Consumer medicine information

HYALASE

Hyaluronidase

BRAND INFORMATION

Brand name

Hyalase

Active ingredient

Hyaluronidase

Schedule

Unscheduled

SUMMARY CMI

HYALASE^®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I given HYALASE?

HYALASE contains the active ingredient hyaluronidase. HYALASE is used as an aid in different medical conditions to allow injected substances to be rapidly dispersed and absorbed.

For more information, see Section 1. Why am I given HYALASE? in the full CMI.

2. What should I know before I am given HYALASE?

Do not use if you have ever had an allergic reaction to hyaluronidase or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I am given HYALASE? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with HYALASE and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How HYALASE is given?

Your doctor will decide what dose you will receive. This depends on the medical situation for which HYALASE has been prescribed for you
HYALASE is given as an injection either into a muscle (intramuscular) or under the skin (subcutaneous). For subcutaneous infusion (an injection given continuously under the skin), the injection is injected into the infusion tubing

More instructions can be found in Section 4. How HYALASE is given? in the full CMI.

5. What should I know while using HYALASE?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are using HYALASE. Tell your doctor or pharmacist as soon as possible if you do not feel well while you are receiving HYALASE
Things you should not do	Do not receive HYALASE to treat any other complaints unless your doctor tells you to.
Driving or using machines	The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration
Drinking alcohol	Using alcohol with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with alcohol
Looking after your medicine	HYALASE will be stored in the pharmacy or on the ward. It is kept where the temperature stays below 25°C

For more information, see Section 5. What should I know while using HYALASE? in the full CMI.

6. Are there any side effects?

All medicines can have side effects, most of them are minor and temporary. However, some side effects may need medical attention. Serious side effects are allergic reactions such as rash, itching, hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing. Less serious side effects are injection site reactions and/or blurred or decreased vision, restricted eye movements, swelling or fluid in the eye when used in eye surgery.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

HYALASE^®

Active ingredient: Hyaluronidase

Consumer Medicine Information (CMI)

This leaflet provides important information about using HYALASE. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using HYALASE.

Where to find information in this leaflet:

1. Why am I given HYALASE?
2. What should I know before I am given HYALASE?
3. What if I am taking other medicines?
4. How HYALASE is given?
5. What should I know while using HYALASE?
6. Are there any side effects?
7. Product details

1. Why am I given HYALASE?

HYALASE contains the active ingredient hyaluronidase. HYALASE is an enzyme and acts to make the tissue between cells more permeable. This allows injected substances to be rapidly dispersed and absorbed.

HYALASE is used in a number of medical conditions. It can be used:

as an aid during the subcutaneous injection of saline or other solutions
with anaesthetic agents (agents that cause loss of feeling) during childbirth
as an aid in prevention of bleeding after childbirth
as an aid in local anaesthesia involving the eye
as an aid in local anaesthesia for fractures
during administration of substances used while taking X-rays

2. What should I know before I am given HYALASE?

Warnings

Do not use HYALASE if:

you are allergic to hyaluronidase, or any of the ingredients listed at the end of this leaflet.
Always check the ingredients to make sure you can use this medicine.

You should not receive HYALASE to reduce the swelling of bites or stings or at sites where infection or cancer is present.

Check with your doctor if you:

have any other medical conditions such as being allergic to any other medicines or any other substances such as foods, preservatives or dyes
take any medicines for any other condition
If you are not sure whether you should receive HYALASE, talk to your doctor or pharmacist.

Your doctor may have prescribed HYALASE for another reason. Ask your doctor if you have any questions about why HYALASE has been prescribed for you.

There is no evidence that HYALASE is addictive.

This medicine is only available with a doctor's prescription

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Like most medicines, HYALASE is not recommended to be used during pregnancy.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Your doctor or pharmacist will discuss the possible risks and benefits of using HYALASE during breastfeeding.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with HYALASE and affect how it works.

HYALASE should not be used with the following medicines:

Adrenaline, a medicine used for the treatment of serious shock or allergic reaction
Furosemide, a medicine used for the treatment of high blood pressure and oedema
Heparin, a medicine used to thin your blood
Phenytoin, a medicine used for seizures.

HYALASE may enhance the adverse events associated with coadministered medicines.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect HYALASE.

