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  5. Label Information: Human Albumin Grifols

FDA Label for Human Albumin Grifols

View Indications, Usage & Precautions

Table of Contents

    1. 1.1 HYPOVOLEMIA
    2. 1.2 CARDIOPULMONARY BYPASS PROCEDURES (TREATMENT ADJUNCT)
    3. 1.3 ACUTE NEPHROSIS (TREATMENT ADJUNCT)
    4. 1.4 HYPOALBUMINEMIA
    5. 1.5 OVARIAN HYPERSTIMULATION SYNDROME
    6. 1.6 NEONATAL HYPERBILIRUBINEMIA
    7. 1.7 ADULT RESPIRATORY DISTRESS SYNDROME (ARDS) (TREATMENT ADJUNCT)
    8. 1.8 PREVENTION OF CENTRAL VOLUME DEPLETION AFTER PARACENTESIS DUE TO CIRRHOTIC ASCITES (TREATMENT ADJUNCT)
    9. 2 DOSAGE AND ADMINISTRATION
    10. 2.1 DOSAGE
    11. 2.2 ADMINISTRATION
    12. 3 DOSAGE FORMS AND STRENGTHS
    13. 4 CONTRAINDICATIONS
    14. 5.1 HYPERSENSITIVITY
    15. 5.2 HYPERVOLEMIA/HEMODILUTION
    16. 5.3 DEHYDRATION
    17. 5.4 ELECTROLYTE IMBALANCE
    18. 5.5 COAGULATION ABNORMALITIES
    19. 5.6 LABORATORY MONITORING
    20. 5.7 APPLICATION PRECAUTIONS
    21. 5.8 TRANSMISSIBLE INFECTIOUS AGENTS
    22. 6 ADVERSE REACTIONS
    23. 6.1 CLINICAL TRIALS EXPERIENCE
    24. 6.2 POST-MARKETING EXPERIENCE
    25. 7 DRUG INTERACTIONS
    26. 8.1 PREGNANCY
    27. 8.2 LABOR AND DELIVERY
    28. 8.3 NURSING MOTHERS
    29. 8.4 PEDIATRIC USE
    30. 8.5 GERIATRIC USE
    31. 11 DESCRIPTION
    32. 12.1 MECHANISM OF ACTION
    33. 12.3 PHARMACOKINETICS
    34. 15 REFERENCES
    35. 16 HOW SUPPLIED/STORAGE AND HANDLING
    36. 17 PATIENT COUNSELING INFORMATION
    37. PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Human Albumin Grifols Product Label

The following document was submitted to the FDA by the labeler of this product Grifols Usa, Llc. The document includes published materials associated whith this product with the essential scientific information about this product as well as other prescribing information. Product labels may durg indications and usage, generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, warnings, inactive ingredients, etc.

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. Human Albumin Grifols® 20% can be used in such cases.1

Human Albumin Grifols 20% 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)



Human Albumin Grifols 20% 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



Human Albumin Grifols 20% 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 Human Albumin Grifols 20% 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 Human Albumin Grifols 20% 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, Human Albumin Grifols 20% 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



Human Albumin Grifols 20% 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



Human Albumin Grifols 20% 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)



Human Albumin Grifols 20% 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)



Human Albumin Grifols 20% 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


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.

IndicationDose
HypovolemiaAdults: Initial dose of 20 g.
If hemodynamic stability is not achieved within 15 to 30 minutes, an additional dose may be given.
Hemodilution may follow administration of Human Albumin Grifols 20%.
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 min is usually indicated.
For renal dialysis, the initial dose should not exceed 20 g and patients should be carefully observed for signs of fluid overload.
Cardiopulmonary bypass proceduresAdults: Initial dose of 25 g. Additional amounts may be administered as clinically indicated.
Acute nephrosisAdults: 25 g together with diuretic once a day for 7 - 10 days.
HypoalbuminemiaAdults: 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: 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 syndromeAdults: 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 hyperbilirubinemia1 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 ascitesAdults: 8 g for every 1000 mL of ascitic fluid removed.

2.2 Administration



Intravenous use only

  • Human Albumin Grifols 20% is a clear and slightly viscous solution. Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if the solution is turbid or if there is sediment in the bottle.
  • Do not freeze.
  • Warm product to room temperature before use if large volumes are administered.
  • Human Albumin Grifols 20% contains no preservatives. Do not begin administration more than 4 hours after the container has been entered. Discard unused portion.
  • Do not dilute with sterile water for injection. The product can be diluted in an isotonic solution (e.g., 5% Dextrose in Water or 0.9% sodium chloride) [see Warnings and Precautions (5.7)].
  • Adjust the infusion rate to the individual circumstances and the indication.

