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

2.1 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

• 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.

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%.

6.1 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

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.

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.