Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Injection:
Generic: 1 g (1 ea)
Solution Reconstituted, Injection [preservative free]:
INVanz: 1 g (1 ea)
Generic: 1 g (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
INVanz: 1 g (1 ea [DSC])
Pharmacology
Mechanism of Action
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins; which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Pharmacokinetics/Pharmacodynamics
Absorption
IM: Almost complete
Distribution
Vdss:
Infants ≥3 months and Children: ~0.2 L/kg
Adolescents 13 to 17 years: ~0.16 L/kg
Adults: ~0.12 L/kg
Metabolism
Non-CYP-mediated hydrolysis to inactive metabolite
Excretion
Urine (~80% as unchanged drug and metabolite); feces (~10%)
Time to Peak
IM: ~2.3 hours
Half-Life Elimination
Infants ≥3 months and Children: ~2.5 hours
Adolescents and Adults: ~4 hours
Protein Binding
Concentration dependent, primarily to albumin: 85% at 300 mcg/mL, 95% at <100 mcg/mL
Use in Specific Populations
Special Populations: Renal Function Impairment
Unbound AUC increased 1.5- and 2.3-fold in those with mild and moderate renal function impairment, respectively. Unbound AUC increased 4.4- and 7.6-fold in those with advanced renal impairment and ESRD, respectively.
Special Populations: Elderly
The total and unbound AUC increased 37% and 67%, respectively, in elderly patients relative to younger patients.
Use: Labeled Indications
Intra-abdominal infection, complicated: For the treatment of complicated intra-abdominal infections caused by Clostridium clostridioforme, Escherichia coli, Eubacterium lentum, Peptostreptococcus spp, Bacteroides distasonis, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, or Bacteroides uniformis.
Pelvic infection: For the treatment of acute pelvic infections, including postpartum endomyometritis, septic abortion, and postsurgical gynecologic infections caused by Streptococcus agalactiae, E. coli, B. fragilis, Porphyromonas asaccharolytica, Peptostreptococcus spp, or Prevotella bivia.
Pneumonia, community acquired: For the treatment of community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae (penicillin-susceptible isolates only), including cases with concurrent bacteremia; Haemophilus influenzae (beta-lactamase-negative isolates only); or Moraxella catarrhalis.
Skin and skin structure infection, complicated: For the treatment of complicated skin and skin structure infections, including diabetic foot infections without osteomyelitis caused by Staphylococcus aureus (methicillin-susceptible isolates only), S. agalactiae, Streptococcus pyogenes, E. coli, Klebsiella pneumoniae, Proteus mirabilis, B. fragilis, Peptostreptococcus spp, P. asaccharolytica, or P. bivia. Ertapenem has not been studied in diabetic foot infections with concomitant osteomyelitis.
Surgical prophylaxis: For the prophylaxis of surgical site infection in adults following elective colorectal surgery.
Urinary tract infection, complicated: For the treatment of complicated urinary tract infections (UTIs), including pyelonephritis caused by E. coli, including cases with concurrent bacteremia or K. pneumoniae.
Note: Methicillin-resistant Staphylococcus aureus, Enterococcus spp, Acinetobacter, Pseudomonas aeruginosa, and penicillin-resistant strains of Streptococcus pneumoniae are resistant to ertapenem while most extended-spectrum beta-lactamase (ESBL)-producing bacteria remain sensitive to ertapenem.
Use: Off Label
Bite wound, treatment (animal or human bite)yes
Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections, ertapenem is an effective and recommended treatment for animal or human bite wounds.
Bloodstream infectioncyes
Data from retrospective studies suggest that ertapenem may be beneficial for the treatment of bloodstream infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae Collins 2012, Gutiérrez-Gutiérrez 2016.
Based on the IDSA guidelines for the diagnosis and management of intravascular catheter-related infection, ertapenem is effective and recommended for the treatment of infection with susceptible organisms (eg, gram-negative bacilli [ESBL positive], Enterobacter spp, Serratia marcescens).
Osteomyelitis and/or discitiscyes
Data from a limited number of patients suggest that ertapenem may be beneficial in the treatment of osteomyelitis Goswami 2011. Clinical experience also suggests the utility of ertapenem in the treatment of osteomyelitis Osmon 2019.
