dering the administration of any other drug with hyaluronidase, it is recommended that appropriate references first be consulted to determine the usual precautions for the use of the other drug; e.g., when epinephrine is injected along with hyaluronidase, the precautions for the use of epinephrine in cardiovascular disease, thyroid disease, diabetes, digital nerve block, ischemia of the fingers and toes etc., should be observed. 7.3 local anesthetics when hyaluronidase is added to a local anesthetic agent, it hastens 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.

is injected subcutaneously over each scapula, followed by injection of the contrast medium at the same sites. ( 2.3 ) 2.1 subcutaneous fluid administration (hypodermoclysis) insert needle with aseptic precautions. with tip lying free and movable between skin and muscle, begin clysis; fluid should start in readily without pain or lump. then inject amphadase ® (hyaluronidase injection) into rubber tubing close to needle. an alternate method is to inject amphadase ® under skin prior to clysis. 150 u 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 andelectrolyte 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. amphadase ® 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. 2.2 absorption and dispersion of injected drugs absorption and dispersion of other injected drugs may be enhanced by adding 50-300 units, most typically 150 u hyaluronidase, to the injection solution. 2.3 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 u of amphadase ® (hyaluronidase injection) is injected subcutaneously over each scapula, followed by injection of the contrast medium at the same sites.

fda at 1-800-fda-1088 or www.fda.gov/medwatch.

dering the administration of any other drug with hyaluronidase, it is recommended that appropriate references first be consulted to determine the usual precautions for the use of the other drug; e.g., when epinephrine is injected along with hyaluronidase, the precautions for the use of epinephrine in cardiovascular disease, thyroid disease, diabetes, digital nerve block, ischemia of the fingers and toes etc., should be observed. 7.3 local anesthetics when hyaluronidase is added to a local anesthetic agent, it hastens 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.

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 the safety and effectiveness of amphadase ® have been established in pediatric patients. use of amphadase ® 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 amphadase ® . 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.

in pediatric patients to avoid over hydration by controlling the rate and total volume of the infusion [see dosage and administration (2.1) ].

nt 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.

ou 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.