Potassium Chloride in Dextrose and Sodium Chloride

Contraindications ( 4 ) 02/2019 Warnings and Precautions ( 5.1 , 5.2 , 5.3 , 5.4 , 5.5 , 5.6 , 5.7 ) 02/2019

1 INDICATIONS AND USAGE Potassium Chloride in Dextrose and Sodium Chloride Injection is indicated as a source of water, electrolytes and calories. Potassium Chloride in Dextrose and Sodium Chloride Injection is indicated as a source of water, electrolytes and calories. ( 1 )

2 DOSAGE AND ADMINISTRATION • Only for intravenous infusion. ( 2.1 , 5.2 ) • See full prescribing information for information on preparation, administration, dosing considerations and instructions for use. ( 2.1 , 2.2 , 2.3 ) 2.1 Important Administration Instructions • Potassium Chloride in Dextrose and Sodium Chloride Injection is only for intravenous infusion [see Warnings and Precautions (5.2) ]. • The osmolarity of Potassium Chloride in Dextrose and Sodium Chloride Injection, ranges from 361 to 641 mOsmol/L (calc). Peripheral administration is generally acceptable; however; consider central vein administration if there is peripheral vein irritation, phlebitis, and/or associated pain especially with higher potassium concentrations. • Do not administer Potassium Chloride in Dextrose and Sodium Chloride Injection simultaneously with blood products through the same administration set because of the possibility of pseudoagglutination or hemolysis. • To prevent air embolism, use a non-vented infusion set or close the vent on a vented set, avoid multiple connections, do not connect flexible containers in series, fully evacuate residual gas in the container prior to administration, do not pressurize the flexible container to increase flow rates, and if administration is controlled by a pumping device, turn off pump before the container runs dry. • Prior to infusion, visually inspect the solution for particulate matter. The solution should be clear and there should be no precipitates. Do not administer unless solution is clear and container is undamaged. • Use of a final filter is recommended during administration of parenteral solutions, where possible. 2.2 Recommended Dosage The choice of the specific potassium chloride, sodium chloride, and dextrose concentrations, rate and volume depends on the age, weight, clinical and metabolic conditions of the patient and concomitant therapy. Electrolyte supplementation may be indicated according to the clinical needs of the patient. The administration rate should be governed, especially for premature infants with low birth weight, during the first few days of therapy, by the patient’s tolerance to dextrose. Increase the infusion rate gradually as indicated by frequent monitoring of blood glucose concentrations [see Warnings and Precautions (5.1) , Use in Specific Populations (8.4) ]. 2.3 Instructions for Use To Open • Do not remove container from overwrap until ready to use. • Tear overwrap down side at slit and remove solution container. • Visually inspect the container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Evaluate the following: o If the outlet port protector is damaged, detached, or not present, discard container. o Check to ensure the solution is clear and there are no precipitates. Discard if there is a color change and/or the appearance of precipitates, insoluble complexes or crystals. o Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard container. Preparation for Administration 1. Suspend container from eyelet support. 2. Remove protector from outlet port at bottom of container. 3. Attach administration set. Refer to complete directions accompanying set. To Add Medication • Additives may be incompatible. Complete information is not available. Do not use additives known or determined to be incompatible. • Consult with pharmacist, if available. If, in the informed judgment of the healthcare provider, it is deemed advisable to introduce additives, use aseptic technique. • When introducing additives, consult the instructions for use of the medication to be added and other relevant literature. • Before adding a substance or medication, verify that it is soluble and/or stable in Potassium Chloride in Dextrose and Sodium Chloride Injection and that the pH range of Potassium Chloride in Dex …

