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The format for this leaflet was set by the Israeli MOH which checked and approved its’ content.

Gelofusine
B. BRAUN MEDICAL

Iso-oncotic gelatine solution for intravenous volume substitution.


Modified Gelatine

Composition
1000 ml of solution for infusion contain:

Active substances
Succinylated Gelatine 40.0 g
(modified fluid gelatine)
average molecular weight
Mw (weight average) 30 000 daltons
Mn (number average) 23 200 daltons
Sodium chloride 7.01 g
Sodium hydroxide 1.36 g

Excipients
Water for injections to 1000 ml

Electrolyte concentrations
Sodium 154 mmol/l
Chloride 120 mmol/l

pH 7.4±0.3
Theoretical osmolarity 274 mosm/l
Gelation point ≤ 3 °C
The gelatine is prepared from the bones of cattle.

Characteristics/Effects
Pharmacological Properties
Gelofusine is a 4 % w/v solution of succinylated gelatine (also known as modified fluid
gelatine) with an average molecular weight of 30 000 daltons (weight average). It has
a relative viscosity of 1.9 at 37 °C and a colloid-osmotic pressure of 34 mmHg. The iso-
electric point is at pH 4.5. The negative charges introduced into the molecule by
succinylation lead to an expansion of the molecule, thus rendering it markedly more
voluminous than unsuccinylated protein chains of the same molecular weight.
The characteristics of Gelofusine result in a sufficient volume effect over about 3 – 4
hours.
Toxicological Properties
The toxicological studies on Gelofusine showed that the product is well tolerated. So, the
maximum dose of the product is limited by its volume and dilution effects.
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Therapeutic Effect
Gelofusine substitutes intravascular volume deficits caused by losses of blood or
plasma. Thus the mean arterial pressure, the left-ventricular end-diastolic pressure, the
cardiac stroke volume, the cardiac index, the oxygen supply and the diuresis are
increased.

Mechanism of Action
The colloid-osmotic pressure of the solution determines the extent of its initial volume
effect. The duration of the effect depends on the clearance of the colloid by re-
distribution and excretion. The volume effect of Gelofusine is equivalent to the
administered amount of solution. So Gelofusine is a plasma substitute, it does not have
a plasma expanding effect. Lost plasma protein is not substituted by Gelofusine.

Pharmacokinetics

Absorption/Distribution
After infusion, Gelofusine is rapidly distributed in the intravascular but in part – regarding
the low molecular weight fraction – also in the interstitial compartment. There is no
evidence that Gelofusine is stored in the reticulo-endothelial system or elsewhere in the
organism.

Metabolism/elimination:
Most of the infused Gelofusine is excreted in urine. Only a minor amount is excreted in
faeces and not more than about 1 % is metabolised. The smaller molecules are
excreted directly by glomerular filtration while the larger molecules first are degraded
proteolytically in the liver and then are also excreted in urine. The proteolytic
metabolism is so adaptable that even under the condition of renal insufficiency no
accumulation of gelatine is observed. After infusion for plasma volume substitution the
half-life time of the intravascular effect of Gelofusine is 4 – 5 hours.

Pharmacokinetics in special clinical situations:


The plasma half-life time of Gelofusine may be prolonged in patients on haemodialysis
(GFR < 0,5 ml/min).

Indications
Colloidal plasma volume substitute for
– prophylaxis and treatment of relative or absolute hypovolaemia,
Further, Gelofusine may be used as plasma volume substitute for
– prophylaxis of hypotension (e.g. during induction of epidural or spinal
anaesthesia),
– haemodilution,
– extra-corporal circulation (heart-lung machine, haemodialysis),

Dosage/Clinical Use
Dosage and infusion rate are adjusted according to individual needs and are
controlled by monitoring the usual circulatory parameters (e.g. blood pressure).
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In order to avoid the occurrence of anaphylactoid/anaphylactic reactions described


under Undesirable Effects, the first 20 – 30 ml should be infused slowly and under careful
observation of the patient.

Recommended doses
For compensation of minor losses of blood or plasma as well as for pre- and
intraoperative routine prophylaxis, as a rule 500 – 1000 ml of Gelofusine will be required,
being infused over 1 – 3 hours.
For compensation of major losses of blood or plasma the average dose is between
1000 and 2000 ml.
In emergency situations or shock conditions an initial dose of 500 ml may be
administered by forced infusion over 5 – 10 min, using a pressure cuff or an infusion
pump. Before starting the infusion, the solution should be warmed to max. 37 °C.
Special caution should be taken so that the air in the container and in the giving set are
expelled before administration. After stabilisation of the cardiovascular situation, the
infusion can be continued with doses corresponding to the actual losses of blood or
plasma. In this case the amount of solution infused may be as much as 10 – 15 l/24 h
(monitor haematocrit!).
In isovolaemic haemodilution, the amount of infused solution corresponds to the
withdrawn plasma volume. As a rule, a dose of 20 ml/kg BW should not be exceeded.
The amount of Gelofusine required during extracorporal circulation depends on the
system used. Normally, volumes between 500 and 1000 ml are required.

Maximum daily dose:


The therapeutic limit is dependent on the dilution effect. If the haematocrit falls below
25 % (in patients at cardiovascular or pulmonary risk, below 30 %), substitution of
erythrocytes or full blood should be considered.

Maximum infusion rate:


The maximum infusion rate depends on the actual cardio-circulatory situation.

Method of administration
Gelofusine is administered intravenously. Only solutions that are clear and free of
precipitate should be infused.
The infusion must be used immediately after preparation. Unused portions of the
solution must not be stored for later use.
If the solution is given under pressure, in case of emergency please refer to the
paragraph “Restrictions for use, warnings”.

