AMPHADASE (Page 2 of 2)

8.5 Geriatric Use

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

11 DESCRIPTION

Amphadase® is a preparation of purified bovine testicular hyaluronidase, a protein enzyme. The exact chemical structure of this enzyme is unknown. However, the amino acid sequence for the primary structure of the enzyme has been deduced from the sequence of purified peptides.

Amphadase® (hyaluronidase injection) is supplied as a sterile, clear, colorless, ready for use solution. Each vial contains 150 USP units of hyaluronidase per mL with 8.5 mg sodium chloride, 1 mg edetate disodium, 0.4 mg calcium chloride, monobasic sodium phosphate buffer, and not more than 0.1 mg thimerosal (mercury derivative).

Amphadase® has an approximate pH of 6.8 and an osmolality of 295 to 355 mOsm.

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 Cl 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.

Results from an experimental study, in humans, on the influence of hyaluronidase in bone repair support the conclusion that this enzyme 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 blood of a number of mammalian species brings about the inactivation of hyaluronidase.

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

13 NONCLINICAL TOXICOLOGY


13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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

Long-term animal studies have not been performed to assess whether hyaluronidase impaired fertility; however, it has been reported that testicular degeneration may occur with the production of organ-specific antibodies against this enzyme following repeated injections. 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.

16 HOW SUPPLIED/STORAGE AND HANDLING

Amphadase® (hyaluronidase injection) is supplied sterile as 150 USP units of hyaluronidase per mL in a 2 mL single-use glass vial with a gray rubber stopper and aluminum flip-off seal.

NDC 0548-9090-10, 1 mL vial, 10 vials/carton.

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

17 PATIENT COUNSELING INFORMATION

17.1 Important Precautions Regarding Amphadase®

Instruct patient that Amphadase® 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

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

You may not receive furosemide, the benzodiazepines, phenytoin, dopamine and/or alpha agonists with Amphadase®. These medications have been found to be incompatible with hyaluronidase.

If you are taking salicylates (e.g., aspirin), steroids (e.g., cortisone or estrogens), or antihistamines your doctor may need to prescribe larger amounts of hyaluronidase for equivalent dispersing effect.

Amphastar Pharmaceuticals, Inc.
Rancho Cucamonga, CA 91730, U.S.A.
Rev. 5/14

6990906P

PRINCIPLE DISPLAY PANEL: Carton: 1mL

NDC 0548-9090-10

Stock No 9091

AMPHADASE® HYALURONIDASE INJECTION, USP

Not for IV use.

See Enclosed Directions.

10 x 1 mL Single Dose Vials

Rx Only

1 mL

Each mL contains 150 USP units hyaluronidase with 8.5 mg sodium chloride,

1 mg edetate disodium, 0.4 mg calcium chloride, monobasic sodium phosphate buffer, and

not more than 0.1 mg thimerosal (mercury derivative).

Usual dosage: See enclosed information for parenteral route and specific conditions.

Amphadase is ready for injection.

Store in Refrigerator

10 Carton
(click image for full-size original)
AMPHADASE
hyaluronidase injection
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0548-9090
Route of Administration SUBCUTANEOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
hyaluronidase (hyaluronidase ) hyaluronidase 150 [USP’U] in 1 mL
Inactive Ingredients
Ingredient Name Strength
sodium chloride 8.5 mg in 1 mL
edetate disodium 1 mg in 1 mL
calcium chloride 0.4 mg in 1 mL
SODIUM PHOSPHATE, MONOBASIC
thimerosal
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0548-9090-10 10 VIAL, SINGLE-DOSE in 1 CARTON contains a VIAL, SINGLE-DOSE
1 1 mL in 1 VIAL, SINGLE-DOSE This package is contained within the CARTON (0548-9090-10)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA021665 10/26/2004
Labeler — Amphastar Pharmaceuticals, Inc. (024736733)
Establishment
Name Address ID/FEI Operations
Amphastar Pharmaceuticals, Inc. 024736733 analysis (0548-9090), manufacture (0548-9090)

Revised: 05/2020 Amphastar Pharmaceuticals, Inc.

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