Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

LACTATED RINGER'S IN PLASTIC CONTAINER (NDA-016682)

(CALCIUM CHLORIDE; POTASSIUM CHLORIDE; SODIUM CHLORIDE; SODIUM LACTATE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

11/05/2025 (SUPPL-127)

Approved Drug Label (PDF)

Other

PLR conversion; please refer to label for complete information

07/24/2024 (SUPPL-124)

Approved Drug Label (PDF)

4 Contraindications

Additions and revisions underlined:

Lactated Ringer’s Injection, USP is contraindicated in:

• Newborns (?28 days of age) 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.

• Patients older than 28 days, including adults, ceftriaxone must not be administered

simultaneously with intravenous calcium-containing solutions, including Lactated

Ringer’s Injection, USP through the same infusion line (e.g., via a Y-connector). If

the same infusion line is used for sequential administration, the line must be

thoroughly flushed between infusions with a compatible fluid.

5 Warnings and Precautions

PRECAUTIONS

Additions and revisions underlined:

Hyperlactatemia

Lactated Ringer’s Injection, USP should be used with caution in severe hepatic

insufficiency, since lactate metabolism may be impaired. In addition, Lactated Ringer’s

Injection, USP may not produce its alkalinizing action in patients with severe hepatic

insufficiency, since lactate metabolism may be impaired.

Administration of solutions containing lactate should be used with caution in

patients with impaired glucose tolerance and diabetes mellitus, as it may result in

hyperglycemia.

Administration of a lactate-containing intravenous solution to infants should take into

account that the metabolic capacity of the liver still matures during the first months of

life, which also affects the biotransformation of lactate..

- Renal clearance of acidic drugs such as salicylates and barbiturates may be increased. Avoid

use of Lactated Ringer’s Injection, USP in patients receiving acidic drugs.

- Renal clearance of alkaline drugs, such as sympathomimetics (e.g., ephedrine,

pseudoephedrine) and dextroamphetamine (dexamphetamine) sulfate, may be decreased.

Avoid use of Lactated Ringer’s Injection, USP in patients receiving

sympathommimetics and dextroamphetamine.

Lithium

Renal sodium and lithium clearance may be increased during administration of Lactated

Ringer’s Injection, USP and result in decreased lithium concentrations. Avoid use of Lactated

Ringer’s Injection, USP in patients receiving drugs with pH dependent renal elimination. If use

cannot be avoided, monitor serum lithium concentrations during concomitant use.

WARNINGS

Newly added information:

Lactated Ringer’s Injection, USP is not for the treatment of lactic acidosis or severe

metabolic acidosis.

10/09/2019 (SUPPL-117)

Approved Drug Label (PDF)

5 Warnings and Precautions

PRECAUTIONS

Additions and/or revisions underlined:

Patients with Renal Impairment

Administration of Lactated Ringer’s Injection, USP in patients with or at risk of severe renal impairment, may result in hyperkalemia and/or fluid overload (see WARNINGS). Avoid Lactated Ringer’s Injection, USP in patients with severe renal impairment or conditions that may cause sodium and/or potassium retention, fluid overload, or edema. If use cannot be avoided, monitor patients with severe renal impairment for development of these adverse reactions.

Patients with Hepatic Impairment

In patients with severe hepatic impairment, lactate metabolism may be impaired and Lactated Ringer’s Injection, USP may not produce alkalization. Consider when monitoring serum lactate levels.

Hypercalcemia

Lactated Ringer’s Injection, USP contains calcium salts and may cause hypercalcemia. Avoid administration of Lactated Ringer’s Injection, USP in patients with hypercalcemia or conditions predisposing to hypercalcemia; and in patients with calcium renal calculi or history of such calculi.

Hyperglycemia

Avoid administration of solutions containing lactate in patients with impaired glucose tolerance and diabetes mellitus, as it may result in hyperglycemia.

