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Hyaluronidase: Drug information

Hyaluronidase: Drug information
(For additional information see "Hyaluronidase: Patient drug information" and see "Hyaluronidase: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Amphadase;
  • Hylenex;
  • Vitrase [DSC]
Pharmacologic Category
  • Antidote, Extravasation;
  • Enzyme
Dosing: Adult
Dispersion and absorption of injected drugs

Dispersion and absorption of injected drugs (adjunctive agent): SUBQ: 50 to 300 units (usual dose: 150 units) either injected prior to drug administration or added to injection solution (consult compatibility reference prior to mixing).

Extravasation management

Extravasation management (off-label use): Note: Administer as soon as extravasation is recognized. Do not use for extravasation of vasoconstrictors (eg, dopamine, norepinephrine [manage with phentolamine]). For extravasation management, skin testing is not necessary prior to use. The concentration of doses used to manage extravasation ranges from 15 units/mL to 150 units/mL; refer to specific vesicant (below) for a description of doses/concentrations used in published case reports and/or reviews:

Aminophylline, amiodarone, calcium solutions, nafcillin, parenteral nutrition/amino acid (4.25%), potassium solutions, and sodium chloride (>1%) extravasation: Intradermal or SUBQ: Inject a total of 1 mL (15 units/mL) as 5 separate 0.2 mL injections (using a tuberculin syringe) around the site of extravasation; if IV catheter remains in place, administer IV through the infiltrated catheter; may repeat in 30 to 60 minutes if no resolution (Ref).

Contrast media extravasation: Note: Information conflicts regarding hyaluronidase in contrast media extravasation management; the American College of Radiology (ACR) Manual on Contrast Media does not recommend hyaluronidase (Ref), while other sources suggest its utility for inoperable cases with compartment syndrome (Ref).

If using hyaluronidase: Intradermal or SUBQ: Dose varies based on the size of infiltration; inject a total of 5 to 250 units (~100 mL contrast reabsorbed per 15 units of hyaluronidase) around the site of extravasation (Ref).

Dextrose 10% to <50% extravasation: Intradermal or SUBQ: Inject a total of 1 mL (15 units/mL) as 5 separate 0.2 mL injections (using a tuberculin syringe) around the site of extravasation; if IV catheter remains in place, administer IV through infiltrated catheter; may repeat in 30 to 60 minutes if no resolution (Ref).

Dextrose 50% extravasation: Intradermal or SUBQ: Inject a total of 1 mL (150 units/mL) as 5 separate 0.2 mL injections administered along the leading edge of erythema (Ref).

Mannitol extravasation: Intradermal or SUBQ: Inject a total of 1 mL (15 units/mL) as 5 separate 0.2 mL injections (using a tuberculin syringe) around the site of extravasation; if IV catheter remains in place, administer IV through the infiltrated catheter; may repeat in 30 to 60 minutes if no resolution (Ref).

Paclitaxel extravasation: IV: Clinical experience suggests hyaluronidase may be used in the management of paclitaxel extravasations (Ref); data is limited. If using hyaluronidase, administer 1 to 6 mL (150 units/mL) into existing IV line, and/or, if needle/cannula has been removed, inject SUBQ in a clockwise manner around area of extravasation. Usual dose is 1 mL hyaluronidase for each 1 mL of extravasated drug; may repeat several times over the next 3 to 4 hours (Ref).

Sodium bicarbonate extravasation: Intradermal or SUBQ: Inject a total of 1 mL (15 units/mL) as 5 separate 0.2 mL injections (using a tuberculin syringe) around the site of extravasation; if IV catheter remains in place, administer IV through the infiltrated catheter; may repeat in 30 to 60 minutes if no resolution (Ref).

Vinca alkaloid (vinblastine, vincristine, vindesine, vinorelbine) extravasation:

If needle/cannula still in place: IV: After gently aspirating to remove extravasated vesicant, administer 1 to 6 mL hyaluronidase (150 units/mL) into existing IV line; the usual dose is 1 mL hyaluronidase for each 1 mL of extravasated drug (Ref).

If needle/cannula has been removed: SUBQ: Inject 1 to 6 mL (150 units/mL) in a clock wise manner using 1 mL for every 1 mL of drug extravasated (Ref) or administer 1 mL (150 units/mL) as 5 separate 0.2 mL injections (using a 25-gauge needle) into the extravasation site (Ref).

