Albumex 5/Albumex 20

Albumex 5/Albumex 20

human albumin

Manufacturer:

CSL Behring

Distributor:

HKRCBTS
Full Prescribing Info
Contents
Human albumin.
Description
The composition of Albumex 5/Albumex 20 are as follows: Human albumin 50 g/L and 200 g/L, sodium 140 mmol/L and 48-100 mmol/L, and octanoate 8 mmol/L and 32 mmol/L, respectively. Albumex 5 also contains chloride 125 mmol/L.
Albumex 5 and Albumex 20 are prepared from pooled human plasma donated by Hong Kong's voluntary non-remunerated donors. Both are a clear, slightly viscous liquid, almost colourless, yellow, amber or green. It is prepared using predominantly chromatographic techniques.
Albumex 5 is a 5% w/v protein solution which is iso-osmotic and iso-oncotic with human serum. It has a nominal osmolality of 260 mOsm/kg, is approximately isotonic and the pH is 6.7-7.3.
Albumex 20 is a 20% w/v protein solution, which is hyperoncotic with human serum and supplies the oncotic equivalence of approximately 4 times its volume of human plasma. It is hypo-osmotic compared to human serum. It has a nominal osmolality of 130 mOsm/kg, is hypotonic and the pH is approximately 7.
Both Albumex 5 and Albumex 20 are heated at 60°C for 10 hrs and incubated at low pH to inactivate viruses.
Action
Pharmacology: 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 (t½) of albumin in vivo is about 20 days and the turnover in an adult is approximately 15 g/day. There is rapid interchange of albumin between the intra- and extravascular spaces.
Albumex 5/Albumex 20 has 2 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 (ie, oncotic pressure).
Albumex 5 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 5 infused.
Albumex 20 is hyperoncotic with human serum and supplies the oncotic equivalence of approximately 4 times its volume of human plasma.
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 6,997 patients to receive either albumin 4% (Albumex 4 in blinded labelling, n=3,497) or saline (n=3,500). The 2 groups had similar baseline characteristics.
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. Death from any cause during 28 days after randomisation was the primary outcome measure. There were 726/3,473 (20.9%) deaths in the albumin group and 729/3,460 (21.1%) deaths in the saline group (relative risk of death 0.99, 95% confidence interval 0.91-1.09, p=0.87).
There were no statistically significant differences between the 2 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 the hospital (15.3±9.6 and 15.6±9.6, respectively, p=0.3), 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, respectively, p=0.41). The proportion of patients with new single or multiple organ failure was similar in the 2 groups (p=0.85). There was no significant difference in survival times during the first 28 days between the 2 groups (p=0.96).
This study concluded that in a heterogeneous group of patients in the ICU, the use of either albumin 4% or normal saline (0.9%) 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 prehospital, surgery or emergency department settings.
Predefined subgroup 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 3-8) who received albumin 4% 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.
Pharmacokinetics: There is no specific pharmacokinetic information on Albumex 5/Albumex 20. The general information provided is based on published data for albumin.
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 eg, severe burns or septic shock.
Under normal conditions, the average t½ 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, <10% of infused albumin leaves the intravascular compartment during the first 2 hrs following infusion. There is considerable individual variation in the effect of 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.
Indications/Uses
Albumex 5: 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 1st-line replacement. Albumex 5 may, however, be the initial plasma expander of choice if shock is associated with significant hypoalbuminaemia (albumin concentration <25 g/L), or if it is clinically desirable to avoid the infusion of large volumes of crystalloid solutions. Albumex 5 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 eg, seriously ill patients with multiple organ failure or the systemic capillary leak syndrome.
Cardiopulmonary Bypass: Albumex 5 may be used for priming the pump for cardiopulmonary bypass surgery for patients with poor left ventricular function, and other complicating factors eg, long bypass time, anaemia or repeat surgery. For postoperative hypovolaemia Albumex 5 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 5 is indicated as a replacement solution in plasma exchange procedures, particularly when the volume exchanged exceeds 20 mL/kg bodyweight. In patients with thrombotic thrombocytopenic purpura, fresh frozen plasma may be a preferred replacement.
Albumex 20: Hypoproteinaemia in the Acutely Ill Patient: Albumex 20 is administered when there are existing or anticipated clinical problems or complications from reduced oncotic pressure, and/or as an adjunct to diuretic therapy.
Shock: Albumex 20 may be used for the resuscitation of patients in shock due to acute loss of blood or plasma, but human albumin 5% is preferred when available.
Burns: Extensive burns are followed by sequential shifts in the distribution of body water, salt and proteins, resulting in hypovolaemic shock and circulatory failure.
Initially (during the first 24 hrs), there is an increased vascular permeability leading to loss of water and proteins into the extravascular compartment and haemoconcentration. Large volumes of crystalloid solutions should be infused to restore the constricted intravascular fluid space, and smaller amounts of Albumex 20 are required to maintain adequate plasma volume and colloid osmotic pressure.
