Hyaluronidase

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.

• 1. Indications and Usage HYLENEX recombinant is an endoglycosidase indicated as an adjuvant in subcutaneous fluid administration for achieving hydration ( 1.1 ) to increase the dispersion and absorption of other injected drugs ( 1.2 ) in subcutaneous urography for improving resorption of radiopaque agents ( 1.3 ) 1.1.

• 4. Contraindications HYLENEX recombinant is contraindicated in patients with known hypersensitivity to hyaluronidase or any of the excipients in HYLENEX recombinant.contraindicated

2. Dosage and administration See Full Prescribing Information for all approved routes of administration. ( 2.1 ) Subcutaneous Fluid Administration : Inject 150 USP units HYLENEX recombinant prior to subcutaneous fluid administration. It will facilitate absorption of 1,000 mL or more of solution. The dosage of subcutaneous fluids administered is dependent upon the age, weight, and clinical condition of the patient as well as laboratory determinations. The rate and volume of subcutaneous fluid administration should not exceed those employed for intravenous infusion. ( 2.2 ) Increasing Dispersion and Absorption of Injected or Subcutaneously Infused Drugs : Inject 50 units to 300 units (most typically 150 USP units) HYLENEX recombinant prior to drug administration. Alternatively, add 50 units to 300 units (most typically 150 USP units) HYLENEX recombinant to the injection solution. ( 2.3 ) Subcutaneous Urography : Inject 75 USP units HYLENEX recombinant subcutaneously over each scapula, followed by injection of the contrast medium at the same sites. ( 2.4 ) 2.1. Important Administration Instructions HYLENEX recombinant should not be administered intravenously. Its effects relative to dispersion and absorption of other drugs are not produced when it is administered intravenously because the enzyme is rapidly inactivated. HYLENEX recombinant may be administered for infiltration use, interstitial use, intramuscular use, intraocular use, peribulbar use, retrobulbar use, soft tissue use or subcutaneous use.

5. Warnings and Precautions Spread of Localized Infection ( 5.1 ) Ocular Damage ( 5.2 ) 5.1. 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. 5.2. Ocular Damage Hyaluronidase should not be applied directly to the cornea. It is not for topical use.

6. Adverse Reactions 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 mild local injection site reactions such as erythema and pain. Hyaluronidase has been reported to enhance the adverse reactions associated with co-administered drug products. Edema has been reported most frequently in association with subcutaneous fluid administration. Allergic reactions (urticaria or 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. Allergic and anaphylactic-like reactions have been reported, rarely. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Halozyme,ºInc. at 1-877-877-1679 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

8. Use in Specific Populations Pediatric Use: The dosage of subcutaneous fluids administered is dependent upon the age, weight, and clinical condition of the patient. 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. Special care must be taken in pediatric patients to avoid over hydration by controlling the rate and total volume of the infusion. ( 2.2 , 8.4 , 14 ) 8.1. Pregnancy Risk Summary There are no adequate and well-controlled studies of HYLENEX recombinant administration in pregnant women to inform a drug-associated risk. Subcutaneous administration of HYLENEX recombinant to pregnant mice throughout organogenesis did not produce teratogenic effects at clinically relevant doses. Administration of HYLENEX recombinant to mice in a pre-/postnatal study did not produce adverse effects on offspring at clinically relevant doses. Human Data Limited available data with HYLENEX recombinant in pregnant women have not identified any potential risks. Animal Data In an embryofetal development study, subcutaneous administration of hyaluronidase to pregnant mice throughout organogenesis produced reduced fetal weight and increased numbers of fetal resorptions at daily doses greater or equal to 3 mg/kg (approximately 360,000 USP units/kg).

Metabolism

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

• Oct 26, 2004BLABLA021665Amphastar Pharm
• Dec 2, 2005BLABLA021859Halozyme Therap
• Jun 22, 2017BLABLA761064Genentech Inc
• Feb 28, 2019BLABLA761106Genentech Inc
• May 1, 2020BLABLA761145Janssen Biotech
• Jun 29, 2020BLABLA761170Genentech Inc
• Jun 20, 2023BLABLA761304Argenx Bv
• Sep 12, 2024BLABLA761347Genentech Inc

1. 1Off Label Use1,41615%
2. 2No Adverse Event1,03911%
3. 3Diarrhoea8238.6%
4. 4Fatigue7477.8%
5. 5Rash5515.8%
6. 6Pain5235.5%
7. 7Asthenia4785.0%
8. 8Pyrexia4654.9%
9. 9Dyspnoea4474.7%
10. 10Nausea4194.4%
11. 11Headache4184.4%
12. 12Malaise4034.2%
13. 13Dizziness4024.2%
14. 14Pruritus3914.1%
15. 15Vomiting3884.1%