Based on the IDSA guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults, ertapenem is an effective and recommended agent for the treatment of native vertebral osteomyelitis due to Enterobacteriaceae.
Pneumonia, hospital acquired or ventilator associatedc
Clinical experience suggests the utility of ertapenem in the treatment of hospital-acquired or ventilator-associated pneumonia caused by ESBL-producing organisms Klompas 2019.
Prosthetic joint infectionyes
Based on the IDSA guidelines for the diagnosis and management of prosthetic joint infection, ertapenem is an effective and recommended agent for the treatment of prosthetic joint infection.
Contraindications
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; known hypersensitivity to local anesthetics of the amide type due to the use of lidocaine as a diluent (IM use only).
Dosage and Administration
Dosing: Adult
Note: Generally reserved for patients with pathogens that are resistant to other antibiotics, such as extended-spectrum beta-lactamase (ESBL)-producing organisms (Munoz-Price 2019). Unlike other carbapenems (eg, doripenem, imipenem, meropenem), ertapenem lacks activity against Pseudomonas aeruginosa.
Bite wound infection, treatment (animal or human bite) (alternative agent) (off-label use): IV: 1 g once daily. Duration of treatment for established infection (which may include oral step-down therapy) is typically 5 to 14 days and varies based on patient-specific factors, including clinical response (Baddour 2019a; Baddour 2019b; IDSA [Stevens 2014]).
Bloodstream infection (pathogen-directed therapy for susceptible gram-negative organisms) (off-label use): IV: 1 g once daily (IDSA [Mermel 2009]). Duration is 7 to 14 days, depending on source and extent of infection, as well as clinical response; a 7-day duration is recommended for patients with uncomplicated Enterobacteriaceae bacteremia who respond appropriately to antibiotic therapy (Moehring 2019; Yahav 2018).
Diabetic foot infection, moderate to severe: IM, IV: 1 g once daily. Duration (which may include oral step-down therapy) is usually 2 to 4 weeks in the absence of osteomyelitis but varies based on patient-specific factors, including clinical response (IDSA [Lipsky 2012]; Weintrob 2019).
Intra-abdominal infection, community acquired (mild to moderate infection, low-risk patients):
Cholecystitis, acute: IV: 1 g once daily; continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (Gomi 2018; SIS/IAI [Mazuski 2017]; SIS/IDSA [Solomkin 2010]; Vollmer 2019).
Other intra-abdominal infections (eg, perforated appendix, appendiceal abscess, cholangitis, diverticulitis): IM, IV: 1 g once daily. Total duration of therapy (which may include oral step-down therapy) is 4 to 7 days following adequate source control (SIS/IAI [Mazuski 2017]; SIS/IDSA [Solomkin 2010]); for infections managed without surgical or percutaneous intervention, a longer duration may be necessary (Barshak 2019; Pemberton 2019).
Osteomyelitis and/or discitis (pathogen-directed therapy for susceptible gram-negative organisms) (off-label use): IV: 1 g once daily, generally for ≥6 weeks depending on patient-specific factors, such as extent of infection, debridement, and clinical response. Shorter courses are appropriate if the affected bone is completely resected (eg, by amputation) (IDSA [Berbari 2015]; Osmon 2019).
Pelvic infection, acute (eg, postpartum and postsurgical gynecologic infections) (alternative agent): IM, IV: 1 g once daily; duration of therapy varies based on type of infection.
Pneumonia (alternative agent):
Community-acquired pneumonia, empiric therapy (inpatients without risk factors for Pseudomonas aeruginosa): IM, IV: 1 g once daily as part of an appropriate combination regimen. Duration (which may include oral step-down therapy) is for a minimum of 5 days and varies based on disease severity and response to therapy; patients should be afebrile for ≥48 hours and clinically stable before therapy is discontinued (File 2019; IDSA/ATS [Mandell 2007]).
Hospital-acquired pneumonia or ventilator-associated pneumonia (pathogen-directed therapy for extended-spectrum beta-lactamase-producing organisms) (off-label use): IV: 1 g once daily (Bassetti 2007). Duration is 7 days but may be individualized based on response to therapy (Klompas 2019).
