ADVERSE REACTIONS SECTION.

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 Ringers Products. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish 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.. 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)] 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.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Ringers Injection is 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.. 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.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Ringers Injection is 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.. 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.. 12.2 Pharmacodynamics. The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of Ringers Injection have not been fully characterized.. 12.3 Pharmacokinetics. Elimination Metabolism/Excretion Potassium: Normally about 80 to 90% of the potassium intake is excreted in the urine; the remainder is excreted in feces and to smaller extent, in perspiration.Sodium and Chloride: The distribution and excretion of sodium (Na+) and chloride (Cl-) are largely under the control of the kidney which maintains balance between intake and output.

DESCRIPTION SECTION.

11 DESCRIPTION. Ringers Injection USP is sterile, nonpyrogenic solution for fluid and electrolyte replenishment in single-dose container for intravenous administration.Composition, osmolarity, pH, ionic concentration and caloric content are shown in Table 1. Table 1Size (mL)Composition (g/L)OsmolarityNormal physiologic osmolarity range is approximately 280 to 310 mOsmol/L.(mOsmol/L) (calc)pHIonic Concentration (mEq/L)Caloric Content (kcal/L)Sodium Chloride, USPCalcium Chloride, USPPotassium Chloride, USPSodiumPotassiumCalciumChlorideRingers Injection, USP10008.60.330.33105.8(5.0 to7.5)14744.51560The chemical name, structural formula, and molecular weight of the active ingredients are shown in Table 2.Table 2IngredientsMolecular FormulaMolecular WeightSodium Chloride USP58.44Potassium Chloride USP74.55Calcium Chloride Dihydrate USP147.02Not made with natural rubber latex, PVC or DEHP.The plastic container is made from multilayered film developed for parenteral drugs. It contains no plasticizers and has minimal leachables. The solution contact layer is rubberized copolymer of ethylene and propylene. The container-solution unit is 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 tamper evident plastic protector and the other is medication addition site [see Dosage and Administration (2.3)]. Sodium Chloride USP. Potassium Chloride USP. Calcium Chloride Dihydrate USP.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. The recommended dosage and duration are based on the patients 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)Ringers Injection is for intravenous use (2.3)Do not administer Ringers 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). The recommended dosage and duration are based on the patients 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). Ringers Injection is for intravenous use (2.3). Do not administer Ringers 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 Ringers Injection is based on the patients age, weight, clinical condition, and concomitant therapy. Evaluate the patients clinical status and monitor changes in electrolyte concentrations especially during prolonged use of Ringers 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 Ringers Injection solution for particulate matter and discoloration. Do not administer Ringers Injection unless the solution is clear and the container seals are intact.If additives are determined to be compatible with Ringers 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 Ringers Injection preparation instructions [see Warnings and Precautions (5.2)]:Use non-vented infusion set or close the vent on vented set.Use dedicated line without any connections (do not connect flexible containers in series).The use of pressure infusion is not recommended as 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 pumping device to administer Ringers Injection, turn off the pump before the container is empty.Preparation Instructions for EXCEL(R) ContainersTear 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.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.If supplemental medication is desired, follow directions below [see Dosage and Administration (2.3)].Preparation for AdministrationRemove plastic protector from sterile set port at bottom of container.Attach administration set according to its accompanying directions.. Use non-vented infusion set or close the vent on vented set.. Use dedicated line without any connections (do not connect flexible containers in series).. The use of pressure infusion is not recommended as 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 pumping device to administer Ringers Injection, turn off the pump before the container is empty.. 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.. 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.. If supplemental medication is desired, follow directions below [see Dosage and Administration (2.3)].. Remove plastic protector from sterile set port at bottom of container.. Attach administration set according to its accompanying directions.. 2.3 Important Administration Instructions. Ringers Injection is for intravenous use. Use immediately after opening the container. Discard the unused portion.It is recommended that intravenous administration apparatus be replaced at least once every 24 hours.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.. 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. 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 DrugIncompatibilities. Do not administer Ringers 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 Ringers Injection may be administered sequentially if the infusion lines are thoroughly flushed between infusions with compatible fluid [see Warnings and Precautions (5.1)].Do not administer Ringers Injection simultaneously with citrate anticoagulated/preserved blood through the same administration set because of the likelihood of coagulation precipitated by the calcium content of Ringers Injection.

DRUG INTERACTIONS SECTION.