Adult Respiratory Distress Syndrome: The clinical syndrome is characterised by inadequate oxygenation secondary to pulmonary interstitial oedema, complicating shock and postoperative states resulting in a decreased central venous pressure, decreased plasma albumin concentration, rising blood pressure, reduced cardiac output, lowered pulse rate and a falling renal output.
The acute condition can be controlled by diuretics and Albumex 20 in amounts sufficient to maintain vital signs.
In patients who have undergone abdominal surgery, the IV administration of albumin solution (20%) immediately after the operation has been shown to improve lung compliance and gaseous exchange.
Haemodialysis: Albumex 20 may be used to assist with the rapid removal of excess extravascular fluid and to maintain perfusion pressure.
Plasma Exchange: Therapeutic plasma exchange is a procedure in which approximately 1 plasma volume is exchanged with a colloid replacement solution. The choice of replacement fluid and its concentration are determined by the particular clinical situation and the frequency of the procedure.
Iso-oncotic albumin solution is the preferred replacement material. If the patient's serum albumin level is not maintained, concentrated albumin (20%) may be indicated. If exchange occurs less frequently than once a week, less concentrated colloids may be appropriate.
Dosage/Direction for Use
Albumex 5: Hypovolaemia/Shock: The management of hypovolaemic shock usually requires the IV infusion of at least Albumex 5 1 L 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: The infusion rate should be adjusted to match the rate of removal.
Albumex 20: Hypoproteinaemia in the Acutely Ill Patient: The usual daily dose is human albumin 50-75 g (Albumex 20 250-375 mL). The rate of administration should not exceed 2 mL/min, as more rapid infusion may precipitate circulatory overload and pulmonary oedema.
The infusion of Albumex 20 is not justified in hypoproteinaemic states associated with chronic cirrhosis, malabsorption, protein losing enteropathies, pancreatic insufficiency or undernutrition.
Shock: The dose should be determined by the patient's condition and response to treatment. The usual initial dose of human albumin 20 g (Albumex 20 100 mL) may be administered as a blood volume expander at a rate of 2-4 mL/min.
The rate of infusion may be increased in emergencies and repeated in 15-30 min, if necessary. The total dose should not exceed the level of albumin found in the normal individual ie, about 2 g/kg bodyweight in the absence of active bleeding.
If concentrated albumin (>5%) is given, it should be accompanied by the IV infusion of a crystalloid solution. Failure to supply this additional fluid may lead to dehydration of the tissues.
The precise nature and strength of the crystalloid solution will depend on the requirements of the patient for electrolytes and fluid.
Burns: The usual dose is human albumin 20-80 g (Albumex 20 100-400 mL) given daily at the rate of about 1 mL/min.
Beyond 24 hrs, Albumex 20 can be used to maintain plasma colloid osmotic pressure.
A reasonable goal is the maintenance of a plasma albumin concentration of 25 g/L or a colloid osmotic pressure of 20 mmHg. The continuing need for albumin is occasioned by losses from denuded areas and decreased albumin synthesis.
Acute Respiratory Distress Syndrome: Commence with a dose of human albumin 50 g (Albumex 20 250 mL) over the first 24 hrs together with diuretic therapy. Thereafter, the dose is adjusted to maintain vital signs, particularly central venous pressure, urine output and plasma albumin concentration.
Haemodialysis: Patients with significant fluid overload prior to dialysis may benefit from the administration of human albumin 20-40 g (Albumex 20 100-200 mL) at the end of the dialysis procedure.
Plasma Exchange: Replace albumin removed on a gram-for-gram basis eg, removal of plasma 2.5 L should be accompanied by replacement of human albumin 125 g (Albumex 20 625 mL), either prediluted or followed by 4-5 volumes of an appropriate crystalloid solution.
Administration: Should always be administered by IV infusion using appropriate IV administration equipment. Albumex 5/Albumex 20 is packaged in a glass bottle that must be vented during use.
Albumex 20: In some cases, a dose of albumin is added to a suitable crystalloid solution in the proportion of Albumex 20 1 mL to crystalloid solution 4 mL and administered by the usual IV technique.
Dilution of Concentrated Albumin 20%: If Albumex 20 is diluted to an iso-oncotic protein concentration (albumin 4-5%) prior to administration, this must be done with a crystalloid solution eg, saline 0.9%. Under no circumstances should water be used since the lower tonicity will lead to intravascular haemolysis.
Recommended Procedure: Remove the plastic cover from the seal.
Apply a suitable antiseptic to the exposed part of the rubber stopper and allow to dry.
Stand the bottle upright and insert the air vent needle vertically in 1 of the indentations of the stopper. It is preferable to use a long airway needle fitted with a filter. If not available, a short needle attached to a non-wettable filter may be used.
Clamp the tubing of the giving set and insert the perforator vertically through 1 of the other indentations of the stopper. Should the stopper become dislodged, do not use this bottle and discard the solution appropriately.
Invert the bottle and attach the hanger to a support approximately one metre above the patient.