4. How HYALASE is given?

How much is given

Your doctor will decide what dose you will receive. This depends on the medical situation for which HYALASE has been prescribed for you
Ask your doctor if you want to know more about the dose of HYALASE you receive.

How long is it given

Your doctor will tell you how long you will be given HYALASE.

How is HYALASE given

HYALASE should only be administered by trained professionals, with appropriate handling, in a hospital or clinic environment
HYALASE is given as an injection either into a muscle (intramuscular) or under the skin (subcutaneous). For subcutaneous infusion (an injection given continuously under the skin), the injection is injected into the infusion tubing

If you use too much HYALASE

As HYALASE is given to you under the supervision of your doctor, it is very unlikely that you will receive too much. However, if you experience any side effects after being given HYALASE or if you think that you have been given too much HYALASE, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using HYALASE?

Things you should do

If you are about to be started on any new medicine tell your doctor, dentist or pharmacist that you are receiving HYALASE.

If you plan to have surgery, tell your doctor or dentist that you are receiving HYALASE.

Call your doctor straight away if you:

do not feel well while you are receiving HYALASE

Remind any doctor, dentist or pharmacist you visit that you are taking HYALASE.

Things you should not do

Do not receive HYALASE to treat any other complaints unless your doctor tells you to.
Do not self-administer HYALASE.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how HYALASE affects you.

Drinking alcohol

Using alcohol with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with alcohol.

Looking after your medicine

HYALASE will be stored in the pharmacy or on the ward. It is kept where the temperature stays below 25°C.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are receiving HYALASE.

Ask your doctor or pharmacist to answer any questions you may have.

Less serious side effects

Less serious side effects

What to do

When used in eye surgery the following may occur:

Blurred or decreased vision, restricted eye movements, swelling or fluid in the eye

The following may occur at the injection site:

Swelling of skin
Local irritation
Infection
bleeding
bruising

Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effects	What to do
Allergic reactions: rash, itching, hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing	Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people. Tell your doctor or pharmacist if you notice anything else that is making you feel unwell.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What HYALASE contains

Active ingredient (main ingredient)	hyaluronidase
Other ingredients (inactive ingredients)	sodium hydroxide

Do not take this medicine if you are allergic to any of these ingredients.

What HYALASE looks like

HYALASE is supplied in clear glass ampoules which contain a white or pale yellowish white freeze-dried plug and are available in packs of 5 ampoules (AUST R 27749).

Who supplies HYALASE

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park, NSW 2113
Toll Free Number (medical information): 1800 818 806
Email: [email protected]

This leaflet was prepared in 06 July 2020.
hyalase-cmi-v2-06jul20

Published by MIMS January 2021

BRAND INFORMATION

Brand name

Hyalase

Active ingredient

Hyaluronidase

Schedule

Unscheduled

1 Name of Medicine

Hyaluronidase.

2 Qualitative and Quantitative Composition

Hyalase is a purified and standardised preparation of the enzyme hyaluronidase in the form of a sterile, freeze-dried powder.
Each ampoule contains 1,500 international units of hyaluronidase.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

White or pale yellowish white, sterile, freeze-dried powder for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Hypodermoclysis.
Obstetric anaesthesia.
Prevention of post-partum haemorrhage (with ergometrine).
As an aid to local anaesthesia in ophthalmology.
As an aid to local anaesthesia in fracture reduction.
Subcutaneous administration of radiopaque substances in pyelography.

4.2 Dose and Method of Administration

Prior to use.

Dissolve the freeze-dried powder in approximately 1 mL of sterile pyrogen-free distilled water or directly in the solution with which the Hyalase has to be combined.
The solution should be used immediately after preparation. Hyalase is for one dose in one patient only. Discard any remaining contents.

Hypodermoclysis.

