Lactated Ringers

RECENT MAJOR CHANGES Dosage and Administration ( 2.1 , 2.2 , 2.3 , 2.4 ) 10/2025 Contraindications ( 4 ) 10/2025 Warnings and Precautions ( 5.1 , 5.2 , 5.3 , 5.4 , 5.5 , 5.6 , 5.7 , 5.8 , 5.9 ) 10/2025

1 INDICATIONS AND USAGE Lactated Ringer’s Injection is indicated for use as a source of water and electrolytes or as an alkalinizing agent in adults and pediatric patients. Lactated Ringer’s Injection is indicated for use as a source of water and electrolytes or as an alkalinizing agent in adults and pediatric patients. ( 1 )

2 DOSAGE AND ADMINISTRATION The recommended dosage and duration is based on the patient’s age, weight, clinical condition, and concomitant therapy. ( 2.1 ) To reduce the risk of air embolism, adhere to the preparation instructions. ( 2.2 , 5.2 ) Lactated Ringer’s Injection is for intravenous use. ( 2.3 ) Instructions for Intravenous Administration of Plastic Container. ( 2.4 ) Do not administer Lactated Ringer’s Injection simultaneously with ceftriaxone in neonates (28 days of age or younger) due to serious risks. ( 2.5 ) See full prescribing information for information dosage considerations, preparation, administration, and drug incompatibilities. ( 2 ) 2.1 Dosage Considerations The recommended dosage and duration of Lactated Ringer’s Injection is directed by a physician based on the patient’s age, weight, clinical condition, and concomitant therapy. Evaluate the patient’s clinical status and monitor changes in electrolyte concentrations especially during prolonged use of Lactated Ringer’s Injection to optimize clinical status. 2.2 Important Preparation Instructions Visually inspect the Lactated Ringer’s Injection solution for particulate matter and discoloration. Do not administer Lactated Ringer’s Injection unless the solution is clear and the container and seals are intact. If additives are determined to be compatible with Lactated Ringer’s Injection then using aseptic technique, mix thoroughly; do not store solutions containing additives. After mixing, do not use if there is discoloration or formation of precipitates. To reduce the risk of air embolism, adhere to the following Lactated Ringer’s Injection preparation instructions [see Warnings and Precautions (5.2) ] : Use a non-vented infusion set or close the vent on a vented set. Use a dedicated line without any connections (do not connect flexible containers in series). The use of pressure infusion is not recommended as a method to increase flow rates. However, if pressure infusion is required, ensure that any air within the bag is fully evacuated prior to initiation of infusion. If using a pumping device to administer Lactated Ringer’s Injection, turn off the pump before the container is empty. Preparation Instructions 1. Check for minute leaks by squeezing solution container firmly. If leaks are found, discard solution as sterility may be impaired. If supplemental medication is desired, follow directions below before preparing for administration [see Dosage and Administration (2.3) ] . 2. Inspect each container. Read the label. Ensure solution is the one ordered and is within the expiration date. 3. Invert container and carefully inspect the solution in good light for cloudiness, haze, or particulate matter. Any container which is suspect should not be used. 4. If supplemental medication is desired, follow directions below [see Dosage and Administration (2.3) ] . Preparation for Administration 1. Remove plastic protector from sterile set port at bottom of container. 2. Attach administration set according to its accompanying directions. 2.3 Important Administration Instructions Lactated Ringer’s Injection is for intravenous use. Use immediately after opening the container. Discard the unused portion. Some additives may be incompatible [see Dosage and Administration (2.4) ] . To Add Medication Before Solution Administration 1. Prepare medication site by removing the additive port closure. Swab the exposed medication site before puncturing. 2. Using syringe with 18-22 gauge needle, puncture medication port and inner diaphragm and inject. 3. Squeeze and tap ports while ports are upright and mix solution and medication thoroughly. To Add Medication During Solution Administration 1. Close clamp on the set. 2. Prepare medication site by removing the additive port closure. Swab the exposed medication site before puncturing. 3. Using syringe with 18-22 gauge needle of appropriate length (at least 5/8 inch), puncture resealable medication port and inner diaphragm and inject. 4 …

