Ertapenem (INVanz) is a broad-spectrum antibiotic that belongs to the Carbapenem group. It is used in the treatment of serious infections of the abdomen, pelvis, genital tract, and bones and joints.

Ertapenem (INVanz) Uses:

• Moderate-to-severe infections:

  • Acute pelvic infections:

    • Used or the treatment of acute pelvic infections, including:
      • septic abortion, postpartum endomyometritis, and postsurgical gynecologic infections caused by:
        • Streptococcus agalactiae,
        • Bacteroides fragilis,
        • Escherichia coli,
        • Porphyromonas asaccharolytica,
        • Peptostreptococcus spp, or
        • Prevotella bivia.

  • Community-acquired pneumonia:

    • Used 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.

  • Complicated intra-abdominal infections:

    • For the treatment of complicated intra-abdominal infections caused by:
      • E. coli,
      • Clostridium clostridioforme,
      • Bacteroides distasonis,
      • Bacteroides ovatus,
      • Eubacterium lentum,
      • Peptostreptococcus spp,
      • B. fragilis,
      • Bacteroides thetaiotaomicron, or
      • Bacteroides uniformis.

  • Complicated skin and skin structure infections:

    • For the treatment of complicated skin and skin structure infections, including diabetic foot infections without osteomyelitis caused by:
      • Staphylococcus aureus (methicillin-susceptible isolates only),
      • Streptococcus pyogenes,
      • S. agalactiae,
      • E. coli,
      • Proteus mirabilis,
      • B. fragilis,
      • Klebsiella pneumoniae,
      • Peptostreptococcus spp,
      • P. asaccharolytica, or
      • P. bivia.
    • Ertapenem has not been studied in diabetic foot infections with concomitant osteomyelitis.

  • Complicated urinary tract infections:

    • Used for the treatment of complicated urinary tract infections (UTIs), including pyelonephritis caused by:
      • E. coli, including cases with concurrent bacteremia or K. pneumoniae.

  • Prophylaxis of surgical-site infection in colorectal surgery:

    • Used for the prophylaxis of surgical site infection in adults following elective colorectal surgery.

Note:

• Methicillin-resistant Staphylococcus aureus, penicillin-resistant strains of Streptococcus pneumoniae, Enterococcus spp, Acinetobacter, and Pseudomonas aeruginosa are resistant to ertapenem while most extended-spectrum beta-lactamase (ESBL)-producing bacteria remain sensitive to ertapenem.

• Off Label Use of Ertapenem in Adults:

  • Used in intravascular catheter-associated bloodstream infection
  • Used in osteomyelitis, native vertebral
  • Used in prosthetic joint infection
  • Used in skin and soft tissue necrotizing infections
  • Used in surgical Site Infection

Ertapenem (INVanz) Dose in Adults

Note:

• IV therapy may be administered for up to 14 days;
• IM for up to 1 weak

Ertapenem (INVanz) Dose in the treatment of Intra-abdominal infection:

• IM, IV: 1 g once in a day 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.

Ertapenem (INVanz) Dose in the treatment of native vertebral Osteomyelitis, due to Enterobacteriaceae (off-label):

• IV: 1 g once in a day for 6 weeks.

Ertapenem (INVanz) Dose in the treatment of Pelvic infections (acute):

• IM, IV: 1 g once in a day for 3-10 days

Ertapenem (INVanz) Dose in the treatment of community-acquired Pneumonia, (inpatients [non-ICU], without risk factors for Pseudomonas):

• IM, IV: 1 g once daily for 5 to 7 days in combination with a macrolide for empiric therapy.

Ertapenem (INVanz) Dose in the Prophylaxis of the surgical site following colorectal surgery:

• IV: 1 g as a single dose given 1 hour preoperatively

Ertapenem (INVanz) Dose in the treatment of Skin and skin structure infections (excluding diabetic foot infections with osteomyelitis):

• IM, IV: 1 g once in a day for 7 to 14 days.
• Notes:
  • For diabetic foot infections, the recommended treatment duration is up to 4 weeks depending on the severity of infection and response to therapy.

Ertapenem (INVanz) Dose in the treatment of Intravenous catheter-related bloodstream infection (off-label):

• IV: 1 g once in a day.

Ertapenem (INVanz) Dose in the treatment of prosthetic joint infection:

• Enterobacter spp (off-label use):

  • IV: 1 g every 24 hours for 4 to 6 weeks.

Ertapenem (INVanz) Dose in the treatment of Skin and soft tissue necrotizing infections (off-label):

• IV: 1 g once daily in combination with an agent effective against MRSA (eg, vancomycin, daptomycin linezolid) for empiric therapy of polymicrobial (mixed) infections.
• Continue until further debridement is not required, the patient has clinically improved, and the patient is afebrile for 48 to 72 hours.

Ertapenem (INVanz) Dose in the treatment of Surgical site infection (intestinal or genitourinary tract surgery) (off-label):

• IV: 1 g once in a day.

