Hyaluronidase – Uses, Dosage, Side Effects, Interaction

Last updated: February 8, 2026Reviewed date: February 8, 2026Reading time: 20 min read
Hyaluronidase - Uses, Dosage, Side Effects, Interaction
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Article Summary

Hyaluronidase is an injectable enzyme with potential adjuvant activity. Upon subcutaneous administration, hyaluronidase modifies the permeability of connective tissue by hydrolyzing hyaluronic acid. This temporarily decreases interstitial viscosity and allows drugs that are co-injected to spread rapidly through the interstitial space, thereby facilitating absorption and/or distribution of the co-injected agents. Hyaluronidase is an enzyme used to improve the absorption and dispersion of parenterally administered fluids,...

Key Takeaways

  • This article explains Mechanism of Action in simple medical language.
  • This article explains Indications in simple medical language.
  • This article explains Contraindications in simple medical language.
  • This article explains Dosage in simple medical language.
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Definition

Hyaluronidase is an injectable enzyme with potential adjuvant activity. Upon subcutaneous administration, hyaluronidase modifies the permeability of connective tissue by hydrolyzing hyaluronic acid. This temporarily decreases interstitial viscosity and allows drugs that are co-injected to spread rapidly through the interstitial space, thereby facilitating absorption and/or distribution of the co-injected agents.

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” that allowed for increased permeability of the connective tissue. Hyaluronidase 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 products in the United States on 5 May 2004.

An enzyme that catalyzes the random hydrolysis of 1,4-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate. (From Enzyme Nomenclature, 1992) There have been used as ANTINEOPLASTIC AGENTS to limit .

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” that allowed for increased permeability of the connective tissue.[rx] Hyaluronidase has been used in surgical settings for at least the past 60 years to improve the diffusion of local anesthetics.[rx]

Hyaluronidase was first used in prescription products in the United States on 5 May 2004.

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.

Indications

  • Hyaluronidase is indicated for subcutaneous fluid administration for hydration and increasing resorption of radiopaque agents in subcutaneous urography. Hyaluronidase is also indicated by multiple routes to increase the dispersion of other injectable drugs.
  • Hyaluronidase is indicated for subcutaneous fluid administration for hydration and increasing resorption of radiopaque agents in subcutaneous urography. Hyaluronidase is also indicated by multiple routes to increase the dispersion of other injectable drugs.
  • As an adjuvant in subcutaneous fluid administration (hypodermoclysis) for achieving hydration.
  • As an adjuvant in subcutaneous urography for improving the resorption of radiopaque agents
  • Hyaluronidase is an enzyme used to improve the absorption and dispersion of parenterally administered fluids, drugs, and contrast agents
  • Parenteral rehydration therapy
  • Parenteral drug administration
  • Subcutaneous urography

FDA Approved Indications

  • Absorption and dispersion enhancer of injected drugs
  • Subcutaneous fluid administration for hydration therapy – hypodermoclysis
  • Subcutaneous urography to improve absorption of radiopaque agents

Non-FDA Approved Uses

  • Extravasation of medications from intravenous lines management
  • Adjunct to local anesthetic eye blocks for ophthalmic surgery
  • Keloid scar treatment – involves cryosurgery followed by injections with hyaluronidase, triamcinolone, and 5-fluorouracil
  • Reversing cosmetic facial fillers composed of hyaluronic acid

Contraindications

  • Hyaluronidase hypersensitivity.
  • Extravasation, intravenous administration.
  • Ocular exposure, ocular surgery.
  • .
  • Children, hypervolemia, infants.
  • Pregnancy.
  • Breast-feeding.
  • .

Strengths: 150 units; 1500 units; 150 units/mL; human recombinant 150 units/mL; 200 units/mL; 6200 units

Hypodermoclysis

  • After inserting the needle, begin clysis with the tip of the needle lying free and movable between the skin and muscle. The fluid should start in readily without or lump. Then hyaluronidase should be injected into the rubber tubing close to the needle.
  • Alternate method: Inject hyaluronidase under the skin before clysis. 150 to 200 units will facilitate the absorption of 1000 mL or more of the solution.
  • The dose, rate of injection, and type of solution should be individualized; the rate of infusion and volume of administration should not exceed those used for intravenous infusion.
  • Hypovolemia may occur if electrolyte-free solutions are given.
  • Adding adequate quantities of electrolytes and/or controlling the volume and rate of administration will prevent hypovolemia.