3 DOSAGE FORMS AND STRENGTHS Potassium Chloride in Dextrose and Sodium Chloride Injection, USP are clear solutions in 500 mL and 1000 mL single-dose, flexible containers: 500 mL flexible container • 10 mEq/500 mL Potassium Chloride, 5% Dextrose and 0.2% Sodium Chloride • 10 mEq/500 mL Potassium Chloride, 5% Dextrose and 0.33% Sodium Chloride • 10 mEq/500 mL Potassium Chloride, 5% Dextrose and 0.45% Sodium Chloride 1000 mL flexible container • 20 mEq/L Potassium Chloride, 5% Dextrose and 0.2% Sodium Chloride • 10 mEq/L Potassium Chloride, 5% Dextrose and 0.45% Sodium Chloride • 20 mEq/L Potassium Chloride, 5% Dextrose and 0.45% Sodium Chloride • 30 mEq/L Potassium Chloride, 5% Dextrose and 0.45% Sodium Chloride • 40 mEq/L Potassium Chloride, 5% Dextrose and 0.45% Sodium Chloride • 20 mEq/L Potassium Chloride, 5% Dextrose and 0.9% Sodium Chloride • 40 mEq/L Potassium Chloride, 5% Dextrose and 0.9% Sodium Chloride Potassium Chloride in Dextrose and Sodium Chloride Injection is available in multiple strengths. See full prescribing information for detailed description of each formulation. ( 3 )

4 CONTRAINDICATIONS Potassium Chloride in Dextrose and Sodium Chloride Injection is contraindicated in patients with: • known hypersensitivity to potassium chloride, dextrose and/or sodium chloride [see Warnings and Precautions 5.1) ] • clinically significant hyperkalemia [see Warnings and Precautions (5.2) ] • clinically significant hyperglycemia [see Warnings and Precautions (5.3) ] • Known hypersensitivity to potassium chloride, dextrose, or sodium chloride ( 4 , 5.1 ) • Clinically significant hyperkalemia ( 4 , 5.2 ) • Clinically significant hyperglycemia ( 4 , 5.3 )

