2.1 Dosage Considerations

The recommended dosage and duration of Lactated Ringer’s and Dextrose (5%) Injection is based on the patient’s age, weight, clinical condition, and concomitant therapy. Evaluate the patient’s clinical status and monitor changes in blood glucose and electrolyte concentrations, especially during prolonged use of Lactated Ringer’s and Dextrose (5%) Injection to optimize clinical status.

2.2 Important Preparation Instructions

Visually inspect the Lactated Ringer’s and Dextrose (5%) Injection solution for particulate matter and discoloration. Do not administer Lactated Ringer’s and Dextrose (5%) Injection unless the solution is clear and the container seals are intact.

If additives are determined to be compatible with Lactated Ringer’s and Dextrose (5%) 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 and Dextrose (5%) Injection [see Warnings and Precautions (5.2)]:

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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).

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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 and Dextrose (5%) Injection, turn off the pump before the container is empty.

Preparation Instructions

1.

Tear overwrap downside at slit and remove solution container.

2.

Visually inspect the container.

o

If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired.

o

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.

3.

Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution as sterility may be impaired.

4.

If supplemental medication is desired, follow directions below [see Dosage and Administration (2.3)].

Preparation for Administration

1.

Suspend container from eyelet support.

2.

Remove protector from outlet port at bottom of container.

3.

Attach administration set according to its accompanying directions.

2.3 Important Administration Instructions

Lactated Ringer’s and Dextrose (5%) Injection is for intravenous use.

Use immediately after removing the overwrap. Discard the unused portion.

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Use a peripheral vein to administer Lactated Ringer’s and Dextrose (5%) Injection if the final dextrose concentration is 5% or less, and the osmolarity is less than 900 mOsm/L.

•

Consider using a central vein to administer hypertonic solutions with osmolarity of 900 mOsm/L or more to avoid venous irritation [see Warnings and Precautions (5.7)].

Some additives may be incompatible [see Dosage and Administration (2.4) and Contraindications (4)].

To Add Medication Before Solution Administration

1.

Prepare medication site.

2.

Using syringe with 19 to 22 gauge needle, puncture resealable medication port and inject.

3.

Mix solution and medication thoroughly. For high density medication such as potassium chloride, squeeze ports while ports are upright and mix thoroughly.

To Add Medication During Solution Administration

1.

Close clamp on the set.

2.

Prepare medication site.

3.

Using syringe with 19 to 22 gauge needle, puncture resealable medication port and inject.

4.

Remove container from IV pole and/or turn to an upright position.

5.

Evacuate both ports by squeezing them while container is in the upright position.

6.

Mix solution and medication thoroughly.

7.

Return container to in use position and continue administration.

2.4 Drug Incompatibilities

Do not administer Lactated Ringer’s and Dextrose (5%) 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 and Dextrose (5%) 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 and Dextrose (5%) 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 and Dextrose (5%) Injection.

5.1 Serious Risk with Concomitant Use with Ceftriaxone

Precipitation of ceftriaxone-calcium can occur when ceftriaxone is mixed with calcium-containing solutions, such as Lactated Ringer’s and Dextrose (5%) 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.

Lactated Ringer’s and Dextrose (5%) 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 Lactated Ringer’s and Dextrose (5%) Injection may be administered sequentially if the infusion lines are thoroughly flushed between infusions with a 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 a non-vented infusion set or close the vent on a vented set and use a dedicated line without any connections.

If administration is controlled by a 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 Lactated Ringer’s solution. Stop the Lactated Ringer’s and Dextrose (5%) Injection infusion immediately and treat patient accordingly if signs or symptoms of a hypersensitivity reaction develop. Initiate appropriate treatment as clinically indicated.

5.4 Potassium Imbalances

Hyperkalemia

Potassium-containing solutions, including Lactated Ringer’s and Dextrose (5%) 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 Lactated Ringer’s and Dextrose (5%) 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 Lactated Ringer’s and Dextrose (5%) Injection is similar to the concentration in plasma. It is insufficient to normalize the serum potassium in patients with severe hypokalemia.

5.5 Hyponatremia

Lactated Ringer’s and Dextrose (5%) 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, patients with cardiac or pulmonary failure, or patients 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 Lactated Ringer’s and Dextrose (5%) 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 Neonatal Hypoglycemia

Neonates, especially preterm neonates with low birth weight, are at increased risk of developing hypoglycemia. Closely monitor blood glucose concentration during treatment with intravenous dextrose solutions to ensure adequate glycemic control in order to avoid potential long-term adverse effects.

5.7 Hyperglycemia and Hyperosmolar Hyperglycemic State

Administration of solutions containing dextrose and lactate in patients with impaired glucose tolerance including those with diabetes mellitus may worsen hyperglycemia. Hyperglycemia is associated with an increase in serum osmolality, which can result in hypovolemia and electrolyte imbalances due to osmotic diuresis.

Patients with underlying central nervous system disease or renal impairment who receive dextrose infusions may be at greater risk of developing hyperosmolar hyperglycemic state.

While using Lactated Ringer’s and Dextrose (5%) Injection, closely monitor blood glucose concentrations and treat hyperglycemia to maintain glucose concentrations within normal limits. Anti-diabetic drugs may need to be started or dosages of these drugs may need to be increased to maintain optimal blood glucose concentrations.

5.8 Hypercalcemia

Lactated Ringer’s and Dextrose (5%) Injection contains calcium salts and may cause hypercalcemia. Avoid administration of Lactated Ringer’s and Dextrose (5%) 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.

