Hyaluronidase

This is not a complete list of Hyaluronidasedrug interactions. Ask your doctor or pharmacist for more information.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Hyaluronidase falls into category C:

In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans, though. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

OR

There are no well-controlled studies that have been done in pregnant women. Hyaluronidase should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

OR

No studies have been done in animals, and no well-controlled studies have been done in pregnant women. Hyaluronidase should be given to a pregnant woman only if clearly needed.

Hyaluronidase is available in the following forms:

• Injectable Solution
• Topical Cream
• Topical Lotion
• Topical Ointment

• Antidote, Extravasation
• Enzyme

Extravasation management

Based on the Oncology Nursing Society (ONS) and the European Society for Medical Oncology (ESMO) and European Oncology Nursing Society (EONS), and other clinical experiences, hyaluronidase may be used for extravasation management of several drug extravasations (eg, aminophylline, calcium salts, contrast agents, dextrose, epipodophyllotoxins, mannitol, nafcillin, parenteral nutrition, phenytoin, potassium salts, vinca alkaloids) [ESMO/EONS [Perez Fidalgo 2012]], [Macara 1983], [ONS [Polovich 2009]], [Rowlett 2012], [Schulmeister 2011], [Weigand 2009], [Zenk 1981].

Local anesthetic adjuvant

Data from three prospective, randomized, double-blinded studies using hyaluronidase as an adjuvant for local anesthetic administration (eg, peribulbar block) including a pharmacokinetic study supports the use of hyaluronidase in this setting [Kallio, 2000], [Moharib 2002], [Nathan 1996], [Van Den Berg 2001]. Clinical experience also suggests the utility of hyaluronidase as an adjuvant for local anesthetic administration [Barash 2010], [Lai 2003].

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

Amphadase, Hylenex: Store intact vials in refrigerator at 2°C to 8°C (36°F to 46°F); do not freeze.

Vitrase: Store intact vials in refrigerator at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. If adding to other injectable solutions, store admixture at 15°C to 25°C (59°F to 77°F) and use within 6 hours.

Alpha-/Beta-Agonists: Hyaluronidase may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Management: Avoid the use of hyaluronidase to enhance 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. Exceptions: Dipivefrin; EPINEPHrine (Nasal); EPINEPHrine (Oral Inhalation); Isometheptene; Pseudoephedrine. Consider therapy modification

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

Corticosteroids: 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. Exceptions: Beclomethasone (Nasal); Budesonide (Nasal); Ciclesonide (Nasal); Desonide; Dexamethasone (Ophthalmic); Difluprednate; Flunisolide (Nasal); Fluocinolone (Ophthalmic); Fluticasone (Nasal); Hydrocortisone (Ophthalmic); Loteprednol; Mometasone (Nasal); PrednisoLONE (Ophthalmic); Triamcinolone (Nasal); Triamcinolone (Ophthalmic). Consider therapy modification

DOPamine: Hyaluronidase may enhance the adverse/toxic effect of DOPamine. Management: Avoid the use of hyaluronidase to enhance dispersion or absorption of dopamine. Use of hyaluronidase for other purposes in patients receiving dopamine may be considered as clinically indicated. Consider therapy modification

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

Local Anesthetics: Hyaluronidase may enhance the adverse/toxic effect of Local Anesthetics. Exceptions: Benzocaine; Benzydamine; Cocaine; Dibucaine; Dyclonine; Ethyl Chloride; Hexylresorcinol; Lidocaine (Ophthalmic); Lidocaine (Topical); Pramoxine; Proparacaine; Tetracaine (Ophthalmic); Tetracaine (Topical). Monitor therapy

Phenylephrine (Systemic): Hyaluronidase may enhance the vasoconstricting effect of Phenylephrine (Systemic). Management: Avoid the use of hyaluronidase to enhance dispersion or absorption of phenylephrine. Use of hyaluronidase for other purposes in patients receiving phenylephrine may be considered as clinically indicated. Avoid combination

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

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).

• Sensitization: Discontinue if sensitization occurs (a skin test may be performed to determine hypersensitivity).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Albumin: Some products may contain albumin; albumin carries an extremely remote risk for transmission of viral diseases, Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD). No cases of transmission of viral diseases, CJD, or vCJD have been identified for licensed albumin or albumin contained in other licensed products.

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: 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.

Adverse events have not been observed in animal reproduction studies (not conducted with all products). Administration during labor did not cause any increase in blood loss or differences in cervical trauma. It is not known whether it affects the fetus if used during labor. Hyaluronidase has been evaluated for use prior to intracytoplasmic sperm injection (ICSI) to increase male fertility (DeVos, 2008; Evison, 2009).