LACTATED RINGERS

Lactated Ringer’s Injection USP is a sterile, nonpyrogenic solution for fluid and electrolyte replenishment in a single-dose container intended 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 pH may be adjusted with Hydrochloric Acid NF or Sodium Hydroxide NF. Ionic Concentration (mEq/L) Caloric Content (kcal/L) Sodium Chloride, USP Sodium Lactate Potassium Chloride, USP Calcium Chloride, USP Sodium Potassium Calcium Chloride Lactate Lactated Ringer’s Injection, USP 250 500 1000 6 3.1 0.3 0.2 275 6.2 (6.0 to 7.5) 130 4 3 110 28 9 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 Sodium Lactate 112.06 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 Sodium Lactate Potassium Chloride USP Calcium Chloride Dihydrate USP

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 )

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 ) Do not administer Lactated 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 Lactated 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 Lactated 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 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 preparation instructions for Lactated Ringer’s Injection [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 for EXCEL ® Containers Tear overwrap down at notch and remove solution container. 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) ] . Inspect each container. Read the label. Ensure solution is the one ordered and is within the expiration date. 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. Preparation for Administration Remove plastic protector from sterile set port at bottom of container. Attach administration set. Refer to complete directions accompanying set. 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 Prepare medication site. Using syringe with 18-22 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 18-22 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. Evacuate both ports by tapping and squeezing them while container is in the upright position. Mix solution and medication thoroughly. Return container to in use position and continue administration. 2.4 Drug Incompatibilities Do not administer Lactated Ringer’s Injection simultaneously with ceftriaxone in neonates (28 days of age or younger) due to serious risks [see Contraindications (4) and Warnings and Precautions (5.1) ]. However, in patients older than 28 days, ceftriaxone and Lactated Ringer’s Injection may be administered sequentially if the infusion lines are thoroughly flushed between infusions with a compatible fluid [see Warnings and Precautions (5.1) ] . Do not administer Lactated Ringer’s Injection simultaneously with citrate anticoagulated/preserved blood through the same administration set because of the likelihood of coagulation precipitated by the calcium content of Lactated Ringer’s Injection.

Lactated 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 sodium lactate [see Warnings and Precautions (5.3) ]. Concomitant treatment with ceftriaxone in neonates (28 days of age or younger). ( 4 ) Patients with known hypersensitivity to any components of Lactated Ringer’s Injection. ( 4 )

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) ] Acid/Base Imbalances [see Warnings and Precautions (5.8) ] The following adverse reactions have been identified during postapproval use of Lactated 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 .

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 in patients with severe metabolic acidosis or severe hepatic impairment, assessment of the patient’s clinical status should not solely rely on the measurement of serum lactate.