Consumer medicine information

Albumex 4

Albumin, human

BRAND INFORMATION

Brand name

Albumex 4

Active ingredient

Albumin, human

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Albumex 4.

What is in this leaflet

This leaflet answers some common questions about Albumex® 4. It does not contain all the available information about Albumex® 4. It does not take the place of talking to your doctor.

All medicines have benefits and risks. Your doctor has weighed the benefits that Albumex® 4 will have for you against the risks.

If you have any concerns about using this medicine, ask your doctor. Follow your doctor’s advice even if it is different from what this leaflet says.

Please read this leaflet carefully and keep it for future reference.

The information in this leaflet is subject to change. Please check with your doctor whether there is any new information about this medicine that you should know since you were last treated.

What Albumex® 4 is used for

Albumex® 4 may be used:

  • when the blood volume is low (hypovolaemia)
  • during heart-lung bypass surgery
  • in procedures where the patient’s plasma is replaced (plasma exchange).

Acute loss of blood or plasma (plasma is the non-cellular part of the blood) may occur due to trauma, after heart-lung bypass surgery, and in patients with multiple organ failure or leaky small blood vessels.

The main functions of Albumex® 4 are to replace and retain fluid in the blood vessels, and to carry other chemicals through the blood stream.

Ask your doctor if you have any questions about why Albumex® 4 has been prescribed for you.

Before you are given Albumex® 4

When you must not take it

Do not take Albumex® 4 if you are allergic to:

  • human albumin
  • any of the ingredients listed at the end of this leaflet.

Before you are given it

Tell your doctor if you:

  • are allergic to any other food or medicine
  • have any other medical conditions such as a history of heart or kidney disease, low blood pressure, breathing difficulties, decreased number of red blood cells (anaemia) or a tendency to bleed or bruise easily
  • are taking or using any other medicines. These include medicines bought from pharmacies, supermarkets and health food stores.
  • are pregnant or breast-feeding.

If you want further information, consult your doctor.

About blood products

Albumex® 4 is manufactured from human plasma (the liquid component of blood) collected by Australian Red Cross Lifeblood. When medicines are made from human blood and injected into you, it is possible that viruses or other substances could be present in the medicine and cause an illness. These could be viruses such as hepatitis, human immunodeficiency virus (HIV), or parvovirus B19 and theoretically the Creutzfeldt-Jakob Disease (CJD) agent. There could also be other infectious agents, some of which may not yet have been discovered.

To reduce the risk of this happening, extra steps are taken when manufacturing this medicine. Strict controls are applied when selecting blood donors and donations. The medicine is specially treated to remove and kill certain viruses. This special treatment is considered effective against viruses known as enveloped viruses such as HIV, and hepatitis B and C viruses, and the non-enveloped virus, hepatitis A. This treatment also reduces the risk of parvovirus B19 exposure. Despite these measures, the risk of viral and other agent’s infectivity cannot be totally eliminated.

Vaccines are available against some of these viruses and your doctor will be able to help you decide whether it is worthwhile having any of those vaccines.

Please discuss the risks and benefits of this medicine with your doctor.

How to use Albumex® 4

Your doctor will be responsible for determining the dose(s) of Albumex® 4 that you are to receive, as appropriate for your condition. Your doctor will give you Albumex® 4 as an infusion, that is, an injection given slowly into the vein.

Side effects

Along with their intended effects, medicines may cause some unwanted side effects, which can sometimes be serious. Furthermore, individual patients may react differently to similar doses of the same medicine. This applies to Albumex® 4, although severe reactions during/after Albumex® 4 administration are rare. You may need medical treatment if you get some of the side effects.

Tell your doctor immediately if you notice any of the following symptoms which may be signs of a serious allergy or anaphylaxis, as the infusion of Albumex® 4 should be stopped:

  • feeling faint (fall in blood pressure)
  • irregular or faster heart beat
  • difficulty in breathing
  • reddening of the skin (flushing)
  • dizziness
  • rash
  • feeling sick.

Tell your doctor if you notice any of the following and they worry you:

  • nausea or vomiting
  • chills or fever
  • itching.

Some laboratory abnormalities have also been associated with albumin administration. Your doctor may take blood samples to closely monitor some important elements in your body.

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice any other effects during or after treatment with Albumex® 4.

Do not be alarmed by this list of possible side effects.

This medicine does not generally cause any undesired reactions.