3 DOSAGE FORMS AND STRENGTHS Injection: Lactated Ringer’s Injection, USP as a clear, sterile, and nonpyrogenic solution packaged in single-dose containers: 250 mL, 500 mL, and 1,000 mL. Lactated Ringer’s Injection USP in Excel ® Containers: Lactated Ringer’s Injection USP 1000 mL ( 3 ) Lactated Ringer’s Injection USP 500 mL ( 3 ) Lactated Ringer’s Injection USP 250 mL ( 3 )

CONTRAINDICATIONS: As for other calcium-containing infusion solutions, concomitant administration of ceftriaxone and Lactated Ringer's Injection is contraindicated in newborns (≤ 28 days of age), even if separate infusion lines are used (risk of fatal ceftriaxone-calcium salt precipitation in the neonate's bloodstream). In patients older than 28 days (including adults), ceftriaxone must not be administered simultaneously with intravenous calcium-containing solutions, including Lactated Ringer's Injection, through the same infusion line (e.g., via Y-connector). If the same infusion line is used for sequential administration, the line must be thoroughly flushed between infusions with a compatible fluid. Lactated Ringer's Injection is contraindicated in patients with a known hypersensitivity to sodium lactate.

ADVERSE REACTIONS Allergic reactions or anaphylactoid symptoms such as localized or generalized urticaria and pruritus; periorbital, facial, and/or laryngeal edema; coughing, sneezing, and/or difficulty with breathing have been reported during administration of Lactated Ringer's Injection USP. The reporting frequency of these signs and symptoms is higher in women during pregnancy. Reactions which may occur because of the solution or the 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. Symptoms may result from an excess or deficit of one or more of the ions present in the solution; therefore, frequent monitoring of electrolyte levels is essential. Hypernatremia may be associated with edema and exacerbation of congestive heart failure due to the retention of water, resulting in an expanded extracellular fluid volume. Reactions reported with the use of potassium-containing solutions include nausea, vomiting, abdominal pain and diarrhea. The signs and symptoms of potassium intoxication include paresthesias of the extremities, areflexia, muscular or respiratory paralysis, mental confusion, weakness, hypotension, cardiac arrhythmias, heart block, electrocardiographic abnormalities and cardiac arrest. Potassium deficits result in disruption of neuromuscular function, and intestinal ileus and dilatation. If infused in large amounts, chloride ions may cause a loss of bicarbonate ions, resulting in an acidifying effect. Abnormally high plasma levels of calcium can result in depression, amnesia, headaches, drowsiness, disorientation, syncope, hallucinations, hypotonia of both skeletal and smooth muscles, dysphagia, arrhythmias and coma. Calcium deficits can result in neuromuscular hyperexcitability, including cramps and convulsions. Although the metabolism of lactate to bicarbonate is a relatively slow process, aggressive administration of sodium lactate may result in metabolic alkalosis. Careful monitoring of blood acid-base balance is essential during the administration of sodium lactate. The physician should also be alert to the possibility of adverse reactions to drug additives. Prescribing information for drug additives to be administered in this manner should be consulted. 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.