Monitoring of Serum Lactate Levels

Administration of Lactated Ringer’s Injection, USP may result in an iatrogenic increase in serum lactate levels and interfere with interpretation of serum lactate levels in patients with severe metabolic acidosis including lactic acidosis.

Pediatric Use

… The warnings, precautions and adverse reactions identified in the label copy should be observed in the pediatric population.

Administration of a lactate-containing intravenous solution to infants should take into account that the liver and kidneys are still maturing during the first year of life, which also affects the biotransformation and renal excretion of lactate.

Pediatric patients are at increased risk of developing hyponatremia as well as for developing encephalopathy as a complication of hyponatremia (see WARNINGS).

Geriatric Use

Geriatric patients are at increased risk of developing electrolyte imbalances. Lactated Ringer's Injection, USP is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.

Therefore, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Consider monitoring renal function in elderly patients.

Drug Interactions

Ceftriaxone

For information on interaction with ceftriaxone – see CONTRAINDICATIONS.

Other Drugs that Increase the Risk of Hyponatremia

Administration of Lactated Ringer’s Injection, USP to patients treated concomitantly with medications associated with hyponatremia may increase the risk of developing hyponatremia.

Avoid use of Lactated Ringer’s Injection, USP in patients receiving products, such as diuretics, and certain antiepileptic and psychotropic medications. Drugs that increase the vasopressin effect reduce renal electrolyte free water excretion and may also increase the risk of hyponatremia following treatment with intravenous fluids. If use cannot be avoided, monitor serum sodium concentrations.

Other Products that Affect Fluid and/or Electrolyte Balance

Administration of Lactated Ringer’s Injection, USP to patients treated concomitantly with drugs associated with sodium and fluid retention may increase the risk of hypernatremia and volume overload. Avoid use of Lactated Ringer’s Injection, USP in patients receiving such products, such as corticosteroids or corticotropin. If use cannot be avoided, monitor serum electrolytes, fluid balance and acid-base balance.

Other Products that Cause Hyperkalemia

Administration of Lactated Ringer’s Injection, USP to patients treated concurrently or recently with products that are associated with hyperkalemia increases the risk of severe and potentially fatal hyperkalemia, in particular in the presence of other risk factors for hyperkalemia.

Avoid use of Lactated Ringer’s Injection, USP to patients receiving such products (e.g., potassium sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, or the immunosuppressants tacrolimus and cyclosporine). If use cannot be avoided, monitor serum potassium concentrations.

Lithium

Renal sodium and lithium clearance may be increased during administration of Lactated Ringer’s Injection, USP and result in decreased lithium concentrations. Avoid use of Lactated Ringer’s Injection, USP in patients receiving lithium. If use cannot be avoided, monitor serum lithium concentrations during concomitant use.

Digoxin

Administration of calcium may increase the effects of digitalis and lead to serious or fatal cardiac arrhythmia. In patients treated with digoxin, consider reducing the volume, and/or rate of administration of Lactated Ringer’s Injection, USP.

Other Drugs that Increase the Risk of Hypercalcemia

Avoid Lactated Ringer’s Injection, USP in patients treated with thiazide diuretics or vitamin D, as these can increase the risk of hypercalcemia.

Drugs with pH Dependent Renal Elimination

Due to the alkalinizing action of lactate (formation of bicarbonate), Lactated Ringer’s Injection, USP may interfere with the elimination of drugs with pH dependent renal elimination. Renal clearance of acidic drugs may be increased. Renal clearance of alkaline drugs may be decreased.

WARNINGS

Additions and/or revisions underlined:

Potassium Content

The potassium concentration in Lactated Ringer’s Injection, USP is similar to the concentration in plasma; however, it is insufficient to produce a useful effect in case of severe potassium deficiency. Lactated Ringer’s Injection, USP is not recommended for the treatment of severe hypokalemia.

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, have been reported with Lactated Ringer’s Injection, USP (see ADVERSE REACTIONS). Stop the infusion immediately if signs or symptoms of a hypersensitivity reaction develop. Appropriate therapeutic countermeasures must be instituted as clinically indicated.