3 Dosage Forms And Strengths



Human Albumin Grifols 20% is a solution containing 200 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.

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 20% is approximately four 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 Human Albumin Grifols 20%; 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



Human Albumin Grifols 20% 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. 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 Human Albumin Grifols 20%.


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 Human Albumin Grifols 20% 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.


6.1 Clinical Trials Experience



No clinical studies were done using Human Albumin Grifols 20%.


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 Human Albumin Grifols (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



Human Albumin Grifols 20% must not be mixed with other medicinal products.


8.1 Pregnancy



Pregnancy Category C. Animal reproduction studies have not been conducted with Human Albumin Grifols 20%. It is also not known whether Human Albumin Grifols 20% can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Human Albumin Grifols 20% should be given to a pregnant woman only if clearly needed.


8.2 Labor And Delivery



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


8.3 Nursing Mothers



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


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



Human Albumin Grifols 20% is a sterile aqueous solution for single dose intravenous administration containing 20% human albumin (weight/volume). Human Albumin Grifols 20% 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 20% is approximately four times that of normal human plasma.

A liter of Human Albumin Grifols 20% solution contains 130 - 160 milliequivalents of sodium ion. The aluminium content of the solution is not more than 200 micrograms per liter during the shelf life of the product. The product contains no preservatives.

Human Albumin Grifols 20% is manufactured from Source Plasma collected from FDA approved plasmapheresis centers in the United States. Human Albumin Grifols 20% is heated at 60 °C for ten hours against the possibility of transmitting viruses.


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 20% 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, J.L., "Albumin: 1. Background and Use, 2. Guidelines for Clinical Use". JAMA 237; 355-360, 460-463, 1977.
  • 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



Human Albumin Grifols 20% is supplied in single-use, individually laser etched vials.

The following vial sizes of Human Albumin Grifols 20% are available:

NDC Number    Fill Size    Grams Protein
61953-0001-1    50 mL       10 g
61953-0001-2    100 mL     20 g

Each vial has an integral suspension band and a label with a peel-off strip showing the product name and lot number.

Human Albumin Grifols 20% is stable for three years provided the storage temperature does not exceed 30 °C. Protect from freezing.


17 Patient Counseling Information



This product is usually given in a hospital setting.

Inform patients being treated with Human Albumin Grifols 20% 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 Human Albumin Grifols 20% 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 Human Albumin Grifols 20% 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 inactivation and/or removal of certain viruses during the manufacturing process [see Warnings and Precautions (5.8)].

    Manufactured by:
    Instituto Grifols, S.A.
    Barcelona, Spain
    U.S. License No. 1181


Package Label.Principal Display Panel



Principal Display Panel – 50 mL Vial

NDC 61953-0001-3

Albumin (Human) U.S.P. Human Albumin Grifols® 20%

10.0 g 50 mL Rx only.
Dosage and directions for administration, see package insert.
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.

Manufactured by Instituto Grifols, S.A. Barcelona – SPAIN U.S. License No. 1181

Principal Display Panel – 50 mL Carton

GRIFOLS

NDC 61953-0001-1

Albumin (Human)
U.S.P.
Human Albumin
Grifols®

20% Solution
10.0 g 50 mL

DO NOT USE IF TURBID.
DO NOT BEGIN ADMINISTRATION
MORE THAN 4 HOURS AFTER
THE CONTAINER HAS
BEEN ENTERED.

Principal Display Panel – 100 mL Vial

GRIFOLS

NDC 61953-0001-4

Albumin (Human) U.S.P. Human Albumin Grifols® 20% 100 mL

20 g 100 mL Rx only.
CONTENTS: Each 100 mL contains 20 grams Albumin (Human) in aqueous diluent.
Osmotically equivalent to 400 mL of plasma. Sodium range 130-160 milliequivalents per liter.
Dosage and directions for administration, see package insert.
Contains no preservatives. 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.

Manufactured by Instituto Grifols, S.A. Barcelona – SPAIN, U.S. License No. 1181

Principal Display Panel – 100 mL Carton

GRIFOLS

NDC 61953-0001-2

Albumin (Human)
U.S.P.
Human Albumin
Grifols®

20% Solution
20 g 100 mL

DO NOT USE IF TURBID.
DO NOT BEGIN
ADMINISTRATION MORE
THAN 4 HOURS AFTER
THE CONTAINER HAS
BEEN ENTERED.


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