Sodium Chloride

1 INDICATIONS AND USAGE 125 mL Syringe: Sodium Chloride Injection USP 0.9% is indicated for use in flushing compatible contrast agents through Liebel-Flarsheim intravenous administration sets into indwelling intravascular access devices only when delivered by the following Liebel-Flarsheim power injectors: Angiomat ® , Illumena ® , Illumena ® Néo, CT9000 ® , CT9000 ® ADV, Optistat ® , Optivantage ® and Optistar Elite. For use in flushing compatible contrast agents through Liebel-Flarsheim intravenous administration sets into indwelling intravascular access devices ( 1 )

2 DOSAGE AND ADMINISTRATION The 125 mL syringe are for single patient use only. Determine the volume of the saline flush for each patient individually based, in part, on the imaging procedure, the location of the vascular access device, the length of tubing between the Liebel-Flarsheim contrast agent power injector and the vascular access device and the recommendations made on the package insert for the contrast agent. Typical Sodium Chloride Injection USP 0.9% flush volumes following contrast agent administration in adults are 10 to 25 mL per injection at rates not to exceed 10 mL/sec. Use of some Liebel-Flarsheim contrast agent power injectors allows for additional infusion of Sodium Chloride Injection USP 0.9% to maintain the patency of vascular access. Typical infusion rates used for this purpose are in the range of 0.5 to 1 mL per minute. Individualize infusion rates and flush volumes for each patient based on their body weight, fluid status and concomitant medical conditions. Consult the Liebel-Flarsheim contrast agent power injector manual for proper use. For single patient use only. ( 2 ) Determine the volume of flush based on the imaging procedure, location of the vascular access device, length of tubing between power injector and vascular access device, and the contrast agent package insert. ( 2 ) Individualize the volume of flush based on body weight, fluid status and concomitant medical conditions. ( 2 ) Typical flush volumes for adults are 10 to 25 mL per injection at rates not to exceed 10 mL/sec. ( 2 ) May be used for additional infusion to maintain the patency of vascular access at a typical infusion rate of 0.5 to 1 mL per minute. ( 2 ) Do not use if packaging is damaged, wet, or not intact, if syringe or its tip cap shows signs of damage, leakage or displacement. Do not use if solution is hazy, cloudy, discolored, or contains particulate matter. ( 2 ) Use aseptic technique. ( 2 ) Expel residual air from the syringe and tubing prior to connection with the patient’s vascular access. ( 2 ) 2.1 Drug Handling Inspect the syringe for signs of break in sterility. Do not use if the syringe or its tip cap shows signs of damage, leakage or displacement. Do not use if the solution is hazy, cloudy, discolored or contains particulate matter. Use aseptic technique. Expel residual air in both the syringe and tubing prior to connection with the patient’s vascular access. Instructions for assembly and inspection of the Sodium Chloride Injection USP 0.9% syringes prior to use are printed on this sheet. 2.2 125 mL Syringe Assembly and Inspection NOTE: Exterior of syringe is not sterile. Contents of syringe and area under tip cap and piston ribs are sterile and should be treated accordingly. Remove syringe from carton and inspect the area around the tip cap and outside of piston for signs of leakage. Do not use if leakage is observed. Load syringe into power injector. To remove tip cap from syringe, push in and twist off, then discard. The area under the cap is sterile. Caution should now be used when handling. Next remove cap from luer locknut dust cover by twisting to break tamper evident seal. Discard cap. Attach luer locknut to syringe by holding dust cover and screwing to the stop. Remove and discard dust cover when ready to attach sterile connector tubing. Inspecting the 125 mL syringe Twisting off the 125 mL syringe cap Luer locknut detail Removing cap from luer locknut Attaching luer locknut to syringe

3 DOSAGE FORMS AND STRENGTHS Sodium Chloride Injection USP (0.9%) a clear, colorless, odorless solution supplied in 125 mL prefilled syringes contents are sterile Supplied as a clear, colorless, odorless, sterile solution of Sodium Chloride 0.9% for intravenous administration ( 3 ) Supplied in 125 mL prefilled syringes ( 3 )

CONTRAINDICATIONS This solution is contraindicated where the administration of sodium or chloride could be clinically detrimental.