Electrolyte Imbalances

Hyponatremia

Lactated Ringer’s Injection, USP may cause hyponatremia. Hyponatremia can lead to acute hyponatremic encephalopathy characterized by headache, nausea, seizures, lethargy and vomiting. Patients with brain edema are at particular risk of severe, irreversible and life-threatening brain injury.

The risk of hospital acquired hyponatremia is increased in patients with cardiac or pulmonary failure, and in patients with non-osmotic vasopressin release (including SIADH) treated with high volume of Lactated Ringer’s Injection, USP.

The risk for hyponatremia is increased in pediatric patients, elderly patients, postoperative patients, those with psychogenic polydipsia, and in patients treated with medications that increase the risk of hyponatremia (such as diuretics, certain antiepileptic and psychotropic medications). See PRECAUTIONS, Drug Interactions and Pediatric Use.

Patients at increased risk for developing complications of hyponatremia such as hyponatremic encephalopathy, include pediatric patients, women (in particular, premenopausal women), patients with hypoxemia, and patients with underlying central nervous system disease. Avoid Lactated Ringer’s Injection, USP in patients with or at risk for hyponatremia. If use cannot be avoided, monitor serum sodium concentrations.

Rapid correction of hyponatremia is potentially dangerous with risk of serious neurologic complications. Brain adaptations reducing risk of cerebral edema make the brain vulnerable to injury when chronic hyponatremia is too rapidly corrected, which is known as osmotic demyelination syndrome (ODS). To avoid complications, monitor serum sodium and chloride concentrations, fluid status, acid-base balance, and signs of neurologic complications.

WARNINGS contined

Additions and/or revisions underlined:

Fluid Overload

Depending on the volume and the rate of infusion, the intravenous administration of Lactated Ringer’s Injection, USP can cause electrolyte disturbances such as overhydration and congested states, including pulmonary congestion and edema.

Avoid Lactated Ringer’s Injection, USP in patients with or at risk for fluid and/or solute overloading. If use cannot be avoided, monitor fluid balance, electrolyte concentrations and acid base balance, as needed and especially during prolonged use.

Hyperkalemia

Potassium-containing solutions, including Lactated Ringer’s Injection, USP, may increase the risk of hyperkalemia.

Patients at increased risk of developing hyperkalemia include those:

With conditions predisposing to hyperkalemia and/or associated with increased sensitivity to potassium, such as patients with severe renal impairment, acute dehydration, extensive tissue injury or burns, certain cardiac disorders such as congestive heart failure.
Treated concurrently or recently with agents or products that cause or increase the risk of hyperkalemia (see PRECAUTIONS, Drug Interactions).

Avoid use of Lactated Ringer’s Injection, USP in patients with, or at risk for, hyperkalemia. If use cannot be avoided, monitor serum potassium concentrations.

Alkalosis

Because lactate is metabolized to bicarbonate, administration of Lactated Ringer’s Injection, USP may result in, or worsen, metabolic alkalosis. Avoid intravenous administration of Lactated Ringer’s Injection, USP in patients with alkalosis or at risk for alkalosis.

6 Adverse Reactions

Post-Marketing Adverse Reactions

Additions and/or revisions underlined:

The following adverse reactions associated with the use of Lactated Ringer’s Injection, USP were identified in clinical trials or postmarketing reports. Because postmarketing reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency, reliably, or to establish a causal relationship to drug exposure.

Hypersensitivity and infusion reactions: angioedema, chest pain, chest discomfort, … pyrexia, headache, laryngeal edema and sneezing, infection at the site of injection, extravasation and infusion site anesthesia (numbness).

Metabolism and Nutrition Disorders: hyperkalemia, hyponatremia, hypervolemia.

General Disorders and Administration Site Conditions: phlebitis, infusion site inflammation… infusion site burning.

Nervous System Disorders: hyponatremic encephalopathy.

Other

Update reflects labeling change from October 2019.