ALBUMIN (HUMAN)
25% SOLUTION (Baxter Healthcare)


Description

Albumin (Human) 25% is a sterile aqueous solution for intravenous use, mainly containing the albumin component of human plasma. The effective oncotic pressure of the 25% solution largely depends on its albumin content and is approximately five times that of human plasma. Sodium bicarbonate is used to adjust the pH to 6.9 ± 0.5. The sodium content of the solution ranges between 130 and 160 meq/L. 0.08 millimole sodium caprylate and 0.08 millimole sodium N-acetyltryptophanate per gram albumin are added as stabilizers or prevent denaturation during heating. The solution is heat-treated at 60°C for 10 hours for inactivation of hepatitis viruses.

Clinical Pharmacology

Albumin is a very soluble, globular protein (MW 66,500) accounting for 70-80% of the colloid osmotic pressure of plasma which is the predominant reason for its clinical use. The rationale for this is the Starling concept of the capillary balance of hydrostatic and oncotic pressure gradients across the capillary walls as the determinant of the fluid - i.e., volume - distribution between the intravascular and the interstitial compartments (12). Albumin is distributed throughout the extracellular water; 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 half life of 15-20 days in the circulation (2,8), with a turnover of approximately 15 g per day.

When injected intravenously, Albumin (Human) 25% will draw approximately 3.5 times its volume of additional fluid into the circulation within 15 minutes, if the recipient is adequately hydrated. The additional fluid will reduce the hemoconcentration and decrease blood viscosity. The degree and duration of volume expansion depends upon the initial blood volume. In patients with diminished blood volume, the effect of infused Albumin (Human) may persist many hours. The hemodilution lasts for a much shorter time when Albumin (Human) is administered to individuals with normal blood volume. The minimum plasma albumin level necessary to prevent or reverse peripheral edema is unknown. Although it varies from patient to patient, there is some evidence that it is approximately 2.5 g/dL. This concentration provides a plasma oncotic pressure of 20 mm Hg (the equivalent of a total protein concentration of 5.2 g/dL).

Albumin is a transport protein which binds naturally occurring therapeutic and toxic materials in the circulation. The binding properties of albumin may provide an indication for its use in severe hemolytic disease of the newborn, where it may lower the plasma concentration of free bilirubin pending or in conjunction with an exchange transfusion (14). This effect may also be relevant in certain cases of acute liver failure with rapidly increasing levels of serum bilirubin, particularly in the presence of severe hypoproteinemia.

Albumin (Human) 25% offers minimal risk of hemorrhagic diathesis or blockage of the reticuloendothelial system. It does not impair coagulation or platelet function. Antibodies, including isoagglutinins, have been removed, thus enabling the product to be used without regard to the patient's blood group or blood factors.

Indications and Usage

General Principles

The two main indications for the use of Albumin (Human) 25% - are a plasma or blood volume deficit and the oncotic deficit resulting from hypoproteinemia.

Volume Deficit

Since the oncotic pressure of Albumin (Human) 25% solution is about five times that of normal human serum, it will expand the plasma volume if interstitial water is available for an inflow through the capillary walls. However, many patients suffering from an acute volume deficit also have some degree of interstitial dehydration. In the absence of overhydration, the treatment of an acute volume deficit with Albumin (Human) 25% should, therefore, include isotonic electrolyte solutions with an albumin: electrolyte ratio of 1:3 or 1:4. By contrast, chronic volume deficits have usually been at least partially compensated for by the renal retention of sodium and water with some degree of tissue edema, and in these circumstances a trial with Albumin (Human) 25% only is indicated.

Oncotic Deficit

The common causes of hypoproteinemia are protein-calorie malnutrition, defective absorption in gastrointestinal disorders, faulty albumin synthesis (e.g., in chronic hepatic failure), increased protein catabolism after operation or in sepsis, and abnormal renal losses of albumin in chronic kidney disease. In these situations, the circulating plasma volume is usually maintained by the renal retention of sodium and water, but this is associated with tissue edema and an oncotic deficit. Though relief of the underlying pathology is the definitive therapy for the restoration of the plasma protein level, this process takes time to become effective and the rapid correction of an oncotic deficit by the administration of Albumin (Human) 25%, possibly in conjunction with a diuretic, may be indicated.