ADVERSE REACTIONS Post-Marketing Adverse Reactions The following adverse reactions have been identified during postapproval use of 0.9% Sodium Chloride Injection, USP. 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 following adverse reactions have been reported in the post-marketing experience during use of 0.9% Sodium Chloride Injection, USP and include the following: Hypersensitivity reactions : hypersensitivity/infusion reactions, including hypotension, pyrexia, tremor, chills, urticaria, rash, and pruritus. General disorders and administration site condition s: infusion site reactions, such as infusion site erythema, injection site streaking, burning sensation, and infusion site urticaria. Metabolism and nutrition disorders : hypernatremia, hyperchloremic metabolic acidosis, and hyponatremia, which may be symptomatic. Nervous System Disorders : Hyponatremic encephalopathy. If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.

DRUG INTERACTIONS Caution must be exercised in the administration of 0.9% Sodium Chloride Injection, USP to patients receiving corticosteroids or corticotropin. Carcinogenesis, Mutagenesis, Impairment of Fertility Studies have not been performed with Sodium Chloride Injection, USP to evaluate the potential for carcinogenesis, mutagenesis or impairment of fertility. Pregnancy: Teratogenic Effects Pregnancy Category C Animal reproduction studies have not been conducted with Sodium Chloride Injection, USP. It is also not known whether Sodium Chloride Injection, USP can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Sodium Chloride Injection, USP should be given to a pregnant woman only if clearly needed. Labor and Delivery Studies have not been conducted to evaluate the effects of Sodium Chloride Injection, USP on labor and delivery. Caution should be exercised when administering this drug during labor and delivery. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Sodium Chloride Injection, USP is administered to a nursing mother. Pediatric Use The use of Sodium Chloride Injection, USP in pediatric patients is based on clinical practice. Plasma electrolyte concentrations should be closely monitored in the pediatric population as this population may have impaired ability to regulate fluids and electrolytes. Geriatric Use Clinical studies of Sodium Chloride Injection, USP did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Do not administer unless solution is clear and container is undamaged. Discard unused portion.

8 USE IN SPECIFIC POPULATIONS Pregnancy: It is not known whether Sodium Chloride Injection USP 0.9% can cause fetal harm. ( 8.1 ) Pediatrics: Safety and effectiveness have not been established in pediatric patients. ( 8.4 ) Geriatrics: Dosing for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. ( 8.5 ) 8.1 Pregnancy Risk Summary Administration of Sodium Chloride Injection USP 0.9% is not known to cause major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with Sodium Chloride Injection USP 0.9.% All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. 8.2 Lactation Risk Summary Appropriate administration of Sodium Chloride Injection USP 0.9% is not known to cause harm to a breastfed infant. 8.4 Pediatric Use Safety and effectiveness of Sodium Chloride Injection USP 0.9% administered by power injection in pediatric patients have not been established. Administration of Sodium Chloride Injection USP 0.9% to pediatric patients by power injection is not recommended. When performing manual injection of Sodium Chloride Injection USP 0.9% to pediatric patients, take into account the patient’s weight, fluid status, and concomitant medical conditions to determine if use of Sodium Chloride Injection USP 0.9% is appropriate. The safety of manual injection of Sodium Chloride Injection USP 0.9% in pediatric patients is supported by reported clinical experience with intravenous infusion and flush of sodium chloride injection in pediatric patients. To minimize the risk of fluid overload, use the smallest dose of Sodium Chloride Injection USP 0.9% necessary for manually flushing contrast agent through the vascular access line. 8.5 Geriatric Use No clinical studies of Sodium Chloride Injection USP 0.9% were conducted. Other reported clinical experience with sodium chloride injection has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

