What it is and what it is used for

FOR The name of your medicine is Hyalase®. The active ingredient in Hyalase® is hyaluronidase. Hyalase® is an enzyme, a natural substance that activates processes in the body. It is used to temporarily break down the natural barriers in the body tissues so that injections or fluids injected under the skin or into muscle are more easily spread and absorbed. Hyalase® is also used to enable excess fluids and blood in the tissues to be more easily reabsorbed. 2. BEFORE YOU ARE GIVEN HYALASE® You should not be given Hyalase®: are known to be allergic to hyaluronidase

• iftoyou reduce the swelling of bites or stings
• at sites infection or malignancy (cancerous growth) is present
• directly where the front of the eye
• if you areonto in premature labour for which there is no explanation. • Hyalase® should not be administered by Intravenous Injection. Hyalase® should not be used to enhance the absorption and dispersion of dopamine and/or alpha agonist drugs. If you are taking dopamine or clonidine, or any other alpha agonist drug, please tell your doctor or nurse before you are given this medicine. If you have any doubts about whether this medicine should be administered then talk to your doctor or nurse before it is given to you. Pregnancy and breast-feeding You should let your doctor know if you are pregnant, wish to become pregnant, or are breast-feeding before Hyalase® is administered. Driving and using machines Hyalase® has not been reported to affect ability to drive or operate machines. 3. HOW HYALASE® SHOULD BE GIVEN
• The usual dose for Hyalase® is 1500 International Units (iu)
• Hyalase® for injection is dissolved in water for injections, normal saline or the solution to be injected
• Your doctor or nurse will give the injection either into a muscle (intramuscular) or under the skin (subcutaneous)
• For an injection given continuously under the skin (subcutaneous infusion), the injection is injected into the infusion tubing. Your doctor will decide the dose and route of administration that is best for you. If you do not understand what you are being given, or are in any doubt, ask your doctor or nurse. If you think you have been given too much Hyalase® Your doctor will decide which dose is best for you. If you think too much medicine has been given to you contact your doctor or nurse. If you think you have missed a dose If you think that an injection has been missed, speak to you doctor or nurse.

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SUMMARY OF PRODUCT CHARACTERISTICS 1. Name of Proprietary Medicinal Product Hyalase® 1500 I.U. Powder for Solution for Injection/Infusion. 2. Qualitative and Quantitative Composition Each ampoule contains 1500 international units of Hyaluronidase. For excipients see section 6.1 3. Pharmaceutical Form Powder for solution for injection/infusion. A white, sterile freeze-dried powder for solution for injection or infusion. 4. Clinical Particulars 4.1 Therapeutic Indications Hyalase® can be used to enhance permeation of subcutaneous or intramuscular injections, local anaesthetics and subcutaneous infusions and to promote resorption of excess fluids and blood in the tissues. 4.2 Posology and Method of Administration Adults, children and the elderly: With subcutaneous infusion (hypodermoclysis): 1500iu of Hyalase® dissolved in 1ml of water for injections or normal saline injected into the site, before the infusion is set up, or injected into the tubing of the infusion set, about 2cm back from the needle, at the start of the infusion. 1500iu is sufficient for administration of 500-1000ml of most fluids. Refer to Section 4.4 for information on solutions for hypodermoclysis. Care should be taken in young children and the elderly to control the speed and total volume of fluid administered and to avoid over-hydration, especially in renal impairment. With subcutaneous or intramuscular injections: 1500iu of Hyalase® dissolved directly in the solution to be injected. With local anaesthetics: 1500iu Hyalase® is mixed with the quantity of local anaesthetic solution to be used. In ophthalmology, 15iu of Hyalase® per ml is recommended. Extravasation: Where dispersal rather than localisation is indicated, 1500iu of Hyalase® in 1ml water for injections or normal saline infiltrated into the affected area as soon as possible after the extravasation is noted. Haematoma: 1500iu of Hyalase® dissolved in 1ml water for injections or normal saline infiltrated into the affected area. Immediately before use dissolve the freeze-dried powder in approximately 1ml of water for injections or directly in the solution with which Hyalase® is to be combined. 4.3 Contraindications Hypersensitivity to hyaluronidase. Not to be used for intravenous injections. 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. 4.4 Special Warnings and Precautions for Use Do not apply directly to the cornea. Not to be used to enhance the absorption and dispersion of dopamine and/or alpha agonist drugs. Solutions for subcutaneous administration should be isotonic with extracellular fluid. Hyalase® is physically compatible with the commonly used infusion fluids. Use in hypodermoclysis has been reported with 0.9% sodium chloride, 0.18% sodium chloride with 4% glucose, 0.45% sodium chloride with 2.5% glucose and 5% glucose. Potassium 34mmol/litre has been administered by hypodermoclysis in isotonic glucose or saline with 1500I.U/litre hyaluronidase. Electrolyte-free fluids are less preferable than those containing electrolytes and should not be given too rapidly. Hyalase® has also been mixed with morphine, diamorphine, hydromorphone, chlorpromazine, metoclopramide, promazine, dexamethasone, local anaesthetics and adrenaline (see 6.2. Incompatibilities). 4.5 Interactions with Other Medicaments products and Other Forms of Interaction None stated. 4.6 Pregnancy and Lactation It is not known whether the drug enters breast milk although it is unlikely to harm the breast-fed infant. Caution should be exercised in administering it to nursing mothers. There is no evidence on the drug's safety in human pregnancy nor is there evidence from animal work that it is free from hazard. Avoid use in pregnancy unless there is no safer alternative. 4.7 Effects on Ability to Drive and to Use Machines None known.