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 Ringers Injection due to the increased risk of digoxin toxicity with calcium-containing solutions. (7.3). 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 Ringers Injection due to the increased risk of digoxin toxicity with calcium-containing solutions. (7.3). 7.1 Drugs that Affect Electrolyte and/orFluid Balance. Hyperkalemia Administration of Ringers 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 Ringers 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 Ringers 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 Ringers 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 Ringers Injection in patients treated with thiazide diuretics or vitamin 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 Ringers 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 Ringers 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 Ringers Injection and lithium and may result in decreased lithium concentrations. Avoid use of Ringers 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 Ringers Injection may increase digoxins effects and lead to digoxin toxicity including serious or fatal cardiac arrhythmias. In digoxin-treated patients, consider reducing the volume and/or rate of Ringers Injection administration.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL. RingersInjection USP REF L7800NDC 0264-7780-00DIN 01936034HK 22699 1000 mL EXCEL(R) CONTAINEREach 100 mL contains: Sodium Chloride USP 0.86 g;Calcium Chlorideo2H2O USP 0.033 g;Potassium Chloride USP 0.03 g; Water for Injection USP qspH: 5.8 (5.0-7.5); Calc. Osmolarity: 310 mOsmol/literElectrolytes (mEq/liter):Na+ 147; K+ 4; Ca++ 4.5; Cl- 156Sterile, nonpyrogenic. Single dose container. Do not use in series connection.For intravenous use only. Use only if solution is clear and container and sealsare intact.WARNINGS: Do Not Administer Simultaneously With Blood. Some additivesmay be incompatible. Consult with pharmacist. When introducing additives,use aseptic techniques. Mix thoroughly. Do not store.Recommended Storage: Room temperature (25C). Avoid excessive heat.Protect from freezing. See Package Insert.Do not remove overwrap until ready for use. After removing the overwrap,check for minute leaks by squeezing container firmly. If leaks are found,discard solution as sterility may be impaired.Not made with natural rubber latex, PVC or DEHP. Rx only EXCEL is registered trademark of B. Braun Medical Inc.B. Braun Medical Inc.Bethlehem, PA 18018-3524 USA1-800-227-2862www.bbraun.comIn Canada, distributed by: B. Braun of Canada, Ltd. Scarborough, Ontario M1H 2W4Y94-003-233 LD-139-3EXPLOT. Other Symbol. 1000 mL Container Label L7800.

USE IN SPECIFIC POPULATIONS SECTION.

