Vitrase

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Common side effects may include:

• pain, itching, or redness where the injection was given; or
• swelling in your hands, feet, or body areas.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Included as part of the PRECAUTIONS section.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

The following adverse reactions have been identified during post-approval use of hyaluronidase products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most frequently reported adverse reactions have been local injection site reactions.

Hyaluronidase has been reported to enhance the adverse reactions associated with co-administered drug products. Edema has been reported most frequently in association with hypodermoclysis.

Allergic reactions (urticaria,� angioedema) have been reported in less than 0.1% of patients receiving hyaluronidase. Anaphylactic-like reactions following retrobulbar block or intravenous injections have occurred, rarely.

Read the entire FDA prescribing information for Vitrase (Hyaluronidase Injection)

• Bausch & Lomb Incorporated

• Ista Pharmaceuticals, Inc.

Your doctor will check your progress closely while you are receiving this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to receive it.

This medicine is made from donated human blood products. Some human blood products have transmitted viruses to people who have received them, although the risk is low. Human donors and donated blood are both tested for viruses to keep the transmission risk low. Talk with your doctor about this risk if you are concerned.

Some people may be allergic to this medicine. Tell your doctor if you develop a rash, hives, red or itching skin, or troubled breathing after you receive hyaluronidase.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

• If you have an allergy to hyaluronidase or any other part of Vitrase (hyaluronidase injection).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have an infection or skin problem where the shot will be given.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Vitrase with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Spread of Localized Infection

Hyaluronidase should not be injected into or around infected or acutely inflamed area because of the danger of spreading to a localized infection. Hyaluronidase should not be used to reduce the swelling of bites or stings.

Ocular Damage

Vitrase should not be applied directly to the cornea.

Enzyme Inactivation with Intravenous Administration

Vitrase should not be used for intravenous injections because the enzyme is rapidly inactivated.

Pregnancy

Pregnancy Category C: Animal reproduction studies have not been conducted with Vitrase. Human studies on the effect of intravaginal hyaluronidase in sterility due to oligospermia indicated the hyaluronidase may have aided conception. Thus, it appears that hyaluronidase may not adversely affect fertility in females. Vitrase should be given to a pregnant woman only if clearly needed.

Labor and Delivery

Administration of hyaluronidase during labor was reported to cause no complications: no increase in blood loss or differences in cervical trauma were observed.

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.

Pediatric Use

The safety and effectiveness of Vitrase have been established in pediatric patients. Use of Vitrase in these patients is supported by evidence from adequate and well controlled studies. Clinical hydration requirements for children can be achieved through administration of subcutaneous fluids facilitated with Vitrase.

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)].

Geriatric Use

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

Mechanism of Action

Hyaluronidase is a spreading or diffusing substance, 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 the glucosamine moiety and C4 of glucuronic acid. This temporarily decreases the viscosity of the cellular cement and promotes diffusion 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 albumen-hyaluronic acid complex as the enzyme cleaves the hyaluronic acid component.

Pharmacodynamics

In the absence of hyaluronidase, material injected subcutaneously spreads 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 Units/mL) to adult humans indicated that at 24 hours the restoration of the barrier is incomplete and inversely related to the dosage of enzyme; 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 this enzyme alone, in the usual clinical dosage, does not deter bone healing.

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.