Subcutaneous fluid administration

Subcutaneous fluid administration (hypodermoclysis adjunctive agent): SUBQ: 150 units (Amphadase and Hylenex) or 200 units (Vitrase) followed by SUBQ isotonic fluid administration ≥1,000 mL or may be added to small volumes (≤200 mL) of SUBQ replacement fluid. Rate and volume of a single hypodermoclysis should not exceed those used for infusion of IV fluids.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Hyaluronidase: Pediatric drug information")

Skin test

Skin test: Infants, Children, and Adolescents: Intradermal: 0.02 mL (Amphadase 3 units, Hylenex 3 units, or Vitrase 4 units) of a 150 units/mL (Amphadase, Hylenex) or 200 units/mL (Vitrase) solution. Positive reaction consists of a wheal with pseudopods appearing within 5 minutes and persisting for 20 to 30 minutes with localized itching (transient erythema is not considered a positive reaction). Skin testing is not necessary prior to use for extravasation management.

Dehydration, treatment to facilitate subcutaneous fluid replacement

Dehydration, treatment to facilitate subcutaneous fluid replacement: Infants, Children, and Adolescents:

SubQ following SubQ infusion: SubQ: Dose dependent on volume to be infused; administer into rubber tubing close to needle after initiation of subcutaneous isotonic fluid; fluid administration rate is dependent upon age, weight, and clinical condition of the patient, as well as laboratory determinations.

Amphadase: 150 units facilitates absorption of ≥1,000 mL of solution.

Vitrase: 200 units facilitates absorption of ≥1,000 mL of solution.

SubQ prior to SubQ infusion: SubQ: Dose dependent on volume to be infused; administer into rubber tubing close to needle prior to initiation of subcutaneous isotonic fluid; fluid administration rate is dependent upon age, weight, and clinical condition of the patient, as well as laboratory determinations.

Amphadase, Hylenex: 150 units facilitates absorption of ≥1,000 mL of solution.

Vitrase: 200 units facilitates absorption of ≥1,000 mL of solution.

Added to SubQ replacement solution: SubQ: Dose dependent on volume to be infused, generally recommended for smaller volumes (eg, 200 mL); rate and volume of a single clysis should not exceed those used for infusion of IV fluids.

Amphadase, Hylenex: 150 units facilitates absorption of ≥1,000 mL of solution.

Vitrase: 200 units facilitates absorption of ≥1,000 mL of solution.

Dispersion/absorption enhancement of injected drugs

Dispersion/absorption enhancement of injected drugs: Children and Adolescents: Amphadase, Hylenex, Vitrase: 50 to 300 units added to injection solution (consult compatibility reference prior to mixing); some preparations (Hylenex) may be administered SubQ prior to drug needing dispersed.

Dispersion of subcutaneous immunoglobulin: Limited data available: Hylenex: Children ≥2 years and Adolescents: 75 units of hyaluronidase per gram of immunoglobulin; hyaluronidase added to dose of subcutaneous immunoglobulin. Dosing based on open-label prospective studies in patients with primary immunodeficiencies requiring immunoglobulin (Ref).

Extravasation

Extravasation: Limited data available: Infants, Children, and Adolescents: SubQ, intradermal: Use 4 to 5 separate 0.2 mL injections of a 15 or 150 units/mL solution into the extravasation site at the leading edge as soon as possible (preferably within 1 hour) after extravasation is recognized (Ref). Note: Some centers may determine concentration of hyaluronidase based upon the medication risk of tissue toxicity (risk determined by pH, osmolarity, known tissue toxicity) or by volume of extravasation, so for smaller volumes (<100 mL), a less concentrated solution (15 units/mL) has been used (Ref).

Urography, subcutaneous

Urography, subcutaneous: Infants, Children, and Adolescents: SubQ: 75 units over each scapula followed by injection of contrast medium at the same site; patient should be in the prone position during drug administration.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; hyaluronidase exerts its effects locally and is rapidly inactivated in the blood; adverse effects would not be expected.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; hyaluronidase exerts its effects locally and is rapidly inactivated in the blood; adverse effects would not be expected.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.

Cardiovascular: Edema

Local: Injection site reaction

<1%, postmarketing, and/or case reports: Anaphylactic-like reactions (retrobulbar block or IV injections), anaphylaxis, angioedema, hypersensitivity reaction, urticaria

Contraindications

Hypersensitivity to hyaluronidase or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Use with caution in patients with reported history of bee sting allergy; hyaluronidase is an active component in bee venom (Lee 2010).