7 DRUG INTERACTIONS Drugs that Affect Electrolyte and/or Fluid Balance : Avoid concomitant use. If concomitant use cannot be avoided, closely monitor electrolyte concentrations and fluid balance. ( 7.1 ) Lithium : Avoid concomitant use. If concomitant use is unavoidable monitor serum lithium concentrations more frequently. ( 7.2 ) Digoxin : Consider reducing the volume or rate of Lactated Ringer’s Injection due to the increased risk of digoxin toxicity with calcium-containing solutions. ( 7.3 ) Drugs with pH-Dependent Renal Elimination : Renal clearance of acidic drugs may be increased. In contrast, renal clearance of alkaline drugs may be decreased. ( 7.4 ) 7.1 Drugs that Affect Electrolyte and/or Fluid Balance Hyperkalemia Administration of Lactated Ringer’s Injection to patients concomitantly treated or recently treated with drugs that are associated with hyperkalemia increases the risk of severe and potentially fatal hyperkalemia, especially in the presence of other hyperkalemia risk factors . Avoid use of Lactated Ringer’s Injection in patients receiving drugs that are associated with hyperkalemia (e.g., potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, or calcineurin inhibitors). If concomitant use cannot be avoided, closely monitor serum potassium concentrations during concomitant use [see Warnings and Precautions (5.4) ]. Hyponatremia Administration of Lactated Ringer’s Injection to patients treated concomitantly with drugs associated with hyponatremia may increase the risk of developing hyponatremia. These drugs include diuretics and those that cause SIADH (e.g., arginine vasopressin analogs, certain antiepileptic, psychotropic, or cytotoxic drugs). Avoid use of Lactated Ringer’s Injection in patients receiving such drugs. If use cannot be avoided, closely monitor serum sodium concentrations during concomitant use [see Warnings and Precautions (5.5) ] . Hypercalcemia Avoid the use of Lactated Ringer’s Injection in patients treated with thiazide diuretics or vitamin D because these drugs can increase the risk of hypercalcemia. If use cannot be avoided, closely monitor serum calcium concentrations during concomitant use [see Warnings and Precautions (5.6) ]. Hypernatremia and Fluid Retention Administration of Lactated Ringer’s Injection to patients treated concomitantly with drugs associated with sodium and fluid retention (e.g., corticosteroids or corticotropin) may increase the risk of hypernatremia and volume overload. Avoid use of Lactated Ringer’s Injection in patients receiving such drugs. If use cannot be avoided, closely monitor serum electrolytes, fluid balance, and acid-base balance during concomitant use. 7.2 Lithium Renal sodium and lithium clearance may be increased during concomitant use of Lactated Ringer’s Injection and lithium and may result in decreased lithium concentrations. Avoid use of Lactated Ringer’s Injection in patients receiving lithium. If use cannot be avoided, increase the frequency of monitoring of serum lithium concentrations during concomitant use. 7.3 Digoxin Administration of calcium via use of Lactated Ringer’s Injection may increase digoxin’s effects and lead to digoxin toxicity including serious or fatal cardiac arrhythmias. In digoxin-treated patients, consider reducing the volume and/or rate of Lactated Ringer’s Injection administration . 7.4 Drugs with pH-Dependent Renal Elimination Due to the alkalinizing action of lactate (formation of bicarbonate), Lactated Ringer’s Injection may interfere with the elimination of drugs with pH-dependent renal elimination. Renal clearance of alkaline drugs may be decreased. In contrast, renal clearance of acidic drugs may be increased. 7.5 Interference of Lactated Ringer’s Injection with Interpretation of Serum Lactate Levels in Patients with Severe Metabolic Acidosis or Severe Hepatic Impairment Because administration of Lactated Ringer’s Injection may interfere with the interpretation of serum lactate levels i …

