FDA批准重组人类透明质酸酶注射剂（Recombinant Human Hyaluronidase Injection，商品名Hylenex）作为其他注射药物的辅助药物（促进吸收和扩散），用于皮下注射以及皮下尿路造影术中促进不透射线物质的吸收 日前宣布HYLENEX复合剂（透明质酸酶人体注射剂）在眼科市场上市。该药物用于促进其他注射药物的吸收和扩散。HYLENEX是第一个，也是唯一一个人体复合透明质酸酶医疗产品。百特公司提供的产品以一毫升单独包装，每支含有150个单位的透明质酸酶。 “作为一种复合蛋白质，HYLENEX代表着先进的和更加稳 定的透明质酸酶供应，巧妙地解决了历史上与动物获取产品相伴随的质量和供应问题。”Halozyme医疗有限公司副总裁兼首席科学官GregoryFrost博士说，“此外，从复合来源取得的人体蛋白质帮助减轻了对种间病原传送的担忧，降低了动物获取产品产生免疫反应的潜在可能。” 由于HYLENEX被引入眼科市场，百特将继续发展它的INFUSE临床项目。在这个项目中，HYLENEX和其他溶液或药物将被皮下注射给患者。INFUSE试验正在测试HYLENEX是否有可能为静脉注射有困难的患者提供一种替代性注射途径。 HYLENEX获得了美国食品药品管理局的许可，作为一种散布介质提高其他注射药物的吸收和扩散程度，以及用于皮下水合作用。HYLENEX的研发是与Halozyme医疗有限公司 HYLENEX重组-重组人注射透明质酸 百特医疗用品公司 HYLENEX重组（人类注射透明质酸） 初步U. S.批准：2005年   适应症 HYLENEX重组是一个组织的渗透性改性剂作为辅助显示 在实现水化皮下输液 增加其他注射毒品的分散和吸收 在皮下尿路造影改善透X线的代理商的吸收   剂量和用法 皮下积液管理： 注入150 U HYLENEX重组前皮下积液管理。这将有利于吸收1000毫升或更多的解决方案。皮下液体管理的剂量取决于病人的年龄，体重和临床状况以及实验室测定。皮下输液的速度和量不应超过静脉滴注就业者 增加注射毒品的分散和吸收： 50-300 U（最典型的150 U）HYLENEX重组注射液。物理或化学的不兼容性的参考咨询建议 皮下尿路造影： 注入75 ü在每个肩胛骨HYLENEX重组皮下，注射造影剂在相同的网站   剂型和优势 150美国药典单位/ ml单剂量小瓶   禁忌 超敏反应   警告和注意事项 局部感染传播 眼损伤 静脉给药的酶失活   不良反应 最常见的不良反应有轻度局部注射部位反应； 过敏性和过敏性反应的报道，很少； 1-866-888-2472或FDA报告疑似不良反应，请联系百特医疗用品公司，在1 - 800 - FDA - 1088或www.fda.gov / MedWatch通报。   药物相互作用 速尿，地西泮和苯妥英不与透明质酸。 不应该用来提高多巴胺和/或α受体激动剂药物的分散和吸收透明质酸 局部麻醉药：透明质酸赶忙发病和效果的持续时间缩短，增加全身反应的发生率。 大剂量水杨酸，可的松，促肾上腺皮质激素，雌激素或抗组胺药可能需要分散效果相当于较大数额的透明质酸。 在特殊人群中使用 儿童用药：儿童的临床水化要求，可以通过管理HYLENEX重组促进皮下流体实现。皮下液体管理的剂量取决于病人的年龄，体重和临床状况以及实验室测定。对于早产儿或新生儿期间，每日剂量不应超过25毫升/公斤体重，和管理率不应大于2毫升每分钟。在皮下积液管理，必须特别注意​​在儿童患者中，控制率和输液总量，以避免过度水化。 耐心辅导资料17 修订日期：12/2009 These highlights do not include all the information needed to use HYLENEX recombinant safely and effectively. See full prescribing information for HYLENEX recombinant. HYLENEX recombinant (hyaluronidase human injection) Initial U.S. Approval: 2005 HYLENEX recombinant is indicated as an adjuvant in subcutaneous fluid administration for achieving hydration. HYLENEX recombinant is indicated as an adjuvant to increase the dispersion and absorption of other injected drugs. HYLENEX recombinant is indicated as an adjunct in subcutaneous urography for improving resorption of radiopaque agents. Always use aseptic precautions. Lightly pinch the skin up into a small mound and insert the needle/catheter into the subcutaneous space. Inject HYLENEX recombinant through the catheter hub or injection port closest to the needle/catheter. Begin administration of the injection solution. Solution should start in readily. 150 U of HYLENEX recombinant injected prior to start of subcutaneous fluid administration will facilitate absorption of 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 of body weight, and the rate of administration should not be greater than 2 mL per minute. Dispersion and absorption of other injected drugs may be enhanced by adding 50-300 U, most typically 150 U hyaluronidase, to the injection solution. It is recommended that appropriate references be consulted regarding physical or chemical incompatibilities before adding HYLENEX recombinant to a solution containing another drug. 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 HYLENEX recombinant is injected subcutaneously over each scapula, followed by injection of the contrast medium at the same sites. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. 150 USP units/mL single dose vials HYLENEX is contraindicated in patients with known hypersensitivity to hyaluronidase or any of the excipients in HYLENEX. A preliminary skin test for hypersensitivity to HYLENEX recombinant can be performed. The skin test is made by an intradermal injection of approximately 0.02 mL (3 Units) of a 150 Unit/mL solution. A positive reaction consists of a wheal with pseudopods appearing within 5 minutes and persisting for 20 to 30 minutes and accompanied by localized itching. Transient vasodilation at the site of the test, i.e., erythema, is not a positive reaction. Hyaluronidase should not be injected into or around an infected or acutely inflamed area because of the danger of spreading a localized infection. Hyaluronidase should not be used to reduce the swelling of bites or stings. Hyaluronidase should not be applied directly to the cornea. It is not for topical use. HYLENEX recombinant should not be administered intravenously. Its effects relative to dispersion and absorption of other drugs are not produced when it is administered intravenously because the enzyme is rapidly inactivated. 