Hyaluronidase – Uses, Overdose, and Warnings


Hyaluronidase is an enzyme used to improve the absorption and dispersion of parenterally administered fluids, drugs, and contrast agents. The action of hyaluronidase was first described in 1936, and named in 1939. Early research into hyaluronidase identified it as a “spreading factor” which allowed for increased permeability of the connective tissue. It has been used in surgical settings for at least the past 60 years to improve the diffusion of local anesthetics. Hyaluronidase was first used in prescription products in the United States on 5 May 2004.

Properties and characteristics of Hyaluronidase

Drug class Enzyme
Brand Names Amphadase, Hylenex, Vitrase
Synonyms Hialuronidasa, Hyaluronidase, Hyaluronidase (bovine), Hyaluronidase bovine, hyaluronidase-fihj, hyaluronidase-zzxf, Hyaluronidase, bovine, Hyaluronidasum, Hyaluronoglucosaminidase
Molecular Formula C2455H3775N617O704S21
Molecular Mass 53871.08 g·mol−1
Structural formula of main components
Pure active ingredient Hyaluronidase
Appearance Powder and yellow-brown
Melting point 257°C(lit.)
Solubility Soluble in water, practically insoluble in acetone and in anhydrous ethanol
Storage −20°C
Available Forms Injection, powder, for solution
Prescription Doctors’ prescription is required

Hyaluronidase Uses: Labelled indications

  • Absorption and dispersion of injected drugs: As an adjuvant to increase the absorption and dispersion of other injected drugs.
  • Subcutaneous fluid administration: As an adjuvant in subcutaneous fluid administration (hypodermoclysis) for achieving hydration.
  • Subcutaneous urography: As an adjunct in subcutaneous urography for improving resorption of radiopaque agents.

Off label uses

Extravasation management

Based on the Oncology Nursing Society (ONS) and the European Society for Medical Oncology (ESMO) and European Oncology Nursing Society (EONS), and other clinical experiences, hyaluronidase may be used for extravasation management of several drug extravasations (eg, amiodarone, aminophylline, calcium salts, dextrose, epipodophyllotoxins, mannitol, nafcillin, parenteral nutrition, phenytoin, potassium salts, vinca alkaloids)

Local anesthetic adjuvant

Data from three prospective, randomized, double-blinded studies using hyaluronidase as an adjuvant for local anesthetic administration (eg, peribulbar block) including a pharmacokinetic study supports the use of hyaluronidase in this setting. Clinical experience also suggests the utility of hyaluronidase as an adjuvant for local anesthetic administration

What are side effects of Hyaluronidase?

Common side effects of Hyaluronidase include:

  • Injection site reactions, and
  • Allergic reactions:
    • Itching,
    • Swelling of the lips/around the eyes/skin, or
    • Anaphylactic-like reactions

Seek medical care if you have the following serious side effects:

  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;
  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Mechanism of action

Hyaluronidase cleaves hyaluronic acid at the glucosaminidic bond between C1 of glucosamine and C4 of glucuronic acid. Hyaluronic acid is a key component of the extracellular matrix. Injection of hyaluronidase with other fluids, drugs, or radiopaque agents improves the ability of these other compounds to permeate the extracellular space more easily.

Hyaluronidase with other Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Adenovirus Vaccine, Live
  • Bacillus of Calmette and Guerin Vaccine, Live
  • Benzocaine
  • Bupivacaine
  • Bupivacaine Liposome
  • Butacaine
  • Chloroprocaine
  • Cholera Vaccine, Live
  • Cocaine
  • Dengue Tetravalent Vaccine, Live
  • Dibucaine
  • Ebola Zaire Vaccine, Live
  • Etidocaine
  • Influenza Virus Vaccine, Live
  • Lidocaine
  • Measles Virus Vaccine, Live
  • Mepivacaine
  • Mumps Virus Vaccine, Live
  • Poliovirus Vaccine, Live
  • Prilocaine
  • Procaine
  • Proparacaine
  • Propoxycaine
  • Ropivacaine
  • Rotavirus Vaccine, Live
  • Rubella Virus Vaccine, Live
  • Smallpox Monkeypox Vaccine, Live Non-Replicating
  • Smallpox Vaccine
  • Tetracaine
  • Typhoid Vaccine, Live
  • Varicella Virus Vaccine, Live
  • Yellow Fever Vaccine
  • Zoster Vaccine, Live

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

The presence of other medical problems may affect the use of hyaluronidase. Make sure you tell your doctor if you have any other medical problems.

  • Infection at the injection site—The chance of side effects may be increased.

Dose and method of administration

Adults, children and the elderly

With subcutaneous infusion (hypodermoclysis): 1500iu of Hyaluronidase 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 Hyaluronidase dissolved directly in the solution to be injected.

With local anaesthetics: 1500iu Hyaluronidase is mixed with the quantity of local anaesthetic solution to be used. In ophthalmology, 15iu of Hyaluronidase per ml is recommended.

Extravasation: Where dispersal rather than localisation is indicated, 1500iu of Hyaluronidase 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 Hyaluronidase 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 Hyaluronidase is to be combined.


Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

  • Blurred vision
  • Chills
  • Confusion
  • Dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • Fast, pounding, or irregular heartbeat or pulse
  • Nausea or vomiting
  • Redness of the skin
  • Sweating
  • Swelling
  • Unusual tiredness or weakness
  • Unusually warm skin

Warnings of Hyaluronidase

Serious drug interactions can occur when certain medicines are used together with hyaluronidase. Tell your doctor about all your current medicines.

Before taking this medicine

You should not be treated with hyaluronidase if you are allergic to it.

Your doctor may perform a skin test to see if you are allergic to hyaluronidase before you receive the medication.

Some medicines can cause unwanted or dangerous effects when used with hyaluronidase. Your doctor may change your treatment plan if you also use:

  • Furosemide (Lasix);
  • Phenytoin (Dilantin);
  • A sedative or anxiety medication (such as diazepam, lorazepam, alprazolam, Valium, Xanax, Ativan, Tranxene, and others);
  • Aspirin or salicylates;
  • Cortisone or ACTH (Corticotropin);
  • Estrogens; or
  • An antihistamine (such as a cold or allergy medicine).

Tell your doctor if you are pregnant.

It may not be safe to breast-feed while using hyaluronidase. Ask your doctor about any risk.

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