Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

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.

MEROPENEM AND SODIUM CHLORIDE IN DUPLEX CONTAINER (NDA-202106)

(MEROPENEM)

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

Download Data

Expand all

12/03/2024 (SUPPL-9)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Rhabdomyolysis

Newly added subsection:

Rhabdomyolysis has been reported with the use of meropenem [see Adverse Reactions (6.2)]. If signs or symptoms of rhabdomyolysis such as muscle pain, tenderness or weakness, dark urine, or elevated creatine phosphokinase are observed, discontinue Meropenem for Injection and Sodium Chloride Injection and initiate appropriate therapy.

6 Adverse Reactions

Additions and/or revisions underlined:

The following adverse reactions have been identified during post-approval use of meropenem, including meropenem for injection. 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.

…

Musculoskeletal Disorders: rhabdomyolysis

05/12/2020 (SUPPL-7)

Approved Drug Label (PDF)

5 Warnings and Precautions

Development of Drug-Resistant Bacteria

(Additions and/or revisions underlined)

Prescribing Meropenem for Injection and Sodium Chloride Injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Severe Cutaneous Adverse Reactions

(Newly added subsection)

Severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme (EM) and acute generalized exanthematous pustulosis (AGEP) have been reported in patients receiving meropenem [see Adverse Reactions (6.2)]. If signs and symptoms suggestive of these reactions appear, Meropenem for Injection and Sodium Chloride Injection should be withdrawn immediately and an alternative treatment should be considered.

6 Adverse Reactions

(Additions and/or revisions underlined)

The following are discussed in greater detail in other sections of labeling:

Hypersensitivity Reactions [see Warnings and Precautions (5.1)]
Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.2)]
Seizure Potential [see Warnings and Precautions (5.3)]
Risk of Breakthrough Seizures Due to Drug Interaction with Valproic Acid [see Warnings and Precautions (5.4)]
Clostridioides difficile – Associated Diarrhea [see Warnings and Precautions (5.5)]

Post-Marketing Experience

(Additions and/or revisions underlined)

Immune System Disorders: angioedema.

Skin and Subcutaneous Disorders: toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme (EM) and acute generalized exanthematous pustulosis (AGEP).

01/19/2018 (SUPPL-3)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Hypersensitivity Reactions

(Additions and/or revisions underlined)

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. These reactions are more likely to occur in individuals with a history of sensitivity to multiple allergens.

There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another beta-lactam. Before initiating therapy with Meropenem for Injection USP and Sodium Chloride Injection USP, it is important to inquire about previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams, and other allergens. If an allergic reaction to Meropenem for Injection USP and Sodium Chloride Injection USP occurs, discontinue the drug immediately.

5.2 Seizure Potential

(Additions and/or revisions underlined)

Seizures and other adverse CNS experiences have been reported during treatment with meropenem for injection. These experiences have occurred most commonly in patients with CNS disorders (e.g., brain lesions or history of seizures) or with bacterial meningitis and/or compromised renal function [see Adverse Reactions (6.1) and Drug Interactions (7.2)].

During clinical investigations, 2904 immunocompetent adult patients were treated for non-CNS infections with the overall seizure rate being 0.7% (based on 20 patients with this adverse event). All meropenem-treated patients with seizures had pre-existing contributing factors. Among these are included prior history of seizures or CNS abnormality and concomitant medications with seizure potential. Dosage adjustment is recommended in patients with advanced age and/or adult patients with creatinine clearance of 50 mL/min or less [see Dosage and Administration (2.2)].

Close adherence to the recommended dosage regimens is urged, especially in patients with known factors that predispose to convulsive activity. Anti-convulsant therapy should be continued in patients with known seizure disorders. If focal tremors, myoclonus, or seizures occur, evaluate neurologically, place on anti-convulsant therapy if not already instituted, and re-examine the dosage of Meropenem for Injection USP and Sodium Chloride Injection USP to determine whether it should be decreased or discontinued.

