

20% – 25% human albumin solutions are relatively low in electrolytes compared to 4% – 5% human albumin solutions. Monitor regularly the electrolyte status of the patient and take appropriate steps to restore or maintain the electrolyte balance when albumin is administered.

5.5 Coagulation Abnormalities

Regular monitoring of coagulation and hematology parameters is necessary 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).

5.6 Laboratory Monitoring

Monitor regularly hemodynamic parameters during administration of ALBUTEIN 25%; this may include:

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

5.7 Application Precautions

ALBUTEIN 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)].

5.8 Transmissible Infectious Agents

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 ALBUTEIN 25%.

6 Adverse Reactions

The most serious adverse reactions are anaphylactic shock, heart failure and pulmonary edema

The most common adverse reactions are anaphylactoid type reactions.

Adverse reactions to ALBUTEIN 25% normally resolve when the infusion rate is slowed or the infusion is stopped. In case of severe reactions, the infusion is stopped and appropriate treatment initiated.


The most common adverse reactions are anaphylactoid type reactions. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Grifols Biologicals LLC at 1-888-GRIFOLS (1-888-474-3657) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience

No clinical studies were done using ALBUTEIN 25%.

6.2 Post-Marketing Experience

Because adverse reactions are reported voluntarily post-approval from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to product exposure. The following adverse reactions have been identified during post approval use of human albumin, including ALBUTEIN (all strengths) in decreasing order of significance:

• Anaphylactic shock
• Heart failure
• Pulmonary edema
• Hypotension
• Tachycardia
• Vomiting
• Urticaria
• Rash
• Headache
• Chills
• Fever
• Flushing
• Nausea

7 Drug Interactions

ALBUTEIN 25% must not be mixed with other medicinal products.

8 Use In Specific Populations

8.1 Pregnancy

Risk Summary There is no data with ALBUTEIN 25% use in pregnant women to inform a drug-associated risk. Animal reproduction studies have not been conducted with ALBUTEIN 25%. It is not known whether ALBUTEIN 25% can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. ALBUTEIN 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 defect 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 ALBUTEIN 25% in human milk, the effect on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ALBUTEIN 25% and any potential adverse effects on the breastfed infant from ALBUTEIN 25%.    

8.4 Pediatric Use

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

8.5 Geriatric Use

11 Description

ALBUTEIN 25% is a sterile, aqueous solution for single-dose intravenous administration containing 25% human albumin (weight/volume). ALBUTEIN 25% 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 protein. The colloid osmotic effect of human albumin 25% is approximately five times that of normal human plasma. A liter of ALBUTEIN 25% solution contains 130-160 milliequivalents of sodium ion. 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 25% is manufactured from Source Plasma collected from FDA approved plasmapheresis centers in the United States.  ALBUTEIN 25% is heated at 60 °C for ten hours, a process that has the capacity to inactivate viruses.

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. 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