Allow the tubing to fill by adjusting the clamp. Insert the giving set needle into a vein and adjust the rate of flow.
When the bottle is empty, clamp the tubing and transfer the air vent needle and the needle at the upper end of the giving set to a further bottle of Albumex 5/Albumex 20 or to a bottle containing a crystalloid solution, according to requirements.
Should leakage become evident during administration, cease the infusion and discard the solution appropriately. Recommence the infusion with a new bottle and giving set.
Overdosage
Excess human albumin may lead to circulatory overload (see Precautions).
Contraindications
History of allergy to Albumex 5/Albumex 20. Albumin is contraindicated in patients with cardiac failure, pulmonary oedema or severe anaemia.
Albumex 20: The infusion of Albumex 20 is not justified in hypoproteinaemic states associated with chronic cirrhosis, malabsorption, protein losing enteropathies, pancreatic insufficiency or undernutrition.
In chronic nephrosis, infused albumin solution (20%) is promptly excreted by the kidneys with no relief of the chronic oedema.
Special Precautions
Allergic Reactions: Hypersensitivity reactions occur rarely when human albumin solutions are administered because of the human origin of Albumex 5/Albumex 20. Should an anaphylactic reaction to Albumex 5/Albumex 20 develop, the infusion should be stopped and treatment instituted with adrenaline, hydrocortisone and antihistamines, as appropriate.
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.
When being infused with Albumex 5 they should be carefully monitored for this potential complication.
At the 1st clinical signs of cardiovascular 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.
In the presence of dehydration, as Albumex 20 is hyperoncotic, it must be given with or followed by crystalloid solution (see Dosage & Administration).
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.
In chronic nephrosis, infused albumin solution (20%) is promptly excreted by the kidneys with no relief of the chronic oedema.
Albumex 5/Albumex 20 contains trace elements of aluminium (≤200 mcg/L). Accumulation of aluminium in patients with chronic renal insufficiency has led to toxic manifestations eg, 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: Albumex 5/Albumex 20 is made from human plasma. Products made from human plasma may contain infectious agents eg, 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 Albumex 5/Albumex 20 are effective against enveloped viruses eg, human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), and the non-enveloped virus, hepatitis A (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.
Any case of infection associated with the use of Albumex 5/Albumex 20 should be reported to the Hong Kong Red Cross Blood Transfusion Service, together with details of batches given.
Albumex 5: Hypotension: It has been associated with human albumin solutions. Hypotension following administration of albumin can aggravate myocardial depression when present in patients with shock.
Albumex 20: The sodium levels in Albumex 20 are 48-100 mmol/L. This should be noted when Albumex 20 is used in patients requiring sodium restriction.
The colloid osmotic effect of Albumex 20 is approximately 4 times that of plasma and patients should always be monitored for symptoms of circulatory overload (see Monitoring Advice under Cautions for Usage).
Administration of albumin can aggravate myocardial depression when present in patients with shock. A paradoxical effect or refractory oliguria has been reported in burn patients receiving albumin, possibly because of insufficient accompanying crystalloids.
Carcinogenicity and Genotoxicity: Specific studies have not been conducted.
Impairment of Fertility: No studies examining the effect of Albumex 5/Albumex 20 have been conducted.
Use in pregnancy & lactation: Reproductive toxicity studies with Albumex 5/Albumex 20 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 5/Albumex 20 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 5/Albumex 20 may be excreted in milk. No safety information is available.
Use in children: There have been no specific clinical studies of Albumex 5/Albumex 20 in children.
Use in the elderly: There have been no specific clinical studies of Albumex 5/Albumex 20 in the elderly.
Use In Pregnancy & Lactation
Use in pregnancy & lactation: Reproductive toxicity studies with Albumex 5/Albumex 20 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 5/Albumex 20 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 5/Albumex 20 may be excreted in milk. No safety information is available.
Adverse Reactions
Adverse reactions to albumin solutions are uncommon and are usually mild and transient.
Adverse reactions reported with albumin solutions in general include hypotension, chills, fever, allergic reactions including anaphylaxis, urticaria, skin rashes, nausea, vomiting and increased salivation. Mild reactions eg, mild hypotension, flushing, urticaria, fever and nausea normally disappear rapidly when the infusion rate is slowed down or the infusion is stopped (see Monitoring Advice under Cautions for Usage).
Very rarely, severe reactions eg, anaphylactic shock may occur. In these cases, the infusion should be stopped and an appropriate treatment should be initiated.
Adverse Events in Clinical Trials: Although formal clinical studies with Albumex 20 have not been conducted to determine the frequency or severity of adverse events, results from studies with Albumex 4 and 5 (albumin 4% and 5% solutions, respectively) may be applicable.
Adverse reactions by body system from the SAFE study comparing albumin and saline are provided in the table. (See table.)

