Brand name: INVanz
Drug class: Carbapenems
VA class: AM130
Chemical name: [4R-[3(3S*,5S*),4α,5β,6βS*)]]-(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
Molecular formula: C₂₂H₂₄N₃NaO₇S
CAS number: 153832-38-3

Medically reviewed by Drugs.com on Jun 28, 2023. Written by ASHP.

Introduction

Antibacterial; carbapenem β-lactam antibiotic.^{1 2 3 4}

Uses for Ertapenem

Gynecologic Infections

Treatment of moderate to severe acute pelvic infections (including postpartum endomyometritis, septic abortion, postsurgical infections) caused by susceptible Streptococcus agalactiae (group B streptococci), Escherichia coli, Bacteroides fragilis, Porphyromonas asaccharolytica, Peptostreptococcus, or Prevotella bivia.¹

Intra-abdominal Infections

Treatment of complicated intra-abdominal infections caused by susceptible E. coli, Clostridium clostridioforme, Eubacterium lentum, Peptostreptococcus, B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, or B. uniformis.¹

Respiratory Tract Infections

Treatment of moderate to severe community-acquired pneumonia (CAP) caused by susceptible Streptococcus pneumoniae (penicillin-susceptible strains only), including cases with concurrent bacteremia.¹

Treatment of moderate to severe CAP caused by susceptible Haemophilus influenzae (non-β-lactamase-producing strains only) or Moraxella catarrhalis.¹

Skin and Skin Structure Infections

Treatment of complicated skin and skin structure infections, including diabetic foot infections without concurrent osteomyelitis, caused by susceptible Staphylococcus aureus (oxacillin-susceptible [methicillin-susceptible] strains only), Streptococcus agalactiae, S. pyogenes (group A β-hemolytic streptococci), E. coli, Klebsiella pneumoniae, Proteus mirabilis, Bacteroides fragilis, Peptostreptococcus species, Porphyromonas asaccharolytica, or Prevotella bivia.^{1 c}

Urinary Tract Infections (UTIs)

Treatment of complicated UTIs (including pyelonephritis) caused by susceptible E. coli (including cases with concurrent bacteremia) or Klebsiella pneumoniae.¹

Ertapenem Dosage and Administration

Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion or IM injection.¹

Administered once daily in adolescents ≥13 years of age and adults.^c Administered twice daily in children 3 months to 12 years of age.^c

IM route may be used as an alternative to the IV route in treatment of those infections for which IM therapy is appropriate.¹ Duration of IM therapy should be ≤7 days.¹ Solutions reconstituted for IM administration should not be given IV.¹

IV Infusion

Reconstitution and Dilution

Reconstitute 1-g vial with 10 mL of sterile water for injection, 0.9% sodium chloride injection, or bacteriostatic water for injection.¹ Shake well to ensure complete dissolution of the drug.¹ The appropriate dose should be withdrawn from the vial and diluted in 0.9% sodium chloride to provide a solution containing ≤20 mg/mL.^c For a 1-g dose, dilute in 50 mL of 0.9% sodium chloride.¹

Rate of Administration

Administer by IV infusion over 30 minutes.¹

IM Administration

Inject IM deeply into a large muscle mass, such as the gluteus or lateral part of the thigh.¹ Use caution to avoid inadvertent injection into a blood vessel.¹

Reconstitution

Reconstitute 1-g vial with 3.2 mL of 1% lidocaine injection (without epinephrine) and shake thoroughly to ensure dissolution.¹ Administer within 1 hour of reconstitution.^c

Dosage

Available as ertapenem sodium; dosage expressed in terms of ertapenem.¹

Duration of therapy depends on the type and severity of infection.¹ IV route may be continued for ≤14 days; IM route may be continued for ≤7 days.¹

Pediatric Patients

Gynecologic Infections

IV or IM

Children 3 months to 12 years of age: 15 mg/kg twice daily (up to 1 g daily) for 3–10 days.^c

Adolescents ≥13 years of age: 1 g once daily for 3–10 days.^c

Intra-abdominal Infections

IV or IM

Children 3 months to 12 years of age: 15 mg/kg twice daily (up to 1 g daily) for 5–14 days.^c

Adolescents ≥13 years of age: 1 g once daily for 5–14 days.^c

Respiratory Tract Infections

Community-acquired Pneumonia

IV or IM

Children 3 months to 12 years of age: 15 mg/kg twice daily (up to 1 g daily).^c Usual duration is 10–14 days; treatment may be switched to an appropriate oral anti-infective after ≥3 days.^c

Adolescents ≥13 years of age: 1 g once daily.^c Usual duration is 10–14 days; treatment may be switched to an appropriate oral anti-infective after ≥3 days.^c

Skin and Skin Structure Infections

IV or IM

Children 3 months to 12 years of age: 15 mg/kg twice daily (up to 1 g daily) for 7–14 days.^c

