Hyaluronidase (Hylenex) is an enzyme formulation that degrades hyaluronic acid. It is used to enhance the tissue penetration of drugs by increasing cell membrane permeability.

Indications of Hyaluronidase (Hylenex):

• Absorption and dispersion of injected drugs:

  • It is given as an adjuvant to increase the absorption and dispersion of other injected drugs.

• Subcutaneous fluid administration:

  • It is indicated 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.

• Off Label Use of Hyaluronidase in Adults:

  • Extravasation management
  • Local anesthetic adjuvant

Hyaluronidase (Hylenex) dose in adults:

Skin test:

• 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.
  • A wheal with pseudopods appearing within 5 minutes and persisting for 20-30 minutes with localized itching (transient erythema is not considered a positive reaction)is considered as a positive reaction.
  • Before using hyaluronidase for extravasation management, a skin test is not required.

Hyaluronidase (Hylenex) dose in Dehydration:

• Hypodermoclysis: SubQ:
  • 150 or 200 units followed by subcutaneous isotonic fluid administration ≥1000 ml or may be added to small volumes (≤200 ml) of subcutaneous replacement fluid.
  • The rate and volume of a single clysis should not exceed those used for the infusion of IV fluids.

Hyaluronidase (Hylenex) dose in the dispersion/absorption enhancement of injected drugs:

• SubQ: 50 to 300 units (usual dose: 150 units) either given before drug administration or added to injection solution (consult compatibility reference prior to mixing).

Hyaluronidase (Hylenex) dose in extravasation management (off-label):

Note:

• It should be given as soon as extravasation is recognized.
• Its use in extravasation of vasoconstrictors (eg, dopamine, norepinephrine) is not recommended[manage with phentolamine]).
• Skin testing is not necessary for extravasation management. 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, dextrose <50%, nafcillin, parenteral nutrition/amino acid (4.25%), potassium solutions, and sodium chloride (>1%)
  • Intradermal or SubQ: Inject a total of 1 to 1.7 ml(15 units/ml) as 5 separate 0.2 to 0.3 ml injections (using a 25-gauge needle) into the area of extravasation at the leading edge in a clockwise manner.
• Contrast media extravasation:
  • Information conflicts regarding hyaluronidase in contrast media extravasation management;
  • the American College of Radiology Manual on Contrast Media does not recommend hyaluronidase (ACR 2018), while other sources suggest its utility.
  • If using hyaluronidase, inject a total of 1 to 1.7 mL (15 units/mL) as five separate 0.2 to 0.3 ml intradermal or SubQ injections (using a 25-gauge needle) into the area of extravasation at the leading edge in a clockwise manner or the injection of a total of 5 ml (150 units/ml) as five separate 1 ml injections around the extravasation site have been also used successfully.
• Dextrose 50% extravasation:
  • Injection of a total of 1 ml(150 units/ml) as five separate 0.2 ml injections administered along the leading edge of erythema has also been used successfully for dextrose 50% extravasation.
• Mannitol: SubQ:
  • Administer multiple injections of 0.5 to 1 mL (15 units/mL) around the periphery of the extravasation or
  • Intradermal or SubQ:
    • Inject a total of 1 to 1.7 ml (15 units/ml) as 5 separate 0.2 to 0.3 ml injections (using a 25-gauge needle) into area of extravasation at the leading edge in a clockwise manner.
• Paclitaxel: IV:
  • Management of paclitaxel extravasation can be done by hyaluronidase, however, data is limited.
  • If using hyaluronidase, administer 1 to 6 ml (150 units/ml) into the existing IV line, and/or, if needle/cannula has been removed, inject subcutaneously in a clockwise manner around the area of extravasation.
  • The usual dose is 1 ml hyaluronidase for every 1 ml of the extravasated drug; may repeat several times over the next 3 to 4 hours.
• Sodium bicarbonate: SubQ:
  • Administer 4 to 5 separate 0.2 ml injections (15 units/ml) around the area of extravasation or
  • Intradermal or SubQ:
    • Inject a total of 1 to 1.7 ml (15 units/ml) as 5 separate 0.2 to 0.3 ml injections (using a 25-gauge needle) into the area of extravasation at the leading edge in a clockwise manner.

• 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 the existing IV line; the usual dose is 1 ml hyaluronidase for every 1 ml of the extravasated drug.
  • If needle/cannula has been removed: SubQ:
    • Inject 1 to 6 ml (150 units/ml) in a clockwise manner using 1 ml for every 1 ml of drug extravasated or administer 1 ml(150 units/ml) as 5 separate 0.2 ml injections (using a 25-gauge needle) into the extravasation site.

Hyaluronidase (Hylenex) Retrobulbar/peribulbar block (adjuvant in bupivacaine-lidocaine mixture) (off-label):

• 75 units (150 units/ml concentration) or 7.5 units (150 units/ml concentration) for every 1 ml of a 1:1 mixture of bupivacaine 0.75% and lidocaine 2%;
• administer a total of 6 to 8 ml of mixture divided evenly between retrobulbar and peribulbar injections.

Hyaluronidase dose in children:

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.
    • A wheal with pseudopods appearing within 5 minutes and persisting for 20 to 30 minutes with localized itching is considered as a positive reaction (transient erythema is not considered a positive reaction).
    • Before extravasation management, skin testing is not required.