Subcutaneous Urography

  • With the patient prone, inject 75 Units subcutaneously over each , followed by injection of contrast medium at the same sites

Hypodermoclysis

After inserting the needle, begin clysis with the tip of the needle lying free and movable between the skin and muscle. The fluid should start in readily without pain or lump. Then hyaluronidase should be injected into the rubber tubing close to the needle.

Alternate method: Inject hyaluronidase under the skin before clysis. 150 to 200 units will facilitate the absorption of 1000 mL or more of the solution.

Under 3 years of age:

  • Limit the volume of a single class to 200 mL

Premature Infants or During the Period:

  • Maximum daily dosage: 25 mL/kg of body weight
  • The maximum rate of administration: 2 mL/minute
  • The dose, rate of injection, and type of solution should be individualized; the rate of infusion and volume of administration should not exceed those used for intravenous infusion.
  • Hypovolemia may occur if electrolyte-free solutions are given.
  • Adding adequate quantities of electrolytes and/or controlling the volume and rate of administration will prevent hypovolemia.

Pediatric Dose for Subcutaneous Urography

  • With the patient prone, inject 75 Units subcutaneously over each scapula, followed by injection of contrast medium at the same sites
  • As an adjuvant in subcutaneous urography for improving the resorption of radiopaque agents

Administration advice:

  • Do not give intravenously
  • For infiltration, interstitial, intramuscular, intraocular, peribulbar, retrobulbar, soft tissue, or subcutaneous use.

Side Effects

The Most Common

  • tiredness
  • difficulty falling asleep or staying asleep
  • pain, burning, or in the hands or feet
  • of the hands, ankles, or feet
  • muscle spasms
  • , swelling, , or redness of the skin at the injection site
  • unusual bruising or bleeding
  • pale skin, , or
  • , , or other signs of infection
  • yellow eyes or skin; dark urine; or pain or discomfort in right upper stomach area
  • , feeling faint, swollen legs, or shortness of breath (especially if you are being treated for amyloidosis)

More Common

  • swelling in your hands, feet, or other body areas; or
  • pain, swelling, itching, or redness where the injection was given.
  • 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

Rare

  • Cough
  • difficulty swallowing
  • dizziness
  • fast heartbeat
  • hives or welts
  • itching
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • redness of the skin
  • skin rash
  • tightness in the chest
  • unusual tiredness or weakness

Drug Interaction

Pregnancy and Lactation

AU TGA pregnancy category: Exempt
US FDA pregnancy category: Not assigned

Pregnancy

Medications exempted from pregnancy classification are not absolutely safe for use in pregnancy in all circumstances. Some exempted medicines, for example, the complementary medicine, St John’s Wort, may interact with other medicines and induce unexpected adverse effects in the mother and/or fetus.

Lactation

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for this medication as well as any potential adverse effects from this drug or the underlying maternal condition.

How should this medicine be used?

Daratumumab and hyaluronidase-fihj injection comes as a solution (liquid) to be injected subcutaneously (just under the skin) into the abdomen (stomach) over 3 to 5 minutes. The length of your treatment will depend on your condition and how well your body responds to treatment.

A doctor or nurse will watch you closely while you are receiving the medication and afterwards to be sure you are not having a serious reaction to the medication. You will be given other medications to help prevent and treat reactions to daratumumab and hyaluronidase-fihj before and after you receive your medication. Tell your doctor or nurse immediately if you experience any of the following symptoms: difficulty breathing or shortness of breath, chest pain, wheezing, throat tightness and irritation, cough, runny or stuffy nose, headache, itching, nausea, vomiting, fever, chills, rash, hives, blurred vision or other vision changes, or dizziness or lightheadedness.

Your doctor may temporarily or permanently stop your treatment. This depends on how well the medication works for you and the side effects you experience. Be sure to tell your doctor how you are feeling during your treatment with daratumumab and hyaluronidase-fihj. Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient. Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient.

What special precautions should I follow?