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 experiences have been mild local injection site reactions such as erythema and pain. Hyaluronidase has been reported to enhance the adverse events associated with co-administered drug products. Edema has been reported most frequently in association with subcutaneous fluid administration. Allergic reactions (urticaria or 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. Furosemide, the benzodiazepines and phenytoin have been found to be incompatible with hyaluronidase. Hyaluronidase should not be used to enhance the dispersion and absorption of dopamine and/or alpha agonist drugs. When considering 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. 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. 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. Pregnancy Category C. Animal reproduction studies have not been conducted with HYLENEX recombinant. It is also not known whether HYLENEX recombinant can cause fetal harm when administered to a pregnant woman. HYLENEX recombinant should be given to a pregnant woman only if clearly needed. Administration of hyaluronidase during labor was reported to cause no complications: no increase in blood loss or differences in cervical trauma were observed. 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. 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) ]. No overall differences in safety or effectiveness have been observed between elderly and younger adult patients. HYLENEX recombinant is a purified preparation of the enzyme recombinant human hyaluronidase. HYLENEX recombinant is produced by genetically engineered Chinese Hamster Ovary (CHO) cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20). The purified hyaluronidase glycoprotein contains 447 amino acids with an approximate molecular weight of 61,000 Daltons. HYLENEX recombinant is supplied as a sterile, clear, colorless, nonpreserved, ready for use solution. Each mL contains 150 USP units of recombinant human hyaluronidase with 8.5 mg sodium chloride, 1.4 mg dibasic sodium phosphate, 1.0 mg albumin human, 0.9 mg edetate disodium, 0.3 mg calcium chloride, and sodium hydroxide added for pH adjustment. HYLENEX recombinant has an approximate pH of 7.4 and an osmolality of 290 to 350 mOsm. 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 C1 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. 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. 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. 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. 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. HYLENEX recombinant facilitated the administration of subcutaneous fluids in pediatric patients with mild to moderate dehydration in an open-label, multicenter, single arm study in fifty-one (51) patients. A subcutaneous injection of 1 mL (150 U) of HYLENEX recombinant was immediately followed by subcutaneous infusion of isotonic fluids in either the mid-anterior thigh or the inter-scapular area of the upper back. The safety and flow rate of subcutaneously administered Lactated Ringer's (LR) solution with and without HYLENEX recombinant was evaluated in a prospective, randomized, double-blinded, placebo-controlled, within-subject, single-center study in fifty-four (54) healthy volunteers. The mean HYLENEX recombinant facilitated infusion rate was 464 mL/hr versus 118 mL/hr for the saline control (p < 0.001, paired t-test). HYLENEX recombinant is supplied sterile as 150 USP units of nonpreserved recombinant human hyaluronidase per mL in a single-use glass vial. 1 mL Single Dose Vial available in boxes of 4 (NDC 60977-319-03) Not Recommended for IV Use. Store unopened in a refrigerator at 2° to 8°C (36° to 46° F). DO NOT FREEZE. Instruct patient that HYLENEX recombinant 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. 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. You may not receive furosemide, the benzodiazepines, phenytoin, dopamine and/or alpha agonists with HYLENEX. 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. Baxter and Hylenex are registered trademarks of Baxter International Inc. Halozyme is a registered trademark of Halozyme Therapeutics, Inc. Baxter Marketed by: Baxter Healthcare CorporationDeerfield, IL 60015 USA HalozymeTHERAPEUTICS Manufactured for: Halozyme Therapeutics, Inc.San Diego, CA 92121 By Baxter Pharmaceutical Solutions LLCBloomington, IN 47403 For Product Inquiry 1 800 ANA DRUG (1-800-262-3784) PRINCIPAL DISPLAY PANEL - 1 mL Vial Carton NDC 60977-319-02 Hylenex 1 mLrecombinant(hyaluronidasehuman injection) 150 USP units/mLNOT FOR IV USERx onlyREFRIGERATE Single Dose Vial Marketed by Baxter Healthcare Corporation Deerfield, IL 60015 USAManufactured for Halozyme Therapeutics, Inc. San Diego, CA 92121by Baxter Pharmaceutical Solutions LLCBloomington, IN 47403