Imipenem-cilastatin-relebactam photo: source credit Merck
KEY POINTS
- Imipenem-cilastatin-relebactam (Recarbrio) is the combination of three molecules…
- Imipenem is a carbapenem and beta-lactam antibiotic that inhibits bacterial cell wall synthesis through binding to penicillin binding proteins
- Cilastatin is a dehydropeptidase-I (DHP-I) inhibitor that prevents inactivation of imipenem by renal DHP-I
- Has no antibacterial activity
- Relebactam is a class A/C beta-lactamase inhibitor
- Previously named MK-7655 during drug development
- FDA-approved July 17th, 2019 in patients 18 years and older with limited or no treatment options. Current approvals include:
- Complicated urinary tract infection, including pyelonephritis
- Complicated intra-abdominal infections
- Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP)
- Imipenem-cilastatin (Primaxin) has been available for decades, but imipenem-cilastatin-relebactam is a new product
- Is the first FDA-approved product to include relebactam
- Relebactam can restore the activity of imipenem-cilastatin in resistant organisms, including some carbapenem-resistant Klebsiella and Pseudmonas
- Is the first FDA-approved product to include relebactam
- Imipenem-cilastatin-relebactam should be reserved for patients who have infection with drug-resistant bacteria
- Dose as 1.25 grams (imipenem 500 mg, cilastatin 500 mg, relebactam 250 mg) IV every 6 hours, administered over 30 minutes
- Adjust doses downwards in patients with CrCl below 90 mL/min
- Not recommended in CrCl below 15 mL/min if dialysis not started within 48 hours
- Product maintains potency for 2 hours at room temperature and 24 hours under refrigeration
- Beware potential seizures and central nervous reactions
- Consider avoiding use for patients on ganciclovir since generalized seizures have been reported
- Avoid use in patients on valproic acid (VPA) or divalproex sodium since a reduction in VPA levels may lead to seizures
- The most common side effects in clinical trials were: diarrhea, nausea, headache, vomiting, alanine aminotransferase increased, aspartate aminotransferase increased, phlebitis/infusion site reactions, pyrexia, and hypertension
- RECARBRIO –> RE (relebactam) – CARB (carbapenem) – RIO (trio of molecules)
- Thanks @ABsteward!
RESOURCES
- Recarbrio package insert
- FDA news release for imipenem-cilastatin-relebactam approval
- Defining the Role of Novel β-Lactam Agents That Target Carbapenem-Resistant Gram-Negative Organisms
- RESTORE-IMI trial description
- In Vitro Activity of MK-7655, a Novel β-Lactamase Inhibitor, in Combination with Imipenem against Carbapenem-Resistant Gram-Negative Bacteria
- Phase 2, Dose-Ranging Study of Relebactam with Imipenem-Cilastatin in Subjects with Complicated Intra-abdominal Infection
- In Vitro Activity of Imipenem–Relebactam against Gram-Negative ESKAPE Pathogens Isolated by Clinical Laboratories in the United States in 2015 (Results from the SMART Global Surveillance Program)
- Prospective, randomized, double-blind, Phase 2 dose-ranging study comparing efficacy and safety of imipenem/cilastatin plus relebactam with imipenem/cilastatin alone in patients with complicated urinary tract infection
- Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of Relebactam, a β-Lactamase Inhibitor, in Combination with Imipenem and Cilastatin in Healthy Participants
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