Hyaluronidase

Hyaluronidase
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]

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Overview

Hyaluronidase is a dermatological agent, enzyme and tissue permeability modifier that is FDA approved for the treatment of Subcutaneous Fluid Administration, Dispersion and Absorption of Injected Drugs, Subcutaneous Urography. Common adverse reactions include {{{adverseReactions}}}.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Subcutaneous Fluid Administration (Hypodermoclysis)

Insert needle with aseptic precautions. With tip lying free and movable between skin and muscle, begin clysis; fluid should start in readily without pain or lump. Then inject Amphadase® (hyaluronidase injection) into rubber tubing close to needle. An alternate method is to inject Amphadase® under skin prior to clysis. 150 U will facilitate absorption of 1,000 mL or more of solution. As with all parenteral fluid therapy, observe effect closely, with same precautions for restoring fluid andelectrolyte balance as in intravenous injections. The dose, the rate of injection, and the type of solution (saline, glucose, Ringer’s, etc.) must be adjusted carefully to the individual patient. When solutions devoid of inorganic electrolytes are given by hypodermoclysis, hypovolemia may occur. This may be prevented by using solutions containing adequate amounts of inorganic electrolytes and/or controlling the volume and speed of administration. Amphadase® may be added to small volumes of solution (up to 200 mL), such as small clysis for infants or solutions of drugs for subcutaneous injection. For infants and children less than 3 years old, the volume of a single clysis should be limited to 200 mL; and in premature infants or during the neonatal period, the daily dosage should not exceed 25 mL/kg of body weight; the rate of administration should not be greater than 2 mL per minute. For older patients, the rate and volume of administration should not exceed those employed for intravenous infusion.

Absorption and Dispersion of Injected Drugs

Absorption and dispersion of other injected drugs may be enhanced by adding 50-300 Units, most typically 150 U hyaluronidase, to the injection solution.

Subcutaneous Urography

The subcutaneous route of administration of urographic contrast media is indicated when intravenous administration cannot be successfully accomplished, particularly in infants and small children. With the patient prone, 75 U of Amphadase® (hyaluronidase injection) is injected subcutaneously over each scapula, followed by injection of the contrast medium at the same sites.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Hyaluronidase in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Hyaluronidase in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Hyaluronidase FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Hyaluronidase in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Hyaluronidase in pediatric patients.

Contraindications

Hypersensitivity to hyaluronidase or any other ingredient in the formulation is a contraindication to the use of this product. A preliminary skin test for hypersensitivity to Amphadase® can be performed. The skin test is made by an intradermal injection of approximately 0.02 mL (3 Units) of a 150 Unit/mL solution. A positive reaction consists of a wheal with pseudopods appearing within 5 minutes and persisting for 20 to 30 minutes and accompanied by localized itching. Transient vasodilation at the site of the test, i.e., erythema, is not a positive reaction. Discontinue Amphadase® if sensitization occurs.

Warnings

Spread of Localized Infection

Hyaluronidase should not be injected into or around an infected or acutely inflamed area because of the danger of spreading a localized infection. Hyaluronidase should not be used to reduce the swelling of bites or stings.

Ocular Damage

Hyaluronidase should not be applied directly to the cornea.

Enzyme Inactivation with Intravenous Administration

Hyaluronidase should not be used for intravenous injections because the enzyme is rapidly inactivated.

Adverse Reactions

Clinical Trials Experience

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.

Postmarketing Experience

There is limited information regarding Hyaluronidase Postmarketing Experience in the drug label.

Drug Interactions

It is recommended that appropriate references be consulted regarding physical or chemical incompatibilities before adding Amphadase® to a solution containing another drug.

Incompatibilities

Furosemide, the benzodiazepines and phenytoin have been found to be incompatible with hyaluronidase.

Drug-Specific Precautions

Hyaluronidase should not be used to enhance the dispersion and absorption of dopamine and/or alpha agonist drugs. When considering the administration of any other drug with hyaluronidase, it is recommended that appropriate references first be consulted to determine the usual precautions for the use of the other drug; e.g., when epinephrine is injected along with hyaluronidase, the precautions for the use of epinephrine in cardiovascular disease, thyroid disease, diabetes, digital nerve block, ischemia of the fingers and toes etc., should be observed.

Local Anesthetics

When hyaluronidase is added to a local anesthetic agent, it hastens the onset of analgesia and tends to reduce the swelling caused by local infiltration, but the wider spread of the local anesthetic solution increases its absorption; this shortens its duration of action and tends to increase the incidence of systemic reaction.

Salicylates, Cortisone, ACTH, Estrogens and Antihistamines

Patients receiving large doses of salicylates, cortisone, ACTH, estrogens or antihistamines may require larger amounts of hyaluronidase for equivalent dispersing effect, since these drugs apparently render tissues partly resistant to the action of hyaluronidase.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C No adequate and well controlled studies have been conducted with Amphadase® in pregnant women. No adequate and well controlled animal studies have been conducted with Amphadase® to determine reproductive effects. Amphadase® should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Hyaluronidase in women who are pregnant.

