Ertapenem (Invanz)
ertapenem sodium
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Complicated intra-abdominal infections | Adults & pediatrics ≥3 months | Monotherapy | FDA Approved |
| Complicated skin & skin structure infections (incl. diabetic foot without osteomyelitis) | Adults & pediatrics ≥3 months | Monotherapy | FDA Approved |
| Community-acquired pneumonia | Adults & pediatrics ≥3 months | Monotherapy | FDA Approved |
| Complicated urinary tract infections (incl. pyelonephritis) | Adults & pediatrics ≥3 months | Monotherapy | FDA Approved |
| Acute pelvic infections (postpartum endomyometritis, septic abortion, post-surgical gynecologic) | Adults & pediatrics ≥3 months | Monotherapy | FDA Approved |
| Surgical site infection prophylaxis (elective colorectal surgery) | Adults only | Prophylaxis (single dose) | FDA Approved |
Ertapenem is a Group 1 carbapenem designed for community-acquired mixed aerobic-anaerobic infections. It provides reliable coverage against Enterobacterales (including many ESBL-producing strains), methicillin-susceptible staphylococci, streptococci, and a wide range of anaerobes including Bacteroides fragilis. Importantly, ertapenem lacks clinically useful activity against Pseudomonas aeruginosa, Acinetobacter species, enterococci, and MRSA, which distinguishes it from broader-spectrum carbapenems and may exert less selection pressure for resistance among these nosocomial pathogens.
ESBL-producing Enterobacterales bloodstream infections: Retrospective data support ertapenem as an effective option for bacteraemia caused by ESBL-producing E. coli and K. pneumoniae when the isolate is susceptible. Evidence quality: Moderate.
Osteomyelitis (susceptible organisms): Limited data from case series suggest clinical benefit when used as outpatient parenteral therapy for osteomyelitis due to susceptible gram-negative bacilli. Evidence quality: Low.
Intravascular catheter-related infections: IDSA guidelines recommend ertapenem for catheter-related infections caused by susceptible organisms including ESBL-positive gram-negative bacilli. Evidence quality: Moderate.
Dosing
Adult Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Complicated intra-abdominal infection | 1 g IV/IM once daily | 1 g once daily | 1 g/day | Duration 5–14 days Source control essential; adjust based on culture data |
| Complicated skin/soft tissue infection (including diabetic foot) | 1 g IV/IM once daily | 1 g once daily | 1 g/day | Duration 7–14 days (up to 28 days for diabetic foot with oral step-down) Does not cover MRSA or Pseudomonas; add vancomycin if needed |
| Community-acquired pneumonia | 1 g IV/IM once daily | 1 g once daily | 1 g/day | Duration 10–14 days IV-to-oral step-down after ≥3 days if improving; only covers penicillin-susceptible S. pneumoniae |
| Complicated UTI / pyelonephritis | 1 g IV/IM once daily | 1 g once daily | 1 g/day | Duration 10–14 days Oral step-down possible after ≥3 days parenteral therapy |
| Acute pelvic infection | 1 g IV/IM once daily | 1 g once daily | 1 g/day | Duration 3–10 days |
| Colorectal surgery prophylaxis | 1 g IV ×1 | N/A | 1 g single dose | Give 1 hour before incision Single dose only; no post-operative doses needed |
Pediatric Dosing (3 months to 12 years)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| All approved indications | 15 mg/kg IV/IM BID | 15 mg/kg BID | 1 g/day | Twice-daily dosing required due to faster clearance IV infusion over 30 min; IM reconstituted with 1% lidocaine |
Renal Impairment Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| CrCl >30 mL/min | 1 g once daily | 1 g once daily | 1 g/day | No adjustment needed |
| CrCl ≤30 mL/min (incl. ESRD) | 500 mg once daily | 500 mg once daily | 500 mg/day | 50% dose reduction Half-life markedly prolonged in ESRD (~14 h) |
| Hemodialysis patient (dose given <6 h before HD) | 500 mg once daily | 500 mg + 150 mg post-HD | 650 mg on HD day | Supplemental 150 mg after HD session If dose given ≥6 h before HD, no supplement needed |
Ertapenem is the only carbapenem suitable for once-daily dosing in adults, making it a practical choice for outpatient parenteral antibiotic therapy (OPAT). Its 4-hour half-life and high protein binding support sustained bactericidal concentrations against susceptible organisms with a single daily infusion. Ensure IM reconstitution uses 1% lidocaine without epinephrine; never administer the IM preparation intravenously.