Prosthetic joint infection (pathogen-directed therapy for susceptible gram-negative organisms) (off-label use): IV: 1 g every 24 hours; duration varies, but is generally 4 to 6 weeks for patients who undergo resection arthroplasty (IDSA [Osmon 2013]).
Skin and soft tissue infection (select surgical site infections [intestinal, GU tract], necrotizing infections): IV: 1 g once daily; for necrotizing infections, use as part of an appropriate combination regimen. Duration varies based on extent of infection, clinical response, and other patient-specific factors; for necrotizing infections, continue until further debridement is not necessary and the patient has improved clinically and is afebrile for 48 to 72 hours (IDSA [Stevens 2014]).
Surgical prophylaxis (colorectal surgery) (alternative agent): IV: 1 g within 60 minutes prior to surgical incision (ASHP/IDSA/SIS/SHEA [Bratzler 2013]). Note: Postoperative prophylaxis is not recommended in clean and clean-contaminated surgeries (CDC [Berríos-Torres 2017]). Some experts recommend against using ertapenem for surgical prophylaxis out of concern for inducing resistance (Anderson 2019).
Urinary tract infection, complicated (including pyelonephritis) (alternative agent): Outpatients: IM, IV: 1 g as a single dose, followed by 5 to 14 days of appropriate oral therapy. Note: For patients at risk for multi-drug resistant infection, can continue daily ertapenem pending culture and susceptibility testing results (Hooton 2019).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
General dosing, susceptible infection (Bradley 2019; Red Book [AAP 2018]): Due to limited clinical data, ertapenem is usually reserved for extended-spectrum beta-lactamase (ESBL) infections with urinary sources or soft tissue infections when adequate source control has been achieved (Hsu 2014). Unlike other carbapenems (eg, doripenem, imipenem, meropenem), ertapenem lacks activity against Pseudomonas aeruginosa.
Infants and Children: IM, IV: 15 mg/kg/dose twice daily; maximum dose: 500 mg/dose.
Adolescents: IM, IV: 1,000 mg once daily.
Intra-abdominal infection, complicated: Note: Guidelines recommend a treatment duration of 4 to 7 days (provided source controlled) for community-acquired, mild to moderate infections (IDSA [Solomkin 2010]); manufacturer labeling suggests a duration of 5 to 14 days; however, longer durations (>7 days) have not been associated with improved outcomes (IDSA [Solomkin 2010]).
Infants ≥3 months and Children: IM, IV: 15 mg/kg/dose twice daily; maximum dose: 500 mg/dose.
Adolescents: IM, IV: 1,000 mg once daily.
Pelvic infections, acute:
Infants ≥3 months and Children: IM, IV: 15 mg/kg/dose twice daily for 3 to 10 days based on severity of infection; maximum dose: 500 mg/dose.
Adolescents: IM, IV: 1,000 mg once daily for 3 to 10 days based on severity of infection.
Pneumonia, community-acquired: Note: Guidelines suggest a usual duration of therapy of 10 days (including both parental and possible switch to appropriate oral step-down therapy); however, longer duration may be necessary for some organisms and/or complicated infections (IDSA [Bradley 2011]).
Infants ≥3 months and Children: IM, IV: 15 mg/kg/dose twice daily for 10 to 14 days; maximum dose: 500 mg/dose.
Adolescents: IM, IV: 1,000 mg once daily for 10 to 14 days.
Skin and skin structure infections, complicated or necrotizing: Note: For complicated infection, continue therapy for 7 to 14 days. For necrotizing infection, use in combination with an agent effective against MRSA (eg, vancomycin, linezolid, daptomycin) for empiric therapy of polymicrobial (mixed) infections. Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (IDSA [Stevens 2014]).
Infants ≥3 months and Children: IM, IV: 15 mg/kg/dose twice daily; maximum dose: 500 mg/dose.
Adolescents: IM, IV: 1,000 mg once daily.
Surgical prophylaxis: Limited data available: Children and Adolescents: IV: 15 mg/kg within 60 minutes prior to surgical incision; maximum dose: 1,000 mg/dose (ASHP/IDSA [Bratzler 2013]).
Urinary tract infections (including pyelonephritis): Note: Duration includes possible switch to appropriate oral therapy after at least 3 days of parenteral treatment, once clinical improvement demonstrated.