5.3 Risk of Breakthrough Seizures Due to Drug Interaction with Valproic Acid

(Additions and/or revisions underlined)

The concomitant use of meropenem and valproic acid or divalproex sodium is generally not recommended. Case reports in the literature have shown that co-administration of carbapenems, including meropenem, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. Increasing the dose of valproic acid or divalproex sodium may not be sufficient to overcome this interaction. Consider administration of antibacterial drugs other than carbapenems to treat infections in patients whose seizures are well controlled on valproic acid or divalproex sodium. If administration of Meropenem for Injection USP and Sodium Chloride Injection USP is necessary, consider supplemental anti-convulsant therapy [see Drug Interactions (7.2)].

5.8 Potential for Neuromotor Impairment

(Additions and/or revisions underlined)

Alert patients receiving meropenem for injection on an outpatient basis regarding adverse events such as seizures, delirium, headaches and/or paresthesias that could interfere with mental alertness and/or cause motor impairment. Until it is reasonably well established that meropenem for injection is well tolerated, advise patients not to operate machinery or motorized vehicles [see Adverse Reactions (6.1)].

6 Adverse Reactions

6.1 Adverse Reactions from Clinical Trials

(Additions and/or revisions underlined)

Adverse Laboratory Changes

Adverse laboratory changes that were reported and occurring in greater than 0.2% of the patients were as follows:

Hepatic: increased alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, lactate dehydrogenase (LDH), and bilirubin

Hematologic: increased platelets, increased eosinophils, decreased platelets, decreased hemoglobin, decreased hematocrit, decreased white blood cell (WBC), shortened prothrombin time and shortened partial thromboplastin time, leukocytosis, hypokalemia

Renal: increased creatinine and increased blood urea nitrogen (BUN)

Pediatric Patients with Bacterial Meningitis:

In the meningitis studies, the rates of seizure activity during therapy were comparable between patients with no CNS abnormalities who received meropenem and those who received comparator agents (either cefotaxime or ceftriaxone). In the meropenem for injection treated group, 12/15 patients with seizures had late onset seizures (defined as occurring on day 3 or later) versus 7/20 in the comparator arm. The meropenem group had a statistically higher number of patients with transient elevation of liver enzymes.

6.2 Post-Marketing Experience

(Additions and/or revisions underlined)

The following adverse reactions have been identified during post-approval use of meropenem for injection. 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.

Worldwide post-marketing adverse reactions not otherwise listed in the Adverse Reactions from Clinical Trials section of this prescribing information and reported as possibly, probably, or definitely drug related are listed within each body system in order of decreasing severity.

Blood and Lymphatic System Disorders: agranulocytosis, neutropenia, and leukopenia; a positive direct or indirect Coombs test, and hemolytic anemia.

Immune System Disorders: angioedema and drug rash with eosinophilia and systemic symptoms (DRESS syndrome).

Skin and Subcutaneous Disorders: toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme.

(Additions and/or revisions underlined)

The following are discussed in greater detail in other sections of labeling:

Hypersensitivity Reactions [see Warnings and Precautions (5.1)]

Seizure Potential [see Warnings and Precautions (5.2)]
Risk of Breakthrough Seizures Due to Drug Interaction with Valproic Acid [see Warnings and Precautions (5.3)]
Clostridium difficile – Associated Diarrhea [see Warnings and Precautions (5.4)]
Development of Drug-Resistant Bacteria [see Warnings and Precautions (5.5)]
Overgrowth of Nonsusceptible Organisms [see Warnings and Precautions (5.6)]
Thrombocytopenia [see Warnings and Precautions (5.7)]
Potential for Neuromotor Impairment [see Warnings and Precautions (5.8)]
High Sodium Load [see Warnings and Precautions (5.9)]

8 Use in Specific Populations

8.1 Pregnancy

(Pregnancy and Lactation Labeling Rule (PLLR) conversion; extensive changes – please refer to label)

8.2 Lactation

(Pregnancy and Lactation Labeling Rule (PLLR) conversion; additions and/or revisions underlined)

Risk Summary

Meropenem has been reported to be excreted in human milk. No information is available on the effects of meropenem on the breastfed –child or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Meropenem for Injection USP and Sodium Chloride Injection USP in the DUPLEX® Container and any potential adverse effects on the breastfed-child from Meropenem for Injection USP and Sodium Chloride Injection USP in the DUPLEX® Container or from the underlying maternal conditions.