Click on icon to see table/diagram/image

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 from the current generation Albumex 4 (which may be applicable to Albumex 5) which primarily involve hypotensive and allergic reactions, and also chills and fever as with Albumex 20. The main adverse reactions reported during routine surveillance for Albumex 5/Albumex 20 are as follows: Hypotension, tachycardia, dyspnoea, flushing, dizziness, chills, pyrexia; Albumex 5: Nausea, anaphylactoid/anaphylactic reaction, urticaria, pruritus and rash (pruritic, macular, generalised); Albumex 20: Hypertension, decreased oxygen saturation and muscle spasms.
Although true anaphylactic reactions are believed to occur rarely, no reports of anaphylaxis have been received.
Drug Interactions
Interactions with Other Medicines: Hypotension has been reported in patients given albumin who are on angiotensin-converting enzyme (ACE) inhibitors. The addition of other drugs to Albumex 5/Albumex 20 has not been evaluated. (See Compatibility with Other Fluids.)
Effect on Laboratory Tests: Albumin is an endogenous plasma protein so no specific effects on laboratory tests are anticipated. However, administration of Albumex 5 which may contain some bound bilirubin has been shown to result in elevated serum bilirubin in some patients.
Compatibility with Other Fluids: The addition of other drugs to Albumex 5/Albumex 20 has not been evaluated.
Albumex 5/Albumex 20 should not be mixed with protein hydrolysates, amino acid solutions, solutions containing alcohol or solutions containing drugs that bind to albumin eg, calcium-channel blockers, antibiotics and benzodiazepines.
Caution For Usage
Albumex 5/Albumex 20 does not contain an antimicrobial preservative. It must, therefore, be used immediately after opening the bottle. Any unused solution should be discarded appropriately. Use in 1 patient on 1 occasion only.
It is strongly recommended that every time Albumex 5/Albumex 20 is administered to a patient, the name and batch number be recorded in order to maintain a link between the patient and the batch of Albumex 5/Albumex 20.
If Albumex 5/Albumex 20 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.
Albumex 5/Albumex 20 is normally clear or slightly opalescent, but if it appears to be turbid by transmitted light, it must not be used and the bottle should be returned unopened to the Hong Kong Red Cross Blood Transfusion Service.
Monitoring Advice: It is recommended that blood pressure is monitored during administration of Albumex 20.
Albumex 5/Albumex 20: To avoid circulatory overload, the rate and volume of infusion should be monitored frequently.
Myocardial function should also be monitored eg, central venous pressure, arterial pressure and pulse rate.
It is also recommended that plasma electrolytes, prothrombin time, biochemistry and haematological status should be monitored.
Do not use after expiry date.
Storage
Store below 30°C. Albumex 5/Albumex 20 must not be frozen. Protect from light.
ATC Classification
B05AA01 - albumin ; Belongs to the class of blood substitutes and plasma protein fractions. Used as blood substitutes.
Presentation/Packing
Albumex 5: Soln for infusion 12.5 g/250 mL x 1's.
Albumex 20: Soln for infusion 10 g/50 mL x 1's.
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