Infants ≥3 months and Children: IM, IV: 15 mg/kg/dose twice daily for 10 to 14 days; maximum dose: 500 mg/dose.
Adolescents: IM, IV: 1,000 mg once daily for 10 to 14 days.
Reconstitution
IM: Reconstitute 1 g vial with 3.2 mL of 1% lidocaine HCl injection (without epinephrine). Shake well.
IV: Reconstitute 1 g vial with 10 mL of SWFI, 0.9% sodium chloride injection, or bacteriostatic water for injection using a syringe with a 21-gauge or smaller diameter needle (use with a needleless IV system is not recommended). Shake well. For adults, transfer dose to 50 mL of 0.9% sodium chloride injection.
Administration
IM: Avoid injection into a blood vessel. Make sure patient does not have an allergy to lidocaine or another anesthetic of the amide type. Administer by deep IM injection into a large muscle mass (eg, gluteal muscle or lateral part of the thigh). Do not administer IM preparation or drug reconstituted for IM administration intravenously.
IV: Infuse over 30 minutes.
Dietary Considerations
Some products may contain sodium.
Storage
Prior to reconstitution, store vials at ≤25°C (77°F). The reconstituted IM solution should be used within 1 hour after preparation. The reconstituted IV solution may be stored at room temperature (25°C [77°F]) and used within 6 hours, or stored for 24 hours under refrigeration (5°C [41°F]) and used within 4 hours after removal from refrigeration. Do not freeze.
Drug Interactions
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy
Probenecid: May increase the serum concentration of Ertapenem. Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification
Tacrolimus (Systemic): Ertapenem may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification
Valproate Products: Carbapenems may decrease the serum concentration of Valproate Products. Management: Concurrent use of carbapenem antibiotics with valproic acid is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional anti-seizure medication. Consider therapy modification
Adverse Reactions
>10%: Gastrointestinal: Diarrhea (6% to 12%)
1% to 10%:
Cardiovascular: Edema (≤3%), chest pain (<2%), phlebitis (<2%), thrombophlebitis (<2%), hypotension (1% to 2%)
Central nervous system: Headache (4% to 7%), altered mental status (3% to 5%), insomnia (3%), dizziness (2%), hypothermia (infants, children, and adolescents: <2%)
Dermatologic: Diaper rash (infants and children: 5%), skin rash (2% to 3%), pruritus (1% to 2%), genital rash (infants, children, and adolescents: <2%), skin lesion (infants, children, and adolescents: <2%)
Endocrine & metabolic: Decreased serum potassium (<2%), increased serum glucose (<2%), increased serum potassium (<2%)
Gastrointestinal: Vomiting (4% to 10%), nausea (6% to 9%), abdominal pain (4% to 5%), constipation (2% to 4%), decreased appetite (infants, children, and adolescents: <2%)
Genitourinary: Vaginitis (1% to 3%), proteinuria (infants, children, and adolescents: <2%)
Hematologic & oncologic: Thrombocythemia (4% to 7%), decreased neutrophils (6%), decreased hemoglobin (5%), decreased hematocrit (3%), leukocyturia (2% to 3%), decreased platelet count (<2%), decreased white blood cell count (<2%), prolonged partial thromboplastin time (<2%), prolonged prothrombin time (<2%), eosinophilia (1% to 2%)
Hepatic: Increased serum alanine aminotransferase (4% to 9%), increased serum aspartate transaminase (4% to 8%), increased serum alkaline phosphatase (4% to 7%)
Infection: Candidiasis (<2%), herpes simplex infection (infants, children, and adolescents: <2%)
Local: Infused vein complication (7%), infusion-site pain (infants, children, and adolescents: 7%), erythema at injection site (infants, children, and adolescents: 4%)
Neuromuscular & skeletal: Arthralgia (infants, children, and adolescents: <2%)
Otic: Otic infection (infants, children, and adolescents: <2%)
Respiratory: Cough (≤4%), dyspnea (1% to 3%), nasopharyngitis (infants, children, and adolescents: <2%), rhinitis (infants, children, and adolescents: <2%), rhinorrhea (infants, children, and adolescents: <2%), upper respiratory tract infection (infants, children, and adolescents: 2%), wheezing (infants, children, and adolescents: <2%)
Miscellaneous: Fever (2% to 5%), swelling (≤3%)
