This information is intended for use by health professionals

1. Name of the medicinal product

Isoplex 4% w/v Solution for Infusion

2. Qualitative and quantitative composition

Succinylated gelatin (Modified Fluid Gelatin) 4% w/v in Water for Injections, also containing electrolytes.

Electrolytes

Sodium ion (Na+)

145 mmol/litre

Chloride ion (Cl¯)

105 mmol/litre

Lactate ion

25 mmol/litre

Potassium ion (K+)

4 mmol/litre

Magnesium ion (Mg2+)

0.9 mmol/litre

3. Pharmaceutical form

Sterile non-pyrogenic solution for infusion.

A clear pale yellow or straw coloured solution contained within a flexible infusion bag.

Key Physico-chemical properties:

Weight average molecular weight (Mw)

30 000 Dalton

Number average molecular weight (Mn)

20 000 Dalton

pH

7.4 + 0.5

Osmolarity

284 mOsm/litre

4. Clinical particulars
4.1 Therapeutic indications

Isoplex is a colloidal plasma substitute indicated for the initial management of hypovolaemic shock caused by, for example, haemorrhage, acute trauma or surgery, burns, sepsis, peritonitis, pancreatitis or crush injury.

Isoplex may be used in the initial treatment of blood loss during pregnancy where plasma volume replacement is needed.

4.2 Posology and method of administration

Isoplex is administered intravenously; the volume and rate of infusion will depend on the condition of the patient. The rate of administration can be increased by the application of pressure to the container or by adjusting the giving set pump. When given rapidly Isoplex should be warmed to no more than 37°C if possible. In severe acute blood loss, Isoplex may be given rapidly (500 ml in 5 – 10 minutes) until signs of hypovolaemia are relieved. When large volumes are given, suitable monitoring should be used to ensure that an adequate haematocrit is maintained (the haematocrit should not be allowed to fall below 25%) and that dilutional effects upon coagulation are avoided. (Expert haematological advice should be sought, especially in cases of massive blood loss).

For massive fluid loss, Isoplex may be used concomitantly with blood, the rate and amount of which depends on the clinical condition of the patient. The haemodynamic status of the patient should be monitored.

If blood is to be given at the same time as Isoplex, it can be given through the same giving set since Isoplex has a negligible calcium content and therefore does not clot blood. Isoplex can also be used to reconstitute packed red cells.

NB No distinction between the recommended doses and dosage schedule for adults, children and the elderly is necessary as the rate of administration depends on the condition of the individual patient.

4.3 Contraindications

Isoplex is contra-indicated in patients with a known hypersensitivity to succinylated gelatin. Hypersensitivity to galactose-α-1,3-galactose (alpha-Gal) or known allergy to red meat (mammal meat) and offal (see section 4.4)

Lactate containing solutions are contra-indicated in patients with liver disease.

4.4 Special warnings and precautions for use

(i) Severe anaphylactic or anaphylactoid reactions have been reported following the intravenous administration of succinylated gelatin. These are rare, having an incidence of between 1 in 6,000 and 1 in 13,000 units administered. However, they may be more likely to occur if Isoplex is given rapidly to normovolaemic patients, and may be assumed to be more hazardous in patients with known allergic conditions such as asthma.

Due to possible cross-reactions involving the allergen galactose-alpha-1,3-galactose (alpha-Gal), the risk of sensitization and consequent anaphylactic reaction to gelatin- containing solutions could be highly increased in patients with history of allergy to red meat (mammal meat) and offal and/or tested positive for anti-alpha-Gal IgE antibodies. Gelatin-containing colloidal solutions should not be used in these patients (see section 4.3)

Treatment: The infusion of Isoplex should be stopped. Further treatment will depend on the severity of the anaphylactic reaction; administration of supplemental oxygen; an alternative infusion fluid; and the parenteral administration of adrenaline (e.g. for adults, 0.5 ml of a 1 in 1,000 solution intramuscularly, repeated every 5 minutes as necessary, or 5 ml of a 1 in 10,000 solution slowly intravenously), and an antihistamine (e.g. chlorpheniramine 10 – 20 mg slowly intravenously) should be considered.