Overdose

Administering a larger than recommended dose to patients with heart failure, certain kidney diseases and long-standing anaemia (decreased number of blood cells), or to patients on heart-lung bypass, may have harmful side effects. During treatment with Albumex® 4, such patients will be observed closely.

Storing Albumex® 4

Store below 30°C. This product must not be frozen. Protect from light. Do not use after the expiry date.

Further information

Albumex® 4 can only be obtained on a doctor’s prescription. This leaflet does not contain all the available information about Albumex® 4. If you need more information about Albumex® 4 and your treatment in general, or if you have any questions or are not sure about something in this leaflet, ask your doctor.

Product description

What it looks like

Albumex® 4 is a clear or slightly non-transparent, almost colourless, yellow, amber or green solution. It is available in glass bottles of 50 mL, 250 mL and 500 mL.

Ingredients

Each bottle of Albumex® 4 is a sterile solution containing human albumin.

  • The 50 mL bottle contains 2 g of human albumin;
  • the 250 mL bottle contains 10 g of human albumin;
  • the 500 mL bottle contains 20 g of human albumin.

Albumex® 4 also contains sodium chloride and sodium octanoate.

Manufacturer

Albumex® 4 is manufactured in Australia by:

CSL Behring (Australia) Pty Ltd
ABN 48 160 734 761
189-209 Camp Road
Broadmeadows VIC 3047
Australia

Distributor

Australian Red Cross Lifeblood

Date of revision

April 2020

Australian Register Numbers
50 mL: AUST R 59154
250 mL: AUST R 72895
500 mL: AUST R 59155

® Registered trademark of CSL Limited

Published by MIMS May 2020

BRAND INFORMATION

Brand name

Albumex 4

Active ingredient

Albumin, human

Schedule

Unscheduled

 

Notes

Distributed by Australian Red Cross Lifeblood

1 Name of Medicine

Human albumin.

6.7 Physicochemical Properties

CAS number.

9048-49-1.

2 Qualitative and Quantitative Composition

Human albumin 4% (40 g/L).
It is a sterile, preservative-free 4% w/v human albumin solution which is iso-oncotic with human serum. It has a nominal osmolality of 260 mOsm/kg, is approximately isotonic and the pH is 6.7 to 7.3.
Albumex 4 is manufactured from human plasma collected by Australian Red Cross Lifeblood. It is prepared using predominantly chromatographic techniques.

The nominal composition of Albumex 4 is as follows.

Human albumin 40 g/L;
Sodium 140 mmol/L;
Chloride 128 mmol/L;
Octanoate 6.4 mmol/L.
Albumex 4 also contains water for injections.

3 Pharmaceutical Form

Solution for intravenous infusion.
Albumex 4 is a clear, slightly viscous liquid; it is almost colourless, yellow, amber or green.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

The manufacturing process for Albumex 4 contains dedicated steps to reduce the possibility of virus transmission including pasteurisation (heating at 60°C for 10 hours) and incubation at low pH to inactivate viruses.

Mechanism of action.

Albumin accounts quantitatively for more than half of the total protein in the plasma and represents about 10% of the protein synthesis activity of the liver. The metabolic half-life of albumin in vivo is about 19 days and the turnover in an adult is approximately 15 g per day. There is rapid interchange of albumin between the intra- and extravascular spaces.
Albumex 4 has two main functions: maintenance of plasma colloid osmotic pressure and carriage of intermediate products in the transport and exchange of tissue metabolites.
The beneficial effect of human albumin for fluid resuscitation is thought to result principally from its contribution to colloid osmotic pressure (i.e. oncotic pressure).
Albumex 4 is iso-oncotic with human serum. When infused into adequately hydrated patients its effect is to expand the circulating blood volume by an amount approximately equal to the volume of Albumex 4 infused.

Clinical trials.

The saline versus albumin fluid evaluation study.

