Ertapenem Sodium - Ertapenem injection, Powder, Lyophilized, For Solution

(Ertapenem)

Check Drug InteractionsCheck known drug interactions.

Ertapenem Sodium - Ertapenem injection, Powder, Lyophilized, For Solution Prescribing Information

Ertapenem for injection is contraindicated in patients with known hypersensitivity to any component of this product or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to beta-lactams.
Due to the use of lidocaine HCl as a diluent, Ertapenem for injection administered intramuscularly is contraindicated in patients with a known hypersensitivity to local anesthetics of the amide type.

The following are described in greater detail in the Warnings and Precautions section

Hypersensitivity Reactions [see Warnings and Precautions (
5.1 Hypersensitivity Reactions
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 Ertapenem for injection, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams and other allergens. If an allergic reaction to Ertapenem for injection occurs, discontinue the drug immediately. Serious anaphylactic reactions require immediate emergency treatment as clinically indicated.
)]
Seizure Potential [see Warnings and Precautions (5.2)]Interaction with Valproic Acid [see Warnings and Precautions (
5.3 Interaction with Valproic Acid
Case reports in the literature have shown that co-administration of carbapenems, including ertapenem, 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. The concomitant use of ertapenem and valproic acid/divalproex sodium is generally not recommended. Anti-bacterials other than carbapenems should be considered to treat infections in patients whose seizures are well controlled on valproic acid or divalproex sodium. If administration of Ertapenem for injection is necessary, supplemental anti-convulsant therapy should be considered [see Drug Interactions ].
)]
Clostridioides difficile
-Associated Diarrhea (CDAD) [see Warnings and Precautions (
5.4
Clostridioides difficile-
Associated Diarrhea (CDAD)
CDAD has been reported with use of nearly all antibacterial agents, including ertapenem, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of
Clostridioides difficile
.
Clostridioides difficile
produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of
Clostridioides difficile
cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against
Clostridioides difficile
may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of
Clostridioides difficile
, and surgical evaluation should be instituted as clinically indicated.
)]
Caution with Intramuscular Administration [see Warnings and Precautions (
5.5 Caution with Intramuscular Administration
Caution should be taken when administering Ertapenem for injection intramuscularly to avoid inadvertent injection into a blood vessel [see Dosage and Administration ].
)]
Development of Drug-Resistant Bacteria [see Warnings and Precautions (
5.6 Development of Drug-Resistant Bacteria
As with other antibiotics, prolonged use of Ertapenem for injection may result in overgrowth of non-susceptible organisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Prescribing Ertapenem for 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.
)]
Laboratory Tests [see Warnings and Precautions (
5.7 Laboratory Tests
While Ertapenem for injection possesses toxicity similar to the beta-lactam group of antibiotics, periodic assessment of organ system function, including renal, hepatic, and hematopoietic, is advisable during prolonged therapy.
)]

Ertapenem for injection is a sterile, synthetic, parenteral, 1-β methyl-carbapenem that is structurally related to beta-lactam antibiotics.

Chemically, Ertapenem for injection is described as [4R-[3(3S*,5S*),4α,5β,6β(R*)]]-3-[[5-[[(3-carboxyphenyl)amino]carbonyl]-3-pyrrolidinyl]thio]-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monosodium salt. Its molecular weight is 497.50. The empirical formula is C₂₂H₂₄N₃O₇SNa, and its structural formula is:

Referenced Image Ertapenem sodium is a white to off-white hygroscopic, weakly crystalline powder. It is soluble in water and 0.9% sodium chloride solution, practically insoluble in ethanol, and insoluble in isopropyl acetate and tetrahydrofuran.

Ertapenem for Injection is supplied as sterile lyophilized powder for intravenous infusion after reconstitution with appropriate diluent [see Dosage and Administration (

2.7 Preparation and Reconstitution for Administration

Vials

Adults and pediatric patients 13 years of age and older

Preparation for intravenous administration:

DO NOT MIX OR CO-INFUSE ERTAPENEM FOR INJECTION WITH OTHER MEDICATIONS. DO NOT USE DILUENTS CONTAINING DEXTROSE (α-D-GLUCOSE).

ERTAPENEM FOR INJECTION MUST BE RECONSTITUTED AND THEN DILUTED PRIOR TO ADMINISTRATION.

Reconstitute the contents of a 1 g vial of Ertapenem for injection with 10 mL of one of the following: Water for Injection, 0.9% Sodium Chloride Injection or Bacteriostatic Water for Injection, using a syringe equipped with a 21-gauge or smaller diameter needle. NOTE: Use with a needleless IV system is not recommended.
Shake well to dissolve and immediately transfer contents of the reconstituted vial to 50 mL of 0.9% Sodium Chloride Injection.
Complete the infusion within 6 hours of reconstitution.

Preparation for intramuscular administration:

ERTAPENEM FOR INJECTION MUST BE RECONSTITUTED PRIOR TO ADMINISTRATION.
Reconstitute the contents of a 1 g vial of Ertapenem for injection with 3.2 mL of 1.0% lidocaine HCl injection [1](
without epinephrine
). Shake vial thoroughly to form solution.
Immediately withdraw the contents of the vial and administer by deep intramuscular injection into a large muscle mass (such as the gluteal muscles or lateral part of the thigh).
The reconstituted IM solution should be used within 1 hour after preparation.
NOTE: THE RECONSTITUTED SOLUTION SHOULD NOT BE ADMINISTERED INTRAVENOUSLY.

Pediatric patients 3 months to 12 years of age

Preparation for intravenous administration:

DO NOT MIX OR CO-INFUSE ERTAPENEM FOR INJECTION WITH OTHER MEDICATIONS.