Dosage form specific issues:

• Albumin: Some products may contain albumin; products containing human albumin may carry a remote risk of viral transmission, including a theoretical risk of Creutzfeldt-Jakob disease transmission.

Other warnings/precautions:

• Administration: For labeled indications, do not administer intravenously (enzyme is rapidly inactivated and desired effects will not be produced); do not inject in or around infected or inflamed areas; may spread localized infection. Do not apply directly to the cornea; not for topical use.

• Appropriate use: Hyaluronidase is ineffective for extravasation management of vasoconstrictors (eg, dopamine, epinephrine, norepinephrine, phenylephrine, vasopressin) or to reduce swelling of bites or stings; do not use in these settings.

• Sensitization to hyaluronidase may occur; a skin test may be performed to determine hypersensitivity by administering 0.02 mL of hyaluronidase intradermally. A positive reaction consists of a wheal with pseudopods appearing within 5 minutes and persisting for 20 to 30 minutes with localized itching (transient erythema is not considered a positive reaction). Discontinue hyaluronidase if sensitization occurs. Skin testing is not necessary prior to use for extravasation management.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection:

Amphadase: 150 units/mL (1 mL) [contains edetate (edta) disodium, thimerosal (thiomersal)]

Solution, Injection [preservative free]:

Hylenex: 150 units/mL (1 mL) [contains albumin human, polysorbate 80]

Vitrase: 200 units/mL (1.2 mL [DSC]) [contains lactose]

Generic Equivalent Available: US

No

Pricing: US

Solution (Amphadase Injection)

150 units/mL (per mL): $66.96

Solution (Hylenex Injection)

150 units/mL (per mL): $66.96

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

For SUBQ administration, lightly pinch skin up and insert needle/catheter. Do not administer IV for labeled uses (enzyme is rapidly inactivated and desired effects will not be produced).

Extravasation management (off-label use): Stop vesicant infusion immediately; leave needle/cannula in place temporarily but do NOT flush the line; if appropriate, gently aspirate extravasated solution from the IV line, then remove needle/cannula. Keep needle/cannula in place for vinca alkaloid extravasation. Elevate extremity and apply dry, warm compresses or dry, cold compresses as appropriate.

Hyaluronidase administration:

Local administration: Intradermal or SUBQ: Inject around the site of extravasation; if IV catheter remains in place, administer IV through the infiltrated catheter (Ref).

Vinca alkaloids: If needle/cannula still in place, administer 1 to 6 mL hyaluronidase (150 units/mL) into the existing IV line; the usual dose is 1 mL hyaluronidase for each 1 mL of extravasated drug (Ref). If needle/cannula has been removed, inject 1 to 6 mL (150 units/mL) SUBQ in a clockwise manner using 1 mL for 1 mL of drug extravasated (Ref) or administer 1 mL (150 units/mL) as 5 separate 0.2 mL injections (25-gauge needle) SUBQ into the extravasation site (Ref).

Administration: Pediatric

Parenteral: Do not administer IV (enzyme is rapidly inactivated and desired effects will not be produced)

Extravasation management: May administer undiluted (150 units/mL) or dilutions may be used. Infiltrate area of extravasation with 4 to 5 small injections at the leading edge; use 25-, 27-, or 30-gauge needles and change needle between each skin entry to prevent bacterial contamination and minimize pain (Ref).

Use: Labeled Indications

Dispersion and absorption of injected drugs: As an adjuvant to increase the dispersion and absorption of other injected drugs.

Subcutaneous fluid administration: As an adjuvant in subcutaneous fluid administration (hypodermoclysis) for achieving hydration.

Subcutaneous urography: As an adjunct in subcutaneous urography for improving resorption of radiopaque agents.