(i) Caution should be exercised in infusing Isoplex in any patient liable to develop circulatory overload (for example, severe congestive cardiac failure or renal failure with oliguria or anuria) since excessive volumes may give rise to circulatory overload and electrolyte imbalance.

Treatment: The infusion of Isoplex should be stopped and the patient treated symptomatically. Electrolytes should be monitored. If necessary, a diuretic can be given to promote fluid loss. Decreased urinary output secondary to shock is not a contraindication unless there is no improvement in urine output after the initial dose of Isoplex.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

4.6 Pregnancy and lactation

There is very little information available on the use of plasma substitutes in pregnant or lactating women. As with all drugs, the benefits and risks must be assessed.

Isoplex may be used in the initial treatment of blood loss during pregnancy where plasma volume replacement is needed.

4.7 Effects on ability to drive and use machines

Not applicable.

4.8 Undesirable effects

The major undesirable effect risk associated with succinylated gelatin is that of a severe anaphylactic or anaphylactoid reaction, the occurrence and treatment of which is discussed in “4.4 Special warnings and precautions for use” (see also section 4.3 notably for hypersensitivity to galactose- α-1,3-galactose (alpha-Gal) and allergy to red meat and offal).

.

A list of rare undesirable effects that have been associated with the administration of succinylated gelatin is given beneath;

Rare effects (>1 in 10,000 to <1 in 1,000)

Immune system disorders

Anaphylactic reaction

Anaphylactoid reaction

Nervous system disorders

Tremor

Cardiac disorders

Tachycardia

Vascular disorders

Hypotension

Hypertension

Respiratory, thoracic and mediastinal disorders

Wheezing

Dysponoea

Hypoxia

Skin and subcutaneous disorders

Urticarial reactions

Sweating

General disorders and administration site reactions

Chills

Pyrexia

Reporting of suspected adverse reactions

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed on this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

As an overdose of Isoplex may give rise to circulatory overload and electrolyte imbalance (see Section 4.4 Special warnings and precautions for use).

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Gelatin agents; ATC code B05A A 06

Isoplex is a colloidal plasma substitute. When used in the treatment of hypovolaemia Isoplex produces significant increases in blood volume, cardiac output, stroke volume, blood pressure, urinary output and oxygen delivery.

Isoplex promotes osmotic diuresis, thereby helping to protect the kidneys from the adverse effects of hypovalaemia,

5.2 Pharmacokinetic properties

The half-life of Isoplex is about 4 hours, with the majority of the dose administered being eliminated by renal excretion within 24 hours.

5.3 Preclinical safety data

There are no preclinical data of relevance to the prescriber, which are additional to those already included in other sections of the SmPC.

6. Pharmaceutical particulars
6.1 List of excipients

Sodium chloride

Sodium lactate

Potassium chloride

Magnesium chloride

Sodium hydroxide/hydrochloric acid

Water for injection

Isoplex contains no preservatives.

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Isoplex does not interfere with blood grouping or cross-matching.

6.3 Shelf life

The shelf life for Isoplex 500 ml and 1,000 ml is 2 years

6.4 Special precautions for storage

Do not store above 25°C. Do not freeze or refrigerate.

6.5 Nature and contents of container

Isoplex is supplied in sterile flexible infusion bags (500 or 1,000 ml), which are overwrapped.

For 500 ml bags, each pack contains 10 units.

For 1,000 ml bags, each pack contains 6 units.

6.6 Special precautions for disposal and other handling

Do not use unless container is free of particles. Do not use if moisture is present between the container and the overwrap, or if the overwrap is damaged. Do not use if the container is not intact before breaking the seal. Check for leaks by squeezing the container before use. For single dose use only. Discard any unused solution immediately after initial use. Do not reconnect any partially used containers.

7. Marketing authorisation holder

Beacon Pharmaceutical Limited

DCC Vital, Westminster Industrial Estate

Repton Road

Measham

DE12 7DT

England

8. Marketing authorisation number(s)

PL 18157/0244

9. Date of first authorisation/renewal of the authorisation

09/06/2010

10. Date of revision of the text

2nd of October 2018