ALBUMEON 20 200 G/L SOLUTION FOR INFUSION - summary of medicine characteristics

Albumeon 20, 200 g/l, solution for infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Albumeon is a solution containing 200 g/l of total protein of which at least 96 % is human albumin.

A vial of 100 ml contains at least 19.2 g of human albumin.

A vial of 50 ml contains at least 9.6 g of human albumin.

The solution is hyperoncotic.

Excipients with known effect:

Sodium 125 mmol per litre.

For the full list of excipients, see section 6.1.

Solution for infusion.

A clear, slightly viscous liquid; it is almost colourless, yellow, amber or green.

4.1 Therapeutic indications

Restoration and maintenance of circulating blood volume where volume deficiency has been demonstrated and use of a colloid is appropriate.

The choice of albumin rather than artificial colloid will depend on the clinical situation of the individual patient, based on official recommendations.

4.2 Posology and method of administration

The concentration of the albumin preparation, dosage and the infusion rate should be adjusted to the patient’s indi­vidual requirements.

Posology

The dose required depends on the size of the patient, the severity of trauma or illness and on continuing fluid and protein losses. Measures of adequacy of circulating volume and not plasma albumin levels should be used to determine the dose required.

If human albumin is to be administered, haemodynamic performance should be monitored regularly; this may include:

– arterial blood pressure and pulse rate

– central venous pressure

– pulmonary artery wedge pressure

– urine output

– electrolyte

– haematocrit / haemoglobin

Paediatric Population

The posology in children and adolescents (0–18 years) is not expected to be different from that of adults.

Method of administration

Albumeon can be directly administered by the intravenous route, or it can also be diluted in an isotonic solution (e.g. 5 % glucose or 0.9 % sodium chloride). For instructions on dilution of the medicinal product before administration, see section 6.6.

The infusion rate should be adjusted according to the individual circumstances and the indication.

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

4.3 Contraindications

Hypersensitivity to albumin preparations or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Suspicion of allergic or anaphylactic type reactions requires immediate discontinuation of the infusion. In case of shock, standard medical treatment for shock should be implemented.

Albumin should be used with caution in conditions where hypervolaemia and its consequences or haemodilution could represent a special risk for the patient.

Examples of such conditions are:

– decompensated cardiac insufficiency

– hypertension

– oesophageal varices

– pulmonary oedema

– haemorrhagic diathesis

– severe anaemia

– renal and post-renal anuria

The colloid-osmotic effect of human albumin 200 g/l 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.

200g/l human albumin solutions are relatively low in electrolytes compared to the 40 – 50 g/l human albumin solutions. When albumin is given, the electrolyte status of the patient should be monitored (see section 4.2) and appropriate steps taken to restore or maintain the electrolyte balance.

Albumin solutions must not be diluted with water for injections as this may cause haemolysis in recipients.

If comparatively large volumes are to be replaced, controls of coagulation and haematocrit are necessary. Care must be taken to ensure adequate substitution of other blood constituents (coagulation factors, electrolytes, platelets and erythrocytes).

Hypervolaemia may occur if the dosage and infusion rate are not adjusted to the patient’s cir­culatory situation. At the first clinical signs of cardiovascular overload

(headache, dyspnoea, jugular vein congestion), or increased blood pressure, raised venous pressure and pulmonary oedema, the infusion is to be stopped immediately.

Albumeon contains 125 mmol sodium per litre. To be taken into consideration by patients on a controlled sodium diet.

Virus safety

Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/re­moval of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.

There are no reports of virus transmissions with albumin manufactured to European Pharmacopoeia specifications by established processes.

It is strongly recommended that every time that Albumeon is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.

4.5 Interaction with other medicinal products and other forms of interaction

No specific interactions of human albumin with other medicinal products are known.