It is emphasized that whereas Albumin (Human) may be necessary to prevent or treat the aforementioned acute complication of hypoproteinemia, it is NOT indicated for treatment of the chronic condition itself.

SPECIFIC INDICATIONS

Acute Circumstances In Which

Albumin (Human) 25%

Use Is Usually Appropriate:

Shock

The definitive treatment of major hemorrhage is the transfusion of red blood cells restoring a normal oxygen transport capacity of the blood. However, the life-threatening event in major hemorrhage is the loss of blood volume and not the erythrocyte deficit. Therefore, the blood volume should, as an emergency measure, be supported by Albumin (Human) 5% or another rapidly acting plasma substitute if blood is not immediately available. This will restore cardiac output and abolish circulatory failure with tissue anoxia. If Albumin (Human) 5% is not available, Albumin (Human) 5% can be prepared by diluting Albumin (Human) 25% with 4 volumes of an appropriate electrolyte solution, such as Ringer's lactate. Alternatively, the two solutions may be administered concurrently. If the patient is severely dehydrated, additional electrolyte solutions may be required.

Burns

An optimal regimen for the use of Albumin (Human), electrolytes, and water in the treatment of burns has not been established. Therapy during the first 24 hours after a severe burn is usually directed at the administration of crystalloid solutions in order to maintain an adequate plasma volume. For continuation of therapy beyond 24 hours, larger amounts of Albumin (Human) and lesser amounts of crystalloid are generally used (14).

Adult Respiratory Distress Syndrome

Several factors are usually involved in the development of the state now commonly called the adult respiratory distress syndrome, one of these being a hypoproteinemic fluid overload. In its initial phase, this may be corrected by the use of Albumin (Human) 25% and a diuretic (11, 14) along with careful hemodynamic and respiratory monitoring of the patient. It must be recognized, however, that the beneficial effects of Albumin (Human) in this condition depend on the integrity of the pulmonary microvasculature. Increased permeability to albumin can negate these beneficial effects, and in such circumstances Albumin (Human) could actually contribute to the respiratory distress.

Cardiopulmonary Bypass

An adequate blood volume during cardiopulmonary bypass can be maintained with crystalloids or colloids (albumin). A commonly employed program is an Albumin (Human) and crystalloid pump prime adjusted so as to achieve a hematocrit of 20% and a plasma albumin level of 2.5 g/100 mL in the patient, but the level to which either may be lowered safely has not yet bet been defined (14).

Hemolytic Disease of the Newborn

Albumin (Human) 25% may be indicated in order to bind and thus detoxify free serum bilirubin in severely hemolytic infants pending an exchange transfusion (14). Caution is recommended in hypervolemic infants.

Acute Nephrosis

Patients with acute nephrosis may prove refractory to cyclophosphamide or steroid therapy and their edema may even be aggravated initially by steroids. In such cases, a response may be elicited by combining Albumin (Human) 25% with an appropriate diuretic, after which the patient may react satisfactorily to drug therapy (14).

Circumstances In Which Albumin (Human) 25% Is Usually Not Justified:

Postoperative Hypoproteinemia

Intraoperative damage of capillary walls, e.g., by blunt dissection, leads to substantial losses of circulating albumin over and above those due to bleeding. However, this redistribution of albumin in the body rarely causes clinically significant hypovolemia, and treatment of the resultant plasma oncotic defect with Albumin (Human) 25% is not usually indicated.

Red Cell Resuspension Media

As a rule, the use of Albumin (Human) for resuspending red cells can be dispensed with. However, in exceptional circumstances such as certain types of exchange transfusions and the use of very large volumes of erythrocyte concentrates and frozen or washed red cells, the addition of Albumin (Human) to the resuspension medium may be indicated in order to provide sufficient volume and/or avoid excessive hypoproteinemia during the subsequent transfusion. If necessary, 20-25 g or more of albumin per liter of red cells should be added as a concentrated solution to the isotonic electrolyte suspension of erythrocytes immediately before transfusion.

Renal Dialysis

Patients undergoing long-term hemodialysis may need Albumin (Human) for the treatment of a volume or an oncotic deficit. The patients should be carefully observed for signs of a circulatory overload to which they are particularly sensitive.

Acute Liver Failure

In acute liver failure, Albumin (Human) may serve the triple purpose of stabilizing the circulation, correcting an oncotic deficit and binding excessive serum bilirubin. The therapeutic approach is guided by the individual circumstances (14).

