Hyaluronidase (human recombinant)

Identification

Name
Hyaluronidase (human recombinant)
Accession Number
DB06205
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Recombinant Enzymes
Description

A purified preparation of the enzyme recombinant human hyaluronidase. Hyaluronidase (human recombinant) (INN Vorhyaluronidase alfa) is produced by genetically engineered Chinese Hamster Ovary (CHO) cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20).1 Hyaluronidase is an enzyme used to improve the absorption and dispersion of parenterally administered fluids, drugs, and contrast agents.9 The action of hyaluronidase was first described in 1936, and named in 1939.3 Early research into hyaluronidase identified it as a "spreading factor" which allowed for increased permeability of the connective tissue.3 Hyaluronidase has been used in surgical settings for at least the past 60 years to improve the diffusion of local anesthetics.6

Hyaluronidase was first used in prescription products in the United States on 5 May 2004.9

Protein chemical formula
Not Available
Protein average weight
61000.0 Da
Sequences
Not Available
Synonyms
  • Hyaluronidase (human recombinant)
  • Hyaluronidase human recombinant
  • Hyaluronidase recombinant human
  • Hyaluronidase, human
  • Recombinant human hyaluronidase
  • Vorhyaluronidase alfa
External IDs
RHUPH-20 / rHuPH20
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
HYLENEX RecombinantInjection, solution150 [USP'U]/1mLSubcutaneousHalozyme, Inc.2005-12-022016-12-31Us
HYLENEX RecombinantInjection, solution150 [USP'U]/1mLSubcutaneousA-S Medication Solutions2005-12-02Not applicableUs
HYLENEX RecombinantInjection, solution150 [USP'U]/1mLSubcutaneousHalozyme, Inc.2005-12-02Not applicableUs
HYLENEX RecombinantInjection, solution150 [USP'U]/1mLSubcutaneousBaxter Laboratories2005-12-022016-12-31Us
HYLENEX Recombinant Professional SampleInjection, solution150 [USP'U]/1mLSubcutaneousHalozyme, Inc.2005-12-022015-03-31Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Darzalex FasproHyaluronidase (human recombinant) (30000 U/15mL) + Daratumumab (1800 mg/15mL)InjectionSubcutaneousJanssen Biotech, Inc.2020-05-01Not applicableUs
Herceptin HylectaHyaluronidase (human recombinant) (10000 U/5mL) + Trastuzumab (600 mg/5mL)Injection, solutionSubcutaneousGenentech, Inc.2019-02-28Not applicableUs
HyqviaHyaluronidase (human recombinant) (160 [USP'U]/1mL) + Human immunoglobulin G (100 mg/1mL)SubcutaneousBaxalta US Inc.2014-09-12Not applicableUs
HyqviaHyaluronidase (human recombinant) (160 [USP'U]/1mL) + Human immunoglobulin G (100 mg/1mL)SubcutaneousBaxalta US Inc.2014-09-12Not applicableUs
HyqviaHyaluronidase (human recombinant) (160 [USP'U]/1mL) + Human immunoglobulin G (100 mg/1mL)SubcutaneousBaxalta US Inc.2014-09-12Not applicableUs
HyqviaHyaluronidase (human recombinant) (160 [USP'U]/1mL) + Human immunoglobulin G (100 mg/1mL)SubcutaneousBaxalta US Inc.2014-09-12Not applicableUs
HyqviaHyaluronidase (human recombinant) (160 [USP'U]/1mL) + Human immunoglobulin G (100 mg/1mL)SubcutaneousBaxalta US Inc.2014-09-12Not applicableUs
Rituxan HycelaHyaluronidase (human recombinant) (2000 U/1mL) + Rituximab (120 mg/1mL)Injection, solutionSubcutaneousGenentech, Inc.2017-06-22Not applicableUs
Rituxan HycelaHyaluronidase (human recombinant) (2000 U/1mL) + Rituximab (120 mg/1mL)Injection, solutionSubcutaneousGenentech, Inc.2017-06-22Not applicableUs
International/Other Brands
Chemophase (Halozyme Therapeutics, Inc) / Enhanze SC (Halozyme Therapeutics, Inc)
Categories
UNII
743QUY4VD8
CAS number
757971-58-7

