Ertapenem

J01D - Other beta-lactam antibacterials ATC J01DH03 Small molecule approved 2001 Parenteral Natural product

🧬 Cross-allergy: Carbapenems

JFDA label: Invanz Vial

Mechanism of Action

Inhibitor of Bacterial penicillin-binding protein — Bacterial penicillin-binding protein inhibitor; Inhibitor of Peptidoglycan D,D-transpeptidase FtsI — Peptidoglycan D,D-transpeptidase FtsI inhibitor; Inhibitor of Cell shape peptidoglycan synthetase penicillin-binding protein 2 — Cell shape peptidoglycan synthetase penicillin-binding protein 2 inhibitor

Target	Action	Gene / class
Bacterial penicillin-binding protein efficacy	INHIBITOR
Cell shape peptidoglycan synthetase penicillin-binding protein 2 efficacy	INHIBITOR	pbpA
Peptidoglycan D,D-transpeptidase FtsI efficacy	INHIBITOR	ftsI

Indications

Approved

Acute pelvic infections
Community-acquired pneumonia
Complicated intra-abdominal infections
Complicated skin and skin structure infections
Complicated urinary tract infections
Moderate-to-severe infections
Prophylaxis of surgical-site infection in colorectal surgery

Off-label

Intravascular catheter-associated bloodstream infection
Osteomyelitis, native vertebral
Prosthetic joint infection
Skin and soft tissue necrotizing infections
Surgical Site Infection

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16 · curated · openfda-label.

Bacteria

Organism	Activity	MIC
Anaerobes	Susceptible	25.0 mg/L
Bacteroides distasonis	Active	—
Bacteroides fragilis	Active	—
Bacteroides fragilis group	Susceptible	1.0 mg/L
Bacteroides ovatus	Active	—
Bacteroides thetaiotaomicron	Active	—
Bacteroides uniformis	Active	—
Bacteroides vulgatus	Active	—
Citrobacter freundii	Active	—
Citrobacter koseri	Active	—
Clostridium clostridioforme	Active	—
Clostridium perfringens	Active	—
Enterobacter aerogenes	Active	—
Enterobacter cloacae	Active	—
Enterobacterales	Susceptible	0.5 mg/L
Escherichia coli	Susceptible	0.5 mg/L
Haemophilus influenzae	Susceptible	0.5 mg/L
Haemophilus parainfluenzae	Active	—
Klebsiella oxytoca	Active	—
Klebsiella pneumoniae	Susceptible	0.5 mg/L
Moraxella catarrhalis	Susceptible	0.5 mg/L
Morganella morganii	Active	—
Prevotella bivia	Active	—
Proteus mirabilis	Susceptible	0.5 mg/L
Proteus vulgaris	Active	—
Providencia rettgeri	Active	—
Providencia stuartii	Active	—
Serratia marcescens	Active	—
Staphylococcus aureus	Active	—
Staphylococcus epidermidis	Active	—
Streptococcus agalactiae	Active	—
Streptococcus pneumoniae	Susceptible	0.5 mg/L
Streptococcus pyogenes	Active	—
Viridans group streptococci	Susceptible	0.5 mg/L
Escherichia coli	Resistant	1.0 mg/L
Klebsiella pneumoniae	Resistant	1.0 mg/L

Class profile

gramStatus	Both
spectrumBreadth	Broad
atypicalCoverage	No
isBactericidal	1
moaCategory	Cell wall synthesis inhibitor (beta-lactam, carbapenem)
pdIndex	Time-dependent
postAntibioticEffect	Short
mrsaCoverage	0
resistanceMechanisms	Carbapenemase (KPC,NDM,OXA-48),Porin mutations,Efflux pumps

Contraindications

Source: Lexicomp

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 Absolute
known hypersensitivity to local anesthetics of the amide type due to the use of lidocaine as a diluent (IM use only) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (2)

Common chest pain, altered mental status (eg, agitation, confusion, disorientation, mental acuity decreased, somnolence, stupor), insomnia, dizziness, hypothermia, skin rash, pruritus, genital rash, nausea, · Edema

Blood and lymphatic system disorders (6)

Common decreased hematocrit · decreased hemoglobin · decreased neutrophils · leukocyturia · leukopenia, increased serum AST, increased serum alkaline · Thrombocythemia

Musculoskeletal and connective tissue disorders (1)

Common Arthralgia, dyspnea, nasopharyngitis

Infections and infestations (1)

Common Herpes simplex infection

Other (1)