ADVERSE REACTIONS Reactions which may occur because of the solutions or technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia. 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. Nausea, vomiting, abdominal pain and diarrhea have been reported with potassium therapy. The signs and symptoms of potassium intoxication include paresthesias of the extremities, flaccid paralysis, listlessness, mental confusion, weakness and heaviness of the legs, hypotension, cardiac arrhythmias, heart block, electrocardiographic abnormalities such as disappearance of P waves, spreading and slurring of the QRS complex with development of a biphasic curve and cardiac arrest. Potassium-containing solutions are intrinsically irritating to tissues. Therefore, extreme care should be taken to avoid perivascular infiltration. Local tissue necrosis and subsequent sloughing may result if extravasation occurs. Chemical phlebitis and venospasm have also been reported. Should perivascular infiltration occur, I.V. administration at that site should be discontinued at once. Local infiltration of the affected area with procaine hydrochloride, 1%, to which hyaluronidase may be added, will often reduce venospasm and dilute the potassium remaining in the tissues locally. Local application of heat may also be helpful. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS • Other Products that Cause Hyperkalemia : Avoid use in patients receiving such products. If use cannot be avoided, monitor serum potassium concentrations. ( 7.1 ) • Lithium : Decreased lithium concentrations with concomitant use; monitor serum lithium concentrations. ( 7.2 ) • Other Products that Affect Glycemic Control, Vasopressin or Fluid and/or Electrolyte Balance : Monitor blood glucose concentrations, fluid balance serum electrolyte concentrations and acid-base balance. ( 7.3 ) 7.1 Other Products that Cause Hyperkalemia Administration of Potassium Chloride in Dextrose and Sodium Chloride Injection in patients treated concurrently or recently with other products that can cause hyperkalemia or increase the risk of hyperkalemia (e.g., potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers) increases the risk of severe and potentially fatal hyperkalemia, in particular in the presence of other risk factors for hyperkalemia [see Warnings and Precautions (5.2) ]. Avoid use of Potassium Chloride in Dextrose and Sodium Chloride Injection in patients receiving such products. If use cannot be avoided, monitor serum potassium concentrations. 7.2 Lithium Renal sodium and lithium clearance may be increased during administration of Potassium Chloride in Dextrose and Sodium Chloride Injection resulting in decreased serum lithium concentrations. Monitor serum lithium concentrations during concomitant use. 7.3 Other Products that Affect Glycemic Control, Vasopressin or Fluid and/or Electrolyte Balance Potassium Chloride in Dextrose and Sodium Chloride Injection can affect glycemic control, vasopressin and fluid and/or electrolyte balance [see Warnings and Precautions (5.3 , 5.4 , 5.5 , 5.6 )]. Monitor blood glucose concentrations, fluid balance, serum electrolyte concentrations and acid-base balance when using Potassium Chloride in Dextrose and Sodium Chloride Injection in patients treated with other substances that affect glycemic control, vasopressin or fluid and/or electrolyte balance.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Appropriate administration of Potassium Chloride in Dextrose Sodium Chloride Injection during pregnancy is not expected to cause adverse developmental outcomes, including congenital malformations. Animal reproduction studies have not been conducted with Potassium Chloride in Dextrose Sodium Chloride Injection. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 to 4% and 15 to 20%, respectively. 8.2 Lactation Risk Summary Sodium and potassium are present in human breast milk. There are no data on the effects of Potassium Chloride in Sodium Chloride and Glucose on a breastfed infant or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Potassium Chloride in Dextrose and Sodium Chloride Injection and any potential adverse effects on the breastfed infant from Potassium Chloride in Dextrose and Sodium Chloride Injection or from the underlying maternal condition. 8.4 Pediatric Use The safety profile of Potassium Chloride in Dextrose and Sodium Chloride Injection in pediatric patients is similar to adults. Neonates, especially premature infants with low birth weight, are at increased risk of developing hypo- or hyperglycemia and therefore need close monitoring during treatment with intravenous glucose solutions to ensure adequate glycemic control in order to avoid potential long term adverse effects. Closely monitor plasma electrolyte concentrations in pediatric patients who may have impaired ability to regulate fluids and electrolytes. In very low birth weight infants, excessive or rapid administration of Potassium Chloride in Dextrose and Sodium Chloride Injection may result in increased serum osmolality and risk of intracerebral hemorrhage. Children (including neonates and older children) are at increased risk of developing hyponatremia as well as for developing hyponatremic encephalopathy. 8.5 Geriatric Use Clinical studies of Potassium Chloride in Dextrose and Sodium Chloride Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients are at increased risk of developing hyponatremia as well as for developing hyponatremic encephalopathy [see Warnings and Precautions (5.4) ]. Potassium Chloride in Dextrose and Sodium Chloride Injection is known to be substantially excreted by the kidney, and the risk of adverse reactions to this product may be greater in patients with impaired renal function [see Warnings and Precautions (5.2) ]. Dose selection for an elderly patient should be cautious, 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. 8.6 Renal Impairment Administration of Potassium Chloride in Dextrose and Sodium Chloride Injection in patients with renal impairment may result in hyponatremia, hyperkalemia and/or fluid overload. Monitor patients with renal impairment for development of these adverse reactions [see Warnings and Precautions (5.2 , 5.5 , 5.6 )].

12.1 Mechanism of Action Potassium Chloride in Dextrose and Sodium Chloride Injection is a source of water, electrolytes and calories. It is capable of inducing diuresis depending on the clinical condition of the patient.

11 DESCRIPTION Potassium Chloride in Dextrose and Sodium Chloride Injection, USP is a sterile, nonpyrogenic solution for fluid and electrolyte replenishment and caloric supply in a single dose container for intravenous administration. It contains no antimicrobial agents. Composition, osmolarity, pH, ionic concentration and caloric content are shown in Table 1. Table 1 Table 1 mEq Potassium/container size Size (mL) Composition (g/L) pH Ionic Concentration (mEq/L) ** Dextrose Hydrous, USP Sodium Chloride, USP (NaCl) Potassium Chloride, USP (KCl) Normal physiologic osmolarity range is approximately 280 to 310 mOsmol/L. Osmolarity (mOsmol/L) (calc.) Sodium Potassium Chloride Caloric Content (kCal/L) Potassium Chloride in 5% Dextrose and 0.2% Sodium Chloride Injection, USP 20 mEq/L 1000 50 2 1.5 361 4.5 (3.5 to 6.5) 34 20 54 170 10 mEq/500 mL 500 50 2 1.5 361 4.5 (3.5 to 6.5) 34 20 54 170 Potassium Chloride in 5% Dextrose and 0.33% Sodium Chloride Injection, USP 10 mEq/500 mL 500 50 3.3 1.5 405 4.5 (3.5 to 6.5) 56 20 76 170 Potassium Chloride in 5% Dextrose and 0.45% Sodium Chloride Injection, USP 10 mEq/L 1000 50 4.5 0.75 426 4.5 (3.5 to 6.5) 77 10 87 170 20 mEq/L 1000 50 4.5 1.5 447 4.5 (3.5 to 6.5) 77 20 97 170 10 mEq/500 mL 500 50 4.5 1.5 447 4.5 (3.5 to 6.5) 77 20 97 170 30 mEq/L 1000 50 4.5 2.24 466 4.5 (3.5 to 6.5) 77 30 107 170 40 mEq/L 1000 50 4.5 3 487 4.5 (3.5 to 6.5) 77 40 117 170 Potassium Chloride in 5% Dextrose and 0.9% Sodium Chloride Injection, USP 20 mEq/L 1000 50 9 1.5 601 4.5 (3.5 to 6.5) 154 20 174 170 0.9% Sodium Chloride Injection, USP 40 mEq/L 1000 50 9 3 641 4.5 (3.5 to 6.5) 154 40 194 170 Dextrose is derived from corn. The VIAFLEX Plus plastic container is fabricated from a specially formulated polyvinyl chloride (PL 146 Plastic). VIAFLEX Plus on the container indicates the presence of a drug additive in a drug vehicle. The VIAFLEX Plus plastic container system utilizes the same container as the VIAFLEX plastic container system. 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 of its chemical components in very small amounts within the expiration period, e.g., di-2-ethylhexyl phthalate (DEHP), up to 5 parts per million. However, the safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies. Image of D-Glucose monohydrate Structural Formula

10 OVERDOSAGE An increased infusion rate of Potassium Chloride in Dextrose and Sodium Chloride Injection can cause: Hyperkalemia • Manifestations of hyperkalemia may include: o disturbances in cardiac conduction and arrhythmias, including bradycardia, heart block, asystole, ventricular tachycardia, ventricular fibrillation, o hypotension, o muscle weakness up to and including muscular and respiratory paralysis, paresthesia of extremities, o gastrointestinal symptoms (ileus, nausea, vomiting, abdominal pain) The presence of any ECG findings that are suspected to be caused by hyperkalemia should be considered a medical emergency. If hyperkalemia is present or suspected, discontinue the infusion immediately and institute close ECG, laboratory and other monitoring and, as necessary, corrective therapy to reduce serum potassium concentrations [see Warnings and Precautions (5.2) ]. Other Electrolyte and Fluid Disorders • hyponatremia, manifestations may include seizures, coma, cerebral edema and death). • hypernatremia, especially in patients with severe renal impairment. • fluid overload (which can lead to central and/or peripheral edema). • Hyperglycemia, hyperosmolality, and adverse effects on water and electrolyte balance, and corresponding complications, which can be fatal [see Warnings and Precautions (5.3 , 5.6 )]. Interventions include discontinuation of the infusion, dose reduction, monitoring of fluid balance, electrolyte concentrations and acid-base balance and institution of appropriate corrective measures such as administration of exogenous insulin.