The Saline versus Albumin Fluid Evaluation (SAFE) study was conducted by the Australian and New Zealand Intensive Care Society Clinical Trials Group. This large multicentre, double blind, prospective randomised controlled trial was conducted to determine the effect of fluid resuscitation with either albumin or saline on mortality in a heterogeneous population of patients in the intensive care unit (ICU). The SAFE study randomised 6997 patients to receive either albumin 4% (Albumex 4 in blinded labelling, n = 3497) or saline (n = 3500). The two groups had similar baseline characteristics. No predetermined clinical margin of superiority or non-inferiority was made. The study was intended to detect a real mortality difference of at least 3% between the treatment groups, based on an enrolment of 7,000 patients and an estimated baseline mortality rate of 15%.
Randomisation was stratified at each centre when the patients were admitted to ICU to ensure that each institution treated equal numbers of patients for each treatment. Patients with burns or those requiring plasmapheresis and those patients admitted to ICU after cardiac bypass surgery and liver transplant were excluded from the study. The statistical results presented derived from an intention to treat analysis. The study was not explicitly a superiority study and no 'per protocol' analysis is available. It is not known to what extent the statistical results of a 'per protocol' analysis would agree with, or differ from, the results of the intention to treat analysis.
Death from any cause during the 28 days after randomisation was the primary outcome measure. There were 726/3473 (20.9%) deaths in the albumin group and 729/3460 (21.1%) deaths in the saline group (relative risk of death 0.99, 95% confidence interval 0.91 to 1.09, p = 0.87).
There were no statistically significant differences between the two groups in the secondary outcomes measured: mean (± SD) number of days spent in ICU (6.5 ± 6.6 in the albumin group and 6.2 ± 6.2 in the saline group, p = 0.44), days spent in hospital (15.3 ± 9.6 and 15.6 ± 9.6 respectively, p = 0.30), days of mechanical ventilation (4.5 ± 6.1 and 4.3 ± 5.7, respectively, p = 0.74) or days of renal replacement therapy (0.5 ± 2.3 and 0.4 ± 2.0, respectively, p = 0.41). The proportion of patients with new single or multiple organ failure was similar in the two groups (p = 0.85). There was no significant difference in survival times during the first 28 days between the two groups (p = 0.96).
On each of the first three study days, the patients who had been randomly assigned to receive albumin received less study fluid than did those assigned to saline, resulting in a greater net positive fluid balance in the saline group on each of those days. The ratios of the volume of albumin to the volume of saline administered during the first four days were as follows: 1:1.3 on day 1, 1:1.6 on day 2, 1:1.3 on day 3, and 1:1.2 on day 4. Overall during the first four days the study showed a ratio of 1.4:1 in the volume of saline used to compare albumin.
This study concluded that in a heterogeneous group of patients in the ICU, use of either 4% albumin or normal (0.9%) saline for fluid resuscitation results in similar mortality at 28 days. The trial did not examine the comparative safety of albumin use as an initial resuscitation fluid in pre-hospital, surgery or emergency department settings.
Predefined sub-group analyses were performed for patients with trauma, severe sepsis and acute respiratory distress syndrome as part of the SAFE study. There was a trend towards increased mortality in patients with trauma treated with albumin, which was due to a worse outcome in those patients with trauma and associated brain injury. Conversely, there was a trend towards a better outcome with albumin in patients with severe sepsis. Both these trends should be interpreted with caution. Specifically designed and appropriately powered studies are needed to establish whether these are real treatment effects or due to chance.
A post hoc, follow-up study of patients with traumatic brain injury enrolled in the SAFE study was published in 2007. This post hoc analysis found that, when comparing albumin with saline for intravascular fluid resuscitation in the ICU, higher mortality rates were observed among patients with severe traumatic brain injury (Glasgow Coma Score, 3 to 8) who received 4% albumin than among those who received saline. The authors note the study was designed post hoc, and some data were collected retrospectively. The authors add it remains possible that the results represent a chance subgroup finding and that the biologic mechanisms for the observed differences in mortality are unclear such that further detailed analyses of biologic mechanisms associated with intracranial hypertension are required.

5.2 Pharmacokinetic Properties

There is no specific pharmacokinetic information on Albumex 4. The general information provided is based on published data for albumin.

Distribution.

Under normal conditions, the total exchangeable albumin pool is 4-5 g/kg bodyweight, of which 40-45% is present intravascularly and 55-60% is in the extravascular space. Increased capillary permeability will alter albumin kinetics and abnormal distribution may occur in conditions such as severe burns or septic shock.

Excretion.

Under normal conditions, the average half-life of albumin is about 19 days. 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 on plasma volume. In some patients the plasma volume can remain increased for some hours. However, in critically ill patients, albumin can leak out of the vascular space in substantial amounts at an unpredictable rate.

5.3 Preclinical Safety Data

Genotoxicity.

No genotoxicity studies have been conducted with Albumex 4.

Carcinogenicity.

No carcinogenicity studies have been conducted with Albumex 4.

4 Clinical Particulars

4.1 Therapeutic Indications

Hypovolaemia/shock.

