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Pronunciation
(er ta PEN em)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of the following moderate-to-severe infections: Complicated intra-abdominal infections, complicated skin and skin structure infections (including diabetic foot infections without osteomyelitis, animal and human bites), complicated UTI (including pyelonephritis), acute pelvic infections (including postpartum endomyometritis, septic abortion, postsurgical gynecologic infections), and community-acquired pneumonia. Prophylaxis of surgical site infection following elective colorectal surgery. Antibacterial coverage includes aerobic gram-positive organisms, aerobic gram-negative organisms, and anaerobic organisms.
Note: Methicillin-resistant Staphylococcus aureus, Enterococcus spp, penicillin-resistant strains of Streptococcus pneumoniae, Acinetobacter, and Pseudomonas aeruginosa, are resistant to ertapenem while most extended-spectrum β-lactamase (ESBL)-producing bacteria remain sensitive to ertapenem.
Use: Unlabeled
Treatment of intravenous catheter-related bloodstream infection
Pregnancy Risk Factor
B
Pregnancy Considerations
With the exception of slightly decreased fetal weights in mice, teratogenic effects and fetal harm have not been shown in animal studies. Adequate and well-controlled studies have not been conducted in pregnant women and it is not known whether ertapenem can cause fetal harm.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Ertapenem is excreted in breast milk. The low concentrations in milk and low oral bioavailability suggest minimal exposure risk to the infant. Although the manufacturer recommends that caution be exercised when administering ertapenem to nursing women, most penicillins and carbapenems are safe for use in breast-feeding. Nondose-related effects could include modification of bowel flora.
Contraindications
Hypersensitivity to ertapenem, other carbapenems (eg, doripenem, imipenem, meropenem), or any component of the formulation; anaphylactic reactions to beta-lactam antibiotics. If using intramuscularly, known hypersensitivity to local anesthetics of the amide type (lidocaine is the diluent).
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 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.
• Pediatrics: Safety and efficacy have not been established in children <3 months of age.
Other warnings/precautions:
• I.M. administration: Doses for I.M. administration are mixed with lidocaine; consult Lidocaine (Systemic) information for associated Warnings/Precautions.
Adverse Reactions
Note: Percentages reported in adults.
1% to 10%:
Cardiovascular: Edema (3%), chest pain (1% to 2%), hypertension (1% to 2%), hypotension (1% to 2%), tachycardia (1% to 2%)
Central nervous system: Headache (6% to 7%); altered mental status (eg, agitation, confusion, disorientation, mental acuity decreased, somnolence, stupor) (3% to 5%); fever (2% to 5%), insomnia (3%), dizziness (2%), fatigue (1%), anxiety (1%)
Dermatologic: Rash (2% to 3%), pruritus (1% to 2%), erythema (1% to 2%)
Endocrine & metabolic: Hypokalemia (2%), hyperglycemia (1% to 2%), hyperkalemia (≤1%)
Gastrointestinal: Diarrhea (9% to 10%), nausea (6% to 9%), abdominal pain (4%), vomiting (4%), constipation (3% to 4%), acid regurgitation (1% to 2%), dyspepsia (1%), oral candidiasis (≤1%)
Genitourinary: Urine WBCs increased (2% to 3%), urine RBCs increased (1% to 3%), vaginitis (1% to 3%)
Hematologic: Thrombocytosis (4% to 7%), hematocrit/hemoglobin decreased (3% to 5%), eosinophils increased (1% to 2%), leukopenia (1% to 2%), neutrophils decreased (1% to 2%), thrombocytopenia (1%), prothrombin time increased (≤1%)
Hepatic: Hepatic enzyme increased (7% to 9%), alkaline phosphatase increase (4% to 7%), albumin decreased (1% to 2%), bilirubin (total) increased (1% to 2%)
Local: Infused vein complications (5% to 7%), phlebitis/thrombophlebitis (2%), extravasation (1% to 2%)
Neuromuscular & skeletal: Weakness (1%), leg pain (≤1%)
Renal: Serum creatinine increased (1%)
Respiratory: Dyspnea (1% to 3%), cough (1% to 2%), pharyngitis (1%), rales/rhonchi (1%), respiratory distress (≤1%)
<1%, postmarketing, and/or case reports: Abdominal distention, aggressive behavior, anaphylactoid reactions, anaphylaxis, anorexia, arrhythmia, asthma, asystole, atrial fibrillation, bicarbonate (serum) decreased, bladder dysfunction, bradycardia, bronchoconstriction, BUN increased, C. difficile-associated diarrhea, cardiac arrest, chills, cholelithiasis, dehydration, delirium, depression, dermatitis, desquamation, diaphoresis, DRESS syndrome, duodenitis, dyskinesia, dysphagia, epistaxis, epithelial (urine) cells increased, esophagitis, facial edema, flank pain, flatulence, flushing, gastritis, gastrointestinal hemorrhage, gout, hallucinations, heart failure, heart murmur, hematoma, hemoptysis, hemorrhoids, hiccups, hypoesthesia, hypoxemia, ileus, injection site induration, injection site pain, jaundice, malaise, monocytes increased, mouth ulcer, muscle spasm, myoclonus, necrosis, nervousness, oliguria/anuria, pain, pancreatitis, paresthesia, pharyngeal discomfort, pleural effusion, pleuritic pain, pyloric stenosis, renal insufficiency, seizure, septicemia, septic shock, sodium (serum) increased, spasm, stomatitis, subdural hemorrhage, syncope, taste perversion, tremor, urinary retention, urticaria, vaginal candidiasis, vaginal pruritus, ventricular tachycardia, vertigo, voice disturbance, vulvovaginitis, weight loss
Metabolism/Transport Effects
None known.