Frequency not defined: Central nervous system: Agitation, confusion, decreased mental acuity, disorientation, drowsiness, stupor
<1%, postmarketing, and/or case reports: Abdominal distention, acid regurgitation, acute generalized exanthematous pustulosis, aggressive behavior, anaphylaxis, anorexia, anuria, anxiety, asthenia, asthma, asystole, ataxia, atrial fibrillation, bladder dysfunction, bradycardia, bronchoconstriction, cardiac arrhythmia, cardiac failure, chills, cholelithiasis, Clostridioides difficile associated diarrhea, decreased serum albumin, dehydration, delirium, dental discoloration, depression, dermatitis, desquamation, diaphoresis, drug reaction with eosinophilia and systemic symptoms, duodenitis, dysgeusia, dyskinesia, dyspepsia, dysphagia, epistaxis, erythema of skin, esophagitis, facial edema, fatigue, flank pain, flatulence, flushing, gastritis, gastrointestinal hemorrhage, gout, hallucination, heart murmur, hematoma, hematuria, hemoptysis, hemorrhoids, hiccups, hypertension, hypoesthesia, hypoxemia, impaired consciousness, increased blood urea nitrogen, increased serum bilirubin, increased serum creatinine, increased serum sodium, induration at injection site, intestinal obstruction, jaundice, lower extremity pain, malaise, muscle spasm, myoclonus, nervousness, nonimmune anaphylaxis, oliguria, oral candidiasis, oral mucosa ulcer, pain, pain at injection site, pancreatitis, paresthesia, pharyngitis, pleural effusion, pleuritic chest pain, pyloric stenosis, rales, renal insufficiency, respiratory distress, rhonchi, seizure, septicemia, septic shock, sore throat, stomatitis, subdural hematoma, syncope, tachycardia, tissue necrosis, tremor, unsteady gait, urinary retention, urticaria, ventricular tachycardia, vertigo, voice disorder, vulvovaginal candidiasis, vulvovaginal pruritus, vulvovaginitis, weight loss
Warnings/Precautions
Concerns related to adverse effects:
- Anaphylaxis/hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis, have been reported (some without a history of previous allergic reactions to beta-lactams).
- CNS effects: Carbapenems have been associated with CNS adverse effects, including confusional states and seizures (myoclonic); use caution with CNS disorders (eg, brain lesions and history of seizures) and adjust dose in renal impairment to avoid drug accumulation, which may increase seizure risk.
- Superinfection: Use may result in fungal or bacterial superinfection, including Clostridioides (formerly Clostridium) difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
- Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required in patients with moderate to severe renal dysfunction. Increased seizure risk has been reported in patients with renal dysfunction.
Concurrent drug therapy issues:
- Valproic acid and derivatives: Carbapenems, including ertapenem, may decrease the serum concentration of divalproex sodium/valproic acid increasing the risk of breakthrough seizures. Concurrent use of carbapenem antibiotics with divalproex sodium/valproic acid is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional antiseizure medication.
Special populations:
- Elderly: Lower doses (based upon renal function) are often required in the elderly.
Other warnings/precautions:
- IM administration: Doses for IM administration are mixed with lidocaine; consult Lidocaine (Systemic) information for associated Warnings/Precautions.
Monitoring Parameters
Periodic renal, hepatic, and hematopoietic assessment during prolonged therapy; neurological assessment
Pregnancy
Pregnancy Considerations
Ertapenem is approved for the treatment of postpartum endomyometritis, septic abortion, and postsurgical infections. Ertapenem may be considered for use as an alternative antibiotic in the treatment of intraamniotic infection (ACOG 712 2017).
Patient Education
What is this drug used for?
- It is used to treat or prevent bacterial infections.
Frequently reported side effects of this drug
- Nausea
- Vomiting
- Diarrhea
- Headache
- Injection site irritation
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Agitation
- Confusion
- Severe loss of strength and energy
- Mood changes
- Seizures
- Tremors
- Abnormal movements
- Severe fatigue
- Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