Hyaluronidase (Hylenex) Dose for Dehydration: Hypodermoclysis:

• Infants, Children, and Adolescents:

  • SubQ prior to infusion: SubQ:
    • 150 units or 200 units, followed by subcutaneous isotonic fluid administration at a rate appropriate for age, weight, and clinical condition of the patient;
    • 150 units facilitate the absorption of ≥1,000 ml of solution.
    • Additional doses have been administered at 24-hour intervals up to a total of 3 doses can be given if the infusion is continued for more than 24 hours.
  • Added to the replacement solution:
    • Dose-dependent on volume to be infused;
    • 150 units of hyaluronidase facilitate the absorption of ≥1,000 ml of fluid;
    • for patients (ie, young infants) who require smaller volumes for replacement fluid (≤100 ml), 15 units added for every 100 ml of replacement fluid has been used at some centers.
    • The maximum daily dose: 150 units/day
  • Maximum clysis volumes:
    • Infants and Children <3 years:
      • The volume of a single clysis should not exceed 200 ml.
    • Children ≥3 years and Adolescents:
      • The rate and volume of a single clysis should not exceed those used for the infusion of IV fluids

Hyaluronidase (Hylenex) dose in the dispersion/absorption enhancement of injected drugs:

• Children and Adolescents:

  • SubQ: 50 to 300 units (usual dose: 150 units) either injected before drug administration or added to injection solution (consult compatibility reference prior to mixing).
  • For dispersion of subcutaneous immunoglobulins in children older than 2 years:
    • 75 units of hyaluronidase per gram of immunoglobulin
    • The drug is added to the dose of immunoglobulin administered subQ.

Hyaluronidase (Hylenex) dose in the treatment of extravasation:

• 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.
  • Note:
    • Some centers may determine the 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.

Hyaluronidase (Hylenex) dose in Urography:

• Infants, Children, and Adolescents:

  • SubQ:
    • 75 units over each scapula followed by injection of contrast medium at the same site.
    • During drug administration, the patient should be in a prone position.

Hyaluronidase (Hylenex) Pregnancy Risk Category: C

• Hyaluronidase was not used to aid in delivery or conception.
• It did not have any adverse maternal and fetal effects. 
• It was not found to cause any increase in blood loss or cervical trauma differences during labor.
• To aid in vitro fertilization, hyaluronidase can also be administered before intracytoplasmic Sperm injection.

Hyaluronidase use during breastfeeding:

• It is unknown if breast milk contains hyaluronidase.
• The manufacturer will inform you about the risks to infants and the benefits to breastfeeding.

Hyaluronidase (Hylenex) Dose adjustment in renal disease:

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

Hyaluronidase (Hylenex) Dose adjustment in liver disease:

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

Side effects of Hyaluronidase (Hylenex):

• Cardiovascular:

  • Edema

• Local:

  • Injection site reaction

Contraindications to Hyaluronidase (Hylenex):

• Hypersensitivity to hyaluronidase and any component of the formulation

Warnings and precautions

• Hypersensitivity

  • Bee venom contains a component called Hyaluronidase.
  • Patients with a history bee sting allergy should not use it.

• Sensitization:

  • Therapy should be stopped in the event of sensitization. A skin test can be done to confirm hypersensitivity.

Hyaluronidase: Drug Interaction

Monitoring parameters:

Extravasation management (off-label use):

• Document and monitor the extravasation site.

How to administer Hyaluronidase (Hylenex)?

As the enzyme is rapidly inactivated and desired effects cannot be produced, it should not be given intravenously for labeled uses.

Extravasation management (off-label use):

• The vesicant infusion should be stopped immediately and the IV line should be disconnected (leave needle/cannula in place).
• The extravasated solution should be gently aspirated from the IV line without flushing the line.
• The needle/cannula should be kept in place for vinca alkaloid extravasation, if appropriate, it can be removed in case of other vesicants.
• The extremity should be elevated.

Hyaluronidase administration:

• Local administration (intradermal or subQ):
  • Using a 150 units/ml concentration, mix 0.1 mLl(of 150 units/ml) with 0.9 ml NS in 1 ml syringe to make final concentration of 15 units/ml;
  • administer a total of 1 to 1.7 ml (15 units/ml) as 5 separate 0.2 to 0.3 ml intradermally and/or subcutaneously into area of extravasation.

Vinca alkaloids:

• If needle/cannula still in place, 1 to 6 ml hyaluronidase (150 units/ml)should be injected into the existing IV line; the usual dose is 1 ml hyaluronidase for every 1 ml of the extravasated drug.
• Injection of 1 to 6 ml (150 units/ml) subcutaneously in a clockwise manner using 1 ml for 1 ml of drug extravasated if the needle has been removed or administer 1 ml (150 units/ml) as 5 separate 0.2 ml injections (25-gauge needle) subcutaneously into the extravasation site.

Retrobulbar/peribulbar administration (off-label use):

• Hyaluronidase should be given according to the standard anesthetic technique after combining hyaluronidase with a 1:1 mixture of bupivacaine 0.75% and lidocaine 2%.

Mechanism of action of Hyaluronidase (Hylenex):

• This causes hydrolysis of hyaluronic acids (one of the main components of tissue cement that resists diffusion of liquids through tissue) and results in altered permeability of connective tissues.
• It causes increased distribution/dispersion and absorption of locally injected or extravasated IV medications.

The beginning of action:

• SubQ: Instant; extravasation usually causes a reduction in swelling within 15-30 minutes.

Duration:

• 24 to 48 hours (variable)

International Brand Names of Hyaluronidase:

• Amphadase
• Hylenex
• Vitrase
• Facidase
• H-lase
• Hyalase
• Hyalasedessau
• Hyalozima
• Hyaluronidase Choay
• Hyanid
• Hyase
• Hyason
• Hylase
• Hylorase
• Hynidase
• Jaluran
• Lasonil
• Longidaza
• Lydase
• Lyrase
• Malinda
• Nydase
• Penetrase
• Permease
• Sprase
• Unidasa
• Vitrase

Hyaluronidase Injection Brand Names in Pakistan: