Potassium Chloride in Lactated Ringers and Dextrose

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.

CONTRAINDICATIONS Solutions containing potassium chloride are contraindicated in diseases where high potassium levels may be encountered. Solutions containing lactate are NOT FOR USE IN THE TREATMENT OF LACTIC ACIDOSIS.

DESCRIPTION Intravenous solution with potassium chloride (I.V. solutions with KCl) is a sterile and nonpyrogenic solution in water for injection. This solution is for administration by intravenous infusion only. See Table for summary of content and characteristics of this solution. The solution contains no bacteriostat, antimicrobial agent or added buffer and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded. This solution is a parenteral fluid, nutrient and/or electrolyte replenisher. Dextrose, USP is chemically designated D-glucose, monohydrate (C 6 H 12 O 6 • H 2 O), a hexose sugar freely soluble in water. It has the following structural formula: Potassium Chloride, USP is chemically designated KCl, a white granular powder freely soluble in water. Sodium Chloride, USP is chemically designated NaCl, a white crystalline powder freely soluble in water. Calcium Chloride, USP is chemically designated calcium chloride dihydrate (CaCl 2 • 2H 2 O), white fragments or granules freely soluble in water. Sodium Lactate, USP is chemically designated monosodium lactate [CH 3 CH(OH)COONa], a 60% aqueous solution miscible in water. It has the following structural formula: Water for Injection, USP is chemically designated H 2 0. The flexible plastic container is fabricated from a specially formulated polyvinylchloride. Water can permeate from inside the container into the overwrap but not in amounts sufficient to affect the solution significantly. Solutions in contact with the plastic container may 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. 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. Structural Formula of Dextrose USP Structural Formula of Sodium Lactate USP

DOSAGE AND ADMINISTRATION This solution should be administered only by intravenous infusion and as directed by the physician. The dose and rate of injection are dependent upon the age, weight and clinical condition of the patient. If the serum potassium level is greater than 2.5 mEq/liter, potassium should be given at a rate not to exceed 10 mEq/hour in a concentration less than 30 mEq/liter. Somewhat faster rates and greater concentrations (usually up to 40 mEq/liter) of potassium may be indicated in patients with more severe potassium deficiency. The total 24-hour dose should not generally exceed 200 mEq of potassium. As reported in the literature, the dosage and constant infusion rate of intravenous dextrose must be selected with caution in pediatric patients, particularly neonates and low birth weight infants, because of the increased risk of hyperglycemia/hypoglycemia. Drug Interactions Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, use aseptic technique, mix thoroughly and do not store. The presence of calcium limits their compatibility with certain drugs that form precipitates of calcium salts, and also prohibits their simultaneous infusion through the same administration set as blood because of the likelihood of coagulation. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. (See PRECAUTIONS.)

INDICATIONS AND USAGE This solution is indicated in patients requiring parenteral administration of potassium chloride and the replacement of extracellular losses of fluids and electrolytes with minimal carbohydrate calories.

WARNINGS Solutions containing calcium ions should not be administered simultaneously through the same administration set as blood because of the likelihood of coagulation. Solutions which contain potassium ions should be used with great care, if at all, in patients with hyperkalemia, severe renal failure and in conditions in which potassium retention is present. To avoid potassium intoxication, do not infuse these solutions rapidly. In patients with severe renal insufficiency or adrenal insufficiency, administration of potassium chloride may cause potassium intoxication. Solutions containing sodium ions should be used with great care, if at all, in patients with congestive heart failure, severe renal insufficiency and in clinical states in which there exists edema with sodium retention. In patients with diminished renal function, administration of solutions containing sodium or potassium ions may result in sodium or potassium retention. Solutions containing lactate ions should be used with great care in patients with metabolic or respiratory alkalosis. The administration of lactate ions should be done with great care where there is an increased level or an impaired utilization of lactate ions, as in severe hepatic insufficiency. The intravenous administration of this solution can cause fluid and/or solute overloading resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentration of administered parenteral solutions. The risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the electrolyte concentrations of such solutions.

OVERDOSAGE In the event of potassium overdosage, discontinue the infusion immediately and institute intensive corrective therapy to reduce serum potassium levels. (See WARNINGS and PRECAUTIONS.)

