Nursing Procedure for Initiating Subcutaneous Fluid Administration with Hylenex Recombinant

Nursing Procedure for Initiating Subcutaneous Fluid Administration with hylenex recombinant

PREP INSERT INFUSE

Please see back cover for Indication and Important Safety Information and accompanying full Prescribing Information. These draft policies and procedures have been adapted from the Infusion Nurses Society (INS), the Oncology Nursing Society (ONS), and the hylenex recombinant (hyaluronidase human injection) prescribing information. It is the responsibility of the healthcare organization considering the use of this procedure to conduct an independent review and assessment to determine applicability and appropriateness of this document to their institution and to any particular clinical setting. Infusion therapies present risks; it is the responsibility of the healthcare organization to manage these risks, including the skills and competency validation of personnel. The healthcare organization that uses these guidelines should be aware that an annual review of organizational policies and procedures should continue to occur in accordance and compliance with regulatory and nonregulatory agencies.

The Purpose of this Guide To outline nursing responsibilities in providing symptom control and/or fluid and electrolyte replacement by administering fluids subcutaneously. Policy Subcutaneous access is utilized to administer fluids via single injection or continuous infusion into the subcutaneous tissue. The fluid is absorbed through both adipose and connective tissue.1 hylenex recombinant is used for subcutaneous fluid administration, enabling enzymatically augmented subcutaneous infusion.

In subcutaneous fluid administration, a catheter is placed in the subcutaneous tissue.1 Skilled and competent nurses knowledgeable in subcutaneous administration and the operation of electronic infusion devices may initiate and manage subcutaneous infusions.1 Some state and facility regulations allow this procedure to be performed by LVNs/LPNs. Please check your state guidelines in regard to administration regulations. The nurse who is administering subcutaneous isotonic fluids and electrolytes should be knowledgeable about the indications for use, appropriate rates of administration, monitoring parameters, adverse effects, stability of infusate, storage requirements, and potential complications.

Fluids given subcutaneously should be isotonic. 2

2 Recommended Equipment1

Gloves Tape Subcutaneous access device Appropriate antiseptic (see “Device Selection and Insertion” for options) Sharps container Subcutaneous infusion set

Syringe Extension tubing (optional)

Gauze Fluid

Transparent semipermeable membrane (TSM) Electronic infusion device (optional)

Safety cannula/needle

Medication hylenex recombinant [hyaluronidase human injection] (1 vial)

Procedure Assessing and Educating Patient1 1. Verify patient’s identity with them or parent/legally authorized guardian. 2. Obtain and review physician’s order for type of fluid, amount, rate, route of administration, frequency, duration, and titration parameters if applicable. PREP INSERT INFUSE 3. Plan patient’s care. 4. Per institutional protocol, obtain consent of patient or his/her parent or legally authorized guardian before administering therapy. 5. Educate patient (or his/her parent or legally authorized guardian) as to purpose and anticipated outcome of therapy, site placement, type of fluid, route of administration, adverse effects, and recognition of signs and symptoms of complications. Also educate concerned parties on possible alternatives to this method of fluid administration and possible complications of the alternatives. Include device operation instructions, if applicable. 6. Assess patient according to facility guidelines. 7. Place patient in a reclining, comfortable position based on site selected.

Prior to Beginning Procedure1 1. Assemble equipment. 2. Wash hands and dry thoroughly. 3. Put on gloves. 4. Use aseptic technique and observe standard precautions.

3 Procedure (continued) Insertion Site Selection 1. Site selection should be based on patient’s anticipated mobility and comfort.1 2. Assess sites for device placement in pediatric and adult patients3: a. Scapula region PREP INSERT INFUSE b. Anterior or lateral aspects of thighs c. Dorsal aspect of upper arm 3. Select insertion site with adequate subcutaneous tissue (a fat fold of at least 1 inch or 2.5 cm when forefinger and thumb are gently pinched together).1 4. Avoid areas with compromised integrity, such as, but not limited to1: a. Edema b. Pain c. Excoriation d. Infection e. Bruise or hematoma f. Scar tissue

Insertion Site Preparation1 1. (Optional Step) Remove excess hair from intended insertion site with clippers or scissors. 2. Wash insertion site with antiseptic soap and water, if necessary. 3. Disinfect insertion site. 4. Cleanse site and allow site to dry. (Do not blow or blot dry.)

