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 indicated for the treatment of complicated intra-abdominal infections caused by the following susceptible gram-negative microorganisms in patients 18 years of age or older who have limited alternative options:
    • 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 indicated for the treatment of complicated urinary tract infections (including pyelonephritis) caused by the following susceptible gram-negative organisms in patients 18 years of age and older who have limited alternative options.
    • E. cloacae,
    • E. coli,
    • K. aerogenes,
    • K. pneumoniae, and
    • P. aeruginosa.

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

Note: Doses are expressed as the combined amount of imipenem, cilastatin, and relebactam.

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:

  • Avoid its use unless hemodialysis is planned within 48 hours after the administration of the drug.

• End-stage renal disease on hemodialysis:

  • 500 mg four times a day (6-hourly)
  • The dose should be administered after hemodialysis and at intervals timed from the end of that hemodialysis session.

• 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

  • With the use of cilastatin and other beta-lactam inhibitors, severe allergic reactions, including anaphylaxis, have been reported.
  • It is important to ask patients about their past reactions to penicillins and carbapenems, cephalosporins or 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.