Recent PubMed references pinned to Hyaluronidase as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Solvent Polarity Shapes Antioxidant Capacity, Preliminary Hyaluronidase Inhibition, and Chemical Profile of Buddleja officinalis Extracts.
  Molecules (Basel, Switzerland) · 2026 · Tian G, Tian Y, Cheng S, et al.
  PMID 42197260DOI 10.3390/molecules31101706
• Aromatic interactions surrounding the Asp-X-Glu motif stabilize the active site of HYAL1 and PH20.
  Biochimica et biophysica acta. Proteins and proteomics · 2026 · Nguyen K, Ho OM, Vu L, et al.
  PMID 42155755DOI 10.1016/j.bbapap.2026.141150
• Hyaluronidase Reverses the Effect of Hyaluronic Acid Without Destroying Normal Skin Structure.
  Journal of cosmetic dermatology · 2026 · Yin B, Jiang Z, Shi J, et al.
  PMID 42136041DOI 10.1111/jocd.70870
• Microbial Hyaluronidases: From Obscure Virulence Factors to Promising Therapeutic Targets.
  Biomolecules · 2026 · Nonoguchi HA, Liu GY, Hajam IA, et al.
  PMID 42072637DOI 10.3390/biom16040516
• Hyaluronidase-activated nanoplatform with dual photosensitizers for targeted and synergistic photodynamic/photothermal antibacterial therapy.
  Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy · 2026 · Zhang X, Zheng Z, Lyu H, et al.
  PMID 41997026DOI 10.1016/j.saa.2026.127900
• Recombinant human hyaluronidase PH20 facilitates rapid subcutaneous infusion: two randomized, double-blind, self-controlled phase III clinical trials.
  European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2026 · Ma H, Lu X, Xiu J, et al.
  PMID 41935547DOI 10.1016/j.ejpb.2026.115070
• Enzymatic depolymerization, structural characterization, and anticoagulant activity evaluation of chondroitin sulfate A oligosaccharides.
  Carbohydrate research · 2026 · Li K, Liu Y, Zhang C, et al.
  PMID 41921298DOI 10.1016/j.carres.2026.109904
• Blocking CEMIP2-mediated low-molecular-weight hyaluronic acid -TGFβ signaling inhibits chemotherapy-associated lymphatic metastasis in gastric cancer.
  Cancer letters · 2026 · Chen H, Cai Q, Chen Y, et al.
  PMID 41912132DOI 10.1016/j.canlet.2026.218462

The 10 most recently updated of 293 ClinicalTrials.gov registrations naming Hyaluronidase as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• MK-3475A±Calderasib (MK-1084) in Completely Resected Stage IIA-IIIB (N2) KRAS G12Cm NSCLC (MK-1084-013)
  Recruiting · Phase 3 · Interventional · 400 enrolled · Merck Sharp & Dohme LLC
  NCT07431827updated 2026-06-12
• Comparing Rituximab and Mosunetuzumab Drug Treatments for People With Low Tumor Burden Follicular Lymphoma
  Recruiting · Phase 3 · Interventional · 600 enrolled · National Cancer Institute (NCI)
  NCT06337318updated 2026-06-11
• Adding Pirtobrutinib to the Usual Treatment for People With Newly Diagnosed Richter Transformation, The PIRAMID Trial
  Not yet recruiting · Phase 3 · Interventional · 102 enrolled · SWOG Cancer Research Network
  NCT07220187updated 2026-06-11
• Adding Biotherapy or Placebo to Standard Treatment for Advanced Kidney Cancer
  Recruiting · Phase 3 · Interventional · 718 enrolled · SWOG Cancer Research Network
  NCT07383441updated 2026-06-11
• A Study of TAK-881 and HyQvia in Healthy Adults
  Completed · Phase 1 · Interventional · 30 enrolled · Takeda
  NCT06895967updated 2026-06-11
• Comparing Combinations of Drugs to Treat Newly Diagnosed Multiple Myeloma (NDMM) When a Stem Cell Transplant is Not a Medically Suitable Treatment
  Recruiting · Phase 3 · Interventional · 510 enrolled · SWOG Cancer Research Network
  NCT05561387updated 2026-06-10
• A Study to Investigate the Pharmacokinetics and Safety of Subcutaneous Rilvegostomig in Adult Participants With Advanced Solid Tumors Previously Treated With Standard of Care Therapy
  Recruiting · Phase 1 · Interventional · 40 enrolled · AstraZeneca
  NCT07161414updated 2026-06-10
• A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer
  Recruiting · Phase 1 · Phase 2 · Interventional · 316 enrolled · Hoffmann-La Roche
  NCT04802759updated 2026-06-09
• Pertuzumab, Trastuzumab, Hyaluronidase-zzxf and Enzalutamide for Treatment of Metastatic Castration-Resistant Prostate Cancer
  Completed · Phase 2 · Interventional · 7 enrolled · Mayo Clinic
  NCT05730712updated 2026-06-09
• Treatment Patterns and Characteristics of Patients Prescribed Opdivo Qvantig
  Completed · Observational · 200 enrolled · Bristol-Myers Squibb
  NCT07636863updated 2026-06-09

Frequently asked questions

How does Hyaluronidase work?

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.

What is Hyaluronidase used for?

According to FDA labeling, Hyaluronidase carries indications including: 1. Indications and Usage HYLENEX recombinant is an endoglycosidase indicated as an adjuvant in subcutaneous fluid administration for achieving hydration ( 1.1 ) to increase the dispersion and absorption of other injected drugs ( 1.2 ) in subcutaneous urography for improving resorption of radiopaque agents ( 1.3 ) 1.1.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Hyaluronidase?

Hyaluronidase is classified as Enzymes, Enzyme Interactions, Cellular Structure Alteration.

What are the brand names for Hyaluronidase?

Hyaluronidase is marketed under brand names including Amphadase, Darzalex Faspro, Herceptin Hylecta, Hylenex, Ocrevus Zunovo, Opdivo Qvantig, Phesgo, Rituxan Hycela.

What are the contraindications for Hyaluronidase?

Hyaluronidase labeling lists contraindications including: 4. Contraindications HYLENEX recombinant is contraindicated in patients with known hypersensitivity to hyaluronidase or any of the excipients in HYLENEX recombinant.. Always consult the full prescribing information and a clinician.