Warning! We cannot accept responsibility for any errors in this proof after approval. Whilst we take extreme care at all times to ensure accuracy to our client's brief, the final responsibility must be taken by our client. IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING FULL APPROVAL OF DESIGN AND TEXT.

Customer

Wockhardt UK Limited

Colours Used

Description

Hyalase 1500i.u. leaflet

Black

Item Code

104295/6

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as current

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Size

460 x 150mm

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Market

UK

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English

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Date

25/01/2022

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Possible side effects

Like all medicines, Hyalase® may cause side-effects in some patients. rarely, severe allergic reactions to Hyalase® may occur, with

• Very difficulty breathing, rapid pulse and profuse sweating. If you develop any of these symptoms, contact your doctor or nurse immediately
• Hyalase® has on rare occasions caused allergic reactions (rash, itching, swelling around the eyes) or soreness, bleeding or bruising at the injection site swelling may occur when Hyalase® is used with
• Local subcutaneous infusions. Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting systems listed below: United Kingdom: Yellow Card Scheme Website: http://www.mhra.gov.uk/yellowcard By reporting side effects you can help provide more information on the safety of this medicine.

How to store it

HYALASE® Keep out of the sight and reach of children

• Hyalase® should not be stored above 25°C. Store the ampoules in the package container in which they were dispensed
• The injection must be used immediately after preparation. Any portion of the contents not used at once should be discarded should not be given if the powder shows signs of discolouration (it should
• Hyalase® be white) should not be used after the expiry date on the label. The expiry date refers
• Hyalase® to the last day of the month. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment. 6. FURTHER INFORMATION What Hyalase® looks like and contents of the pack Hyalase® is a sterile, freeze-dried powder in 1 ml neutral glass ampoule, containing 1500 international units of the active ingredient (hyaluronidase). The registered pack size is 10 x 1ml glass ampoules. Other formats To listen to or request a copy of this information in Braille, large print or audio please call, free of charge: 0800 198 5000 (UK only) Please be ready to give the following information: Product Name

Reference Number

Hyalase® for Injection/Infusion 1500iu/ml PL 29831/0113 Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder: Wockhardt UK Ltd, Ash Road North, Wrexham, LL13 9UF, UK Manufacturer: CP Pharmaceuticals Ltd, Ash Road North, Wrexham, LL13 9UF, UK. Leaflet prepared: January 2022 104295/6

✂ 4.8 Undesirable Effects Oedema has been reported in association with hypodermoclysis. Allergic reactions have included rare reports of periorbital oedema occurring with the use of hyaluronidase in conjunction with local anaesthetics in ophthalmology. Severe allergic reactions including anaphylaxis have been reported rarely. Local irritation, infection, bleeding and bruising occur rarely. 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: United Kingdom: Yellow Card Scheme Website: http://www.mhra.gov.uk/yellowcard 4.9 Overdose No cases of overdose appear to have been reported. 5. Pharmacological Properties 5.1 Pharmacodynamic Properties Hyaluronidase is an enzyme that has a temporary and reversible depolymerising effect on the polysaccharide hyaluronic acid, which is present in the intercellular matrix of connective tissue. 5.2 Pharmacokinetic Properties Not applicable 5.3 Preclinical Safety Data There are no additional pre-clinical data of relevance to the prescriber. 6. Pharmaceutical Properties 6.1 List of Excipients None. 6.2 Incompatibilities Physical incompatibility has been reported with heparin and adrenaline, although in clinical practice very low concentrations of adrenaline are combined with hyaluronidase without problems. Furosemide, the benzodiazepines and phenytoin have been found to be incompatible with hyaluronidase. 6.3 Shelf Life Unopened: 3 years. Once opened use immediately and discard any unused contents. 6.4 Special Precautions for Storage Do not store above 25°C. 6.5 Nature and Contents of Container 1ml neutral glass ampoule containing a plug of white freeze-dried powder. Pack size: 10 ampoules. 6.6 Instructions for Use/Handling The solution should be used immediately after preparation. The appearance of the solution is clear and not more than faintly yellow. For detailed instructions on preparation and administration, see section 4.2. For single use only. Discard any unused contents. 7. Marketing Authorisation Holder Wockhardt UK Ltd Ash Road North Wrexham LL13 9UF 8. Marketing Authorisation Number PL 29831/0113 9. Date of First Authorisation/Renewal of Authorisation April 2008 10. Date of Revision of Text 01/2022

104295/6

Warning! We cannot accept responsibility for any errors in this proof after approval. Whilst we take extreme care at all times to ensure accuracy to our client's brief, the final responsibility must be taken by our client. IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING FULL APPROVAL OF DESIGN AND TEXT.

Customer

Wockhardt UK Limited

Colours Used

Description

Hyalase 1500i.u. leaflet

Black

Item Code

104295/6

Keyline (Non-Printing)

Profile

as current

Text Free Area (Non-Printing)

Size

460 x 150mm

Cirrus_Info_Box

Min.Point Size

Other

Market

UK

Language

English

Standard 374

Barcode Proof By

RPA

Proof No.

1

Date

25/01/2022

Body Text Fonts:

Helvetica Neue

Body Text Ctd.

Actual Min Point Size

9 pt