tens the onset of analgesia and tends to reduce the swelling caused by local infiltration, but the wider spread of the local anesthetic solution increases its absorption; this shortens its duration of action and tends to increase the incidence of systemic reaction. 7.4 salicylates, cortisone, acth, estrogens and antihistamines patients receiving large doses of salicylates, cortisone, acth, estrogens or antihistamines may require larger amounts of hyaluronidase for equivalent dispersing effect, since these drugs apparently render tissues partly resistant to the action of hyaluronidase.

luid administration to facilitate absorption of up to 1,000 ml or more of solution. as with all parenteral fluid therapy, observe effect closely, with the 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 administered subcutaneously, 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. hylenex recombinant may be added to small volumes of solution, such as fluid replacement solutions or solutions of drugs for subcutaneous injection. subcutaneous fluids should be administered as directed by a physician. the dosage of subcutaneous fluids administered is dependent upon the age, weight, and clinical condition of the patient as well as laboratory determinations. 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 and the rate of administration should not be greater than 2 ml per minute. 2.3 dispersion and absorption of injected drugs hylenex can be used to enhance the dispersion and absorption of other injected or subcutaneously infused drugs by pre-administration of hylenex recombinant or by adding 50-300 u, most typically 150 u hyaluronidase, to the injection solution prior to infiltration use, interstitial use, intramuscular use, intraocular use, retrobulbar use, soft tissue use or subcutaneous use. 2.4 subcutaneous urography the subcutaneous route of administration of urographic contrast media may be considered when intravenous administration cannot be successfully accomplished, particularly in infants and small children. with the patient prone, inject 75 u of hylenex recombinant subcutaneously over each scapula, followed by injection of the contrast medium at the same sites.

tens the onset of analgesia and tends to reduce the swelling caused by local infiltration, but the wider spread of the local anesthetic solution increases its absorption; this shortens its duration of action and tends to increase the incidence of systemic reaction. 7.4 salicylates, cortisone, acth, estrogens and antihistamines patients receiving large doses of salicylates, cortisone, acth, estrogens or antihistamines may require larger amounts of hyaluronidase for equivalent dispersing effect, since these drugs apparently render tissues partly resistant to the action of hyaluronidase.

should be given to a pregnant woman only if clearly needed. 8.2 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. 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.

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.