Pharmacology

Indication

Hyaluronidase is indicated for subcutaneous fluid administration for hydration, and increasing resorption of radiopaque agents in subcutaneous urography.9 Hyaluronidase is also indicated by multiple routes to increase the dispersion of other injectable drugs.9

Associated Conditions
Associated Therapies
Pharmacodynamics

Hyaluronidase cleaves hyaluronic acid in the extracellular matrix to improve the dispersion of injectable drugs.5,9 Hyaluronidase has a long duration of action7,8 and a wide therapeutic window.9 Patients should be counselled regarding the risk of spread of localized infection, ocular corneal damage, and inactivation by intravenous administration.9

Mechanism of action

Hyaluronidase cleaves hyaluronic acid at the glucosaminidic bond between C1 of glucosamine and C4 of glucuronic acid.5,9 Hyaluronic acid is a key component of the extracellular matrix.4 Injection of hyaluronidase with other fluids, drugs, or radiopaque agents improves the ability of these other compounds to permeate the extracellular space more easily.5,9

TargetActionsOrganism
AHyaluronic acid
modulator
metabolizer
Humans and other mammals
UTransforming growth factor beta-1
inhibitor
Humans
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Data regarding the absorption of hyaluronidase are not readily available due to hyaluronidase being inactivated in blood.9

Volume of distribution

Data regarding the volume of distribution of hyaluronidase are not readily available due to hyaluronidase being inactivated in blood.9

Protein binding

Data regarding the protein binding of hyaluronidase are not readily available due to hyaluronidase being inactivated in blood.9

Metabolism

Data regarding the metabolism of hyaluronidase is not readily available.9 However, protein drugs are expected to be degraded by proteases and other catalytic enzymes to smaller peptides and amino acids.2

Route of elimination

After nonspecific proteolysis, the amino acids from protein drugs are reused for protein synthesis or further broken down and eliminated by the kidneys.2,8

Half life

Hyaluronidase has a half life of two minutes, but a duration of action of 24-48 hours due to its high potency.7,8

Clearance

Data regarding the clearance of hyaluronidase are not readily available.9

Toxicity

Data regarding overdose of hyaluronidase is not readily available.9 In the even of an overdose, treat patients with symptomatic and supportive measures.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
4-Bromo-2,5-dimethoxyphenethylamineThe risk or severity of adverse effects can be increased when Hyaluronidase (human recombinant) is combined with 4-Bromo-2,5-dimethoxyphenethylamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Hyaluronidase (human recombinant) is combined with 4-Methoxyamphetamine.
ABT-288The therapeutic efficacy of Hyaluronidase (human recombinant) can be decreased when used in combination with ABT-288.
AceprometazineThe therapeutic efficacy of Hyaluronidase (human recombinant) can be decreased when used in combination with Aceprometazine.
AdinazolamThe therapeutic efficacy of Adinazolam can be decreased when used in combination with Hyaluronidase (human recombinant).
AdrafinilThe risk or severity of adverse effects can be increased when Hyaluronidase (human recombinant) is combined with Adrafinil.
AldosteroneThe therapeutic efficacy of Hyaluronidase (human recombinant) can be decreased when used in combination with Aldosterone.
AloxiprinThe therapeutic efficacy of Hyaluronidase (human recombinant) can be decreased when used in combination with Aloxiprin.
AmitrazThe risk or severity of adverse effects can be increased when Hyaluronidase (human recombinant) is combined with Amitraz.
AripiprazoleThe therapeutic efficacy of Hyaluronidase (human recombinant) can be decreased when used in combination with Aripiprazole.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
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Food Interactions
No interactions found.

