HYLENEX Recombinant (Page 2 of 2)

8.3 Nursing Mothers

It is not known whether hyaluronidase is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when hyaluronidase is administered to a nursing woman.

8.4 Pediatric Use

Clinical hydration requirements for children can be achieved through administration of subcutaneous fluids facilitated with HYLENEX recombinant.

The dosage of subcutaneous fluids administered is dependent upon the age, weight, and clinical condition of the patient as well as laboratory determinations. The potential for chemical or physical incompatibilities should be kept in mind [see Drug Interactions (7)].

The rate and volume of subcutaneous fluid administration should not exceed those employed for intravenous infusion. 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.

During subcutaneous fluid administration, special care must be taken in pediatric patients to avoid over hydration by controlling the rate and total volume of the infusion [see Dosage and Administration (2.1)].

8.5 Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger adult patients.

11 DESCRIPTION

HYLENEX recombinant is a purified preparation of the enzyme recombinant human hyaluronidase. HYLENEX recombinant is produced by genetically engineered Chinese Hamster Ovary (CHO) cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20). The purified hyaluronidase glycoprotein contains 447 amino acids with an approximate molecular weight of 61,000 Daltons.

HYLENEX recombinant is supplied as a sterile, clear, colorless, nonpreserved, ready-for-use solution. Each mL contains 150 USP units of recombinant human hyaluronidase with 8.5 mg sodium chloride, 1.4 mg dibasic sodium phosphate, 1 mg albumin human, 1.5 mg L-methionine, 0.2 mg polysorbate 80, and hydrochloric acid and sodium hydroxide added for pH adjustment.

HYLENEX recombinant has an approximate pH of 7.0 and an osmolality of 280 to 340 mOsm/kg.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

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. Hyaluronidase hydrolyzes hyaluronic acid by splitting the glucosaminidic bond between C1 of an N-acetylglucosamine moiety and C4 of a glucuronic acid moiety. This temporarily decreases the viscosity of the cellular cement and promotes dispersion of injected fluids or of localized transudates or exudates, thus facilitating their absorption.

Hyaluronidase cleaves glycosidic bonds of hyaluronic acid and, to a variable degree, some other acid mucopolysaccharides of the connective tissue. The activity is measured in vitro by monitoring the decrease in the amount of an insoluble serum albumin-hyaluronic acid complex as the enzyme cleaves the hyaluronic acid component.

12.2 Pharmacodynamics

In the absence of hyaluronidase, material injected subcutaneously disperses very slowly. Hyaluronidase facilitates dispersion, provided local interstitial pressure is adequate to furnish the necessary mechanical impulse. Such an impulse is normally initiated by injected solutions. The rate and extent of dispersion and absorption is proportionate to the amount of hyaluronidase and the volume of solution.

The reconstitution of the dermal barrier removed by intradermal injection of hyaluronidase (20, 2, 0.2, 0.02, and 0.002 U/mL) to adult humans indicated that at 24 hours the restoration of the barrier is incomplete and inversely related to the dosage of hyaluronidase; at 48 hours, the barrier is completely restored in all treated areas.

Results from an experimental study, in humans, on the influence of hyaluronidase in bone repair support the conclusion that hyaluronidase alone, in the usual clinical dosage, does not deter bone healing.

12.3 Pharmacokinetics

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.

Studies have demonstrated that hyaluronidase is antigenic; repeated injections of relatively large amounts of hyaluronidase preparations may result in the formation of neutralizing antibodies.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Hyaluronidase is found in most tissues of the body. Long-term animal studies have not been performed to assess the carcinogenic or mutagenic potential of hyaluronidase.

Human studies on the effect of intravaginal hyaluronidase in sterility due to oligospermia indicated that hyaluronidase may have aided conception. Thus, it appears that hyaluronidase may not adversely affect fertility in females. In addition, when recombinant human hyaluronidase was administered to cynomolgus monkeys for 39 weeks at dose levels up to 220,000 U/kg, no evidence of toxicity to the male or female reproductive system was found through periodic monitoring of in-life parameters, e.g., semen analyses, hormone levels, menstrual cycles, and also from gross pathology, histopathology and organ weight data.

14 CLINICAL STUDIES

HYLENEX recombinant facilitated the administration of subcutaneous fluids in pediatric patients with mild to moderate dehydration in an open-label, multicenter, single arm study in fifty-one (51) patients. A subcutaneous injection of 1 mL (150 U) of HYLENEX recombinant was immediately followed by subcutaneous infusion of isotonic fluids in either the mid-anterior thigh or the inter-scapular area of the upper back.