5.9 Fluid Overload

Depending on the administered volume and the infusion rate, administration of Lactated Ringer’s and Dextrose (5%) Injection can cause fluid overload, including pulmonary edema.

Avoid Lactated Ringer’s and Dextrose (5%) 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.

5.10 Acid/Base Imbalances

Because lactate is metabolized to bicarbonate, administration of Lactated Ringer’s and Dextrose (5%) Injection may result in, or worsen, metabolic alkalosis. Closely monitor the acid-base balance in patients with, or at risk of, alkalosis.

In patients with severe hepatic impairment, decreased lactate metabolism may result in worsening anion gap metabolic acidosis. Avoid Lactated Ringer’s and Dextrose (5%) Injection in patients with severe hepatic impairment. If use cannot be avoided in these patients, closely monitor serum bicarbonate levels.

5.11 Interference of Lactated Ringer’s and Dextrose (5%) Injection with Interpretation of Serum Lactate Levels in Patients with Severe Metabolic Acidosis

Administration of Lactated Ringer’s and Dextrose (5%) Injection may result in interference with the interpretation of serum lactate levels in patients with severe metabolic acidosis, including lactic acidosis [see Drug Interactions (7.5)].

7.1 Drugs that Affect Electrolyte and/or Fluid Balance

Hyperkalemia

Administration of Lactated Ringer’s and Dextrose (5%) 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 and Dextrose (5%) 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 and Dextrose (5%) 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 and Dextrose (5%) 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 and Dextrose (5%)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 (5.8)].

Hypernatremia and Fluid Retention

Administration of Lactated Ringer’s and Dextrose (5%) 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 and Dextrose (5%) 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 and Dextrose (5%) Injection and lithium and may result in decreased lithium concentrations. Avoid use of Lactated Ringer’s and Dextrose (5%)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 and Dextrose (5%) 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 and Dextrose (5%) Injection administration.

7.4 Drugs with pH-Dependent Renal Elimination

Due to the alkalinizing action of lactate (formation of bicarbonate), Lactated Ringer’s and Dextrose (5%) 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 and Dextrose (5%) Injection with Interpretation of Serum Lactate Levels in Patients with Severe Metabolic Acidosis

Because administration of Lactated Ringer’s and Dextrose (5%) Injection may interfere with the interpretation of serum lactate levels in patients with severe metabolic acidosis, including lactic acidosis, assessment of the patient’s clinical status should not solely rely on the measurement of serum lactate.

8.1 Pregnancy

Risk Summary

Lactated Ringer’s as a source of water and electrolytes and Dextrose (5%) Injection have been used for decades during labor and delivery. Although there are a few case reports that describe adverse effects of dextrose use and no reports of use of Lactated Ringer’s in other stages of pregnancy, exposure to Lactated Ringer’s and Dextrose (5%) Injection during pregnancy in general 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. Therefore, it is not known whether Lactated Ringer’s and Dextrose (5%) Injection can cause fetal harm when administered to a pregnant woman. Lactated Ringer’s and Dextrose (5%) Injection should be given during pregnancy only if the potential benefit justifies the potential risk to the fetus.

8.2 Lactation

Risk Summary

Lactated Ringer’s as a source of water and electrolytes and Dextrose (5%) Injection have 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 and Dextrose (5%) Injection in human Imilk, 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 and Dextrose (5%) Injection and any potential adverse effects on the breastfed infant from Lactated Ringer’s and Dextrose (5%) Injection or from the underlying maternal condition.

8.4 Pediatric Use

Lactated Ringer’s and Dextrose (5%) 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, electrolytes, and calories 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 and Dextrose (5%) 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)]. Pediatric patients are at increased risk for developing hyponatremic encephalopathy [see Warnings and Precautions (5.5)].

Neonates, especially preterm neonates with low birth weight, are at increased risk of developing hypo- or hyperglycemia and therefore need close monitoring during treatment with intravenous glucose solutions including Lactated Ringer’s and Dextrose (5%) Injection to ensure adequate glycemic control to avoid potential long-term adverse reactions [see Warnings and Precautions (5.6, 5.7)]. In very low birth weight neonates, excessive or rapid administration of Lactated Ringer’s and Dextrose (5%) Injection may result in increased serum osmolality and risk of intracranial hemorrhage.

8.5 Geriatric Use

Geriatric patients treated with Lactated Ringer’s and Dextrose (5%) Injection are at increased risk of developing electrolyte imbalances. Lactated Ringer’s and Dextrose (5%) Injection is substantially excreted by the kidney, and the risk of adverse reactions to Lactated Ringer’s and Dextrose (5%) 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 and Dextrose (5%) 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 and Dextrose (5%) 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 metabolism may be impaired, and Lactated Ringer’s and Dextrose (5%) Injection may not produce alkalinization. Closely monitor serum lactate levels and acid-base status in such patients.

12.1 Mechanism of Action

Lactated Ringer’s and Dextrose (5%) Injection is a source of water, electrolytes, and calories, and produces an alkalinizing effect.

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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.

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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.

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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.

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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.

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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).

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Dextrose provides a source of calories. Dextrose may decrease losses of body protein and nitrogen, promotes glycogen deposition and decreases or prevents ketosis if sufficient doses are provided.

12.2 Pharmacodynamics

The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of Lactated Ringer’s and Dextrose (5%) 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 a 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 a balance between intake and output.

Lactate: In the liver, lactate is metabolized to carbon dioxide and water by oxidative metabolism and consumption of hydrogen cations.

Dextrose: Dextrose injected parenterally undergoes oxidation to carbon dioxide and water.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, genetic toxicology, and animal fertility studies have not been conducted with Lactated Ringer’s and Dextrose (5%) Injection.