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HAEMACCEL® 3,5% colloidal intravenous infusion solution

SCHEDULING STATUS:
S1

PROPRIETARY NAME
(and dosage form):

HAEMACCEL^® 3,5% colloidal intravenous infusion solution

COMPOSITION:
Per 100 mL:

Degraded gelatin polypeptides cross-linked via urea bridges (corresponding to 0,63 g nitrogen)	3,5 g
Cations:	mmol
Na+	14,500
K+	0,510
Ca++	0,625
Anions
Cl–	14,500
Traces of PO4– and SO4– plus anionic polypeptides up to isoionic point
Water for injection	to 100 mL
Contains no preservative
Physico-chemical data:
Mean molecular mass	35 000
Relative viscosity (35°C)	1,7 –1,8
Isoelectric point	pH 4,7 ±0,3
pH of infusion solution	7,3 ±0,3
Gel point	below +3°C
Oncotic pressure (37°C)	3,4 to 3,8 kPa (= 350 to 390 mm H2O

IDENTIFICATION:
A clear, colloidal solution in a plastic infusion bottle

PHARMACOLOGICAL CLASSIFICATION:
Category A: 9.4 Plasma expanders

PHARMACOLOGICAL ACTION:
HAEMACCEL^® is sterile, pyrogen-free and does not contain any preservatives.
HAEMACCEL^® when given intravenously, adapts itself to the blood volume situation. The level and duration of the effect on the volume depend on the rate of infusion and the existing volume deficit.
Microchemical, radiochemical and histological studies have demonstrated that HAEMACCEL^® improves the microcirculation; oliguria existing in shock is eliminated, and therefore "shock-kidney" may be prevented.
Microchemical, radiochemical and histological studies have demonstrated that HAEMACCEL^® is not stored in the RES or in the organs. Disturbances of organ functions have not been observed even at higher dosages.
HAEMACCEL^® does not impair coagulation, and does not interfere with blood-typing, even in the case of rapid tests. HAEMACCEL^® is not immunogenic, and thus cannot induce antibody formation.
Infusion of HAEMACCEL^® leads to haemodilution and thus lowers the viscosity of the blood.
HAEMACCEL^® is eliminated unchanged via the kidney and intestine. Fifty per cent of the HAEMACCEL^® administered is excreted within four to eight hours according to the volume required. Excretion is complete 48 hours after the end of the infusion. No retention occurs, since the HAEMACCEL^® molecule can be degraded by endogenous proteases.
Experience has shown that in the given indications (large loss of blood, pronounced shock) rapid and pressure infusions may be administered (see instructions for preparation of bottle for infusion).

INDICATIONS:
Volume-deficiency shock
Loss of blood
Loss of plasma
Exsiccosis
Volume losses during and after surgery. Also in conjunction with a heart-lung machine, and during haemodialysis.
Compatible water soluble drugs may be infused in HAEMACCEL^® and in addition HAEMACCEL^® may be used as a carrier solution for low dose insulin infusion.

CONTRA-INDICATIONS:
Known hypersensitivity to constituents of the preparation.
History of anaphylactoid reactions.
In the following cases below, HAEMACCEL^® is indicated to a restricted extent only. If the physician considers the infusion of HAEMACCEL^® necessary, special precautions should be taken:
Cases where patients are at special risk, such as those with an increased intravascular volume with its resultant effects (increased stroke volume, elevated blood pressure) or where there is increased interstitial fluid or haemodilution, for instance those with conditions like congestive heart failure, hypertension, oesophageal varices, pulmonary oedema, haemorrhagic diathesis, renal and post-renal anuria.
In patients with an increased risk of histamine release e.g. allergic persons or patients with a history of histamine reactions, or patients who had received a drug which releases histamine during the previous seven days.
In the latter cases HAEMACCEL^® may be given only after taking appropriate prophylactic measures (see dosage and directions for use).

WARNINGS
Infuse only clear solutions.
Citrated (preserved) blood should not be mixed with HAEMACCEL^® since the latter's content of calcium ions will cause recalcification. Such blood may however, be transfused immediately before or after infusion of HAEMACCEL^®.

DOSAGE AND DIRECTIONS FOR USE:
The dosage and infusion speed are to be adjusted according to the individual situation and will depend inter alia on the usual circulatory parameters (e.g. blood pressure). The extent and duration of the effect achieved depends on the infusion volume, the infusion speed and the existing volume deficit.
HAEMACCEL^® is ready for use, and is infused intravenously.
The amount and duration of the infusion depend on the loss of circulatory volume and the particular requirements (cardiovascular parameters, respiration, kidney function etc).
The rate of infusion is controlled by monitoring the blood pressure. The drop count can be calculated from the following formula:
Intended amount of infusion in mL divided by 4 x intended infusion time in hours = number of drops per minute.
EXAMPLE: It is intended to infuse 500 mL in one hour:
        500₌ 125 drops per minute
        4x1
In emergencies, where immediate volume replacement is indicated, HAEMACCEL^® may also be infused rapidly (e.g. 500 mL in five to 15 minutes).
Reactions caused by histamine release can be drastically reduced in patients at risk by prophylactic use of H₁ and H₂ receptor antagonists (e.g. cimetidine –10 mg/kg i.v.).
The recommended dosage is as follows:
Adults:
In loss of blood or plasma