Restrictions of Use

Contraindications
Gelofusine must not be administered in the case of:
– hypersensitivity towards gelatine
– hypervolaemia
– hyperhydration
– severe cardiac insufficiency
– recent event of cardiac infarction
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– severe disturbances of blood coagulation


– severe renal insufficiency

Warnings
Gelofusine should only be administered with caution in the cases of:
– known allergic diseases, e.g. asthma,
– hypernatraemia,
– haemorrhagic diathesis,
– states of dehydration,
– left or right ventricular insufficiency.
Special caution should be exercised and doses should be adjusted carefully in patients
with
– blood coagulation disorders,
– renal insufficiency,
– chronic liver diseases.
The following precautions should be observed:
Electrolytes are to be substituted according to specific requirements

Necessary monitoring
During compensation of severe blood losses by massive infusions of Gelofusine, the
haematocrit must be monitored under any circumstances.
Likewise in those situations the dilution effect on coagulation factors should be
observed (critical values: platelet count below 50 000/µl, Quick’s test and aPTT below 35
% of normal). Especially in patients with existing disorders of haemostasis (e.g.
afibrinogenaemia), checks of the serum electrolyte concentrations are required.
Special attention should be paid to the appearance of symptoms of hypocalcaemia
(e.g. signs of tetany, paraesthesia); then corrective measures should be taken. This
applies in particular to patients on medication with digitalis.
Because Gelofusine has no buffering capacity, it has no effect on acidosis.
Because the product does not substitute lost plasma protein, it is advisable to check the
plasma protein concentrations 6 – 12 hours after an operation. If required, deficiencies
should be corrected to a target level of 5 g/100 ml by infusion of human albumin. (It is
necessary to wait 6 hours after an intervention as the biuret protein assay does not
distinguish between gelatine and plasma proteins.)
Attention should be paid to the insufficiency of plasma protein stocks in infants,
children, and the elderly.
When giving the infusion under pressure in case of emergency, special caution should
be taken so that the air in the container and in the giving set are expelled before
administration.

Instruction for Ecoflac®


Infusion (under pressure)
- Insert infusion set
- Hold container upright
- Leave clamp open, expel air from container and fill half of drip chamber
- Turn container and expel air from infusion device
- Close clamp
- Place container in pressure cuff
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- Build up pressure
- Open clamp and start infusion

Pregnancy/Lactation
Pregnancy category C:
Controlled studies have been carried out neither in animals nor in pregnant women.
Because of possible anaphylactoid or anaphylactic reactions, the preparation should
only be administered during pregnancy, if its expected benefits definitely outweigh
possible risks.
It is not known whether Gelofusine passes into breast milk. Sufficient experience with
application during the breast-feeding period and in children under 1 year is not
available.

Undesirable effects
After the administration of Gelofusine infusions, just as of any colloidal volume
substitutes, anaphylactoid or anaphylactic reactions of varying degrees of severity may
occur. These reactions manifest as fever or cutaneous eruptions (urticaria) or sudden
flushing of the face and neck. In rare cases they may proceed over sudden flushing of
the face and neck to drop in blood pressure, shock, cardiac and respiratory arrest.
Severe anaphylactoid reactions (grade III or IV) are rare with an incidence of about
1 : 13 000. Patients receiving Gelofusine must be continuously observed for the
occurrence of anaphylactoid or anaphylactic reactions.

General guidelines for the prophylaxis of adverse reactions:


Adequate information of physicians and nursing staff about the type and severity of
possible adverse reactions that may be encountered after the administration of a
colloidal volume substitute.
Close observation of the patient during infusion, especially while the first 20 – 30 ml of
the solution are being infused.
Availability of all apparatus and medication required for resuscitation.
Stop of infusion immediately, as soon as there are any indications of adverse reactions.
It cannot be predicted by any test procedure which patients are likely to experience
anaphylactic or anaphylactoid reactions, nor is it possible to foresee the course and
severity of any such reaction. Anaphylactic or anaphylactoid reactions caused by
gelatine solutions may either be histamine-mediated or histamine independant.
Histamine release can be prevented by the use of a combination of H1- and H2
receptor blockers. Prophylactic administration of corticosteroids has not proved
effective.
Adverse reactions may occur in conscious and anaesthetized patients. In the acute
phase of volume deficiency shocks so far no anaphylactic or anaphylactoid reaction
has ever been reported.

Interactions
Incompatibilities may occur when the solution is mixed with other medicaments.
Results of compatibility tests will be provided on request.
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Admixture of fat emulsions must be avoided.

Overdose
Overdose of Gelofusine may lead to unintended hypervolaemia associated with
consecutive impairment of heart and lung function. As soon as symptoms of circulatory
overload (headache, dyspnoea, jugular vein congestion) appear, the infusion must be
stopped immediately.

Other information

Incompatibilities
Incompatibilities may occur when the solution is mixed with other medicaments.

Influence on diagnostic methods:


Gelofusine may have an influence on the following clinical-chemical tests, leading to
falsely high values:
erythrocyte sedimentation rate, specific gravity of urine, unspecific plasma protein
assays (e.g. by the biuret method).

Instructions for use


If the solution is administered by forced infusion, using a pressure cuff or an infusion
pump, it should be warmed to body temperature before starting the infusion. Please
refer also to the paragraph “Restrictions for use, warnings”.

Storage
Gelofusine should not be stored above 25 °C.
It must only be used until the date stated on the container after “Exp.”

Available Packages
Ecoflac® : 10 × 500 ml

Date of last revision


July 2002.

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