Hyaluronidase, Ovine

1 INDICATIONS AND USAGE VITRASE is an endoglycosidase indicated as an adjuvant: in subcutaneous fluid administration for achieving hydration. ( 1.1 ) for increasing the dispersion and absorption of other injected drugs. ( 1.2 ) for improving resorption of radiopaque agents, in subcutaneous urography. ( 1.3 ) 1.1 Subcutaneous Fluid Administration (Hypodermoclysis) VITRASE ® (hyaluronidase injection) is indicated as an adjuvant in subcutaneous fluid administration for achieving hydration. 1.2 Dispersion and Absorption of Injected Drugs VITRASE is indicated as an adjuvant to increase the dispersion and absorption of other injected drugs. 1.3 Subcutaneous Urography VITRASE is indicated as an adjuvant in subcutaneous urography for improving resorption of radiopaque agents.

2 DOSAGE AND ADMINISTRATION Draw the desired amount of VITRASE into the syringe to obtain target hyaluronidase activity (USP Units) according to table. ( 2.1 ) Before adding VITRASE to a solution containing another drug check appropriate references regarding physical/chemical incompatibilities. ( 7 ) Subcutaneous Fluid Administration : Inject 200 Units of VITRASE prior to clysis. It will facilitate absorption of 1,000 mL or more of solution. The dosage of subcutaneous fluids administered depends upon the age, weight, clinical condition of the patient, and laboratory determinations. Rate and volume of subcutaneous fluid administration should not exceed those employed for intravenous infusion. ( 2.2 , 8.4 ) Increasing absorption and dispersion of injected drugs : Add 50–300 Units (most typically 150 Units) of VITRASE to the injection solution. ( 2.3 ) Subcutaneous urography : With the patient prone, inject 75 Units of VITRASE subcutaneously over each scapula, followed by injection of the contrast medium at the same sites. ( 2.4 ) 2.1 Important Administration Instructions Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. VITRASE should be administered as discussed below, since its effects relative to absorption and dispersion of other drugs are not produced when it is administered intravenously. Draw the desired amount of VITRASE into the syringe to obtain the target Hyaluronidase Activity (USP Units) according to the table below. Table 1. Amount of VITRASE Solution Withdrawn Per Target Hyaluronidase Activity Target Hyaluronidase Activity (USP Units) Volume Withdrawn from Vial (mL) 50 Units 0.25 mL 75 Units 0.38 mL 150 Units 0.75 mL 200 Units 1.00 mL After admixture with drug, store at 15°C to 25°C (59°F to 77°F) and use within 6 hours. Consult the Prescribing Information of other drugs for additional storage information. 2.2 Dosage for Subcutaneous Fluid Administration (Hypodermoclysis) Insert needle with aseptic precautions. With tip free and movable between skin and muscle, begin clysis; fluid should start in readily without pain or lump. Then inject VITRASE into rubber tubing close to needle. An alternate method is to inject VITRASE under skin prior to clysis. 200 Units will facilitate absorption of 1,000 mL or more of solution. As with all parenteral fluid therapy, observe effect closely, with same precautions for restoring fluid and electrolyte balance as in intravenous injections. The dose, the rate of injection, and the type of solution (saline, glucose, Ringer’s, etc.) must be adjusted carefully to the individual patient. When solutions devoid of inorganic electrolytes are given by hypodermoclysis, hypovolemia may occur. This may be prevented by using solutions containing adequate amounts of inorganic electrolytes and/or controlling the volume and speed of administration. VITRASE may be added to small volumes of solution (up to 200 mL), such as small clysis for infants or solutions of drugs for subcutaneous injection. For infants and children less than 3 years old, the volume of a single clysis should be limited to 200 mL; and in premature infants or during the neonatal period, the daily dosage should not exceed 25 mL/kg of body weight; the rate of administration should not be greater than 2 mL per minute. For older patients, the rate and volume of administration should not exceed those employed for intravenous infusion. 2.3 Dosage for Absorption and Dispersion of Injected Drugs Absorption and dispersion of other injected drugs may be enhanced by adding 50 Units to 300 Units, most typically 150 Units of VITRASE to the injection solution. 2.4 Dosage for Subcutaneous Urography The subcutaneous route of administration of urographic contrast media is indicated when intravenous administration cannot be successfully accomplished, particularly in infants and small children. With the patient prone, 75 Units of VITRASE are injected subcutaneously over each scapula, followed by injection of the contrast medium at the same sites.

6 ADVERSE REACTIONS 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 (e.g., 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. Allergic and anaphylactic-like reactions have been reported, rarely. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Bausch & Lomb Incorporated at 1-800-553-5340 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 including humans 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.