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 ) 10/2025

1 INDICATIONS AND USAGE Ringer's Injection is indicated for use as a source of water and electrolytes in adults and pediatric patients. Ringer's Injection is indicated for use as a source of water and electrolytes in adults and pediatric patients. ( 1 )

2 DOSAGE AND ADMINISTRATION The recommended dosage and duration are 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 ) Ringer's Injection is for intravenous use ( 2.3 ) Do not administer Ringer's Injection simultaneously with ceftriaxone in neonates (28 days of age or younger) due to serious risks. ( 2.4 ) See full prescribing information for information dosage considerations, preparation, administration, and drug incompatibilities. ( 2 ) 2.1 Dosage Considerations The recommended dosage and duration of Ringer's Injection is 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 Ringer's Injection to optimize clinical status. Fluid administration should be based on calculated maintenance or replacement fluid requirements for each patient. 2.2 Important Preparation Instructions Visually inspect the Ringer's Injection solution for particulate matter and discoloration. Do not administer Ringer's Injection unless the solution is clear and the container is undamaged and the container seals are intact. If additives are determined to be compatible with 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 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 Ringer's Injection, turn off the pump before the container is empty. To Open: Tear outer wrap at notch and remove solution container. If supplemental medication is desired, follow directions below before preparing for administration. 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. Preparation for Administration (Use aseptic technique) Close flow control clamp of administration set. Remove cover from outlet port at bottom of container. Insert piercing pin of administration set into port with a twisting motion until the set is firmly seated. NOTE: See administration set carton for complete directions. Suspend container from hanger. Squeeze and release drip chamber to establish proper fluid level in chamber. Open flow control clamp and clear air from set. Close clamp. Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture. Regulate rate of administration with flow control clamp. 2.3 Important Administration Instructions 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 Prepare medication site. Using syringe with the recommended gauge needle, puncture medication port and inner diaphragm and inject. Squeeze and tap ports while ports are upright and mix solution and medication thoroughly. To Add Medication During Solution Administration Close clamp on the set. Prepare medication site. Using syringe with the recommended gauge needle of appropriate length (at least 5/8 inch), puncture resealable medication port and inner diaphragm and inject. Remove container from IV pole and/or turn to an upright position. …

3 DOSAGE FORMS AND STRENGTHS Injection: Ringer's Injection USP as a clear, sterile, and nonpyrogenic solution packaged in a single-dose flexible plastic container: 1,000 mL. Injection: Ringer's Injection USP packaged in single-dose flexible plastic container: 1,000 mL ( 3 )

4 CONTRAINDICATIONS Ringer's Injection is contraindicated in: Neonates (28 days of age or younger) who are receiving concomitant treatment with ceftriaxone, even if separate infusion lines are used, due to the risk of fatal ceftriaxone-calcium salt precipitation in the neonate's bloodstream [see Warnings and Precautions (5.1) and Specific Populations (8.4) ] . Patients with known hypersensitivity to any components of Ringer's Injection [see Warnings and Precautions (5.3) ] . Concomitant treatment with ceftriaxone in neonates (28 days of age or younger). ( 4 ) Patients with known hypersensitivity to Ringer's Injection. ( 4 )

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Serious Risk with Concomitant Use with Ceftriaxone [see Warnings and Precautions (5.1) ] Air Embolism [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Potassium Imbalances [see Warnings and Precautions (5.4) ] Hyponatremia [see Warnings and Precautions (5.5) ] Hypercalcemia [see Warnings and Precautions (5.6) ] Fluid Overload [see Warnings and Precautions (5.7) ] The following adverse reactions have been identified during postapproval use of Ringer’s Products. 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: General Disorders and Administration Site Conditions : Phlebitis, extravasation, infusion site inflammation, infusion site swelling, infusion site rash, infusion site pruritus, infusion site erythema, infusion site pain, infusion site burning, and infusion site hypoaesthesia. Hypersensitivity Reactions and Infusion Reactions : Angioedema, chest pain/discomfort, bradycardia or tachycardia, hypotension, respiratory distress, bronchospasm, dyspnea, cough, urticaria, rash, pruritus, erythema, flushing, throat irritation, paresthesia, oral hypoesthesia, dysgeusia, nausea, anxiety, pyrexia, headache, laryngeal edema, sneezing, and injection site infection. Metabolism and Nutrition Disorders : Hyperkalemia, hyponatremia, and hypervolemia. Nervous System Disorders : Hyponatremic encephalopathy. Common adverse reactions include infusion site reactions and symptoms of hypersensitivity reactions (e.g., pruritus, dyspnea, urticaria, rash, cough). ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact B. Braun Medical Inc. at 1-833-425-1464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