Device Selection and Insertion 1. Select 24-gauge 3/4-inch flexible catheter, subcutaneous needle infusion set (SubQ button), or access device with 25- to 27-gauge 1/2-inch winged steel infusion set (butterfly needle). Inspect access set for defects. Select a continuous subcutaneous access device of the smallest gauge and shortest length necessary to establish subcutaneous access. 2. Prepare equipment and prime infusion set. 3. Lift skin into small mound.1 4. Insert infusion set/catheter bevel up into prepared site.1 5. Secure device and follow facility protocol for dressing. 6. Observe for negative blood return. If blood return is observed1: a. Remove device and select new insertion site b. Prepare new site c. Use new sterile infusion set 7. Secure administration-set tubing to skin to prevent accidental dislodgment.1 8. Label dressing per facility guidelines. hylenex recombinant Administration Injection before fluid administration: After obtaining subcutaneous access, inject hylenex recombinant via subcutaneous access device before initiation of fluid administration.PREP 150INSERT U of INFUSE hylenex recombinant will facilitate absorption of 1000 mL or more of solution.

Please see back cover for Indication and Important Safety Information and accompanying full Prescribing Information.

5 Procedure (continued) Subcutaneous Fluid Administration The rate and volume of subcutaneous fluid administration should not exceed those employed for intravenous infusion. 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.4 1. Deliver isotonic solutions subcutaneously.2 2. Inspect fluid container for leaks, cracks, or particulate matter.1 3. Initiate fluid administration per physician’s orders and monitor patient response. 4. Monitor patient’s response and observe for complications at insertion site at regular intervals per facility guidelines. 5. Rotate site per facility policy. 6. Document subcutaneous administration of fluids per facility guidelines.

For Premature Infants/Neonates 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.

Site Maintenance3 1. Observe site per facility policy. 2. Follow facility policy for catheter/needle replacement. 3. Replace catheter/needle if bruising, erythema, or other signs of local irritation or infection appear or if the site is painful to the patient. 4. Change transparent dressing according to facility protocol. 5. Clients, families, significant others, and assistive personnel should be instructed to report any leakage, erythema, edema, or pain at the injection site as soon as possible. Consult the facility’s processes and procedures for specific directions.

6 Device Removal1 1. Obtain and review the physician’s order for infusion discontinuance. 2. Wash hands. 3. Assemble equipment. 4. Put on gloves. 5. Use aseptic technique and observe standard precautions. 6. Place patient in comfortable position. 7. Clamp administration and stop infusion device. 8. Remove transparent dressing and securement tapes. 9. Remove administration set, activating safety mechanism (if applicable); discard in Sharps container. 10. Apply manual pressure with sterile gauze to prevent bleeding and fluid leakage. 11. Cover site with dry dressing. 12. Discard expended equipment in appropriate receptacle(s).

Documentation Document the following in the patient’s permanent medical record: a. Date and time of administration b. Skin integrity and location of access device c. Number of insertion attempts and location of infusion set

7 Indication HYLENEX recombinant (hyaluronidase human injection) is indicated as an adjuvant for subcutaneous fluid administration.

Important Safety Information Hypersensitivity to hyaluronidase or any other Allergic reactions (urticaria or angioedema) have ingredient in the formulation is a contraindication been reported in less than 0.1% of patients to the use of this product. receiving hyaluronidase. Discontinue HYLENEX recombinant Anaphylactic-like reactions following retrobulbar (hyaluronidase human injection) if sensitization block or intravenous injections have occurred, occurs. rarely. Hyaluronidase should not be used to enhance the When hyaluronidase is added to a local anesthetic absorption and dispersion of dopamine and/or agent, it hastens the onset of analgesia and tends alpha agonist drugs. to reduce the swelling caused by local infiltration, Hyaluronidase should not be injected into or but the wider spread of the local anesthetic around an infected or acutely inflamed area solution increases its absorption; this shortens its because of the danger of spreading a localized duration of action and tends to increase the infection. incidence of systemic reaction. Hyaluronidase should not be used to reduce the Edema has been reported most frequently in swelling of bites or stings. association with subcutaneous fluid administration. Hyaluronidase should not be applied directly to During subcutaneous fluid administration, special the cornea. care must be taken in pediatric patients to avoid Hyaluronidase should not be used for intravenous over hydration by controlling the rate and total injections because the enzyme is rapidly volume of the infusion. As with all parenteral fluid inactivated. therapy, use the same precautions for restoring Furosemide, the benzodiazepines and phenytoin fluid and electrolyte balance as in intravenous have been found to be incompatible with therapy. The rate and volume of subcutaneous hyaluronidase. fluid administration should not exceed those The most frequently reported adverse experiences employed for intravenous infusion. have been local injection site reactions. When solutions devoid of inorganic electrolytes Hyaluronidase has been reported to enhance the are given subcutaneously, hypovolemia may occur. adverse events associated with co-administered drug products.

Please see accompanying package insert for full Prescribing Information. References 1. Infusion Nurses Society. Policies and Procedures for Infusion Nursing. 3rd ed. Norwood, MA: Infusion Nurses Society; 2006. 2. Thomas JR, Yocum RC, Haller MF, von Gunten CF. Assessing the role of human recombinant hyaluronidase in gravity-driven subcutaneous hydration: the INFUSE-LR study. J Palliat Med. 2007;10:1312-1320. 3. Camp-Sorrell D, ed. Access Device Guidelines: Recommendations for Nursing Practice and Education. 2nd ed. Pittsburgh, PA: Oncology Nursing Society; 2004. 4. hylenex recombinant (human hyaluronidase injection) prescribing information. Deerfield, IL: Baxter Healthcare Corporation; 2008.