Adolescents ≥13 years of age: 1 g once daily for 7–14 days.^c

Urinary Tract Infections (UTIs)

IV or IM

Children 3 months to 12 years of age: 15 mg/kg twice daily (up to 1 g daily).^c Usual duration is 10–14 days; treatment may be switched to an appropriate oral anti-infective after ≥3 days.^c

Adolescents ≥13 years of age: 1 g once daily.^c Usual duration is 10–14 days; treatment may be switched to an appropriate oral anti-infective after ≥3 days.^c

Adults

Gynecologic Infections

IV or IM

1 g once daily for 3–10 days.¹

Intra-abdominal Infections

IV or IM

1 g once daily for 5–14 days.¹

Respiratory Tract Infections

Community-acquired Pneumonia

IV or IM

1 g once daily.¹ Usual duration is 10–14 days; treatment may be switched to an appropriate oral anti-infective after ≥3 days.¹

Skin and Skin Structure Infections

IV or IM

1 g once daily for 7–14 days.¹ In adults with diabetic foot infections, anti-infective therapy (parenteral or parenteral followed by oral) has been given for up to 28 days.^c

Urinary Tract Infections (UTIs)

IV or IM

1 g once daily.¹ Usual duration is 10–14 days; treatment may be switched to an appropriate oral anti-infective after ≥3 days.¹

Special Populations

Hepatic Impairment

Dosage recommendations not available; pharmacokinetics have not been studied.¹

Renal Impairment

Dosage adjustments recommended in patients with Cl_cr ≤30 mL/minute.¹

Adults with Cl_cr ≤30 mL/minute, including those with end-stage renal disease (Cl_cr ≤10 mL/minute) and those undergoing hemodialysis, should receive 500 mg once daily.¹ If the dose is given within 6 hours prior to hemodialysis, a supplementary dose of 150 mg should be given after the hemodialysis session; supplemental dose not necessary if daily dose is given ≥6 hours prior to hemodialysis.¹ Data not available in pediatric patients undergoing dialysis.^c

Geriatric Patients

No dosage adjustments except those related to renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Cautions for Ertapenem

Contraindications

• Known hypersensitivity to ertapenem, other carbapenems, or any ingredient in the formulation.¹

• History of anaphylactic reaction to β-lactams.¹

• IM injections are prepared using lidocaine hydrochloride and are contraindicated in patients with known hypersensitivity to local anesthetics of the amide type.¹

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible organisms.¹ Careful observation of the patient is essential.¹ Institute appropriate therapy if superinfection occurs.¹

Treatment with anti-infectives may permit overgrowth of clostridia.¹ Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.¹

Some mild cases of C. difficile-associated diarrhea and colitis may respond to discontinuance alone.¹ Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.¹

CNS Effects

Seizures and other CNS effects reported, especially in those with CNS disorders (e.g., brain lesions, history of seizures) and/or renal impairment.¹

Do not exceed recommended dosage, especially in those with known factors that predispose to seizures.¹ Anticonvulsant therapy should be continued in those with known seizure disorders.¹

If focal tremors, myoclonus, or seizures occur, evaluate the patient neurologically, initiate anticonvulsant therapy if necessary, and determine whether ertapenem dosage should be decreased or the drug discontinued.¹

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions (e.g., anaphylaxis) reported with β-lactams.¹

If hypersensitivity occurs, discontinue ertapenem and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).¹

Cross-hypersensitivity

Partial cross-allergenicity among β-lactam antibiotics, including penicillins, cephalosporins, and other β-lactams.¹

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to ertapenem, cephalosporins, penicillins, or other drugs.¹

General Precautions

Laboratory Monitoring

Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.¹

Sodium Content

Contains approximately 6 mEq (137 mg) of sodium per g of ertapenem.¹

Specific Populations

Pregnancy

Category B.¹

Lactation

Distributed into milk.¹ Use with caution.¹

Pediatric Use

Safety and efficacy established in children 3 months to 17 years of age for the treatment of acute pelvic infections, complicated intra-abdominal infections, CAP, complicated skin and skin structure infections, and complicated UTIs.^c Not recommended for the treatment of meningitis; therapeutic concentrations not achieved in CNS.^c Not recommended in infants <3 months of age; data on use in this age group not available.^c

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.¹

Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function.¹ Select dosage with caution and assess renal function periodically since geriatric patients are more likely to have renal impairment.¹

No dosage adjustments except those related to renal function.¹ (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Pharmacokinetics not established.¹

Renal Impairment

Increased AUC.¹ Dosage adjustments recommended in adults with Cl_cr ≤30 mL/minute, including those with end-stage renal disease and those undergoing hemodialysis.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (diarrhea, nausea, vomiting); local reactions (infused vein complication, phlebitis/thrombophlebitis); headache; vaginitis.¹

Drug Interactions

Drugs Metabolized by Hepatic Microsomal Enzymes

Does not inhibit CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, or 3A4; pharmacokinetic interactions unlikely with drugs metabolized by these enzymes.¹