8 USE IN SPECIFIC POPULATIONS • Closely monitor plasma electrolyte concentrations in young pediatric patients with immature kidney function. ( 8.4 ) • Geriatric patients are more likely to have decreased renal function. Consider monitoring renal function and starting the infusion at the low end of the dosing range. ( 8.5 ) • Avoid in patients with severe renal impairment. ( 8.6 ) • Patients with severe hepatic impairment may have impaired lactate metabolism. Closely monitor serum lactate levels and acid-base status. ( 8.7 ) 8.1 Pregnancy Risk Summary Lactated Ringer’s as a source of water and electrolytes has been used for decades during labor and delivery. Although there are no reports of use of Lactated Ringer’s in other stages of pregnancy, exposure during pregnancy is not expected to cause major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with this drug. The 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 Lactated Ringer’s as a source of water and electrolytes has been used for decades and is not expected to cause harm to a breastfed infant. There are no data on the presence of Lactated Ringer’s Injection in human milk, the effects on the 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 Lactated Ringer’s Injection and any potential adverse effects on the breastfed infant from Lactated Ringer’s Injection or from the underlying maternal condition. 8.4 Pediatric Use Lactated Ringer’s Injection is contraindicated in neonates (28 days of age or younger) who are receiving ceftriaxone due to reported deaths that occurred when neonates received ceftriaxone and intravenous calcium-containing solutions concomitantly [see Warnings and Precautions (5.1) ] . The safety and effectiveness of Lactated Ringer’s Injection for use as a source of water and electrolytes or as an alkalinizing agent have been established in pediatric patients of all ages, including neonates. Closely monitor plasma electrolyte concentrations in young pediatric patients with immature kidney function who may have decreased ability to maintain fluid and electrolyte balance [see Warnings and Precautions (5.4 , 5.5 , 5.8 , 5.9 )]. Administration of a lactate-containing intravenous solution, including Lactated Ringer’s Injection to pediatric patients should account for liver and kidney maturation (the kidney function affects the biotransformation and renal excretion of lactate) [see Warnings and Precautions (5.9) ] . 8.5 Geriatric Use Geriatric patients treated with Lactated Ringer’s Injection are at increased risk of developing electrolyte imbalances. Lactated Ringer’s Injection is substantially excreted by the kidney, and the risk of adverse reactions to Lactated Ringer’s Injection may be greater in patients with renal impairment than in patients with normal renal function. Because geriatric patients are more likely to have decreased renal function, consider monitoring renal function in geriatric patients and consider starting the infusion at the low end of the dosing range. 8.6 Renal Impairment Administration of Lactated Ringer’s Injection to patients with or at risk of severe renal impairment, may result in hyperkalemia and/or fluid overload [see Warnings and Precautions (5.4 , 5.7 , 5.9 )]. Avoid Lactated Ringer’s Injection in patients with severe renal impairment. If use cannot be avoided in such patients, monitor for development of these adverse reactions. 8.7 Hepatic Impairment In patients with severe hepatic impairment, lactate met …

12.1 Mechanism of Action Lactated Ringer’s Injection is a source of water, electrolytes, and produces an alkalinizing effect. • Sodium, the major cation of the extracellular fluid, functions primarily in the control of water distribution, fluid balance, and osmotic pressure of body fluids. Sodium is also associated with chloride and bicarbonate in the regulation of the acid-base equilibrium of body fluid. • Potassium, the principal cation of intracellular fluid, participates in carbohydrate utilization and protein synthesis and is critical in the regulation of nerve conduction and muscle contraction, particularly in the heart. • Chloride, the major extracellular anion, closely follows the metabolism of sodium, and changes in the acid-base balance of the body are reflected by changes in the chloride concentration. • Calcium, an important cation, provides the framework of bones and teeth in the form of calcium phosphate and calcium carbonate. In the ionized form, calcium is essential for the functional mechanism of the clotting of blood, normal cardiac function, and regulation of neuromuscular irritability. • Sodium lactate provides sodium and lactate ions. The lactate anion is in equilibrium with pyruvate and has an alkalinizing effect resulting from simultaneous removal by the liver of lactate and hydrogen ions. The sodium ion combines with bicarbonate ion produced from carbon dioxide of the body and thus retains bicarbonate to combat metabolic acidosis (bicarbonate deficiency).