Ertapenem (INVanz) Dose in the treatment of complicated Urinary tract infection, (including pyelonephritis):

• Outpatients:

  • IM, IV: 1 g once, followed by 5 to 14 days of appropriate oral therapy.

Ertapenem (INVanz) Dose in Childrens

Ertapenem (INVanz) General dosing in Children for susceptible infection:

Note:

• IV therapy may be administered for up to 14 days;
• IM for up to 7 days;
• refer to disease-state specific durations.

• Infants and Children:

  • Severe infections:
    • IM, IV: 15 mg per kg per dose two times  daily;
    • The maximum single dose: 500 mg per dose

• Adolescents:

  • IM, IV: 1,000 mg once in a day

Ertapenem (INVanz) Dose in the treatment of complicated Intra-abdominal infection:

Note: IDSA guidelines recommend a treatment duration of 4 to 7 days (provided source controlled) for community-acquired, mild to moderate infections.

• Infants <3 months:

  • IM, IV: 15 mg/kg/dose two times a day.

• Infants ≥3 months and Children:

  • IM, IV: 15 mg/kg/dose two times in a day for 5 to 14 days;
  • The maximum single dose: 500 mg/dose

• Adolescents:

  • IM, IV: 1,000 mg once in a day for 5 to 14 days

Ertapenem (INVanz) Dose in the treatment of acute Pelvic infections:

• Infants <3 months:

  • IM, IV: 15 mg per kg per dose two times a day.

• Infants ≥3 months and Children:

  • IM, IV: 15 mg per kg per dose two times in a day  for 3 to 10 days;
  • The maximum single dose: 500 mg per dose

• Adolescents:

  • IM, IV: 1,000 mg once in a day for 3 to 10 days

Ertapenem (INVanz) Dose in the treatment of community-acquired Pneumonia:

Note: Duration includes a possible switch to appropriate oral step-down therapy after at least 3 days of parenteral treatment, once clinical improvement demonstrated.

• Infants <3 months:

  • IM, IV: 15 mg per kg per dose two times a day.

• Infants ≥3 months and Children:

  • IM, IV: 15 mg per kg per dose two times in a day for 10 to 14 days;
  • The maximum single dose: 500 mg per dose

• Adolescents:

  • IM, IV: 1,000 mg once in a day for 10 to 14 days

Ertapenem (INVanz) Dose in the treatment of complicated or necrotizing Skin and skin structure infections:

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, daptomycin, and linezolid ) for empiric therapy of polymicrobial (mixed) infections.
• Continue until further debridement is not necessary, the patient has clinically improved, and the patient is afebrile for 48 to 72 hours.

• Infants <3 months:

  • IM, IV: 15 mg per kg per dose two times a day.

• Infants ≥3 months and Children:

  • IM, IV: 15 mg per kg per dose two times a day;
  • The maximum single dose: 500 mg per dose

• Adolescents:

  • IM, IV: 1,000 mg once in a day.

Ertapenem (INVanz) Dose in the Surgical prophylaxis:

• Children and Adolescents:

  • IV: 15 mg per kg 60 minutes before the procedure;
  • The maximum dose: 1,000 mg.

Ertapenem (INVanz) Dose in the treatment of Urinary tract infections (including pyelonephritis):

Note: Duration includes a possible switch to appropriate oral therapy after at least 3 days of parenteral treatment, once clinical improvement demonstrated.

• Infants <3 months:

  • IM, IV: 15 mg per kg per dose twice daily.

• Infants ≥3 months and Children:

  • IM, IV: 15 mg per kg per dose twice daily for 10 to 14 days;
  • The maximum single dose: 500 mg/dose

• Adolescents:

  • IM, IV: 1,000 mg once in a day for 10 to 14 days

Ertapenem (INVanz) Pregnancy Risk Category: B

• Ertapenem has been approved for treatment of postpartum septic abortion and postsurgical infections.
• It could be used as an alternative to antibiotics in the treatment for intraamniotic infections.

Ertapenem use during breastfeeding:

• It can be found in breast milk.
• When ertapenem was calculated from the highest concentration of breast milk, its relative infant dose (RID), is less than 1%. This is compared to a maternal weight-adjusted dose of 1 g per days.
• When the RID of medication falls below 10 percent, breastfeeding is generally acceptable.
• The RID of Ertapenem was calculated with a milk content of 0.38 mg per mL. This gives an estimated daily infant dose via breastmilk of 57 mg per kg.
• The milk concentration was determined after maternal administration of ertapenem 1g IV to five lactating mothers at 5-14 days postpartum.
• The milk concentrations were determined randomly 5 days after the last dose.
• Within 24 hours, the milk concentration ranged between 0.13 mcg/mL (lower limit for quantitation) and 0.38 mcg/mL.
• The peak concentrations of the substances were not measured.
• Four women did not test positive for Ertapenem, and one woman tested positive for it in her milk on day 5.
• Breast milk antibiotics can cause non-dose-related changes in the bowel flora.
• According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks to infants and the benefits to mothers.
• Monitor infants for GI disorders, such as thrush and diarrhea (WHO 2002).