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). 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 SummaryExposure to Ringers 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 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 to 4% and 15 to 20%, respectively.. 8.2 Lactation. Risk Summary The use of Ringers Injection is not expected to cause harm to breastfed infant. There are no data on the presence of Ringers 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 mothers clinical need for Ringers Injection and any potential adverse effects on the breastfed infant from Ringers Injection or from the underlying maternal condition.. 8.4 Pediatric Use. Ringers 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 Ringers Injection for use as 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 Ringers Injection are at increased risk of developing electrolyte imbalances. Ringers Injection is substantially excreted by the kidney, and the risk of adverse reactions to Ringers 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 RenalImpairment. Administration of Ringers 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 Ringers Injection in patients with severe renal impairment. If use cannot be avoided in such patients, monitor for development of these adverse reactions.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Serious Risks with Inappropriate Use with Ceftriaxone: Deaths have occurred in neonates (28 days of age or younger) who received concomitant intravenous calcium-containing solutions with ceftriaxone. In patients older than 28 days, ceftriaxone and Ringers Injection may be administered sequentially if the infusion lines are thoroughly flushed between infusions. (4, 5.1, 8.4)Air Embolism: Use non-vented infusion set or close the vent on vented set and use dedicated line without any connections. Pressure infusion is not recommended to increase flow rates, but if necessary, remove all air from the bag prior to initiating infusion. (5.2)Hypersensitivity Reactions: Stop the Ringers Injection infusion immediately if signs or symptoms of hypersensitivity reaction develop. (5.3)Potassium Imbalances, Hyponatremia, Hypercalcemia, Fluid Overload: See Full Prescribing Information for risk management recommendations. (5.4, 5.5, 5.6, 5.7). Serious Risks with Inappropriate Use with Ceftriaxone: Deaths have occurred in neonates (28 days of age or younger) who received concomitant intravenous calcium-containing solutions with ceftriaxone. In patients older than 28 days, ceftriaxone and Ringers Injection may be administered sequentially if the infusion lines are thoroughly flushed between infusions. (4, 5.1, 8.4). Air Embolism: Use non-vented infusion set or close the vent on vented set and use dedicated line without any connections. Pressure infusion is not recommended to increase flow rates, but if necessary, remove all air from the bag prior to initiating infusion. (5.2). Hypersensitivity Reactions: Stop the Ringers Injection infusion immediately if signs or symptoms of hypersensitivity reaction develop. (5.3). Potassium Imbalances, Hyponatremia, Hypercalcemia, Fluid Overload: See Full Prescribing Information for risk management recommendations. (5.4, 5.5, 5.6, 5.7). 5.1 Serious Risk with ConcomitantUse withCeftriaxone. Precipitation of ceftriaxone-calcium can occur when ceftriaxone is mixed with calcium-containing solutions, such as Ringers Injection in the same intravenous administration line. Deaths have occurred in neonates (28 days of age or younger) who received concomitant intravenous calcium-containing solutions with ceftriaxone resulting from calcium-ceftriaxone precipitates in the lungs and kidneys, even when separate infusion lines were used.Ringers Injection is contraindicated in neonates who receive ceftriaxone [see Contraindications (4), Use in Specific Populations (8.4)]. However, in patients older than 28 days, ceftriaxone and Ringers Injection may be administered sequentially if the infusion lines are thoroughly flushed between infusions with compatible fluid.. 5.2 Air Embolism. Cases of air embolism have been reported with pressurized administration of intravenous fluids. Air embolism may result in stroke, organ ischemia and/or infarction, and death. Use non-vented infusion set or close the vent on vented set and use dedicated line without any connections. If administration is controlled by pumping device, care must be taken to discontinue the pumping action before the container is empty. Pressure infusion is not recommended to increase flow rates, but if necessary, ensure all air is removed from the bag before infusion. Refrain from applying excessive pressure (>300mmHg) causing distortion to the container such as wringing or twisting. Such handling could result in breakage of the container [see Dosage and Administration (2.2)].. 5.3 Hypersensitivity Reactions. Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with Ringers Injection. Stop the Ringers Injection infusion immediately and treat patient accordingly if signs or symptoms of hypersensitivity reaction develop. Initiate appropriate treatment as clinically indicated.. 5.4 PotassiumImbalances. Hyperkalemia Potassium-containing solutions, including Ringers Injection, may increase the risk of hyperkalemia. This risk is increased in patients predisposed to hyperkalemia including those with severe renal impairment, acute dehydration, extensive tissue injury or burns, heart failure, or in those using concomitant drugs that are associated with hyperkalemia.Avoid use of Ringers Injection in patients with, or at increased risk for, hyperkalemia. If use cannot be avoided in these patients, closely monitor serum potassium concentrations.Hypokalemia The potassium concentration in Ringers Injection is similar to the concentration in plasma. It is insufficient to normalize the serum potassium in patients with severe hypokalemia.. 5.5 Hyponatremia. Ringers Injection may cause hyponatremia. Hyponatremia can lead to acute hyponatremic encephalopathy characterized by headache, nausea, seizures, lethargy and vomiting. The risk of hospital-acquired hyponatremia is increased in younger pediatric patients, geriatric patients, patients treated with diuretics, and patients with cardiac or pulmonary failure or with the syndrome of inappropriate antidiuretic hormone (SIADH) (e.g., postoperative patients, patients concomitantly treated with arginine vasopressin analogs or certain antiepileptic, psychotropic, or cytotoxic drugs) [see Drug Interactions (7.1), Use in Specific Populations (8.4)]. Avoid Ringers Injection in patients with or at risk for hyponatremia. If use cannot be avoided in these patients, closely monitor serum sodium concentrations. Rapid correction of hyponatremia may result in serious neurologic complications such as osmotic demyelination syndrome (ODS). To avoid complications, monitor serum sodium and chloride concentrations, fluid status, acid-base balance, and neurologic status.. 5.6 Hypercalcemia. Ringers Injection contains calcium salts and may cause hypercalcemia. Avoid administration of Ringers Injection in patients with hypercalcemia, those with calcium-containing renal calculi or history of such calculi, those with conditions predisposing to hypercalcemia, or those treated with concomitant thiazide diuretics or vitamin D.. 5.7 Fluid Overload. Depending on the administered volume and the infusion rate, administration of Ringers Injection can cause fluid overload, including pulmonary edema. Avoid Ringers Injection in patients at risk for fluid and/or solute overload including patients with severe renal impairment. If use cannot be avoided in these patients, monitor fluid balance, electrolyte concentrations and acid base balance, especially during prolonged use.