The safety and flow rate of subcutaneously administered Lactated Ringer’s (LR) solution with and without HYLENEX recombinant was evaluated in a prospective, randomized, double-blinded, placebo-controlled, within-subject, single-center study in fifty-four (54) healthy volunteers. The mean HYLENEX recombinant facilitated infusion rate was 464 mL/hr versus 118 mL/hr for the saline control (p < 0.001, paired t-test).

16 HOW SUPPLIED/STORAGE AND HANDLING

HYLENEX recombinant is supplied sterile as 150 USP units of nonpreserved recombinant human hyaluronidase per mL in a single-use glass vial.

HYLENEX recombinant is supplied in the following packaging:

1 mL Single Dose Vial (NDC 18657-117-01) available in boxes of 4 (NDC 18657-117-04)

Store unopened in a refrigerator at 2° to 8°C (36° to 46° F).

DO NOT FREEZE.

17 PATIENT COUNSELING INFORMATION

17.1 Important Precautions Regarding HYLENEX recombinant

Instruct patient that HYLENEX recombinant is being used to increase the dispersion and absorption of fluids or other injected drugs, as appropriate to the intended use.

Instruct patient that there may be mild local injection site signs and symptoms, such as redness, swelling, itching, or pain localized to the site of injection.

17.2 What Patients Should Know About Adverse Reactions

Patients should be advised that the most frequently reported adverse reactions have been mild local injection site reactions such as redness, swelling, itching, or pain.

Anaphylactic-like reactions, and allergic reactions, such as hives, have been reported rarely in patients receiving hyaluronidases.

17.3 Patients Should Inform Their Doctors If Taking Other Medications

Instruct patients that they may not receive furosemide, the benzodiazepines, phenytoin, dopamine and/or alpha agonists with HYLENEX recombinant. These medications have been found to be incompatible with hyaluronidase.

Patients should be advised that if they are taking salicylates (e.g., aspirin), steroids (e.g., cortisone or estrogens), or antihistamines, they may need to be prescribed larger amounts of hyaluronidase for equivalent dispersing effect.

Hylenex, the Hylenex logo and Halozyme Therapeutics are trademarks of Halozyme, Inc.

U.S. Patent Nos. 7,767,429, 8,202,517, 8,431,124 and 8,431,380

Manufactured for and Marketed by: Halozyme Therapeutics, Inc., San Diego, CA 92121

For Product Inquiry: 1 855 495-3639

Rev. February 2016
LBL301-05

PRINCIPAL DISPLAY PANEL — 1 mL Vial Carton

NDC 18657-117-04

Hylenex®
recombinant 4 x 1 mL
(hyaluronidase
human injection)

150 USP units/mL
NOT FOR IV USE
REFRIGERATE

Rx only

Single Dose Vials
HALOZYME THERAPEUTICS

PRINCIPAL DISPLAY PANEL -- 1 mL Vial Carton
(click image for full-size original)
HYLENEX RECOMBINANT
hyaluronidase (human recombinant) injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:18657-117
Route of Administration SUBCUTANEOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Hyaluronidase (Human Recombinant) (Hyaluronidase (Human Recombinant)) Hyaluronidase (Human Recombinant) 150 [USP’U] in 1 mL
Inactive Ingredients
Ingredient Name Strength
sodium chloride 8.5 mg in 1 mL
SODIUM PHOSPHATE, DIBASIC, UNSPECIFIED FORM 1.4 mg in 1 mL
albumin human 1 mg in 1 mL
Methionine 1.5 mg in 1 mL
polysorbate 80 0.2 mg in 1 mL
hydrochloric acid
sodium hydroxide
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:18657-117-04 4 BOX in 1 CARTON contains a BOX (18657-117-02)
1 NDC:18657-117-02 1 VIAL in 1 BOX This package is contained within the CARTON (18657-117-04) and contains a VIAL (18657-117-01)
1 NDC:18657-117-01 1 mL in 1 VIAL This package is contained within a BOX (18657-117-02) and a CARTON (18657-117-04)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA021859 12/02/2005
Labeler — Halozyme Therapeutics, Inc. (026077359)
Establishment
Name Address ID/FEI Operations
Patheon Manufacturing Services LLC 079415560 MANUFACTURE (18657-117)

Revised: 04/2021 Halozyme Therapeutics, Inc.

Page 2 of 2 1 2

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.