DO NOT USE DILUENTS CONTAINING DEXTROSE (α-D-GLUCOSE).

ERTAPENEM FOR INJECTION MUST BE RECONSTITUTED AND THEN DILUTED PRIOR TO ADMINISTRATION.
Reconstitute the contents of a 1 g vial of Ertapenem for injection with 10 mL of one of the following: Water for Injection, 0.9% Sodium Chloride Injection or Bacteriostatic Water for Injection, using a syringe equipped with a 21-gauge or smaller diameter needle. NOTE: Use with a needleless IV system is not recommended.
Shake well to dissolve and immediately withdraw a volume equal to 15 mg/kg of body weight (not to exceed 1 g/day) and dilute in 0.9% Sodium Chloride Injection to a final concentration of 20 mg/mL or less. Discard vial with unused portion of Ertapenem for injection reconstituted solution.
Complete the infusion within 6 hours of reconstitution.

Preparation for intramuscular administration:

ERTAPENEM FOR INJECTION MUST BE RECONSTITUTED PRIOR TO ADMINISTRATION.
Reconstitute the contents of a 1 g vial of Ertapenem for injection with 3.2 mL of 1.0% lidocaine HCl injection (
without epinephrine
). Shake vial thoroughly to form solution.
Immediately withdraw a volume equal to 15 mg/kg of body weight (not to exceed 1 g/day) and administer by deep intramuscular injection into a large muscle mass (such as the gluteal muscles or lateral part of the thigh). Discard vial with unused portion of Ertapenem for injection reconstituted solution.
The reconstituted IM solution should be used within 1 hour after preparation.
NOTE: THE RECONSTITUTED SOLUTION SHOULD NOT BE ADMINISTERED INTRAVENOUSLY
.

Storage
When prepared with the diluent, Ertapenem for injection maintains satisfactory potency
for 6 hours at room temperature (25°C) or for 24 hours under refrigeration (5°C) and used within 4 hours after removal from refrigeration. Solutions of Ertapenem for injection should not be frozen.
Before administering, see accompanying package circular for Ertapenem for injection.Parenteral drug products should be inspected visually for particulate matter and discoloration prior to use, whenever solution and container permit. Solutions of Ertapenem for injection range from colorless to pale yellow. Variations of color within this range do not affect the potency of the product.

)] and transfer to 50 mL 0.9% Sodium Chloride Injection or for intramuscular injection following reconstitution with 1% lidocaine hydrochloride.

Each single-dose vial contains 1 gram ertapenem, equivalent to 1.046 grams ertapenem sodium. The sodium content is approximately 137 mg (approximately 6.0 mEq).

Each vial of Ertapenem for Injection contains the following inactive ingredients: 175 mg sodium bicarbonate and sodium hydroxide to adjust pH to 7.5.

Ertapenem sodium is a carbapenem antibiotic [see Clinical Pharmacology (

12.4 Microbiology

Mechanism of Action

Ertapenem has

in vitro

activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. The bactericidal activity of ertapenem results from the inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin binding proteins (PBPs). In Escherichia coli, it has strong affinity toward PBPs 1a, 1b, 2, 3, 4 and 5 with preference for PBPs 2 and 3.

Resistance

Ertapenem is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. Ertapenem is hydrolyzed by metallo-betalactamases.

Antimicrobial Activity

Ertapenem has been shown to be active against most isolates of the following microorganisms both

in vitro

and in clinical infections as described in the INDICATIONS AND USAGE section:

Gram-positive bacteria:

Staphylococcus aureus (methicillin susceptible isolates only)

Streptococcus agalactiae

Streptococcus pneumoniae (penicillin susceptible isolates only)

Streptococcus pyogenes

Gram-negative bacteria:

Escherichia coli Haemophilus influenzae (beta-lactamase negative isolates only)

Klebsiella pneumoniaeMoraxella catarrhalis

Proteus mirabilis

Anaerobic bacteria:

Bacteroides fragilis

Bacteroides distasonis

Bacteroides ovatus

Bacteroides thetaiotaomicron

Bacteroides uniformis

Clostridium clostridioforme

Eubacterium lentum

Peptostreptococcus species

Porphyromonas asaccharolytica

Prevotella bivia

The following

in vitro

data are available,

but their clinical significance is unknown.

At least 90% of the following bacteria exhibit an

in vitro

minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ertapenem. However, the efficacy of ertapenem in treating clinical infections due to these bacteria

has not been

established in adequate and well-controlled clinical trials:

Gram-positive bacteria:

Staphylococcus epidermidis (methicillin susceptible isolates only)

Streptococcus pneumoniae (penicillin-intermediate isolates)

Gram-negative bacteria:

Citrobacter freundii Citrobacter koseri

Enterobacter aerogenes

Enterobacter cloacae

Haemophilus influenzae (beta-lactamase positive isolates only)

Haemophilus parainfluenzae

Klebsiella oxytoca (excluding ESBL producing isolates)

Morganella morganii

Proteus vulgaris

Providencia rettgeri

Providencia stuartii

Serratia marcescens

Anaerobic bacteria:

Bacteroides vulgatus

Clostridium perfringens

Fusobacterium spp.

Susceptibility Testing:

For specific information regarding susceptibility testing methods, interpretive criteria, and associated test methods and quality control standards recognized by FDA for ertapenem, please see: https://www.fda.gov/STIC.

)].

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Ertapenem Sodium - Ertapenem injection, Powder, Lyophilized, For Solution

Ertapenem Sodium - Ertapenem injection, Powder, Lyophilized, For Solution Prescribing Information

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