CLINICAL PHARMACOLOGY When administered intravenously, this solution provides a source of water and electrolytes with carbohydrate calories. Solutions containing carbohydrate in the form of dextrose restore blood glucose levels and provide calories. Carbohydrate in the form of dextrose may aid in minimizing liver glycogen depletion and exerts a protein-sparing action. Dextrose injected parenterally undergoes oxidation to carbon dioxide and water. Calcium chloride in water dissociates to provide calcium (Ca ++ ) and chloride (Cl¯) ions. They are normal constituents of the body fluids and are dependent on various physiologic mechanisms for maintenance of balance between intake and output. Approximately 80% of body calcium is excreted in the feces as insoluble salts; urinary excretion accounts for the remaining 20%. Sodium lactate provides sodium (Na + ) and lactate (C 3 H 5 O¯) ions. The lactate anion is in equilibrium with pyruvate and has an alkalizing effect resulting from simultaneous removal by the liver of lactate and hydrogen ions. In the liver, lactate is metabolized to glycogen which is ultimately converted to carbon dioxide and water by oxidative metabolism. The sodium (Na + ) ion combines with bicarbonate ion produced from carbon dioxide of the body and thus retains bicarbonate to combat metabolic acidosis (bicarbonate deficiency). The normal plasma level of lactate ranges from 0.9 to 1.9 mEqK/liter. Intravenous solutions containing potassium chloride are particularly intended to provide needed potassium cation (K + ). Potassium is the chief cation of body cells (160 mEq/liter of intracellular water). It is found in low concentration in plasma and extracellular fluids (3.5 to 5.0 mEq/liter in a healthy adult). Potassium plays an important role in electrolyte balance. Normally about 80 to 90% of the potassium intake is excreted in the urine; the remainder in the stools and to a small extent, in the perspiration. The kidney does not conserve potassium well so that during fasting or in patients on a potassium-free diet, potassium loss from the body continues resulting in potassium depletion. A deficiency of either potassium or chloride will lead to a deficit of the other. Sodium chloride in water dissociates to provide sodium (Na + ) and chloride (Cl¯) ions. Sodium (Na + ) is the principal cation of the extracellular fluid and plays a large part in the therapy of fluid and electrolyte disturbances. Chloride (Cl¯) has an integral role in buffering action when oxygen and carbon dioxide exchange occurs in the red blood cells. The distribution and excretion of sodium (Na + ) and chloride (Cl¯) are largely under the control of the kidney which maintains a balance between intake and output. Water is an essential constituent of all body tissues and accounts for approximately 70% of total body weight. Average normal adult daily requirement ranges from two to three liters (1.0 to 1.5 liters each for insensible water loss by perspiration and urine production). Water balance is maintained by various regulatory mechanisms. Water distribution depends primarily on the concentration of electrolytes in the body compartments and sodium (Na + ) plays a major role in maintaining physiologic equilibrium.

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Potassium Chloride in Lactated Ringers and Dextrose POTASSIUM CHLORIDE, SODIUM CHLORIDE, CALCIUM CHLORIDE, SODIUM LACTATE, and DEXTROSE MONOHYDRATE POTASSIUM CHLORIDE POTASSIUM CATION CHLORIDE ION SODIUM CHLORIDE SODIUM CATION CHLORIDE ION CALCIUM CHLORIDE CALCIUM CATION CHLORIDE ION SODIUM LACTATE SODIUM CATION LACTIC ACID, UNSPECIFIED FORM DEXTROSE MONOHYDRATE ANHYDROUS DEXTROSE WATER

