Recarbrio (Imipenem, cilastatin, and relebactam) is a combination of three drugs - a novel beta-lactamase inhibitor RELEBACTAM and two old drugs imipenem and cilastatin. Relebactam is the third among the novel beta-lactamase inhibitors. The first two are avibactam and vaborbactam. It reduces the MIC of non-susceptible organisms by 128-folds [Ref].

Recarbrio (Imipenem, cilastatin, and relebactam) Indications:

• Complicated Intra-abdominal infection:

  • It is recommended for patients 18 years of age and older who have few other treatment options for serious intra-abdominal infections brought on by the sensitive gram-negative germs listed below:
    • Bacteroides caccae,
    • Bacteroides fragilis,
    • Bacteroides ovatus,
    • Bacteroides thetaiotaomicron,
    • Bacteroides uniformis,
    • Bacteroides vulgatus,
    • Bifidobacterium stercoris,
    • Citrobacter freundii,
    • Enterobacter cloacae,
    • Escherichia coli,
    • Fusobacterium nucleatum,
    • Klebsiella aerogenes,
    • Klebsiella oxytoca,
    • Klebsiella pneumoniae,
    • Parabacteroides distasonis, and
    • Pseudomonas aeruginosa.

• Complicated Urinary tract infection (including pyelonephritis):

  • It is recommended for patients 18 years of age and older who have few other treatment options for serious urinary tract infections (including pyelonephritis) brought on by the susceptible gram-negative pathogens listed below.
    • E. cloacae,
    • E. coli,
    • K. aerogenes,
    • K. pneumoniae, and
    • P. aeruginosa.

Recarbrio ( Imipenem, cilastatin, and relebactam) dose in Adults:

Note: The total amount of imipenem, cilastatin, and relebactam is how doses are expressed.

Recarbrio Dose in the treatment of complicated Intra-abdominal infections:

• 1.25 g intravenously four times a day (6-hourly).
• The usual total duration of the treatment after adequate control of the source infection is 4 to 7 days.
• Patients who are not managed with proper surgical debridement or drainage of any collection may require a longer duration of treatment.

Recarbrio Dose in the treatment of complicated Urinary tract infections (including pyelonephritis):

• 1.25 g intravenously every 6 hours.
• The duration of therapy ranges from 5 - 14 days.

Recarbrio ( Imipenem, cilastatin, and relebactam) use in children:

It has not been studied in children.

Recarbrio Pregnancy Risk Category: C

• Relebactam was not studied during pregnancy.
• Refer to imipenem/cilastatindrug details.

Use of imipenem, Cilastatin, or relebactam during breastfeeding

• It is unknown whether breastmilk contains relebactam.
• Refer to imipenem/cilastatindrug details in lactating women.

Recarbrio Dose in Renal Disease:

Note:

Prior to treatment initiation, eGFR should be calculated using the Cockcroft-Gault formula. Doses mentioned here are expressed as the combined amount of imipenem, cilastatin, and relebactam.

• CrCl ≥ 90 mL/minute:

  • Adjustment in the dose is not necessary.

• CrCl 60 to 89 mL/minute:

  • 1 g four times a day (6-hourly)

• CrCl 30 to 59 mL/minute:

  • 750 mg four times a day (6-hourly)

• CrCl 15 to 29 mL/minute:

  • 500 mg four times a day (6-hourly)

• CrCl <15 mL/minute:

  • If hemodialysis is not anticipated within 48 hours of the drug administration, avoid using it.

• End-stage renal disease on hemodialysis:

  • Four times each day, 500 mg (6-hourly)
  • The dosage should be given at intervals spaced apart from the conclusion of the hemodialysis session and beyond.

• Peritoneal dialysis:

  • Data is limited. Avoid using it in patients on peritoneal dialysis.

Dose in liver disease:

• Liver disease may not have any effect on drug clearance or drug exposure.
• The manufacturer has not recommended any adjustments in the dose in patients with liver disease.