4.6 Fertility, pregnancy and lactation

Pregnancy

No animal reproduction studies have been conducted with Albumeon. Its safety for use in human pregnancy has not been established in controlled clinical trials and therefore it should only be given with caution to pregnant women. However, clinical experience with albumin suggests that no harmful effects on the course of pregnancy, or on the foetus and the neonate are to be expected. However, human albumin is a normal constituent of human blood.

Breast-feeding

It is unknown whether Albumeon is excreted in human milk. Since human albumin is a normal constituent of human blood, treatment of the nursing mother with Albumeon is not expected to present a risk to the breastfed newborn/infant.

Fertility

No animal reproduction studies have been conducted with Albumeon. However, human albumin is a normal constituent of human blood and no harmful effects on the fertility are to be expected.

4.7 Effects on ability to drive and use machines

No effects on the ability to drive and use machines have been observed.

4.8 Undesirable effects

Mild reactions such as flush, urticaria, fever and nausea occur rarely. These reactions normally disappear rapidly when the infusion rate is slowed down or the infusion is stopped. Very rarely, severe reactions such as shock may occur. In these cases, the infusion should be stopped immediately and an appropriate treatment should be initiated.

For safety information with respect to transmissible agents, see section 4.4.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the UK Yellow Card Scheme.

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App store

4.9 Overdose

Hypervolaemia may occur if the dosage and infusion rate are too high. At the first clinical signs of cardiovascular overload (headache, dyspnoea, jugular vein congestion) or increased blood pressure, raised central venous pressure and pulmonary oedema, the infusion should be stopped immediately and the patient's hae­modynamic parameters carefully monitored.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: plasma substitutes and plasma protein fractions, albumin, ATC code: B05AA01.

Human 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.

Physico-chemical data: human albumin 200 g/l has a corresponding hyperoncotic effect.

The most important physiological functions of albumin results from its contribution to oncotic pressure of the blood and transport function. Albumin stabilises circulating blood volume and is a carrier of hormones, enzymes, medicinal products and toxins.

5.2 Pharmacokinetic properties

Distribution

Under normal conditions, the total exchangeable albumin pool is 4 – 5 g/kg body weight, of which 40 – 45 % is present intravascularly and 55 – 60 % 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.

Elimination

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

Human albumin is a normal constituent of human plasma and acts like physiological albumin.

In animals, single dose toxicity testing is of little relevance and does not permit the evaluation of toxic or lethal doses or of a dose-effect relationship. Repeated dose toxicity testing is impracticable due to the development of antibodies to heterologous protein in animal models.

To date, human albumin has not been reported to be associated with embryo-foetal toxicity, oncogenic or mutagenic potential.

No signs of acute toxicity have been described in animal models.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

mmol/l

Sodium ions

Caprylate

N-acetyl-D, L-tryptophan

Chloride ions                 ­max. 100

HCl or NaOH (in small amounts for pH adjustment)

Water for injections

6.2 Incompatibilities

Albumeon must not be mixed with other medicinal products (except the recommended diluents mentioned in section 6.6), whole blood and packed red cells.

6.3 Shelf life

5 years.

Once the container has been opened, the contents have to be used immediately.

6.4 Special precautions for storage

Do not store above +25 °C.

Do not freeze.

Keep the vial in the outer carton in order to protect from light.

6.5 Nature and contents of container

50 ml of solution in a single vial (glass type II) with a stopper (halogenated synthetic elastomer).

100 ml of solution in a single vial (glass type II) with a stopper (halogenated synthetic elastomer).

1 vial per pack.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Method of administration

Albumeon can be directly administered by the intravenous route, or it can also be diluted in an isotonic solution (e.g. 5 % glucose or 0.9 % sodium chloride).

Albumin solutions must not be diluted with water for injections as this may cause haemolysis in recipients.

If large volumes are administered, the product should be warmed to room or body temperature before use.

Do not use solutions which are cloudy or contain residues (deposits/par­ticles). This may indicate that the protein is unstable or that the solution has become contaminated.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.