DESCRIPTION These products are sterile, nonpyrogenic solutions each containing isotonic concentrations of electrolytes (with or without dextrose) in water for injection. The solutions containing dextrose and electrolytes are hypertonic; those containing only electrolytes are isotonic. They are administered by intravenous infusion for parenteral replacement of extracellular losses of fluid and electrolytes, with or without minimal carbohydrate calories. Each 100 mL of Lactated Ringer's Injection, USP contains sodium chloride 600 mg, sodium lactate, anhydrous 310 mg, potassium chloride 30 mg and calcium chloride, dihydrate 20 mg. May contain hydrochloric acid and/or sodium hydroxide for pH adjustment. A liter provides 9 calories (from lactate), sodium (Na + ), 130 mEq, potassium (K + ) 4 mEq, calcium (Ca ++ ) 3 mEq, chloride (Cl − ) 109 mEq and lactate [CH 3 CH(OH) COO − ] 28 mEq. The electrolyte content is isotonic (273 mOsmol/liter, calc.) in relation to the extracellular fluid (approx. 280 mOsmol/liter). The pH of the solution is 6.6 (6.0 − 7.5). Each 100 mL of Lactated Ringer's and 5% Dextrose Injection, USP contains dextrose, hydrous 5 g plus the same ingredients and mEq values as Lactated Ringer's Injection, USP (contains only hydrochloric acid for pH adjustment). A liter provides 179 calories (from dextrose and lactate) and has a hypertonic osmolar concentration of 525 mOsmol (calc.). The pH is 4.9 (4.0 − 6.5). The solutions contain no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and each is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded. The solutions are parenteral fluid, nutrient and/or electrolyte replenishers. 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: Calcium Chloride, USP is chemically designated calcium chloride, dihydrate (CaCl 2 • 2 H 2 O), white fragments or granules freely soluble in water. 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. 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 O. 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 inside the plastic container also can leach out certain of their chemical components in very small amounts before the expiration period is attained. However, the safety of the plastic has been confirmed by tests in animals according to USP biological standards for plastic containers. structural formula dextrose structural formula sodium lactate

OVERDOSAGE In the event of a fluid or solute overload during parenteral therapy, reevaluate the patient's condition and institute appropriate corrective treatment. In the event of overdosage with potassium-containing solutions, discontinue the infusion immediately and institute corrective therapy to reduce serum potassium levels. Treatment of hyperkalemia includes the following: Dextrose Injection USP, 10% or 25%, containing 10 units of crystalline insulin per 20 grams of dextrose administered intravenously, 300 to 500 mL per hour. Absorption and exchange of potassium using sodium or ammonium cycle cation exchange resin, orally and as retention enema. Hemodialysis and peritoneal dialysis. The use of potassium-containing foods or medications must be eliminated. However, in cases of digitalization, too rapid a lowering of plasma potassium concentration can cause digitalis toxicity.

HOW SUPPLIED These solutions are supplied in single-dose flexible plastic containers as follows: NDC No. Product Name Container Size (mL) 0409-7953-02 Manufactured by ICU Medical, Inc., Lake Forest, Illinois, 60045, USA Lactated Ringer's Inj., USP 250 0990-7953-02 Lactated Ringer's Inj., USP 250 0409-7953-03 Manufactured for ICU Medical, Inc., Lake Forest, Illinois, 60045, USA Lactated Ringer's Inj., USP 500 0990-7953-03 , Lactated Ringer's Inj., USP 500 0409-7953-09 , Lactated Ringer's Inj., USP 1000 0990-7953-09 , Lactated Ringer's Inj., USP 1000 0409-7929-03 Lactated Ringer's and 5% Dextrose Inj., USP 500 0990-7929-03 , Lactated Ringer's and 5% Dextrose Inj., USP 500 0409-7929-09 , Lactated Ringer's and 5% Dextrose Inj., USP 1000 0990-7929-09 , Lactated Ringer's and 5% Dextrose Inj., USP 1000 ICU Medical is transitioning NDC codes from "0409" to a"0990" labeler code. Both NDC codes are expected to be in the market for a period of time. Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Protect from freezing. Revised: April, 2020 IFU0000184