Shock prophylaxis	500 –1 500 mL
Volume-deficiency shock	maximum 2 000 mL
In emergencies	volume as required

The blood pressure is the parameter of reference.
Generally, the latest at which consideration must be given to the administration of red cell concentrate or whole blood is when the haematocrit falls below 25 per cent by volume.
Children:
Volume-deficiency shock and in emergencies as required. In the case of new-borns, infants, all children and geriatric patients, human albumin or preserved serum should be used where possible in place of the synthetic colloid, in consideration of inadequate protein reserves or loss of function of proteins (geriatric cases).
Preparation of a bottle for infusion
Plastic bottle
Disinfect surface of the plastic cap. Pull gently to remove the tear ring (do not twist off) and perforate the subjacent sealing disk through the thus formed opening with the piercing part of the infusion set.
For technical reasons there is a residual air volume in the container. Thus, pressure infusions with the plastic infusion bottle must be carried out under controlled conditions only, as the risk of an air embolism can not be excluded.
PLEASE NOTE:
If sterility is maintained, HAEMACCEL^® may be mixed with the customary infusion solutions (saline, glucose, Ringer's solution etc.) and with substance used in circulation therapy, corticosteroids, muscle relaxants, barbiturates, vitamins, streptokinase and antibiotics of the penicillin series, provided they are water-soluble, and also with cefotaxime (Claforan).
There is no objection to mixing heparinised blood with HAEMACCEL^®. Like all other infusion solutions, HAEMACCEL^® should, for physiological reasons, not be administered cold.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
During or after infusion of volume-expanding solutions –including HAEMACCEL^® – transient skin reactions (wheals, urticaria), tachycardia, bradycardia, nausea, vomiting, dyspnoea, hypotension, rise in temperatures and/or shivering may develop. Such reactions subside rapidly on discontinuation of the infusion. Rare cases of severe hypersensitivity reactions reaching as far as shock, have been observed: Here, the treatment required depends on the nature and severity of the side-effects.
Histamine release has been shown to be the cause of anaphylactoid side-effects associated with infusions of HAEMACCEL^®. Histamine induced reactions can be potentiated by rapid infusion.
Furthermore, the above described reactions may occur as a result of the cumulative effect of several histamine-releasing drugs (e.g. anaesthetics, muscle relaxants, analgesics, adrenergic blockers and anticholinergic medicines).
If side-effects occur, the infusion must be discontinued at once. If necessary, treatment should be given as illustrated below:

Immediate measures Clinical symptoms * Subjective complaints (back pain, nausea, flushing etc.)	Measures Stop infusion
* Mild reactions	Corticosteroids and antihistamines
* Dyspnoea, shock or shock fragments	1. Adrenaline i.v. slowly 2. High doses of corticosteroids i.v. slowly 3. # restoration of blood volume, (e.g. human albumin; Ringer's lactate solution). 4. Oxygen
* Cardiac or respiratory arrest	Resuscitation

# If the patient is hypovolaemic and has reacted to HAEMACCEL^® then administer one of the following blood volume substitutes.

Due to the raised calcium content of HAEMACCEL^®, the serum calcium concentrations may be found to be slightly increased temporarily ––especially when large amounts of HAEMACCEL^® are administered by rapid infusion. So far no reports have been received of cases involving clinical signs of hypercalcaemia resulting from an infusion of HAEMACCEL^®.
The infusion of HAEMACCEL^® may result in a temporary increase in the erythrocyte sedimentation rate.
Particular care should be exercised when fluid or volume replacements are administered during or immediately after pregnancy.

Interactions with other agents
In the case of simultaneous administration of cardiac glycosides, the synergistic effect of the calcium in HAEMACCEL^® is to be borne in mind.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
In the case of accidents during infusion, the procedure illustrated above (see side-effects) is recommended.

PRESENTATION:
Plastic infusion bottle with 500 mL

STORAGE INSTRUCTIONS:
Store between 2°C and 25°C. If HAEMACCEL^® is stored above 25°C, the stated expiry date has to be reduced by two years.
Once an infusion bottle has been opened, any unused contents are to be discarded.
Viscosity measurements have shown that freezing and thawing do not lead to any change in the physico-chemical properties.

REFERENCE NUMBER:
F 500 (Act 101/1965)

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
NORISTAN LIMITED
326 Marks Street, Waltloo, Pretoria

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
28 August 1992

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