For product inquiry, please call 1-800-262-3784 or visit www.hylenex.com.

Baxter, Hylenex, and the Hylenex logo are trademarks of Baxter International Inc. Baxter Healthcare Corporation, Route 120 and Wilson Road, Round Lake, IL 60073 660008 5K 02/09 HYLENEX recombinant (hyaluronidase human injection)

Rx Only

DESCRIPTION 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 (hyaluronidase human injection) 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. CLINICAL PHARMACOLOGY 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 an N-acetylglucosamine moiety and C4 of a glucuronic acid moiety. 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 albumin-hyaluronic acid complex as the enzyme cleaves the hyaluronic acid component. When no spreading factor is present, material injected subcutaneously spreads very slowly, but hyaluronidase causes rapid spreading, provided local interstitial pressure is adequate to furnish the necessary mechanical impulse. Such an impulse is normally initiated by injected solutions. The rate of diffusion is proportionate to the amount of enzyme, and the extent is proportionate to the volume of solution. 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 hyaluronidase preparations may result in the formation of neutralizing antibodies. 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 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. INDICATIONS AND USAGE HYLENEX recombinant is indicated as an adjuvant to increase the absorption and dispersion of other injected drugs; for subcutaneous fluid administration; and as an adjunct in subcutaneous urography for improving resorption of radiopaque agents. CONTRAINDICATION Hypersensitivity to hyaluronidase or any other ingredient in the formulation is a contraindication to the use of this product. WARNINGS Discontinue HYLENEX recombinant (hyaluronidase human injection) if sensitization occurs. Hyaluronidase should not be used to enhance the absorption and dispersion of dopamine and/or alpha agonist drugs. 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. Hyaluronidase should not be used for intravenous injections because the enzyme is rapidly inactivated. PRECAUTIONS General Furosemide, the benzodiazepines and phenytoin have been found to be incompatible with hyaluronidase. 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; 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. Laboratory Tests 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. (See Dosage and Administration). 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. Drug Interactions 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. Carcinogenesis, Mutagenesis, Impairment of Fertility 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. Long-term animal studies have not been performed to assess whether hyaluronidase impaired fertility; however, it has been reported that testicular degeneration may occur with the production of organ specific antibodies against this enzyme following repeated injections. 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. Pregnancy Teratogenic Effects—Pregnancy Category C No adequate and well controlled animal studies have been conducted with HYLENEX recombinant to determine reproductive effects. No ad equate and well controlled studies have been conducted with HYLENEX recombinant in pregnant women. HYLENEX recombinant should be used during pregnancy 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. It is not known whether hyaluronidase has an effect on the later growth, development, and functional maturation of the infant. 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 Hyaluronidase may be added to small volumes of solution, such as fluid replacement solutions or solutions of drugs for subcutaneous injection. The potential for chemical or physical incompatibilities should be kept in mind. (See “Dosage and Administration”.) 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, Subcutaneous Fluid Administration”) Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger adult patients. ADVERSE REACTIONS The most frequently reported adverse experiences have been local injection site reactions. Hyaluronidase has been reported to e nhance 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. OVERDOSAGE Symptoms of toxicity consist of local edema or urticaria, erythema, chills, nausea, vomiting, dizziness, tachycardia, and hypotension. The enzyme should be discontinued and supportive measures initiated immediately. DOSAGE AND ADMINISTRATION HYLENEX recombinant (hyaluronidase human injection) should be administered only as discussed below, since its effects relative to absorption and dispersion of other drugs are not produced when it is administered intravenously. Absorption and Dispersion of Injected Drugs Absorption and dispersion 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. Subcutaneous Fluid Administration Insert needle with aseptic precautions. With tip lying free and movable between skin and muscle, begin fluid administration; fluid should start in readily without pain or lump. Then inject HYLENEX recombinant into rubber tubing close to needle. An alternate method is to inject HYLENEX recombinant under skin prior to fluid administration. 150 U 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. 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 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. HOW SUPPLIED HYLENEX recombinant (hyaluronidase human injection) is supplied sterile as 150 USP units of nonpreserved recombinant human hyaluronidase per mL in a single-use 2 mL glass vial with a gray rubber stopper and aluminum flip-off seal. 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.

Baxter and Hylenex are trademarks of Baxter International Inc.

Marketed by: Baxter Healthcare Corporation Deerﬁeld, IL 60015 USA Manufactured for: Halozyme Therapeutics, Inc. San Diego, CA 92121 By Baxter Pharmaceutical Solutions LLC Bloomington, IN 47403

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