Labor and Delivery

Administration of hyaluronidase during labor was reported to cause no complications: no increase in blood loss or differences in cervical trauma were observed.

Nursing Mothers

It is not known whether hyaluronidase is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when hyaluronidase is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of Amphadase® have been established in pediatric patients. Use of Amphadase® in these patients is supported by evidence from adequate and well-controlled studies. Clinical hydration requirements for children can be achieved through administration of subcutaneous fluids facilitated with Amphadase®. The dosage of subcutaneous fluids administered is dependent upon the age, weight, and clinical condition of the patient as well as laboratory determinations. The potential for chemical or physical incompatibilities should be kept in mind [see DRUG INTERACTIONS (7) ]. The rate and volume of subcutaneous fluid administration should not exceed those employed for intravenous infusion. For premature infants or during the neonatal period, the daily dosage should not exceed 25 mL/kg of body weight, and the rate of administration should not be greater than 2 mL per minute. During subcutaneous fluid administration, special care must be taken in pediatric patients to avoid over hydration by controlling the rate and total volume of the infusion

Geriatic Use

No overall differences in safety or effectiveness have been observed between elderly and younger adult patients.

Gender

There is no FDA guidance on the use of Hyaluronidase with respect to specific gender populations.

Race

There is no FDA guidance on the use of Hyaluronidase with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Hyaluronidase in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Hyaluronidase in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Hyaluronidase in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Hyaluronidase in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Hyaluronidase Administration in the drug label.

Monitoring

There is limited information regarding Hyaluronidase Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Hyaluronidase and IV administrations.

Overdosage

There is limited information regarding Hyaluronidase overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

hyaluronoglucosaminidase
Identifiers
EC number	3.2.1.35
CAS number	37326-33-3
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

Hyaluronidase protein (HylP)
Identifiers
Symbol	Hyaluronidase_1
Pfam	PF07212
InterPro	IPR009860
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Hyaluronidase
Identifiers
Symbol	Hyaluronidase_2
Pfam	PF07555
InterPro	IPR011496
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Mechanism of Action

There is limited information regarding Hyaluronidase Mechanism of Action in the drug label.

Structure

Pharmacodynamics

There is limited information regarding Hyaluronidase Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Hyaluronidase Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Hyaluronidase Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Hyaluronidase Clinical Studies in the drug label.

How Supplied

There is limited information regarding Hyaluronidase How Supplied in the drug label.

Storage

There is limited information regarding Hyaluronidase Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Hyaluronidase Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Hyaluronidase interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Hyaluronidase Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Hyaluronidase Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Hyaluronidase

File:Hyaluronidase-1OJN.png
Clinical data
Pregnancy category	C
Routes of administration	subcutaneous
ATC code	B06AA03 (WHO)
Identifiers
IUPAC name Sheep hyaluronidase
CAS Number	488712-31-8
DrugBank	BTD00022
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C2455H3775N617O704S21
Molar mass	53870.9 g/mol

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]

The hyaluronidases (EC 3.2.1.35) are a family of enzymes that degrade hyaluronic acid.

By catalyzing the hydrolysis of hyaluronic acid, a major constituent of the interstitial barrier, hyaluronidase lowers the viscosity of hyaluronic acid, thereby increasing tissue permeability. It is, therefore, used in medicine in conjunction with other drugs in order to speed their dispersion and delivery. The most common application is in ophthalmic surgery, in which it is used in combination with local anesthetics. It also increases the absorption rate of parenteral fluids given by hypodermoclysis, and is an adjunct in subcutaneous urography for improving resorption of radiopaque agents. Hyalurodinase is also used for extravastation of hyperosmolar solutions. usually a 0.2 ml of the drug is injected around the area of extravastation, Total of 1 ml is used.

Some bacteria, such as Staphylococcus aureus, Streptococcus pyogenes, and Clostridium perfringens, produce hyaluronidase as a means for greater mobility through the body's tissues and as an antigenic disguise that prevents their being recognized by phagocytes of the immune system.

In most mammalian fertilization, hyaluronidase is released by the acrosome of the sperm cell after it has reached the oocyte, by digesting proteins in the zona pellucida, thus enabling conception.

Brand names of animal-derived hyaluronidase include Vitrase® (ISTA Pharmaceuticals), Amphadase® (Amphastar Pharmaceuticals) and Wydase®. Wydase®, however, is no longer manufactured. On December 2, 2005, the FDA approved a recombinant hyaluronidase, Hylenex® (Halozyme Therapeutics).

External links

• Hyaluronidase at the US National Library of Medicine Medical Subject Headings (MeSH)