Use: Off-Label: Adult

Extravasation management

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alpha-/Beta-Agonists: Hyaluronidase may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Management: Do not use hyaluronidase to enhance the dispersion or absorption of alpha-/beta-agonists. Use of hyaluronidase for other purposes in patients receiving alpha-/beta-agonists may be considered as clinically indicated. Risk D: Consider therapy modification

Antihistamines: May diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy

Corticosteroids (Systemic): May diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Risk D: Consider therapy modification

Estrogen Derivatives: May diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy

Local Anesthetics: Hyaluronidase may enhance the adverse/toxic effect of Local Anesthetics. Risk C: Monitor therapy

Phenylephrine (Systemic): Hyaluronidase may enhance the vasoconstricting effect of Phenylephrine (Systemic). Management: Do not use hyaluronidase to enhance the dispersion or absorption of phenylephrine. Use of hyaluronidase for other purposes in patients receiving phenylephrine may be considered as clinically indicated. Risk D: Consider therapy modification

Salicylates: May diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy

Reproductive Considerations

Hyaluronidase has been evaluated for use prior to intracytoplasmic sperm injection (ICSI) to aid the in vitro fertilization of human eggs (DeVos 2008; Evison 2009; Majumdar 2013; Moura 2017; Worrilow 2013).

Pregnancy Considerations

Adverse maternal or fetal events were not observed when used as an aid to delivery or an aid to conception. Administration during labor did not cause any increase in blood loss or differences in cervical trauma.

Breastfeeding Considerations

It is not known if hyaluronidase is present in breast milk following therapeutic administration.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

Extravasation management (off-label use): Document and monitor extravasation site for signs and symptoms of extravasation (eg, pain, swelling, erythema, blistering). If visible, mark area of extravasation or infiltration to monitor for expansion.

Mechanism of Action

Enzymatically modifies the permeability of connective tissue through hydrolysis of hyaluronic acid, one of the chief components of tissue cement which offers resistance to diffusion of liquids through tissues; hyaluronidase increases the distribution/dispersion and absorption of locally injected or extravasated IV medications.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: SubQ: Immediate; when used for extravasation, there is usually a reduction in swelling within 15 to 30 minutes after administration (Zenk 1981b)

Duration: 24 to 48 hours (variable)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AT) Austria: Hylase dessau;
  • (AU) Australia: Hyalase;
  • (BE) Belgium: Hyason;
  • (BG) Bulgaria: Hylase;
  • (BR) Brazil: Hyalozima;
  • (CN) China: Hyaiuronidase | Sod.hyaluronidase;
  • (CZ) Czech Republic: Hyasa | Hylase;
  • (DE) Germany: Hylase;
  • (EE) Estonia: Hylase dessau | Lidaza m | Lydasum;
  • (FI) Finland: Hyason;
  • (FR) France: Hyalase;
  • (GB) United Kingdom: Hyalase;
  • (GR) Greece: Hyalase;
  • (HK) Hong Kong: Hyalase | Wockhardt hyalase | Wydase;
  • (HU) Hungary: Hyase | Hyason;
  • (IE) Ireland: Hyalase | Hyaluronidase;
  • (IN) India: Anvase | Entodase | Hinex | Hynidase;
  • (IT) Italy: Jaluran;
  • (JP) Japan: Spractor | Sprase;
  • (KR) Korea, Republic of: Beauty ro | Bmhylunidase | Hidase | Hirax | Hirodase | Hrase | Hyalase | Hyalaze | Hyaline | Hyallap | Hyalnex | Hyalose | Hylase dessau | Hyloline | Hylunidase | Hyrondase | Ldl | Ldrase | Lipoderma | Liporase | Malinda | Medilase | Medirase | Mothers hyludase | Pcld | Purirax | Raneedase | Supofil | Union hyaluronidase;
  • (LT) Lithuania: Entodase | Hexalyse | Hylase | Lydasa | Ronidasa;
  • (LV) Latvia: Hyasa | Hylase | Lydasa | Lydase | Lydazum | Ronidasa;
  • (MY) Malaysia: Hyalase;
  • (NL) Netherlands: Hyason;
  • (NO) Norway: Hylase dessau;
  • (NZ) New Zealand: Hyalase;
  • (PL) Poland: Hyalase | Hylase;
  • (PR) Puerto Rico: Amphadase | Vitrase | Wydase;
  • (PT) Portugal: Hyalase;
  • (QA) Qatar: Hyalase;
  • (RO) Romania: Hyason;
  • (RU) Russian Federation: Biogial | Longidaza | Lydasa | Lydase | Lyrase;
  • (SA) Saudi Arabia: Hyalase;
  • (SE) Sweden: Hyalas;
  • (SG) Singapore: Wydase;
  • (SI) Slovenia: Hylase;
  • (SK) Slovakia: Hyasa;
  • (TW) Taiwan: Hyalase | Sprase;
  • (UA) Ukraine: Lydasa | Lydasa-biopharma
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