References

General References
  1. Bookbinder LH, Hofer A, Haller MF, Zepeda ML, Keller GA, Lim JE, Edgington TS, Shepard HM, Patton JS, Frost GI: A recombinant human enzyme for enhanced interstitial transport of therapeutics. J Control Release. 2006 Aug 28;114(2):230-41. Epub 2006 Jun 7. [PubMed:16876899]
  2. Katsila T, Siskos AP, Tamvakopoulos C: Peptide and protein drugs: the study of their metabolism and catabolism by mass spectrometry. Mass Spectrom Rev. 2012 Jan-Feb;31(1):110-33. doi: 10.1002/mas.20340. Epub 2011 Jun 22. [PubMed:21698655]
  3. Duran-Reynals F: TISSUE PERMEABILITY AND THE SPREADING FACTORS IN INFECTION : A Contribution to the Host:Parasite Problem. Bacteriol Rev. 1942 Dec;6(4):197-252. [PubMed:16350083]
  4. Walker K, Basehore BM, Goyal A, Bansal P, Zito PM: Hyaluronic Acid . [PubMed:29494047]
  5. Gilson RL, Zafar Gondal A: Hyaluronidase . [PubMed:31424747]
  6. Buhren BA, Schrumpf H, Hoff NP, Bolke E, Hilton S, Gerber PA: Hyaluronidase: from clinical applications to molecular and cellular mechanisms. Eur J Med Res. 2016 Feb 13;21:5. doi: 10.1186/s40001-016-0201-5. [PubMed:26873038]
  7. King M, Convery C, Davies E: This month's guideline: The Use of Hyaluronidase in Aesthetic Practice (v2.4). J Clin Aesthet Dermatol. 2018 Jun;11(6):E61-E68. Epub 2018 Jun 1. [PubMed:29942426]
  8. Cavallini M, Gazzola R, Metalla M, Vaienti L: The role of hyaluronidase in the treatment of complications from hyaluronic acid dermal fillers. Aesthet Surg J. 2013 Nov 1;33(8):1167-74. doi: 10.1177/1090820X13511970. Epub 2013 Nov 6. [PubMed:24197934]
  9. FDA Approved Drug Products: Vitrase Hyaluronidase Injection [Link]
External Links
PubChem Substance
347910342
RxNav
1300478
Wikipedia
Hyaluronidase