Before receiving daratumumab and hyaluronidase-fihj injection,

  • tell your doctor and pharmacist if you are allergic to daratumumab, hyaluronidase-fihj, any other medications, or any of the ingredients in daratumumab and hyaluronidase-fihj injection. Ask your pharmacist for a list of the ingredients.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have or have ever had shingles (a painful rash that occurs after infection with herpes zoster or chickenpox), hepatitis B (a virus that infects the liver and may cause severe liver damage), glaucoma (a type of eye disease), high blood pressure, or breathing problems or a lung disease such as chronic obstructive pulmonary disease (COPD; a group of lung diseases, which includes chronic bronchitis and emphysema). If you are being treated for amyloidosis, tell your doctor if you have heart failure or heart disease.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. You should use birth control to prevent pregnancy during your treatment with daratumumab and hyaluronidase-fihj and for at least 3 months after your final dose. Talk to your doctor about types of birth control that will work for you. If you become pregnant while receiving daratumumab and hyaluronidase-fihj injections, call your doctor.
  • if you are having surgery, including dental surgery, tell the doctor or dentist that you are receiving daratumumab and hyaluronidase-fihj injections.

References

  1. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021716s000_HydaseTOC.cfm
  2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021859s009lbl.pdf
  3. https://www.cancer.gov/about-cancer/treatment/drugs/daratumumabandhyaluronidase-fihj
  4. https://en.wikipedia.org/wiki/Hyaluronidase
  5. https://go.drugbank.com/drugs/DB14740
  6. https://www.mayoclinic.org/drugs-supplements/hyaluronidase-injection-route-subcutaneous-route/side-effects/drg-20064183
  7. https://www.drugs.com/mtm/hyaluronidase-injection.html
  8. https://medlineplus.gov/druginfo/meds/a620040.html
  9. https://pubchem.ncbi.nlm.nih.gov/compound/Hyaluronidase
  10. ChemIDplus
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    Hyaluronidase [INN]
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    Hyaluronidase
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  12. EPA Chemicals under the TSCA
    LICENSE
    https://www.epa.gov/privacy/privacy-act-laws-policies-and-resources
    Hyaluronidase
    https://www.epa.gov/chemicals-under-tsca
  13. EPA DSSTox
    LICENSE
    https://www.epa.gov/privacy/privacy-act-laws-policies-and-resources
    Hyaluronidase
    https://comptox.epa.gov/dashboard/DTXSID601021681
  14. European Chemicals Agency (ECHA)
    https://echa.europa.eu/web/guest/legal-notice
    Hyaluronoglucosaminidase
    https://echa.europa.eu/substance-information/-/substanceinfo/100.048.586
    Hyaluronidase
    https://echa.europa.eu/substance-information/-/substanceinfo/100.029.637
    Hyaluronoglucosaminidase
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/83080
  15. ClinicalTrials.gov
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
    https://clinicaltrials.gov/
  16. Drug Induced Liver Injury Rank (DILIrank) Dataset
    https://www.fda.gov/about-fda/about-website/website-policies#linking
    hyaluronidase
    https://www.fda.gov/science-research/liver-toxicity-knowledge-base-ltkb/drug-induced-liver-injury-rank-dilirank-dataset
  17. NCI Thesaurus (NCIt)
    https://www.cancer.gov/policies/copyright-reuse
    https://ncithesaurus.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C87576
  18. EU Clinical Trials Register
    https://www.clinicaltrialsregister.eu/
  19. FDA Purple Book
    Vitrase
    https://purplebooksearch.fda.gov/productdetails?query=021640
    Amphadase
    https://purplebooksearch.fda.gov/productdetails?query=021665
    Hydase
    https://purplebooksearch.fda.gov/productdetails?query=021716
  20. Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
    https://haz-map.com/About
    Hyaluronidase
    https://haz-map.com/Agents/14776
  21. National Drug Code (NDC) Directory
    https://www.fda.gov/about-fda/about-website/website-policies#linking
    HYALURONIDASE
    https://www.fda.gov/drugs/drug-approvals-and-databases/national-drug-code-directory
  22. NIPH Clinical Trials Search of Japan
    https://rctportal.niph.go.jp/en/
  23. WHO Anatomical Therapeutic Chemical (ATC) Classification
    https://www.whocc.no/copyright_disclaimer/
    https://www.whocc.no/atc/
    ATC Code
    https://www.whocc.no/atc_ddd_index/
  24. Medical Subject Headings (MeSH)
    https://www.nlm.nih.gov/copyright.html
    Hyaluronoglucosaminidase
    https://www.ncbi.nlm.nih.gov/mesh/68006821
    MeSH Tree
    http://www.nlm.nih.gov/mesh/meshhome.html
  25. PubChem
    https://pubchem.ncbi.nlm.nih.gov
  26. UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS)
    GHS Classification Tree
    http://www.unece.org/trans/danger/publi/ghs/ghs_welcome_e.html

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  2. Step 2

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