An ordinary two-way subcutaneous infusion set is required with the fluid container supported about 1 metre above the patient. Suitable hypodermic needles (record no. 12) are attached to the connecting rubber tubes after any contained air has been expelled. The needles are then inserted into the subcutaneous tissues at selected sites and the fluid allowed to run in by gravity. The contents of one ampoule of Hyalase (1,500 international units), dissolved in 1 mL of sterile distilled water, are injected through the rubber tubing about 2 to 3 cm from each needle, at the beginning of the infusion.
When this method is employed, approximately 200 mL of fluid can be administered in 20 minutes.
The rate of administration can be further varied by raising or lowering the reservoir, but whenever greater speed is required, with possibly smaller volumes, the rate may be increased by injecting the fluid from a 20 or 50 mL syringe, the appropriate amount of a solution of Hyalase being drawn into the syringe beforehand.
Repeated infusions may be given as required but it is advisable to change the site of injection. As solutions of the enzyme lose their activity in 12-24 hours, it is important that fresh solutions are prepared prior to each administration.
Injection may alternatively be given from a syringe directly into a site into which 1 mL sterile distilled water containing 1,500 international units of Hyalase has previously been injected. The needle should be maintained in the site adopted throughout the procedure, which in this case, should not be unduly prolonged.
It is not advisable to raise the temperature of the fluid prior to infusion since this has been observed to reduce the rate of absorption.

Site of injection.

One of the great advantages of hypodermoclysis is that the possible sites of administration are numerous, irrespective of the position of the patient. Choice may be made, for example, from the axillae pectoral regions, subscapular and trunk areas, thighs and calves. The intramedullary route has also been used successfully (e.g. sternum and tibia).
In children, Gaisford and Evans consider the anterior abdominal wall presents the best site both from the point of view of maximal absorption and freedom from napkin contamination. In this case, one needle is inserted on each side of and about 2 to 3 cm from the umbilicus and directed laterally. In general, 1,500 international units of Hyalase are sufficient for the administration of 500-1,000 mL of most fluids. In the case of whole blood, however, 3,000 units may be required.

Obstetric anaesthesia.

The anaesthetic mixture is prepared as follows: Hyalase 1,500 international units; adrenaline hydrochloride: 0.5 mL of 1,000 dilution; procaine hydrochloride: 30 mL of 1% solution.
Heins' method is as follows: The needle is passed horizontally to the ischial spine, and 5 mL of the solution is deposited here to anaesthetise the pudendal nerve as it enters Alcock's canal. Next, 5 mL of the mixture is infiltrated in the superior portion of the labia minora to anaesthetise the perineal branches of the iloinguinal nerve. The same procedure is carried out on both sides of the perineum.

Prevention of post-partum haemorrhage.

When ergometrine is given intramuscularly, together with Hyalase, at the crowning of the foetal head, the oxytocic effect of the drug is apparent 3-4 minutes earlier than when ergometrine is given alone, and approximates to the effect seen after intravenous ergometrine. This technique is particularly useful when the doctor or midwife is working alone and the intravenous administration of ergometrine is impracticable. Extensive trials have shown that the routine use of intramuscular ergometrine and Hyalase shortens the third stage of labour without increasing the danger of retained placenta, and produces a striking reduction in the incidence of post-partum haemorrhage.
The injection solution is made by dissolving the contents of one ampoule of Hyalase 1,500 international units in 1 mL of ergometrine solution containing 0.5 mg of ergometrine. This solution is prepared a little before it is needed and is held ready in the syringe; at the moment of the crowning or delivery of the foetal head it is injected intramuscularly into the thigh. Correct timing is most important.

As an aid to local anaesthesia in ophthalmology.

The addition of 25 international units of Hyalase to each anaesthetic solution has been shown to give a better diffusion of the solution, a greater area of anaesthesia with less ballooning of the tissues, and more effective akinesia of the orbicularis and extra-ocular muscles. The injection of adrenaline, at a concentration not greater than 1 in 50,000, will maintain the duration of anaesthesia.
To obtain the required amount of Hyalase, dissolve the contents of one ampoule in 1.0 mL of sterile distilled water or the local anaesthetic solution. Each 0.1 mL of this Hyalase solution will contain 150 international units. The appropriate amount of this solution is added to the anaesthetic solution, e.g. 6 mL anaesthetic solution requires 0.1 mL Hyalase solution.

As an aid to local anaesthesia in fracture reduction.