Side Effects of Recarbrio (Imipenem, cilastatin, and relebactam):

• Cardiovascular:

  • Phlebitis

• Central nervous system:

  • Headache

• Gastrointestinal:

  • Diarrhea
  • Vomiting

• Hepatic:

  • Increased serum alanine aminotransferase
  • Increased serum aspartate aminotransferase

• Local:

  • Erythema at the injection site
  • Infusion site pain

• Miscellaneous:

  • Fever

Uncommon side effects of Recarbrio:

• Gastrointestinal:

  • Clostridioides difficile associated diarrhea

Contraindications to Recarbrio (Imipenem, cilastatin, and relebactam) Include:

• You may have severe allergic reactions to the drug or the individual drug, or any component.
• It is possible that cross-reactions with other drugs, such as penicillin or other beta-lactams anti-biotics, may be a factor.

Warnings and precautions

• CNS effects

  • Use of carbapenems has been linked to neurological disorders such as seizures, confessional states, psychiatric problems, and other adverse neurological conditions.
  • Patients with an underlying neurological condition such as a brain tumor or a history seizures should be cautious about taking the drug.
  • To avoid drug accumulation, dosage reduction may be necessary according to creatinine clearance.

• Hypersensitivity reactions

  • There have been reports of severe allergic responses, including anaphylaxis, when using cilastatin and other beta-lactam inhibitors.
  • It is crucial to elicit from patients their prior experiences with penicillins, carbapenems, cephalosporins, and other beta-lactams.
  • If a reaction is observed, the treatment must be stopped immediately and continued.

• Superinfection

  • Extended use of antibiotics, including Recarbrio, may lead to fungal and bacterial overinfection.
  • Clostridium difficile-associated diarrhea (CDAD), is more likely if antibiotics are taken for longer periods of time.

• Renal impairment

  • Patients with a CrCl below 15 ml/minute should not use it unless hemodialysis plans are made within 48 hours.
  • Patients with a CrCl greater than 15 mg/minute will need to adjust their dose according to their CrCl.
  • Patients with kidney dysfunction are more at risk for seizures.

Imipenem, cilastatin, and relebactam: Drug Interaction

Monitor:

Observe the patient for hypersensitivity reaction including anaphylaxis. Monitor renal functions.

How to administer Recarbrio (Imipenem, cilastatin, and relebactam)?

It is administered as an intravenous infusion over 30 minutes.

Mechanism of action of Recarbrio (Imipenem, cilastatin, and relebactam):

Imipenem: Imipenem inhibits penicillin-binding protein synthesis and disrupts the synthesis in bacterial cells. It does this by binding to PBP 2B and PBP 1B.

Cilastatin: Cilastatin prolongs half-life by inhibiting the renal metabolism imipenem. It inhibits renal dehydropeptidase.

Relebactam: Relebactam, a beta-lactamase inhibitor that stops the degradation of imipenem via serine beta-lactamases, is known as "Relebactam". 

These include:

• Sulhydryl Variable,
• Temoneira,
• Cefotaximase-Munich,
• E. cloacae P99,
• Pseudomonas-derived cephalosporinase, and
• Klebsiella-pneumoniae carbapenemase.

Protein binding:

• Imipenem: 20%; cilastatin: 40%; relebactam: 22%.

Metabolism:

• Imipenem is metabolized by dehydropeptidase I in the kidneys. Cilastatin inhibits dehydropeptidase I preventing the metabolism of imipenem. Relebactam is minimally metabolized.

Half-life elimination of Imipenem is 1 hour and that of relebactam is 1.2 hours.

Excretion:

• It is excreted in the Urine (primarily as unchanged drug: imipenem: ~63%; cilastatin: ~77%; relebactam: >90%).

International Brands of Imipenem, cilastatin, and relebactam:

• Recarbrio

Imipenem, cilastatin, and relebactam brands in Pakistan:

No Brands Available in Pakistan.