Pharmacology
Mechanism of Action
Ertapenem is a 1-beta-methyl carbapenem that exerts bactericidal activity by binding to penicillin-binding proteins (PBPs), with preferential affinity for PBP 2 and PBP 3. This binding inhibits the transpeptidation step of peptidoglycan cross-linking, disrupting cell wall synthesis. As the bacterial cell attempts to grow and divide without an intact wall, it becomes osmotically unstable. Simultaneously, accumulated peptidoglycan precursors activate endogenous autolytic enzymes (autolysins and murein hydrolases), accelerating cell lysis. The 1-beta-methyl side chain confers stability against hydrolysis by most serine beta-lactamases, including ESBLs and AmpC enzymes. However, ertapenem is hydrolysed by metallo-beta-lactamases (e.g., NDM, VIM, IMP) and some class A carbapenemases (e.g., KPC). Unlike meropenem and imipenem, ertapenem lacks sufficient affinity for the PBPs of Pseudomonas aeruginosa and Acinetobacter species to achieve clinically relevant activity.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | ~90% bioavailability (IM); Tmax ~2.3 h (IM), end of infusion (IV) | IM route delivers comparable systemic exposure to IV, supporting outpatient use |
| Distribution | Vd ~0.12 L/kg (~8.2 L); 85–95% protein bound (concentration-dependent) | High protein binding prolongs half-life; hypoalbuminaemia raises free drug levels and may increase toxicity risk |
| Metabolism | Hydrolysis of beta-lactam ring to open-ring metabolite; no CYP involvement; not a substrate or inhibitor of CYP1A2, 2C9, 2C19, 2D6, 2E1, 3A4 or P-gp | Minimal drug-interaction potential via hepatic pathways; no dose adjustment for hepatic impairment |
| Elimination | t½ ~4 h; total clearance ~28.4 mL/min; renal clearance ~12.8 mL/min; ~80% excreted in urine (~38% unchanged, ~37% as metabolite); ~10% in faeces | Predominantly renal elimination necessitates dose reduction in severe renal impairment; half-life extends to ~14 h in ESRD |
Side Effects
No clinical or laboratory adverse effects reached an incidence of ≥10% in pivotal trials (n = 1,954 adults). The highest-frequency findings were transaminase elevations (ALT ~8.8%, AST ~8.4%), which are laboratory values and discussed in the Common tier below.
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| ALT / AST elevation | 8.3–8.8% | Transient transaminase rise; rarely clinically significant; monitor hepatic function periodically |
| Diarrhoea | 5.5% | Most common clinical adverse event; typically mild-to-moderate; evaluate for C. difficile if persistent or bloody |
| Infused vein complication | 3.7% | Includes phlebitis and thrombophlebitis; rotate IV sites; infuse over 30 minutes |
| Nausea | 3.1% | Usually mild; may be reduced by slower infusion rate |
| Headache | 2.2% | Typically self-limiting; responds to simple analgesia |
| Vaginitis (females) | 2.1% | Candidal overgrowth; may require antifungal treatment |
| Vomiting | 1.1% | Usually mild; rarely requires anti-emetic therapy |
| Fever | 2.0% | Differentiate drug fever from ongoing infection; usually resolves with discontinuation |
| Abdominal pain | 1.0% | Non-specific; investigate if accompanied by diarrhoea or distension |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Seizures | 0.5% | Median 4–5 days; range 1–14 days | Discontinue ertapenem; initiate anticonvulsant therapy; evaluate neurological status and renal function |
| Neurotoxicity (hallucinations, altered mental status, confusion, encephalopathy) | Rare (~1%) | 1–6 days after initiation | Discontinue ertapenem immediately; consider hemodialysis in severe cases; symptoms typically resolve within 7 days of discontinuation |
| Anaphylaxis / severe hypersensitivity | Rare | Minutes to hours after first dose | Immediately discontinue; epinephrine, airway management; permanent discontinuation |
| Clostridioides difficile-associated diarrhoea (CDAD) | Uncommon | During or up to 2 months post-therapy | Obtain C. difficile testing; discontinue ertapenem; initiate targeted therapy (e.g., fidaxomicin, oral vancomycin) |
| Thrombocytosis | Rare | During therapy | Monitor platelet count; reactive thrombocytosis typically resolves with drug discontinuation |
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Gastrointestinal adverse events | Most common reason | Primarily diarrhoea and nausea; comparable to ceftriaxone and piperacillin-tazobactam arms |
| Infusion-site reactions | Common | Phlebitis, thrombophlebitis; not significantly different from comparator antibiotics |
| Neurological adverse events | Uncommon | Seizures, confusion; more likely with renal impairment or pre-existing CNS conditions |
Ertapenem-associated neurotoxicity (seizures, hallucinations, encephalopathy) occurs disproportionately in elderly patients with renal dysfunction, hypoalbuminaemia, or pre-existing CNS conditions. In the presence of low serum albumin, free (unbound) ertapenem levels rise substantially, increasing CNS penetration and toxicity risk. Consider using the Cockcroft-Gault equation to verify renal function before prescribing, and use alternative antibiotics in patients with advanced renal failure who also have CNS risk factors. If neurotoxicity develops, discontinue ertapenem promptly; symptoms generally resolve within a median of 7 days.