Drug Interactions
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Divalproex: Carbapenems may decrease the serum concentration of Divalproex. Management: Concurrent use of carbapenem antibiotics with divalproex is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional anti-seizure medication. Risk D: Consider therapy modification
Probenecid: May increase the serum concentration of Ertapenem. Risk C: 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 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Valproic Acid: Carbapenems may decrease the serum concentration of Valproic Acid. 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. Risk D: Consider therapy modification
Storage
Before reconstitution store at ≤25°C (77°F).
I.M.: Use within 1 hour after preparation.
I.V.: Reconstituted I.V. solution may be stored at room temperature and must be used within 6 hours or refrigerated, stored for up to 24 hours and used within 4 hours after removal from refrigerator. Do not freeze.
Reconstitution
I.M.: Reconstitute 1 g vial with 3.2 mL of 1% lidocaine HCl injection (without epinephrine). Shake well.
I.V.: Reconstitute 1 g vial with 10 mL of sterile water for injection, 0.9% sodium chloride injection, or bacteriostatic water for injection. Shake well. For adults, transfer dose to 50 mL of 0.9% sodium chloride injection; for children, dilute dose with NS to a final concentration ≤20 mg/mL.
Compatibility
Stable in NS; per manufacturer do not mix with other medications or use diluents containing dextrose.
Y-site administration: Compatible: Daptomycin, heparin, hetastarch in NS, potassium chloride, telavancin, tigecycline. Incompatible: Anidulafungin, caspofungin.
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.
Pharmacodynamics/Kinetics
Absorption: I.M.: Almost complete
Distribution: Vdss:
Children 3 months to 12 years: ~0.2 L/kg
Children 13-17 years: ~0.16 L/kg
Adults: ~0.12 L/kg
Protein binding (concentration dependent, primarily to albumin): 85% at 300 mcg/mL, 95% at <100 mcg/mL
Metabolism: Non-CYP-mediated hydrolysis to inactive metabolite
Bioavailability: I.M.: ~90%
Half-life elimination:
Children 3 months to 12 years: ~2.5 hours
Children ≥13 years and Adults: ~4 hours
Time to peak: I.M.: ~2.3 hours
Excretion: Urine (~80% as unchanged drug and metabolite); feces (~10%)
Dosage
Note: I.V. therapy may be administered for up to 14 days; I.M. therapy for up to 7 days
Usual dosage ranges:
Children 3 months to 12 years: I.M., I.V.: 15 mg/kg twice daily (maximum: 1 g/day)
Children ≥13 years and Adults: I.M., I.V.: 1 g/day
Indication-specific dosing:
Children 3 months to 12 years: I.M., I.V.:
Community-acquired pneumonia, complicated urinary tract infections (including pyelonephritis): 15 mg/kg twice daily (maximum: 1 g/day); 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: 15 mg/kg twice daily (maximum: 1 g/day) for 5-14 days
Pelvic infections (acute): 15 mg/kg twice daily (maximum: 1 g/day) for 3-10 days
Skin and skin structure infections: 15 mg/kg twice daily (maximum: 1 g/day) for 7-14 days
Children ≥13 years and Adults: I.M., I.V.:
Community-acquired pneumonia, complicated urinary tract infections (including pyelonephritis): 1 g/day; duration of total antibiotic treatment: 10-14 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 Enterobacteriaceae, Burkholderia pseudomallei, Acinetobacter pneumonia and considered alternative agents for anaerobes in aspiration pneumonia (IDSA, 2007).
Intra-abdominal infection: 1 g/day for 5-14 days; Note: 2010 IDSA guidelines recommend a treatment duration of 4-7 days (provided source controlled) for community-acquired, mild-to-moderate IAI
Pelvic infections (acute): 1 g/day for 3-10 days
Skin and skin structure infections (including moderate diabetic foot infections and animal or human bites): 1 g/day for 7-14 days (Note: IDSA guidelines recommend ertapenem as the preferred agent for animal bites. [IDSA, 2005].)