Drugs with p-Glycoprotein-mediated Clearance

Does not inhibit and is not a substrate for p-glycoprotein-mediated transport.¹ Pharmacokinetic interaction unlikely with drugs that undergo p-glycoprotein-mediated clearance (e.g., digoxin, vinblastine).¹

Specific Drugs

Ertapenem Pharmacokinetics

Absorption

Bioavailability

Following IM injection, mean bioavailability is approximately 90%;¹ peak plasma concentrations attained in approximately 2.3 hours.¹

Exhibits nonlinear pharmacokinetics because of concentration-dependent plasma protein binding.¹

Distribution

Extent

Distributed into blister fluid.¹

Therapeutic concentrations not achieved in CNS.^c

Crosses the placenta in rats; not known whether crosses the placenta in humans.¹ Distributed into milk.¹

Plasma Protein Binding

Highly bound to plasma protein, principally albumin.¹ 95% bound at plasma concentration <100 mcg/mL and 85% bound at 300 mcg/mL.¹

Elimination

Metabolism

Does not appear to undergo hepatic metabolism.¹ The major metabolite is an inactive ring-opened derivative formed by hydrolysis of the β-lactam ring.¹

Elimination Route

Eliminated principally in urine.¹

Approximately 80% of an IV dose eliminated in urine (38% as unchanged drug and 37% as the ring-opened metabolite) and 10% eliminated in feces.¹

Half-life

Healthy young adults: 4 hours.¹

Pediatric patients 13–17 years of age: 4 hours.^c

Pediatric patients 3 months to 12 years of age: 2.5 hours.^c

Special Populations

Pharmacokinetics in patients with hepatic impairment not established.¹

In patients with severe renal impairment (Cl_cr 5–30 mL/minute per 1.73 m²) or end-stage renal disease, the extent of exposure to unbound drug is increased 4.4- or 7.6-fold, respectively.¹

Stability

Storage

Parenteral

Powder for IM Injection or IV Infusion

≤25°C.¹

Reconstituted and diluted IV solutions may be stored at room temperature, but the infusion should be completed within 6 hours.¹ These solutions may be refrigerated at 5°C for up to 24 hours, but the infusion should be completed within 4 hours after removal from refrigeration.¹ Do not freeze.¹

IM solutions should be used within 1 hour of reconstitution.^c

Compatibility

Reconstitute with sterile water for injection, 0.9% sodium chloride injection, or bacteriostatic water for injection, then dilute in 0.9% sodium chloride.¹

Do not reconstitute or dilute with dextrose-containing solutions or admix with other medications.¹

Parenteral

Solution CompatibilityHID

Incompatible by conventional standards, but recommended for dilution with use in shorter time periods. (See Storage under Stability.)

Drug Compatibility

Actions and Spectrum

• Synthetic carbapenem β-lactam antibiotic; structurally and pharmacologically related to imipenem and meropenem.^{1 2 3 4 5 6}

• Usually bactericidal in action.¹

• Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.¹

• Spectrum of activity includes many gram-positive and -negative aerobic bacteria and some gram-positive and -negative anaerobic bacteria.¹ Stable in the presence of a variety of β-lactamases (including penicillinases, cephalosporinases, and extended-spectrum β-lactamases).¹

• Gram-positive aerobes: Active in vitro and in clinical infections against Staphylococcus aureus, Streptococcus agalactiae (group B streptococci), S. pneumoniae (penicillin-susceptible strains only), and S. pyogenes (group A β-hemolytic streptococci).^{1 3} Also active in vitro against S. pneumoniae (penicillin-intermediate strains)^{1 3} and S. epidermidis (oxacillin- susceptible strains only).^c Oxacillin-resistant (methicillin-resistant) staphylococci and Enterococcus are resistant.¹

• Gram-negative aerobes: Active in vitro and in clinical infections against Escherichia coli, Haemophilus influenzae (β-lactamase-negative strains only), Klebsiella pneumoniae, Moraxella catarrhalis, and Proteus mirabilis.^{1 c} Also active in vitro against Citrobacter, Enterobacter, H. influenzae (β-lactamase-producing strains), H. parainfluenzae, K. oxytoca, Morganella morganii, P. vulgaris, Providencia rettgeri, P. stuartii, and Serratia marcescens.^{1 c}

• Anaerobes: Active in vitro and in clinical infections against Bacteroides fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. uniformis, Clostridium clostridioforme, Eubacterium lentum, Peptostreptococcus, Porphyromonas asaccharolytica, and Prevotella bivia.^{1 2} Also active in vitro against B. vulgaris, C. perfringens, and Fusobacterium.^{1 c}

Advice to Patients

• Importance of informing clinicians of other medical conditions, including history of seizures.¹

• Importance of discontinuing therapy and informing clinician if an allergic or hypersensitivity reaction occurs.¹

• Importance of reporting persistent or worsening symptoms of infection.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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