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 Ringer’s Injection due to the increased risk of digoxin toxicity with calcium-containing solutions. ( 7.3 ) 7.1 Drugs that Affect Electrolyte and/or Fluid Balance Hyperkalemia Administration of 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 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 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 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 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 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 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 Ringer’s Injection and lithium and may result in decreased lithium concentrations. Avoid use of 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 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 Ringer’s Injection administration .

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 ) 8.1 Pregnancy Risk Summary Exposure to Ringer's Injection 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 The use of Ringer's Injection is not expected to cause harm to a breastfed infant. There are no data on the presence of 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 Ringer's Injection and any potential adverse effects on the breastfed infant from Ringer's Injection or from the underlying maternal condition. 8.4 Pediatric Use 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 Ringer's Injection for use as a source of water and electrolytes 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 , 5.6 , 5.7 )] . 8.5 Geriatric Use Geriatric patients treated with Ringer's Injection are at increased risk of developing electrolyte imbalances. Ringer's Injection is substantially excreted by the kidney, and the risk of adverse reactions to 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 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) ] . Avoid Ringer's Injection in patients with severe renal impairment. If use cannot be avoided in such patients, monitor for development of these adverse reactions.

12.1 Mechanism of Action Ringer's Injection is a source of water, and electrolytes. 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.

11 DESCRIPTION Ringer’s Injection USP is a sterile, nonpyrogenic solution for fluid and electrolyte replenishment in a single-dose container for intravenous administration. Composition, osmolarity, pH, ionic concentration and caloric content are shown in Table 1. Table 1 Size (mL) Composition (g/L) Osmolarity Normal physiologic osmolarity range is approximately 280 to 310 mOsmol/L. (mOsmol/L) (calc) pH Ionic Concentration (mEq/L) Caloric Content (kcal/L) Sodium Chloride, USP Calcium Chloride, USP Potassium Chloride, USP Sodium Potassium Calcium Chloride Ringer’s Injection, USP 1000 8.6 0.33 0.3 310 5.8 (5.0 to 7.5) 147 4 4.5 156 0 The chemical name, structural formula, and molecular weight of the active ingredients are shown in Table 2. Table 2 Ingredients Molecular Formula Molecular Weight Sodium Chloride USP 58.44 Potassium Chloride USP 74.55 Calcium Chloride Dihydrate USP 147.02 Not made with natural rubber latex, PVC or DEHP. The plastic container is made from a multilayered film developed for parenteral drugs. It contains no plasticizers and has minimal leachables. The solution contact layer is a rubberized copolymer of ethylene and propylene. The container-solution unit is a closed system and is not dependent upon entry of external air during administration. The container is overwrapped to provide protection from the physical environment and to provide an additional moisture barrier when necessary. The closure system has two ports; the one for the administration set has a tamper evident plastic protector and the other is a medication addition site [see Dosage and Administration (2.3) ]. Sodium Chloride USP Potassium Chloride USP Calcium Chloride Dihydrate USP

10 OVERDOSAGE Excessive administration of Ringer’s Injection can cause: Hyperkalemia and hypernatremia, especially in patients with severe renal impairment. Fluid overload (which can lead to pulmonary and/or peripheral edema). Hypercalcemia Overdose interventions include Ringer’s Injection discontinuation, treatment of electrolyte imbalances, and close monitoring of fluid balance and electrolyte concentrations [see Warnings and Precautions ( 5.4 , 5.5 , 5.6 , 5.7 )].

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Ringer’s Injection USP is supplied sterile and nonpyrogenic in single-dose EXCEL ® Containers packaged 12 per case. It is available in the following presentation: NDC REF Size 0264-7780-00 L7800 1000 mL Canada DIN 01936034 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.] Minimize exposure of Ringer’s Injection USP to heat. Avoid excessive heat. Protect from freezing.