Adults: I.V.:
Prophylaxis of surgical site following colorectal surgery: 1 g given 1 hour preoperatively
Intravenous catheter-related bloodstream infection (unlabeled use): 1 g/day (Note: Carbapenems, including ertapenem, are preferred agents for extended-spectrum β-lactamase (ESBL)-positive Escherichia coli and Klebsiella, Enterobacter, and Serratia [IDSA, 2009].)
Dosage adjustment in renal impairment:
Children: No data available for pediatric patients with renal insufficiency.
Adults:
Clcr >30 mL/minute/1.73 m2: No adjustment required
Clcr ≤30 mL/minute/1.73 m2 and ESRD: 500 mg/day
Hemodialysis: Adults: When the daily dose is given within 6 hours prior to hemodialysis, a supplementary dose of 150 mg is required following hemodialysis.
CAPD: I.V.: 500 mg/day (Cardone, 2011)
Dosage adjustment in hepatic impairment: Adjustments cannot be recommended (lack of experience and research in this patient population).
Administration: I.M.
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 I.M. injection into a large muscle mass (eg, gluteal muscle or lateral part of the thigh). Do not administer I.M. preparation or drug reconstituted for I.M. administration intravenously.
Administration: I.V.
Infuse over 30 minutes
Administration: I.V. Detail
pH 7.5
Monitoring Parameters
Periodic renal, hepatic, and hematopoietic assessment during prolonged therapy; neurological assessment
Dietary Considerations
Some products may contain sodium.
Patient Education
This medication can only be administered intravenously or by intramuscular injections; report warmth, swelling, or irritation at infusion or injection site. Maintain adequate hydration, unless instructed to restrict fluid intake, and nutrition. Report unresolved nausea or vomiting. Report immediately any CNS changes (eg, dizziness, disorientation, headaches, confusion, or seizures). Report prolonged GI effects, persistent diarrhea, vomiting, or abdominal pain; change in respirations or respiratory difficulty; chest pain or palpitations; skin rash; foul-smelling vaginal discharge; or white plaques in mouth.
Geriatric Considerations
According to the package insert, the total and unbound AUCs were increased 37% and 67%, respectively, in healthy men and women ≥65 years of age compared to younger adults. No dose adjustment is required for patients with normal age-adjusted renal function.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Oral candidiasis
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause agitation, confusion, disorientation, decreased mental acuity, sedation, stupor, insomnia, dizziness, or anxiety
Mental Health: Effects on Psychiatric Treatment
Nausea and diarrhea are common; use caution with lithium, valproic acid, and SSRIs. May increase hepatic enzymes; use caution with olanzapine and valproic acid.
Nursing: Physical Assessment/Monitoring
Assess results of culture and sensitivity tests and patient history of previous allergies or adverse drug reactions. Use caution in presence of impaired renal function or CNS disorder. Patient must be monitored closely for adverse reactions, especially CNS adverse effects (history of seizures, head injuries, or other CNS events increases risk).
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
INVanz®: 1 g [contains sodium ~137 mg (~6 mEq)/g]
References
American Thoracic Society and Infectious Diseases Society of America, “Guidelines for the Management of Adults With Hospital-Acquired, Ventilator-Associated, and Healthcare-Associated Pneumonia,” Am J Respir Crit Care Med, 2005, 171(4):388-416.
Cardone KE, Grabe DW, Kulawy RW, et al, “Ertapenem Pharmacokinetics and Pharmacodynamics During Continuous Ambulatory Peritoneal Dialysis,” Antimicrob Agents Chemother, 2011, 56(2):725-30.
Lipsky BA, Berendt AR, Deery HG, et al, “Diagnosis and Treatment of Diabetic Foot Infections,” Clin Infect Dis, 2004, 39(7):885-910.
Lunde JL, Nelson RE, and Storandt HF, “Acute Seizures in a Patient Receiving Divalproex Sodium After Starting Ertapenem Therapy,” Pharmacotherapy, 2007, 27(8):1202-5.
Mandell LA, Wunderink RG, Anzueto A, et al, “Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults,” 2007, Clin Infect Dis, 44(Suppl 2):27-72
Mermel LA, Allon M, Bouza E, et al, “Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection: 2009 Update by the Infectious Diseases Society of America,” Clin Infect Dis, 2009, 49(1):1-45.
Seto AH, Song JC, and Guest SS, “Ertapenem-Associated Seizures in a Peritoneal Dialysis Patient,” Ann Pharmacother , 2005, 39(2):352-6.
Solomkin JS, Mazuski JE, Bradley JS, et al, “Diagnosis and Management of Complicated Intra-Abdominal Infections in Adults and Children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of America,” Clin Infect Dis, 2010, 50(2):133-64.
Stevens DL, Bisno AL, Chambers HF, et al, “Practice Guidelines for the Diagnosis and Management of Skin and Soft-Tissue Infections,” Clin Infect Dis, 2005, 41(10):1373-406.
International Brand Names
Lexi-Comp.com
Last full review/revision February 2012
Content last modified February 2012
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