• Tullis JL. Albumin: 1. Background and Use. 2. Guidelines for Clinical Use. JAMA. 1977;237:355-360, 460-463.
• Vermeulen LC, et al. A Paradigm for Consensus. Arch Intern Med. 1995;155:373-379.
• SAFE Study investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350:2247-2256.
• Sedrakyan A, Gondek K, Paltiel D, et al. Volume expansion with albumin decreases mortality after coronary artery bypass graft surgery. Chest. 2003;123:1853-1857.
• Russell JA, Navickis RJ, Wilkes MM. Albumin versus crystalloid for pump priming in cardiac surgery: meta-analysis of controlled trials. J Cardiothorac Vasc Anesth. 2004;18:429-37.
• American Thoracic Society. Evidence-based colloid use in the critically ill: American Thoracic Society consensus statement. Am J Respir Crit Care Med. 2004;170:1247-59.
• Fliser D, Zurbrüggen I, Mutschler E, et al. Coadministration of albumin and furosemide in patients with nephrotic syndrome. Kidney Int. 1999;55:629-34.
• Mendez CM, McClain CJ, Marsano LS. Albumin Therapy in Clinical Practice. Nutrition in Clinical Practice. 2005;20:314-320.
• Haynes GR, Navickis RJ, Wilkes MM. Albumin administration-what is the evidence of clinical benefit? A systematic review of randomized controlled trials. Eur J Anaesthesiol. 2003 Oct;20(10):771-93.
• Vincent JL, Navickis RJ, Wilkes MM. Morbidity in hospitalized patients receiving human albumin: a meta-analysis of randomized, controlled trials. Crit Care Med. 2004;32:2029-38.
• Skillman JJ, Tanenbaum BJ. Current Topics in Surgical Research. Vol. 2. New York: Academic Press. 1970;523.
• Muir IA, Barclay TL. Burns and their treatment. Chicago: Year Book Medical Publishers. 1974.
• Pruitt BA Jr, Goodwin CW Jr. Current treatment of the extensively burned patient. Surg Annu. 1983;15:331-64.
• Clowes GHA Jr, Vucinic M, Weidner MG. Circulatory and metabolic alterations associated with survival or death in peritonitis: clinical analysis of 25 cases. Ann Surg. 1966;166:866-85.
• Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med.1999;341:403-409.
• Aboulghar M, Evers JH, Al Inany H. Intravenous albumin for preventing severe ovarian hyperstimulation syndrome: a Cochrane review. Hum Reprod. 2002;17:3027-3032.
• Practice Committee of the American Society for Reproductive Medicine. Ovarian hyperstimulation syndrome. Fertil Steril. 2006;86:S178-S183.
• Tsao YC, Yu VY. Albumin in management of neonatal hyperbilirubinaemia. Arch Dis Child. 1972;47:250-256.
• Practice parameter: management of hyperbilirubinemia in the healthy term newborn. Pediatrics. 1994;94(4 pt 1):558-62.
• Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbilirubinemia. N Eng J Med. 2001;344:581-90.
• Martin GS, et al. A randomized, controlled trail of furosemide with or without albumin in hypoproteinemic patients with acute lung injury. Crit Care Med. 2005; 33:1681-1687.
• Ginés P, Cárdenas A, Arroyo V, et al. Management of cirrhosis and ascites. N Engl J Med. 2004;350:1646-54.
• Runyon BA. AASLD Practice Guidelines. Management of adult patients with ascites due to cirrhosis. Hepatology. 2009;49(6):2087-107.
• Moore KP, Wong F, Ginés P, et al. The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club. Hepatology. 2003;38:258-66.

16 How Supplied/storage And Handling

ALBUTEIN FlexBag 25% is supplied in a single-dose, latex-free, flexible container, free of polyvinyl chloride (PVC), diethylhexyl phthalate (DEHP), or other plasticizers. The protective overwrap on each container is also latex-free, and contains no chloride, PVC or plasticizers.  Each container is individually laser-etched with at least the lot number and expiration date.

The following package sizes of ALBUTEIN FlexBag 25% are available in multipacks of 5 FlexBags/carton:

Carton NDC                FlexBag NDC             FlexBags            Fill Size          Grams Protein 68516-5216-9              68516-5216-7             5                         50 mL             12.5 g 68516-5216-0              68516-5216-8             5                         100 mL           25 g

Storage

ALBUTEIN FlexBag 25%, in flexible container, is stable for two years provided the storage temperature does not exceed 30 °C.  Protect from freezing.  Keep the overwrap intact.

17 Patient Counseling Information

This product is usually given in a hospital setting.

Inform patients being treated with ALBUTEIN 25% about the risks and benefits of its use [see Adverse Reactions (6)].

Inform patients to immediately report the following signs and symptoms to their physician:

• Allergic or anaphylactic type reactions [see Warnings and Precautions (5.1)].
• Cardiovascular overload (e.g., headache, dyspnea and jugular venous distention) [see Warnings and Precautions (5.2)].
• Increased blood pressure, raised venous pressure and pulmonary edema [see Warnings and Precautions (5.2)].

Inform patients that ALBUTEIN 25% is a derivative of human plasma and may contain infectious agents that cause disease (e.g., viruses, and theoretically, the CJD agent). Inform patients that the risk that ALBUTEIN 25% may transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing the donated plasma for certain viral agents and by the introduction of steps with capacity for the inactivation and/or removal of certain viruses during the manufacturing process [see Warnings and Precautions (5.8)].

Manufactured by: Grifols Biologicals LLC 5555 Valley BoulevardLos Angeles, CA 90032, U.S.A.U. S. License No. 1694 3063685