NDA019685

Potassium Chloride in Lactated Ringers and Dextrose

POTASSIUM CHLORIDE, SODIUM CHLORIDE, CALCIUM CHLORIDE, SODIUM LACTATE, and DEXTROSE MONOHYDRATE

0990-7111

HUMAN PRESCRIPTION DRUG

INTRAVENOUS

PRINCIPAL DISPLAY PANEL - 1000 mL Bag Label 20 mEq POTASSIUM ADDED 1000 mL NDC 0990-7111-09 20 mEq POTASSIUM CHLORIDE in Lactated Ringer's and 5% Dextrose Injection, USP EACH 100 mL CONTAINS POTASSIUM CHLORIDE 179 mg; SODIUM CHLORIDE 600 mg; SODIUM LACTATE, ANHYDROUS 310 mg; CALCIUM CHLORIDE, DIHYDRATE 20 mg; DEXTROSE, HYDROUS 5 g IN WATER FOR INJECTION. MAY CONTAIN HCl FOR pH ADJUSTMENT. ELECTROLYTES PER 1000 mL (NOT INCLUDING IONS FOR pH ADJUSTMENT): POTASSIUM 24 mEq; SODIUM 130 mEq; CHLORIDE 129 mEq; CALCIUM 2.7 mEq; LACTATE 28 mEq. 563 mOsmol/LITER (CALC.) pH 4.9 (3.5 to 6.5) NOT FOR USE IN THE TREATMENT OF LACTIC ACIDOSIS. ADDITIVES MAY BE INCOMPATIBLE. CONSULT WITH PHARMACIST, IF AVAILABLE. WHEN INTRODUCING ADDITIVES, USE ASEPTIC TECHNIQUE, MIX THOROUGHLY AND DO NOT STORE. SINGLE-DOSE CONTAINER. FOR I.V. USE. USUAL DOSAGE: SEE INSERT. STERILE, NONPYROGENIC. USE ONLY IF SOLUTION IS CLEAR AND CONTAINER IS UNDAMAGED. MUST NOT BE USED IN SERIES CONNECTIONS. Rx ONLY 3 V CONTAINS DEHP IMP0000048 ICU Medical, Inc., Lake Forest, Illinois, 60045, USA icumedical PRINCIPAL DISPLAY PANEL - 1000 mL Bag Label

POTASSIUM CHLORIDE IN LACTATED RINGER'S AND 5% DEXTROSE INJECTION, USP Flexible Plastic Container R x only

HOW SUPPLIED Intravenous solution with potassium chloride (I.V. solution with KCl) is supplied in single-dose flexible plastic container. See Table: Potassium Chloride in Lactated Ringer’s and 5% Dextrose Injection, USP List No. mEq Potassium Added Size (mL) COMPOSITION (g/L) Calculated Osmolarity (mOsmol/L) Dextrose, Hydrous Potassium Chloride Sodium Chloride Sodium Lactate, Anhydrous Calcium Chloride Dihydrate 7111 20 mEq 1000 50 1.79 6 3.1 0.2 563 NDC No. 0409-7111-09 0990-7111-09 Potassium Chloride in Lactated Ringer’s and 5% Dextrose Injection, USP (Continued) pH Approx. Ionic Concentrations (mEq/L) Approx. kcal/L Calcium (Ca++) Sodium (Na + ) Potassium (K + ) Chloride (Cl¯) Lactate 4.9 (3.5 to 6.5) 2.7 130 24 129 28 179 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: March, 2020 IFU0000167 ICU Medical, Inc., Lake Forest, Illinois, 60045, USA

PRECAUTIONS Clinical evaluation and periodic laboratory determinations are necessary to monitor changes in fluid balance, electrolyte concentrations and acid-base balance during prolonged parenteral therapy or whenever the condition of the patient warrants such evaluation. Solutions containing dextrose should be used with caution in patients with known subclinical or overt diabetes mellitus. Caution must be exercised in the administration of parenteral fluids, especially those containing sodium ions, to patients receiving corticosteroids or corticotropin. Potassium replacement therapy should be guided primarily by serial electrocardiograms. Plasma potassium levels are not necessarily indicative of tissue potassium levels. High plasma concentrations of potassium may cause death through cardiac depression, arrhythmias or arrest. Potassium-containing solutions should be used with caution in the presence of cardiac disease, particularly in digitalized patients or in the presence of renal disease. Solutions containing lactate ions should be used with caution as excess administration may result in metabolic alkalosis. Care should be exercised to insure that the needle (or catheter) is well within the lumen of the vein and that extravasation does not occur. Do not administer unless solution is clear and container is undamaged. Discard unused portion. Pregnancy Category C. Animal reproduction studies have not been conducted with dextrose, potassium chloride or Lactated Ringer’s Injection. It is also not known whether dextrose, potassium chloride or Lactated Ringer’s Injection can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Dextrose, potassium chloride or Lactated Ringer’s Injection should be given to a pregnant woman only if clearly needed. Pediatric Use: The safety and effectiveness in the pediatric population are based on the similarity of the clinical conditions of the pediatric and adult populations. In neonates or very small infants the volume of fluid may affect fluid and electrolyte balance. Frequent monitoring of serum glucose concentrations is required when dextrose is prescribed to pediatric patients, particularly neonates and low birth weight infants. In very low birth weight infants, excessive or rapid administration of dextrose injection may result in increased serum osmolality and possible intracerebral hemorrhage.