Very Common Gastrointestinal: Diarrhea

Dosing

Source: Lexicomp

Note: IV therapy may be administered for up to 14 days; IM for up to 7 days Community-acquired pneumonia and complicated urinary tract infections (including pyelonephritis): IM, IV: 1 g once daily; duration of total antibiotic treatment: 10 to 14 days; duration includes possible switch to appropriate oral therapy after at least 3 days of parenteral treatment, once clinical improvement demonstrated. Note: The carbapenems, including ertapenem, are preferred agents for Enterobacter spp and Burkholderia pseudomallei, and are considered alternative agents for anaerobes in aspiration pneumonia (IDSA 2007). Intra-abdominal infection: IM, IV: 1 g once daily for 5 to 14 days; Note: 2010 IDSA guidelines recommend a treatment duration of 4 to 7 days (provided source controlled) for community-acquired, mild to moderate intra-abdominal infections (Solomkin 2010) Osteomyelitis, native vertebral due to Enterobacteriaceae (off-label use): IV: 1 g once daily for 6 weeks (IDSA [Berbari 2015]) Pelvic infections (acute): IM, IV: 1 g once daily for 3-10 days Prophylaxis of surgical site following colorectal surgery: IV: 1 g as a single dose given 1 hour preoperatively Skin and skin structure infections (excluding diabetic foot infections with osteomyelitis): IM, IV: 1 g once daily for 7 to 14 days. Notes: For diabetic foot infections, recommended treatment duration is up to 4 weeks depending on severity of infection and response to therapy (Lipsky 2012). Intravenous catheter-related bloodstream infection (off-label use): IV 1 g once daily (Note: Carbapenems, including ertapenem, are preferred agents for extended-spectrum β-lactamase [ESBL]-positive Escherichia coli and Klebsiella, Enterobacter, and Serratia [IDSA, 2009].) Prosthetic joint infection: Enterobacter spp (off-label use): IV: 1 g every 24 hours for 4 to 6 weeks (Osmon 2013) Skin and soft tissue necrotizing infections (off-label use): IV: 1 g once daily 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]). Surgical site infection (intestinal or genitourinary tract surgery) (off-label use): IV: 1 g once daily (IDSA [Stevens, 2014]).

(For additional information see "Ertapenem: Pediatric drug information") Note: IV therapy may be administered for up to 14 days; IM therapy for up to 7 days Infants ≥3 months and Children: Community-acquired pneumonia and complicated urinary tract infections (including pyelonephritis): IM, IV: 15 mg/kg twice daily (maximum: 1 g daily); duration of total antibiotic treatment: 10-14 days (Note: Duration includes possible switch to appropriate oral therapy after at least 3 days of parenteral treatment, once clinical improvement demonstrated.) Intra-abdominal infection: IM, IV: 15 mg/kg twice daily (maximum: 1 g daily) for 5-14 days Pelvic infections (acute): IM, IV: 15 mg/kg twice daily (maximum: 1 g daily) for 3-10 days Skin and skin structure infections: IM, IV: 15 mg/kg twice daily (maximum: 1 g daily) for 7-14 days Skin and soft tissue necrotizing infections (off-label use): IV: 15 mg/kg every 12 hours 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]). Adolescents: Community-acquired pneumonia, complicated urinary tract infections (including pyelonephritis): Refer to adult dosing. Intra-abdominal infection: Refer to adult dosing. Pelvic infections (acute): Refer to adult dosing. Skin and skin structure infections (excluding diabetic foot infections with osteomyelitis): Refer to adult dosing.

Refer to adult dosing.

Children: No data available for pediatric patients with renal insufficiency. Adults: CrCl >30 mL/minute/1.73 m2: No dosage adjustment necessary. CrCl ≤30 mL/minute/1.73 m2 and ESRD: 500 mg/day Hemodialysis: When the daily dose is given within 6 hours prior to hemodialysis, a supplementary dose of 150 mg is required following hemodialysis. If ertapenem is given at least 6 hours prior to hemodialysis, no supplementary dose is needed. CAPD: IV: 500 mg daily (Cardone, 2011)

Adjustments cannot be recommended (lack of experience and research in this patient population).

Warnings & Precautions

Source: Lexicomp

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 C. difficile-associated diarrhea 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.

Pregnancy & Lactation

Pregnancy

FDA category B Teratogenic

Teratogenic effects were not observed in animal reproduction studies. Ertapenem is approved for the treatment of postpartum endomyometritis, septic abortion, and postsurgical infections. Information related to use during pregnancy has not been located.

Lactation

Ertapenem is excreted in breast milk. The low concentrations in milk and low oral bioavailability suggest minimal exposure risk to the infant. The manufacturer recommends that caution be exercised when administering ertapenem to nursing women. Nondose-related effects could include modification of bowel flora.

Monitoring

Efficacy	Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin)
Toxicity	Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea)
Clinical pearl	Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship).
Counseling	Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h.

Chemistry & Properties

Formula	C22H25N3O7S
Molecular weight	475.52 g/mol
IUPAC name	(4R,5S,6S)-3-[(3S,5S)-5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
CAS	153832-46-3
PubChem CID	150610
InChIKey	`JUZNIMUFDBIJCM-ANEDZVCMSA-N`
logP	0.94 (XLogP -1.5)
Polar surface area	156.27 Å²
H-bond acceptors / donors	7 / 5
Drug-likeness (QED)	0.36
Lipinski violations	0

SMILES

C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(S[C@@H]3CN[C@H](C(=O)Nc4cccc(C(=O)O)c4)C3)[C@H](C)[C@H]12

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	1.772 h
Volume of distribution	0.117 L/kg
Protein binding	45.7%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Inhibitor	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)

Drug–drug interactions (10, DDInter)

Interacting drug	Severity	Management
Bupropion	major
Iohexol	major
Iopamidol	major
Ethinylestradiol	moderate
Lindane	moderate
Mycophenolic acid	moderate
Pemetrexed	moderate
Picosulfuric acid	moderate
Polyethylene glycol (3350 with electrolytes)	moderate
Sodium sulfate	moderate

Registered Products (4)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Eranza	Tablet (as sodium) 1000 mg	10 VIials	Hikma Pharmaceuticals Co.Ltd/Jordan	—
Ertapenem SLC for Injection	Powder for Injection 1046 mg	10 vial	Land Of Medicine Drug Store	—
Invanz Vial	Vial 1.0 g	1 vial	Adatco Drug Store	—
Penerta	Vial Ertapenem Sodium 1.00 g	10 vial	AL-TAQADDOM PHARMACEUTICAL INDUSTRIES/JORDAN	—