DESCRIPTION 0.9% Sodium Chloride Injection, USP in the Mini-Bag Plus Container System is a sterile, nonpyrogenic solution for intravenous administration after admixture with a single dose powdered or liquid (up to 10 mL) drug vial. It contains no antimicrobial agents. The nominal pH is 5.0 (4.5 to 7.0). Each 100 mL contains 900 mg of Sodium Chloride, USP (NaCl). The osmolarity is 308 mOsmol/L (calculated). Hydrochloric Acid, NF or Sodium Hydroxide, NF may be added for pH adjustment. It contains 154 mEq/L sodium and 154 mEq/L chloride. The Mini-Bag Plus Container is a standard diluent container with an integral drug vial adaptor. It allows for drug admixture after connection to a single dose powdered or liquid (up to 10 mL) drug vial having a 13mm or 20mm closure . A breakaway seal in the tube between the vial adaptor and the container is broken to allow transfer of the diluent into the vial and reconstitution of the drug. The Mini-Bag Plus product mechanically prohibits the transfer of contaminants into and out of the system during and after docking, minimizing environmental and personal exposure. The reconstituted drug is then transferred from the vial into the container diluent and mixed to result in an admixture for delivery to the patient. The VIAFLEX Plastic Container is fabricated from a specially formulated polyvinyl chloride (PL 146 Plastic). Exposure to temperatures above 25°C/77°F during transport and storage will lead to minor losses in moisture content. Higher temperatures lead to greater losses. It is unlikely that these minor losses will lead to clinically significant changes within the expiration period. The amount of water that can permeate from inside the container into the overwrap is insufficient to affect the solution significantly. Solutions in contact with the plastic container can leach out certain chemical components from the plastic in very small amounts. However, biological testing was supportive of the safety of the plastic container materials.

OVERDOSAGE Excessive administration of: • 0.9% Sodium Chloride Injection, USP can cause hypernatremia. • 0.9% Sodium Chloride Injection, USP can cause fluid overload (which can lead to pulmonary and/or peripheral edema). See WARNINGS and ADVERSE REACTIONS . When assessing an overdose, any additives in the solution must also be considered. The effects of an overdose may require immediate medical attention and treatment. Interventions include discontinuation of Sodium Chloride Injection, USP administration, dose reduction, and other measures as indicated for the specific clinical constellation (e.g., monitoring of fluid balance, electrolyte concentrations and acid base balance).

16 HOW SUPPLIED/STORAGE AND HANDLING Sodium Chloride Injection USP 0.9% is a clear, colorless, odorless solution containing 9 mg/mL of sodium chloride. Sodium Chloride Injection USP 0.9% is supplied in 125 mL prefilled syringes containing 125 mL of solution. Each syringe is sealed with rubber closures and the contents are sterile. The 125 mL syringe is supplied with a luer locknut adapter which is cleared for manufacture and distribution as a device under 510(K) number 862653. The syringes are contained in shipping cartons with the following configurations: Volume Packaging NDC 125 mL in plastic syringes 20 syringes per carton 0019-1188-81 125 mL in plastic RFID-Tagged Syringes* 20 syringes per carton 0019-1188-27 *Radio Frequency Identification (RFID) Technology RFID-Tagged Syringe Description This information is for Ultraject ® syringes containing Sodium Chloride Injection USP 0.9% that has been labeled with a Radio Frequency Identification (RFID) tag. When used with an RFID-enabled Optivantage Injector, this tag allows for the exchange of product information such as lot number, expiration, concentration, and identification of the syringe as being unused prior to use and used after product administration. Patient information is not utilized in any form with this RFID technology. Sodium Chloride Injection USP 0.9% product quality is not impacted with the use of this RFID tag. Sodium Chloride Injection USP 0.9% RFID syringes require no special handling and should be stored at the conditions listed for the drug product. RFID-Tagged Syringe Directions for Use For the RFID technology to function, the syringe must be used with an Optivantage Injector with RFID technology. Function of the RFID technology is not dependent on syringe orientation as it is placed in the injector. Instructions for use of the injector are provided on the injector interface screens and operator’s manual. If the RFID tag is damaged or otherwise non-functional, the injector will notify the user. Should this occur, the Sodium Chloride Injection USP 0.9% syringe with the non-functional RFID tag may still be used but no data will be transferred to the injector. Regarding interference with medical devices, the RFID tag and injector system meet the IEC 60601-1-2 requirements for emission and immunity standards for medical devices. Follow all manufacturers’ guidelines and do not operate any part of the Optivantage Injector System and RFID-tagged syringes within 6 inches (15 cm) of a pacemaker and/or defibrillator. Storage Store Sodium Chloride Injection USP 0.9% syringes and RFID-tagged syringes at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. PROTECT FROM FREEZING Manufactured by: Liebel-Flarsheim Company LLC Raleigh, NC 27616 Made in USA GBT 11880919 Issued: 9/19 Guerbet