A member of the Carbapenem family of antibiotics, ertapenem (INVanz) is a broad-spectrum drug. Serious infections of the vaginal tract, pelvis, abdomen, bones, and joints are all treated with it.

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:

    • Infections of the skin and skin structure that are difficult to cure, such as diabetic foot infections that don't result in osteomyelitis,:
      • 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.
    • There are no studies on ertapenem for concurrent osteomyelitis and diabetic foot infections.

  • Complicated urinary tract infections:

    • Utilised to treat complex urinary tract infections (UTIs), such as pyelonephritis brought on by:
      • E. coli, including instances where bacteremia is also present, or K. pneumoniae.

  • Prophylaxis of surgical-site infection in colorectal surgery:

    • used to prevent surgical site infections after elective colorectal surgery in adults.

Note:

• Methicillin-resistant Ertapenem is not effective against most extended-spectrum beta-lactamase (ESBL)-producing bacteria, but it is effective against penicillin-resistant strains of Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus spp., Acinetobacter, and Pseudomonas aeruginosa.

• 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:
  • For community-acquired, mild to severe intra-abdominal infections, 2010 IDSA guidelines suggest a treatment period of 4 to 7 days (given source controlled).

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 given once daily for 5–7 days together with a macrolide as part of 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:
  • Depending on the severity of the infection and the patient's response to treatment, a recommended course of treatment for diabetic foot infections can last up to 4 weeks.

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 each day for four to six weeks.

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

• IV: For the first treatment of polymicrobial (mixed) infections, administer 1 g once daily in conjunction with an MRSA-fighting medication (vancomycin, daptomycin, or linezolid, for example).
• Continue until no more debridement is necessary, the patient has shown improvement in their clinical condition, and they have been asymptomatic 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 one time 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 Children

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: According to IDSA standards, mild to moderate infections acquired in the community should be treated for 4 to 7 days (assuming the source is under control).

• 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 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 one time a day for 3 to 10 days

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

Note: Once clinical improvement has been seen for at least three days of parenteral treatment, it may be time to move to an appropriate oral step-down medication.

• 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.
• Use an MRSA-effective medication (such as vancomycin, daptomycin, or linezolid) in conjunction with a necrotizing infection for initial treatment of polymicrobial (mixed) infections.
• Continue until no more debridement is required, the patient has shown improvement in their clinical condition, and the patient has been asymptomatic 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 may include a transition to suitable oral therapy following at least 3 days of parenteral therapy, once clinical improvement is evident.

• 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 the treatment of postoperative infections and septic postpartum abortion.
• In the treatment of intraamniotic infections, it might be used instead of antibiotics.

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.
• Ertapenem's RID was computed using milk with a concentration of 0.38 mg per mL. This results in an estimated 57 mg per kg daily newborn dosage when given through breastmilk.
• 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:

  • Dosage adjustment is not required.

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

  • 500 mg per day.

• Hemodialysis:

  • A supplement dosage of 150 mg is needed after hemodialysis when the daily dose is administered within 6 hours of the procedure.
  • Ertapenem doesn't require a second dosage if it is administered at least 6 hours before hemodialysis.

• 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):

Individuals who have previously experienced anaphylactic reactions to beta-lactams or who are known to be hypersensitive to any ingredient in the product or other medications in the same class; Due to the use of lidocaine, amide-type local anaesthetic hypersensitivity has been described (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

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: