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

2.1 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.

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.

1. After checking that protective overwrap is not damaged, remove it by tearing the slots at either end (refer to Figure 1).
   
   
2. Suspend the inner bag from the eyelet support (refer to Figure 2).
   
   
3. 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).
   
   
4. 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.
   
   
   
   
   

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%.

6.1 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

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

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

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.