Preservation of an adequate circulating blood volume should be the primary aim of therapy. The initial resuscitating fluid should not be a human blood product, but rather an alternative plasma volume expander should be used as first-line replacement. Albumex 4 may, however, be the initial plasma expander of choice if shock is associated with significant hypoalbuminaemia (albumin concentration less than 25 g/L), or if it is clinically desirable to avoid the infusion of large volumes of crystalloid solutions.
Albumex 4 may also be useful following initial resuscitation with crystalloid or synthetic colloid solutions in patients in whom extended support of the intravascular volume is required, such as seriously ill patients with multiple organ failure or the systemic capillary leak syndrome.

Cardiopulmonary bypass.

Albumex 4 may be used for priming the pump for cardiopulmonary bypass surgery for patients with poor left ventricular function, and other complicating factors such as long bypass time, anaemia or repeat surgery. For post-operative hypovolaemia, Albumex 4 may be used if further colloid is required after a moderate amount of synthetic colloid (1-2 L) has been given, or there is ongoing bleeding or anaemia, until cross matched blood is available.

Plasma exchange.

Albumex 4 is indicated as a replacement solution in plasma exchange procedures, particularly when the volume exchanged exceeds 20 mL/kg body weight. In patients with thrombotic thrombocytopenic purpura, fresh frozen plasma may be a preferred replacement.

4.3 Contraindications

Albumex 4 must not be used if there is a history of allergy to this product. Albumin is contraindicated in patients with cardiac failure, pulmonary oedema or severe anaemia.

4.4 Special Warnings and Precautions for Use

Allergic reactions.

Hypersensitivity reactions occur rarely when human albumin solutions are administered because of the human origin of the product. Should an anaphylactic reaction to Albumex 4 develop, the infusion should be stopped and treatment instituted with adrenaline (epinephrine), hydrocortisone and antihistamines as appropriate.

Hypotension.

Hypotension has been associated with human albumin solutions. Hypotension following administration of albumin can aggravate myocardial depression when present in patients with shock.

Circulatory overload.

Patients with a history of cardiac failure or pulmonary oedema or who have renal insufficiency, severe or stabilised chronic anaemia or are on cardiopulmonary bypass are at special risk of developing circulatory overload if the dosage and rate of infusion are not adjusted to the patient's circulatory situation. Patients should be carefully monitored for this potential complication.
At the first clinical signs of circulatory overload (headache, dyspnoea, jugular vein congestion), or increased blood pressure or raised venous pressure associated with pulmonary oedema, the infusion is to be stopped immediately.
The rise in blood pressure which may follow rapid administration of albumin necessitates observation of the injured patient to detect bleeding points which failed to bleed at the lower blood pressure; otherwise, new haemorrhage and shock may occur.
The use of albumin for fluid resuscitation of patients with traumatic brain injury is not recommended.
Albumex 4 contains trace amounts of aluminium (≤ 200 microgram/L). Accumulation of aluminium in patients with chronic renal insufficiency has led to toxic manifestations such as hypercalcaemia, vitamin D-refractory osteodystrophy, anaemia and severe progressive encephalopathy. Therefore, when large volumes of albumin are contemplated for administration to such patients, serious consideration of these potential risks relative to the anticipated benefits should be given.

Pathogen safety.

This product is made from human plasma. Products made from human plasma may contain infectious agents such as viruses and, theoretically, Creutzfeldt-Jakob Disease (CJD) agents 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 infectious agents and by testing for the presence of certain viral markers.
In addition, virus inactivation/removal procedures are included in the manufacturing process. The current process and procedures applied in the manufacture of this product are effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), and the non-enveloped virus, hepatitis A virus (HAV). These procedures contribute significantly to ensure freedom from parvovirus B19.
Despite these measures, such products may still potentially transmit disease. There is also the possibility that other known or unknown infectious agents may be present in such products.
Vaccination for patients in receipt of medicinal products from human plasma should be considered where appropriate.

Use in the elderly.

There have been no specific clinical studies of Albumex 4 in the elderly.

Paediatric use.

There have been no specific clinical studies of Albumex 4 in children.

Effects on laboratory tests.