Drug Interactions
Ertapenem does not undergo hepatic metabolism via cytochrome P450 enzymes and is not a substrate or inhibitor of P-glycoprotein. Consequently, metabolic drug interactions are minimal. The key interactions involve pharmacokinetic interference with renal excretion and a pharmacodynamic effect on valproic acid metabolism.
Monitoring
-
Renal Function
Baseline, then periodically
Routine Serum creatinine and estimated CrCl before initiation. Repeat during therapy in patients with baseline renal impairment or receiving prolonged courses. Dose reduction required if CrCl falls to ≤30 mL/min. -
Hepatic Function
Baseline, then as indicated
Routine ALT/AST elevations occur in approximately 8–9% of patients. Typically transient and self-resolving. Check liver enzymes at baseline and if symptoms of hepatotoxicity develop. -
Neurological Status
Throughout therapy
Trigger-based Monitor for signs of neurotoxicity: tremors, myoclonus, seizures, confusion, hallucinations, or altered consciousness. Higher risk in elderly patients with renal dysfunction, hypoalbuminaemia, or pre-existing CNS conditions. Discontinue if neurological symptoms develop. -
Serum Albumin
Baseline
Trigger-based Low albumin increases free ertapenem levels. If albumin <3.5 g/dL, heightened vigilance for neurotoxicity is warranted. Consider alternative antibiotics in patients with combined hypoalbuminaemia and renal impairment. -
Stool / GI Symptoms
Throughout and post-therapy
Trigger-based Evaluate for C. difficile infection if diarrhoea develops, especially if watery, persistent, or bloody. CDAD can occur up to 2 months after completion of antibiotic therapy. -
Valproic Acid Levels
If co-administered
Trigger-based Monitor valproic acid trough levels daily if concurrent use is unavoidable. Expect rapid decline (up to 70–95%) within 24 hours. Supplemental anticonvulsant therapy may be necessary. -
Complete Blood Count
Baseline, then periodically
Routine Eosinophilia, thrombocytosis, and leucopenia have been reported. Periodic CBC is advisable during prolonged therapy (>7 days).
Contraindications & Cautions
Absolute Contraindications
- Known hypersensitivity to ertapenem or any component of the formulation
- History of anaphylaxis to any beta-lactam antibiotic (penicillins, cephalosporins, or carbapenems)
- Hypersensitivity to amide-type local anaesthetics (applies to IM administration only, as lidocaine is the diluent)
Relative Contraindications (Specialist Input Recommended)
- Concurrent valproic acid therapy: Rapid, profound reduction in valproic acid levels makes co-administration generally inadvisable. If no alternative antibiotic exists, specialist co-management with neurology is essential, supplemental anticonvulsant therapy should be initiated, and valproic acid levels must be monitored intensively.
- Severe renal impairment (CrCl ≤30) with concurrent CNS risk factors: Combination of advanced renal failure, hypoalbuminaemia, elderly age, and pre-existing brain lesions or seizure history increases neurotoxicity risk substantially. The European Medicines Agency does not recommend ertapenem when CrCl is below 30 mL/min.
Use with Caution
- History of penicillin allergy (non-anaphylactic): Cross-reactivity between carbapenems and penicillins is estimated at <1%; use with standard monitoring in patients with mild penicillin allergy.
- CNS disorders (brain lesions, epilepsy): Increased risk of seizures, particularly if dose is not adjusted for renal function.
- Paediatric patients <3 months: No data available; not recommended.
- Meningitis: Not recommended in paediatric patients due to insufficient CSF penetration.
- Pregnancy and lactation: Use only if benefit outweighs risk; ertapenem is excreted in breast milk at low concentrations.
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. These reactions are more likely in individuals with a history of sensitivity to multiple allergens. Before initiating ertapenem, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams, and other allergens. If an allergic reaction occurs, the drug should be discontinued immediately and appropriate emergency treatment initiated.