The method described by Thorpe is as follows:
"Before injection the local anaesthetic agent (for Colles fracture, 20 mL of 1% procaine) is mixed with 1,500 international units of Hyalase. Two injections are made: the bulk of the solution is put directly into the fracture haematoma from the extensor aspect of the forearm, and 2-3 mL are infiltrated around the ulnar styloid process. The anaesthetic solution diffuses rapidly all around the injured areas and the fracture can be manipulated as soon as the needle is withdrawn."
For Pott's fracture, Thorpe recommends 40 mL of 1% procaine and 1,500 international units of Hyalase.

Radiography.

The following method for the subcutaneous administration of radiopaque substances with hyaluronidase in pyelography is that now generally adopted.
(a) The contents of one ampoule of Hyalase are dissolved in 1.0 mL sterile distilled water (a fresh solution must be prepared on each occasion).
(b) 0.5 mL of Hyalase solution is then added to 5.0 mL of 35% diodone solution and made up to 15.0 mL with sterile distilled water (this operation may be carried out in a 20 mL syringe).
(c) 15 mL of the mixture are injected subcutaneously in the scapular region and are followed immediately by a further 15.0 mL at another site, e.g. the contralateral scapular region.
(d) The area of injection is massaged vigorously to aid dispersion. Normally renal secretion commences five minutes after injection, adequate concentration is obtained in 24-25 minutes and is equal to that obtained by the intravenous method.

Note.

The volumes stated are also applicable to children aged from a few weeks to five years provided that renal function is not grossly impaired.

4.3 Contraindications

Hypersensitivity to hyaluronidase.
Not to be used to reduce the swelling of bites or stings or at sites where infection or malignancy is present.
Not to be used for anaesthetic procedures in cases of unexplained premature labour.
Not to be used for intravenous injections because the enzyme is rapidly inactivated.
Not to be used to enhance the absorption and dispersion of dopamine and/or alpha agonist drugs.
Not to be injected into or around an infected or acutely inflamed area because of the danger of spreading a localised infection.

4.4 Special Warnings and Precautions for Use

Do not apply directly to the cornea.
Solutions for subcutaneous administration should be isotonic with extracellular fluid.
Physical incompatibility has been reported with heparin and adrenaline.
Furosemide (frusemide), the benzodiazepines and phenytoin have been found to be incompatible with hyaluronidase.

Use in renal impairment.

See Section 4.2 Dose and Method of Administration, Radiography.

Use in the elderly.

No data available.

Paediatric use.

See Section 4.2 Dose and Method of Administration, Site of injection, Radiography.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Physical incompatibility has been reported with heparin and adrenaline.
Furosemide (frusemide), the benzodiazepines and phenytoin have been found to be incompatible with hyaluronidase.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
As there are no adequate and well-controlled studies conducted with Hyalase, it should be avoided in pregnancy.
It is not known whether the drug enters breast milk. Caution should be exercised in administering it to breast-feeding mothers.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Oedema has been reported in association with hypodermoclysis.
Allergic reactions have included rare reports of orbital and/or periorbital oedema and/or periorbital inflammation occurring with the use of hyaluronidase in conjunction with local anaesthetics in ophthalmology.
Eye disorders such as conjunctival oedema (chemosis) and/or conjunctival inflammation, restricted eye movements, decreased visual acuity, blurred vision and exophthalmos (proptosis) have been reported.
Severe allergic reactions including anaphylaxis have been reported rarely.
Local irritation, infection, bleeding and bruising occur rarely.
Hyaluronidase has been reported to enhance the adverse events associated with coadministered drug products.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms of toxicity consist of local oedema or urticaria, erythema, chills, nausea, vomiting, dizziness, tachycardia and hypotension. The enzyme should be discontinued and supportive measures initiated immediately.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Enzymes, ATC code: B06AA03.

Mechanism of action.

Hyaluronidase has a temporary and reversible depolymerizing action on the polysaccharide hyaluronic acid which is present in the intercellular matrix of connective tissue. The intercellular "cement" is thereby made more permeable, permitting the rapid dispersal and absorption of injected substances; the reduction of tissue tension; and the rapid dispersal of extravascular fluid in joint and tissue damage.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

No data available.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium hydroxide.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Available in packs of 1, 5 or 10. 1 mL neutral glass ampoules.
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

No data available.

CAS number.

9001-54-1.

7 Medicine Schedule (Poisons Standard)

Unscheduled.

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HYALASE

Hyaluronidase

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