Ascites

The use of Albumin (Human) for blood volume support may be indicated if circulatory instability follows the withdrawal of large amounts (>1500 mL) of ascitic fluid.

Third Space Problems of Infectious Origin

The sequestration of protein-rich fluid during acute peritonitis, pancreatitis, mediastinitis or extensive cellulitis will very rarely be of sufficient magnitude to require the treatment of a volume of an oncotic deficit with Albumin (Human)(1).

There is no valid reason for the use of Albumin (Human) as an intravenous nutrient.

Contraindications

The use of Albumin (Human) is contraindicated in patients with a history of an incompatibility reaction to such preparations (see Adverse Reactions ). In addition, the Albumin (Human) may be contraindicated in patients with cardiac failure, pulmonary edema or severe anemia because of the risk of acute circulatory overload. Also, Albumin (Human) has been reported to contain trace amounts of aluminum (5,6). Accumulations of aluminum in patients with chronic renal insufficiencies has led to toxic manifestations such as hypercalcemia, vitamin D-refractory osteodystrophy, anemia, and severe progressive encephalopathy (6,7,15). Therefore, when large volumes of Albumin (Human) are contemplated for administration to such patients, serious consideration of these potential risks relative to the anticipated benefits should be given.

Warnings

Albumin (Human) is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. ALL infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to our U.S. distributor at (800) 423-2862. The physician should discuss the risks and benefits of this product with the patient.

THERE EXISTS A RISK OF POTENTIALLY FATAL HEMOLYSIS AND ACUTE RENAL FAILURE FROM THE INAPPROPRIATE USE OF STERILE WATER-FOR-INJECTION AS A DILUENT FOR ALBUMIN (HUMAN) 25%. ACCEPTABLE DILUENTS INCLUDE 0.9% SODIUM CHLORIDE OR 5% DEXTROSE IN WATER.

ALBUMIN (HUMAN) 25% MUST NOT BE USED IF THE SOLUTION IS TURBID.

ALBUMIN (HUMAN) 25% MUST BE INFUSED IMMEDIATELY AND WITHOUT INTERRUPTION AFTER PERFORATION OF THE R/C BOTTLE. DO NOT BEGIN ADMINISTRATION MORE THAN 4 HOURS AFTER THE CONTAINER HAS BEEN ENTERED. PARTIALLY USED BOTTLES MUST BE DISCARDED.

ALBUMIN (HUMAN) 25% MUST NOT BE GIVEN THROUGH INFUSION SETS WHICH HAVE ALREADY BEEN USED OR ARE INTENDED FOR SIMULTANEOUS INFUSION OF PROTEIN HYDROLYSATE OR SOLUTIONS CONTAINING ALCOHOL.

Precautions

Adequate precautions should be taken against circulatory overload; this can be done, for example, by the measurement of the pulmonary wedge pressure. Special caution is indicated in patients with stabilized chronic anemia or renal insufficiency. 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 blood pressure.

Certain components used in the packaging of this product contain natural rubber latex.

PREGNANCY CATEGORY C. Albumin (Human) 25% - Animal reproduction studies have not been conducted with Albumin (Human) 25%. It is also not known whether Albumin (Human) 25% can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Albumin (Human) 25% should be given to a pregnant woman only if clearly needed.

Adverse Reactions

Though very rare, adverse reactions such as chills, fever, tachycardia, hypotension, urticaria, skin rash and nausea may occur (4,9,10,13).

The symptoms may disappear if the infusion is slowed or stopped for a short period of time. If necessary, the intravenous administration of 50 to 200 mg of prednisolone may be useful (10).

Dosage and Administration

The dosage of Albumin (Human) 25% is based on the principles outlined in the section of Indications and Usage but should always be adapted to the individual situation. The quantities required may be underestimated because of hidden extravascular deficits, and the effect of Albumin (Human) infusion on the serum protein level should, therefore, be checked by laboratory analysis.

The appropriate Albumin (Human) 25% dose for the treatment of a volume deficit should be estimated from the recipient's hemodynamic response (3) and precautions taken to safeguard against circulatory overload. In the absence of active hemorrhage, the total dose should not exceed the normal circulating albumin mass, i.e., 2 g per kg body weight.