Patient Counselling
Purpose of Therapy
Ertapenem is a powerful injectable antibiotic used to treat serious bacterial infections in the abdomen, skin, lungs, urinary tract, and pelvis. It works by destroying the bacterial cell wall, leading to bacterial death. It is given once daily, which makes it practical for home-based intravenous therapy. Ertapenem does not treat viral infections such as the common cold or influenza.
How to Take
Ertapenem is administered as a 30-minute intravenous infusion or as an intramuscular injection by a healthcare professional. It is typically given once daily at the same time each day. The full course of treatment should be completed even if symptoms improve early, as stopping prematurely can promote antibiotic resistance and treatment failure.
Sources
- Ertapenem for Injection prescribing information (Invanz). Merck & Co., Inc. DailyMed/FDA. DailyMed Primary source for all FDA-approved dosing, indications, contraindications, adverse reactions, and pharmacokinetic data.
- Ertapenem for Injection prescribing information. Apotex Corp. DailyMed. DailyMed Generic ertapenem label confirming identical dosing and safety profile.
- Invanz (ertapenem) FDA label, 2012 revision. FDA Historical FDA label providing complete pharmacokinetic tables, clinical trial data, and hemodialysis dosing guidance.
- Solomkin JS, Yellin AE, Rotstein OD, et al. Ertapenem versus piperacillin/tazobactam in the treatment of complicated intra-abdominal infections. Ann Surg. 2003;237(2):235-245. doi:10.1097/01.SLA.0000048551.00286.11 Phase III trial establishing non-inferiority of ertapenem to piperacillin-tazobactam for complicated intra-abdominal infections.
- Lipsky BA, Armstrong DG, Citron DM, et al. Ertapenem versus piperacillin/tazobactam for diabetic foot infections (SIDESTEP). Clin Infect Dis. 2005;41(10):1462-1471. doi:10.1086/497151 Pivotal trial supporting ertapenem for diabetic foot infections without osteomyelitis.
- Ortiz-Ruiz G, Caballero-Lopez J, Friedland IR, et al. A study evaluating the efficacy, safety, and tolerability of ertapenem versus ceftriaxone for the treatment of community-acquired pneumonia. Clin Infect Dis. 2002;34(8):1076-1083. doi:10.1086/339543 Established ertapenem’s non-inferiority to ceftriaxone for CAP requiring hospitalization.
- Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and IDSA. Clin Infect Dis. 2010;50(2):133-164. doi:10.1086/649554 IDSA/SIS guideline listing ertapenem as a recommended single-agent option for community-acquired intra-abdominal infections.
- Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by IDSA. Clin Infect Dis. 2014;59(2):e10-52. doi:10.1093/cid/ciu296 IDSA guideline recommending ertapenem for moderate-to-severe polymicrobial skin infections and animal bite wounds.
- Livermore DM, Sefton AM, Scott GM. Properties and potential of ertapenem. J Antimicrob Chemother. 2003;52(3):331-344. doi:10.1093/jac/dkg375 Comprehensive review of ertapenem’s microbiological spectrum, PBP binding affinities, and beta-lactamase stability.
- Zhanel GG, Johanson C, Embil JM, et al. Ertapenem: review of a new carbapenem. Expert Rev Anti Infect Ther. 2005;3(1):23-39. doi:10.1586/14787210.3.1.23 Review article covering microbiologic, pharmacokinetic, and clinical trial data.
- Nix DE, Majumdar AK, DiNubile MJ. Pharmacokinetics and pharmacodynamics of ertapenem: an overview for clinicians. J Antimicrob Chemother. 2004;53 Suppl 2:ii23-28. doi:10.1093/jac/dkh205 Detailed PK/PD analysis establishing rationale for once-daily dosing, renal dose adjustment, and protein binding data.
- Teppler H, Gesser RM, Friedland IR, et al. Safety and tolerability of ertapenem. J Antimicrob Chemother. 2004;53(Suppl 2):ii75-81. doi:10.1093/jac/dkh209 Comprehensive safety analysis across 2,046 patients and 240 healthy volunteers from Phase IIb/III clinical trials.
- Miller AD, Ball AM, Bookstaver PB, et al. Characterizing ertapenem neurotoxicity: a systematic review and experience at a tertiary medical center. Open Forum Infect Dis. 2024;11(5):ofae211. doi:10.1093/ofid/ofae211 Systematic review of 125 cases of ertapenem neurotoxicity identifying risk factors: renal dysfunction, elderly age, hypoalbuminaemia, and pre-existing CNS conditions.