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentType 1 Diabetes Mellitus1
0TerminatedTreatmentMalignant Neoplasm of Pancreas / Pancreatic Ductal Adenocarcinoma1
1Active Not RecruitingTreatmentMalignancies1
1CompletedNot AvailableDiabetes Mellitus1
1CompletedNot AvailableHealthy Volunteers1
1CompletedBasic ScienceType 1 Diabetes Mellitus1
1CompletedHealth Services ResearchDiabetes Mellitus1
1CompletedOtherHealthy Volunteers3
1CompletedOtherRisk Factors for or a Diagnosis of Osteoporosis1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Malignant Neoplasm of Stomach1
1CompletedTreatmentSuperficial Bladder Cancer1
1Not Yet RecruitingTreatmentRecurrent B-Cell Non-Hodgkin Lymphoma / Recurrent Follicular Lymphoma / Recurrent Indolent Adult Non-Hodgkin Lymphoma / Recurrent Marginal Zone Lymphoma / Refractory B-Cell Non-Hodgkin Lymphoma / Refractory Follicular Lymphoma / Refractory Indolent Adult Non-Hodgkin Lymphoma / Refractory Marginal Zone Lymphoma1
1RecruitingTreatmentDisseminated Sclerosis1
1RecruitingTreatmentLymphoma, B-Cell / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentMultiple Myeloma (MM)1
1SuspendedTreatmentBurkitt's Lymphoma / KSHV-associated Multicentric Castleman Disease / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
1TerminatedBasic ScienceHealthy Volunteers / High Cholesterol1
1TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2Active Not RecruitingTreatmentPancreatic Adenocarcinoma Metastatic1
1, 2CompletedPreventionCancer, Bladder1
1, 2CompletedTreatmentPrimary Immune Deficiency (PID) / Primary Immunodeficiency Diseases (PID)1
1, 2CompletedTreatmentStage IV Pancreatic Cancer1
1, 2RecruitingTreatmentCancer, Advanced1
1, 2RecruitingTreatmentGastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma or Esophageal Carcinoma1
1, 2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2RecruitingTreatmentMalignant Solid Tumours1
1, 2RecruitingTreatmentNeoplasms by Site1
1, 2RecruitingTreatmentTumors1
1, 2TerminatedSupportive CareLymphedema / Neoplasms, Malignant1
2Active Not RecruitingTreatmentMantle Cell Lymphoma (MCL)1
2CompletedNot AvailableHereditary Angioedema1
2CompletedNot AvailableType 1 Diabetes Mellitus1
2CompletedNot AvailableType 2 Diabetes Mellitus1
2CompletedPreventionHereditary Angioedema / Hereditary Angioedema (HAE)1
2CompletedTreatmentAllergic Contact Dermatitis1
2CompletedTreatmentType 1 Diabetes Mellitus2
2CompletedTreatmentType 2 Diabetes Mellitus1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
2RecruitingTreatmentCutaneous Melanoma, Stage III / Cutaneous Melanoma, Stage IV / Stage III Melanoma / Stage IIIA Skin Melanoma / Stage IIIB Skin Melanoma / Stage IIIC Skin Melanoma / Stage IV Skin Melanoma / Unresectable Melanoma1
2TerminatedTreatmentPancreatic Adenocarcinoma Non-resectable1
2WithdrawnTreatmentPancreatic Adenocarcinoma Metastatic / Stage IV Pancreatic Cancer AJCC v81
2, 3CompletedTreatmentPrimary Immunodeficiency Diseases (PID) / Primary Immunodeficiency Disorders1
3Active Not RecruitingPreventionPrimary Immunodeficiency Diseases (PID)1
3Active Not RecruitingTreatmentNovel Coronavirus Infectious Disease (COVID-19) / Polyradiculoneuropathy, Chronic Inflammatory Demyelinating1
3Active Not RecruitingTreatmentSmoldering Multiple Myeloma (SMM)1
3CompletedTreatmentPrimary Immunodeficiency Diseases (PID)2
3RecruitingTreatmentMultiple Myeloma (MM)1
3RecruitingTreatmentPolyradiculoneuropathy, Chronic Inflammatory Demyelinating1
4Active Not RecruitingTreatmentPrimary Immunodeficiency Diseases (PID)1
4CompletedTreatmentDehydration3
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentType 1 Diabetes Mellitus2
4TerminatedTreatmentDehydration1
4Unknown StatusTreatmentType 1 Diabetes Mellitus1
4WithdrawnTreatmentDehydration1
Not AvailableCompletedNot AvailableExposure During Pregnancy1
Not AvailableCompletedTreatmentPain Management1
Not AvailableNot Yet RecruitingTreatmentMultifocal Motor Neuropathy (MMN)1
Not AvailableRecruitingNot AvailableCongenital Immunodeficiency / Secondary Immune Deficiency1
Not AvailableWithdrawnTreatmentUpper Eyelid Surgery1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionSubcutaneous
Injection, solutionSubcutaneous
Injection, solutionSubcutaneous150 [USP'U]/1mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7767429No2010-08-032027-09-23Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Small molecule
Organism
Humans and other mammals
Pharmacological action
Yes
Actions
Modulator
Metabolizer
References
  1. FDA Approved Drug Products: Amphadase (hyaluronidase) injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Type iii transforming growth factor beta receptor binding
Specific Function
Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negati...
Gene Name
TGFB1
Uniprot ID
P01137
Uniprot Name
Transforming growth factor beta-1
Molecular Weight
44340.685 Da
References
  1. Chang NS: Hyaluronidase activation of c-Jun N-terminal kinase is necessary for protection of L929 fibrosarcoma cells from staurosporine-mediated cell death. Biochem Biophys Res Commun. 2001 May 4;283(2):278-86. [PubMed:11327694]
  2. Locci P, Marinucci L, Lilli C, Martinese D, Becchetti E: Transforming growth factor beta 1-hyaluronic acid interaction. Cell Tissue Res. 1995 Aug;281(2):317-24. [PubMed:7648625]
  3. Chang NS: Hyaluronidase enhancement of TNF-mediated cell death is reversed by TGF-beta 1. Am J Physiol. 1997 Dec;273(6 Pt 1):C1987-94. [PubMed:9435505]
  4. Chang NS: Transforming growth factor-beta protection of cancer cells against tumor necrosis factor cytotoxicity is counteracted by hyaluronidase (review). Int J Mol Med. 1998 Dec;2(6):653-9. [PubMed:9850732]

Drug created on March 19, 2008 10:17 / Updated on July 06, 2020 11:39

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