Albumin is an endogenous plasma protein so no specific effects on laboratory tests are anticipated. However, administration of Albumex 4 which may contain some bound bilirubin has been shown to result in elevated serum bilirubin in some patients.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Hypotension has been reported in patients given albumin who are on angiotensin converting enzyme (ACE) inhibitors. The addition of other medicines to Albumex 4 has not been evaluated (see Section 6.2 Incompatibilities).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No studies examining the effect of Albumex 4 on fertility have been conducted.
Reproductive toxicity studies with Albumex 4 in animals have not been conducted. Such studies are impracticable due to the development of antibodies to human albumin in animal models.
The use of Albumex 4 in human pregnancy has not been established in controlled clinical trials; therefore, it should be given to pregnant women only if clearly needed.
Like endogenous serum albumin, Albumex 4 may be excreted in milk. No safety information is available.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions to albumin solutions are uncommon and are usually mild and transient.
Adverse reactions with albumin solutions in general include hypotension, chills, fever and allergic reactions including anaphylaxis, urticaria, skin rashes, nausea, vomiting and increased salivation. Mild reactions such as mild hypotension, flushing, urticaria, fever, and nausea normally disappear rapidly when the infusion rate is slowed down or the infusion is stopped (see Section 4.2 Dose and Method of Administration, Monitoring advice).
Very rarely, severe allergic reactions such as anaphylactic shock may occur. In these cases, the infusion should be stopped and an appropriate treatment should be initiated (see Section 4.4 Special Warnings and Precautions for Use).

Adverse events in clinical trials.

Adverse reactions by body system from the SAFE study comparing albumin and saline are provided in Table 1.
In an earlier generation of Albumex, when used in plasma exchange, 1% (1/99) of patients had a clinically significant increase in prothrombin time and there was a reduction in levels of potassium, calcium, bicarbonate, total serum protein concentrations and platelet count. These results could reasonably be expected in a plasma exchange procedure.

Post-marketing surveillance.

Post-market reporting of adverse reactions is voluntary and from a population of uncertain size, and consequently it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.
Overall a low number of reports have been received for the current generation Albumex 4 which primarily involve hypotensive and allergic reactions. The main adverse reactions reported during routine surveillance for the current product are as follows: hypotension, tachycardia, flushing, dizziness, nausea, chills, pyrexia, dyspnoea, anaphylactoid/anaphylactic reaction, urticaria, pruritus and rash (pruritic, macular, generalised). True anaphylactic reactions occur rarely.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Dosage.

Hypovolaemia/shock.

The management of hypovolaemic shock usually requires the intravenous (IV) infusion of at least one litre of Albumex 4 into an average adult patient.
The total volume required cannot be accurately predicted, since it depends on such factors as the initial extracellular fluid volume deficit and the continuing rate of fluid loss.

Plasma exchange.

In plasma exchange the infusion rate should be adjusted to match the rate of removal.

Monitoring advice.

To avoid circulatory overload the rate and volume of infusion should be monitored frequently.
Myocardial function should also be monitored, e.g. central venous pressure, arterial pressure and pulse rate.
It is also recommended that plasma electrolytes, prothrombin time, biochemistry and haematological status be monitored.

Method of administration.

Caution.

Albumex 4 contains no antimicrobial preservative. It must, therefore, be used immediately after opening the bottle. Any unused solution should be discarded appropriately. Use in one patient on one occasion only.
Albumex 4 is normally clear or slightly opalescent. If it appears to be turbid by transmitted light, it must not be used and the bottle should be returned unopened to Australian Red Cross Lifeblood.
Albumex 4 should always be administered by intravenous infusion using appropriate IV administration equipment. Albumex 4 is packaged in a glass bottle that must be vented during use.
If the product has been stored in the refrigerator it should be allowed to reach room temperature before administration. Do not use if the solution has been frozen.
It is strongly recommended that every time Albumex 4 is administered to a patient, the name and batch number of the product be recorded in order to maintain a link between the patient and the batch of the product.

4.7 Effects on Ability to Drive and Use Machines

No effects on ability to drive and use machines have been observed. However, adverse effects of Albumex include dizziness which could affect the ability to drive or use machines (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.9 Overdose

Excess human albumin may lead to circulatory overload (see Section 4.4 Special Warnings and Precautions for Use).
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

Unscheduled.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

The addition of other drugs to Albumex 4 has not been evaluated.
Albumex 4 should not be mixed with protein hydrolysates, amino acid solutions, solutions containing alcohol, or solutions containing drugs that bind to albumin, e.g. calcium channel blockers, antibiotics and benzodiazepines.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C (Do not freeze). Protect from light. Do not use after the expiry date.

6.5 Nature and Contents of Container

Albumex 4 is issued in glass bottles in three sizes:
2 g of human albumin in 50 mL of electrolyte solution.
10 g of human albumin in 250 mL of electrolyte solution.
20 g of human albumin in 500 mL of electrolyte solution.
Albumex 4 is packaged in latex free materials.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes