Hyaluronidase Injection

Mechanism Of Action

Hyaluronidase is a dispersion agent, which modifies the permeability of connective tissue through the hydrolysis of hyaluronic acid, a polysaccharide found in the intercellular ground substance of connective tissue, and of certain specialized tissues, such as the umbilical cord and vitreous humor. Hyaluronic acid is also present in the capsules of type A and C hemolytic streptococci. Hyaluronidase hydrolyzes hyaluronic acid by splitting the glucosaminidic bond between Cl of an N-acetylglucosamine moiety and C4 of a glucuronic acid moiety. This temporarily decreases the viscosity of the cellular cement and promotes dispersion of injected fluids or of localized transudates or exudates, thus facilitating their absorption.

Hyaluronidase cleaves glycosidic bonds of hyaluronic acid and, to a variable degree, some other acid mucopolysaccharides of the connective tissue. The activity is measured in vitro by monitoring the decrease in the amount of an insoluble serum albumin-hyaluronic acid complex as the enzyme cleaves the hyaluronic acid component.

Pharmacodynamics

In the absence of hyaluronidase, material injected subcutaneously disperses very slowly. Hyaluronidase facilitates dispersion, provided local interstitial pressure is adequate to furnish the necessary mechanical impulse. Such an impulse is normally initiated by injected solutions. The rate and extent of dispersion and absorption is proportionate to the amount of hyaluronidase and the volume of solution.

Results from an experimental study, in humans, on the influence of hyaluronidase in bone repair support the conclusion that this enzyme alone, in the usual clinical dosage, does not deter bone healing.

Pharmacokinetics

Knowledge of the mechanisms involved in the disappearance of injected hyaluronidase is limited. It is known, however, that the blood of a number of mammalian species brings about the inactivation of hyaluronidase.

Studies have demonstrated that hyaluronidase is antigenic: repeated injections of relatively large amounts of this enzyme may result in the formation of neutralizing antibodies.

Important Precautions Regarding Amphadase®

Instruct patient that Amphadase® is being used to increase the dispersion and absorption of fluids or other injected drugs, as appropriate to the intended use.

Instruct patient that there may be mild local injection site signs and symptoms, such as redness, swelling, itching, or pain localized to the site of injection.

What Patients Should Know About Adverse Reactions

The most frequently reported adverse reactions have been mild local injection site reactions such as redness, swelling, itching, or pain.

Anaphylactic-like reactions, and allergic reactions, such as hives, have been reported rarely in patients receiving hyaluronidases.

Patients Should Inform Their Doctors If Taking Other Medications

You may not receive furosemide, the benzodiazepines, phenytoin, dopamine and/or alpha agonists with Amphadase® . These medications have been found to be incompatible with hyaluronidase. If you are taking salicylates (e.g., aspirin), steroids (e.g., cortisone or estrogens), or antihistamines your doctor may need to prescribe larger amounts of hyaluronidase for equivalent dispersing effect.

Subcutaneous Fluid Administration

VITRASE® (hyaluronidase injection) is indicated as an adjuvant in subcutaneous fluid administration for achieving hydration.

Dispersion And Absorption Of Injected Drugs

VITRASE is indicated as an adjuvant to increase dispersion and absorption of other injected drugs.

Subcutaneous Urography

VITRASE is indicated as an adjuvant in subcutaneous urography for improving resorption of radiopaque agents.

The following adverse reactions have been identified during post-approval use of hyaluronidase products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most frequently reported adverse reactions have been local injection site reactions.

Hyaluronidase has been reported to enhance the adverse reactions associated with co-administered drug products. Edema has been reported most frequently in association with hypodermoclysis.

Allergic reactions (urticaria,  angioedema) have been reported in less than 0.1% of patients receiving hyaluronidase. Anaphylactic-like reactions following retrobulbar block or intravenous injections have occurred, rarely.

• Hylenex

© Amphadase Patient Information is supplied by Cerner Multum, Inc. and Amphadase Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Hyaluronidase is a genetically designed protein.

Hyaluronidase is used as an aid in helping your body absorb other injected medications.

Hyaluronidase is also used to help contrast dyes in your body show more clearly on certain types of x-rays or scans.

Hyaluronidase may also be used for purposes not listed in this medication guide.

• It is used to help other drugs get into the body.
• It may be given to you for other reasons. Talk with the doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into the skin.
• You will be given a test dose before your first dose.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very bad irritation where the shot was given.
• Redness or swelling where the shot is given.
• Pain where the shot was given.

Consult your pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.