Ertapenem (INVanz) Dose in Kidney Disease:

• CrCl >30 mL/minute/1.73 m²:

  • No dosage adjustment is required.

• CrCl ≤30 mL/minute/1.73 m² and ESRD:

  • 500 mg per 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 once in a day.

Ertapenem (INVanz) Dose in Liver disease:

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

Common Side Effects of Ertapenem (INVanz):

• Gastrointestinal:

  • Diarrhea

Less Common Side Effects of Ertapenem (INVanz):

• Cardiovascular:

  • Edema
  • Chest Pain
  • Phlebitis
  • Thrombophlebitis
  • Hypotension

• Central Nervous System:

  • Headache
  • Altered Mental Status
  • Insomnia
  • Dizziness
  • Hypothermia

• Dermatologic:

  • Diaper Rash
  • Skin Rash
  • Pruritus
  • Genital Rash
  • Skin Lesion

• Gastrointestinal:

  • Vomiting
  • Nausea
  • Abdominal Pain
  • Constipation
  • Decreased Appetite

• Genitourinary:

  • Erythrocyturia
  • Vaginitis

• Hematologic & Oncologic:

  • Thrombocythemia
  • Decreased Neutrophils
  • Decreased Hemoglobin
  • Decreased Hematocrit
  • Leukocyturia
  • Leukopenia
  • Eosinophilia

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST
  • Increased Serum Alkaline

• Infection:

  • Herpes Simplex Infection

• Local:

  • Infused Vein Complication

• Neuromuscular & Skeletal:

  • Arthralgia

• Otic:

  • Otic Infection

• Respiratory:

  • Cough
  • Dyspnea
  • Nasopharyngitis
  • Rhinitis
  • Rhinorrhea
  • Upper Respiratory Tract Infection
  • Wheezing

• Miscellaneous:

  • Fever

Contraindications to Ertapenem (INVanz):

Patients who have anaphylactic reactions to beta -lactams or are known to be hypersensitive to any component of the product, or other drugs in this same class; Hypersensitivity to local anesthetics, amide-type, has been documented due to the use lidocaine (IM only).

Warnings and precautions

• Anaphylaxis or hypersensitivity reactions

  • There have been reports of severe hypersensitivity reactions including anaphylaxis (some with no history of allergic reactions to beta-lactams).

• CNS effects

  • Carbapenems have been linked to CNS adverse effects such as confusional states and seizures (myoclonic).
  • CNS disorders, such as brain lesions or history of seizures, should be treated with caution. To avoid drug accumulation and increase seizure risk, adjust the dose for renal impairment.

• Superinfection

  • You may get fungal or bacterial superinfections, such as C. difficile associated diarrhea (CDAD), and pseudomembranous collitis.
  • CDAD was observed for over 2 months after post-antibiotic treatment.

• Renal impairment

  • Patients with impaired renal function should be cautious. Dosage adjustment is required for patients with severe to moderate renal dysfunction.
  • Patients with renal dysfunction have been shown to be at greater risk of seizure.

Ertapenem: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)
BCG Vaccine (Immunization)	Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization).
Lactobacillus and Estriol	Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol.
Probenecid	May increase the serum concentration of Ertapenem.
Tacrolimus (Systemic)	Ertapenem may increase the serum concentration of Tacrolimus (Systemic).
Risk Factor D (Consider therapy modification)
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.
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.
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.
Risk Factor X (Avoid combination)
BCG (Intravesical)	Antibiotics may diminish the therapeutic effect of BCG (Intravesical).
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.

Monitoring parameters:

• Liver functions,
• Periodic renal and hematopoietic assessment during prolonged therapy;
• neurological assessment

How to administer Ertapenem (INVanz)?

IM:

• Avoid injection into a blood vessel.
• Make sure the 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

Mechanism of action of Ertapenem (INVanz):

• By binding to penicillin-binding proteins, inhibits bacterial cell wall formation.
• This in turn inhibits the final step of peptidoglycan synthesis in bacterial cells walls.
• Bacteria eventually lyse because of the continuing activity of cell wall enzymes (mureinhydrlases and autolysins), while cell wall assembly is stopped.

Absorption:

• IM: Almost complete

Distribution: V :

• Infants ≥3 months and Children: ~0.2 L per kg
• Adolescents 13 to 17 years: ~0.16 L per kg
• Adults: ~0.12 L per kg

Protein binding (concentration-dependent, primarily to albumin):

• 85 percent  at 300 mcg per mL, 95 percent  at less than 100 mcg per mL

Metabolism:

• Non-CYP-mediated hydrolysis to inactive metabolites

Bioavailability:

• IM: ~90 percent

Half-life elimination:

• Infants ≥3 months and Children: ~2.5 hours
• Adolescents and Adults: ~4 hours

Time to peak: IM:

• ~2.3 hours

Excretion:

• Urine (~80% as unchanged drug and metabolite);
• feces (~10%)

International Brands of Ertapenem:

• Etropen
• INVanz

Ertapenem Brand Names in Pakistan:

Ertapenem Injection 1 g
Invanz	OBS (Searle)