Patients with acute nephrosis may respond to a combination of 100 mL of Albumin (Human) 25% and an appropriate diuretic, repeated daily for about one week. For hemolytic disease of the newborn, the dosage is 4 mL of Albumin (Human) 25% /kg body mass, to be given about one hour prior to ordering exchange transfusion. If Albumin (Human) is considered necessary for a renal dialysis patient, the initial dose should not exceed 100 mL of the 25% solution.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

To prepare Albumin (Human) 25% for administration, remove outer seal to expose central portion of rubber stopper and cleanse stopper with germicidal solution before use in syringes. Follow directions for use if the solution is administered by an intravenous injection set.

Albumin (Human) 25% must be administered INTRAVENOUSLY. The venipuncture site should not be infected or traumatized, and should be prepared with standard aseptic technique. The solution is compatible with whole blood or packed red cells as well as the usual electrolyte and carbohydrate solutions intended for intravenous use. By contrast, it should not be mixed with protein hydrolysates, amino acid mixtures, or solutions containing alcohol. It is ready for use as contained in the bottle and may be given without regard to the blood group of the recipient.

Only clear solutions of a light yellowish or amber color should be administered.

How Supplied

Puncture vial containing 20 mL of Albumin (Human) 25%.

Puncture vial containing 50 mL of Albumin (Human) 25%.

Puncture vial containing 100 mL of Albumin (Human) 25%.

The package may be supplied with an intravenous injection set.

STORAGE

Albumin (Human) 25% can be stored for 3 years at a temperature not exceeding 30°C (86°F).

Protect from freezing.

References

  1. CLOWES, G.H.A., Jr., VUCINIC, M., and WEIDNER, M.G.: Ann. Surg. 163, 866 (1966). 
  2. JANEWAY, C.A.: In: Sgouris, J.T. and Rene A. (eds.): Proceedings of the Workshop on Albumin, DHEW Publication No. (NIH) 76-925, U.S. Government Printing Office, Washington, D.C., p. 3-21 (1976). 
  3. KINNEY, J.M., EGDAHL, R.H., and ZUIDEMA, G.D.: Manual of Preoperative and Postoperative Care, American College of Surgeons, W.B. Saunders Co., Philadelphia (1971). 
  4. LOWENSTEIN, E. In: Sgouris, J.T. and Rene A. (eds.): Proceedings of the Workshop on Albumin, DHEW Publication No. (NIH) 76-925, U.S. Government Printing Office, Washington, D.C., p. 302 (1976). 
  5. MAHARAJ, D., FELL, G.S., BOYCE, B.F., NG, J.P., SMITHE, G.D., BOULTON-JONES, J.M., CUMMING, R.L., and DAVIDSON, J.F.: Brit. Med. J. 295, 693-696 (1987). 
  6. MILLINER, D.S., SHINABERGER, J.H., SHUMAN, P., and COBURN, J.W.: N. Engl. J. Med. 312, 165-167 (1985). 
  7. OTT, S.M., MALONEY, N.A., KLEIN, G.L., ALFREY, A.C., AMENT, M.E., COBURN, J.W., and SHERRAND, D.J.: Ann. of Inter. Med. 98, 910-914 (1983). 
  8. PETERS, T., Jr., In: Putnam, F.W. (ed.): Plasma Proteins, 2nd Edition, Vol. 1, Academic Press, New York, p. 133-181 (1975). 
  9. RING, J. and MESSMER, K.: Lancet 1, 466 (1977). 
  10. RING, J., SEIFERT, J., LOB, G., COULIN, K., and BRENDEL, W.: W. Klin, Wschr. 52, 595 (1974).
  11. SKILLMAN, J.J., PARIKH, B.M., and TANENBAUM, B.J.: Amer. J. Surg. 119, 440 (1970).
  12. STARLING, E.H.: J. Physiol. (London) 19, 312 (1896).
  13. TULLIS, J.L.: J.A.M.A. 237, 355 (1977).
  14. TULLIS, J.L.: J.A.M.A. 237, 460 (1977).
  15. WILLIS, M.R., and SAVORY, J.A.: Lancet 2, 29-34 (1983).

IMMUNO-U.S., INC.

1200 Parkdale Road

Rochester, MI 48307 USA

Distributed in Canada By:

IMMUNO (Canada) LTD.

U.S. License No. 850         Canadian License No. 227

Rev. July, 1998

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