HOW SUPPLIED Intravenous solutions with potassium chloride (I.V. solution with KCl) are supplied in single-dose flexible plastic containers. See Tables: TABLE 1 Potassium Chloride in 5% Dextrose and 0.225% Sodium Chloride Inj., USP COMPOSITION (g/L) Approx. Ionic Concentrations (mEq/L) mEq Potassium Size (mL) Dextrose, Hydrous Sodium Chloride Potassium Chloride Calculated Osmolarity (mOsmol/L) pH Sodium (Na+) Potassium (K+) Chloride (Cl–) Approximate kcal/L NDC NO. 20 mEq 1000 50 2.25 1.49 370 4.2 (3.5 to 6.5) 38.5 20 58.5 170 0409-7901-09 1 20 mEq 1000 50 2.25 1.49 370 4.2 (3.5 to 6.5) 38.5 20 58.5 170 0990-7901-09 1 ICU Medical is transitioning NDC codes from the "0409" to a "0990" labeler code. Both NDC codes are expected to be in the market for a period of time. TABLE 2 Potassium Chloride in 5% Dextrose and 0.45% Sodium Chloride Inj., USP COMPOSITION (g/L) Approx. Ionic Concentrations (mEq/L) mEq Potassium Size (mL) Dextrose, Hydrous Sodium Chloride Potassium Chloride Calculated Osmolarity (mOsmol/L) pH Sodium (Na+) Potassium (K+) Chloride (Cl–) Approximate kcal/L NDC NO. 10 mEq 1000 50 4.5 0.745 426 4.2 (3.5 to 6.5) 77 10 87 170 0409-7993-09 2 10 mEq 1000 50 4.5 0.745 426 4.2 (3.5 to 6.5) 77 10 87 170 0990-7993-09 1,2 10 mEq 500 50 4.5 1.49 447 4.2 (3.5 to 6.5) 77 20 97 170 0409-7902-03 2 10 mEq 500 50 4.5 1.49 447 4.2 (3.5 to 6.5) 77 20 97 170 0990-7902-03 1,2 20 mEq 1000 50 4.5 1.49 447 4.2 (3.5 to 6.5) 77 20 97 170 0409-7902-09 1,2 20 mEq 1000 50 4.5 1.49 447 4.2 (3.5 to 6.5) 77 20 97 170 0990-7902-09 1,2 30 mEq 1000 50 4.5 2.24 467 4.2 (3.5 to 6.5) 77 30 107 170 0409-7903-09 1 30 mEq 1000 50 4.5 2.24 467 4.2 (3.5 to 6.5) 77 30 107 170 0990-7903-09 1 40 mEq 1000 50 4.5 2.98 487 4.2 (3.5 to 6.5) 77 40 117 170 0409-7904-09 1,2 40 mEq 1000 50 4.5 2.98 487 4.2 (3.5 to 6.5) 77 40 117 170 0990-7904-09 1,2 ICU Medical is transitioning NDC codes from the "0409" to a "0990" labeler code. Both NDC codes are expected to be in the market for a period of time. TABLE 3 Potassium Chloride in 5% Dextrose and 0.9% Sodium Chloride Inj., USP COMPOSITION (g/L) Approx. Ionic Concentrations (mEq/L) mEq Potassium Size (mL) Dextrose, Hydrous Sodium Chloride Potassium Chloride Calculated Osmolarity (mOsmol/L) pH Sodium (Na+) Potassium (K+) Chloride (Cl–) Approximate kcal/L NDC NO. 20 mEq 1000 50 9 1.49 600 4.2 (3.5 to 6.5) 154 20 174 170 0409-7107-09 2 20 mEq 1000 50 9 1.49 600 4.2 (3.5 to 6.5) 154 20 174 170 0990-7107-09 1,2 40 mEq 1000 50 9 2.98 640 4.2 (3.5 to 6.5) 154 40 194 170 0409-7109-09 2 40 mEq 1000 50 9 2.98 640 4.2 (3.5 to 6.5) 154 40 194 170 0990-7109-09 1,2 ICU Medical is transitioning NDC codes from the "0409" to a "0990" labeler code. Both NDC codes are expected to be in the market for a period of time. May contain HCl for pH adjustment. Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Protect from freezing. Revised: December, 2020 1 Manufactured by ICU Medical, Inc., Lake Forest, Illinois, 60045, USA 2 Manufactured for ICU Medical, Inc., Lake Forest, Illinois, 60045, USA IFU0000280