RECARBRIO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RECARBRIO (RECARBRIO).
RECARBRIO (imipenem, cilastatin, and relebactam) combines imipenem, a carbapenem antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), with cilastatin, a renal dehydropeptidase inhibitor that prevents renal metabolism of imipenem, and relebactam, a beta-lactamase inhibitor that inhibits class A and class C beta-lactamases, thereby restoring imipenem activity against resistant bacteria.
| Metabolism | Imipenem is metabolized by renal dehydropeptidase (DHP-I) in the kidneys; cilastatin inhibits this enzyme to increase imipenem half-life. Relebactam is minimally metabolized, with about 90% excreted unchanged in urine. |
| Excretion | Renal elimination: imipenem 60-75% unchanged, cilastatin 70-80% unchanged; relebactam 60-75% unchanged. Fecal/biliary: minor (<5% each). |
| Half-life | Imipenem: 0.8-1 hour; cilastatin: 0.8-1 hour; relebactam: 1.2-1.5 hours. Extended in renal impairment (CrCl <30 mL/min). |
| Protein binding | Imipenem: ~20%; cilastatin: 40-45%; relebactam: ~22%. Primarily albumin. |
| Volume of Distribution | Imipenem: 0.23-0.31 L/kg (distributes into interstitial fluid); cilastatin: 0.2-0.3 L/kg; relebactam: 0.2-0.3 L/kg. Suggests low tissue penetration. |
| Bioavailability | Not applicable (IV only). |
| Onset of Action | IV: Immediate (peak plasma concentrations achieved by end of 30-min infusion). |
| Duration of Action | Dosing interval: 6 hours for normal renal function; prolonged interval in renal impairment. |
1.25 g (imipenem 500 mg + cilastatin 500 mg + relebactam 250 mg) intravenously every 6 hours over 30 minutes.
| Dosage form | POWDER |
| Renal impairment | CrCl ≥90 mL/min: 1.25 g IV every 6 hours; CrCl 60-89: 1 g IV every 6 hours; CrCl 30-59: 500 mg IV every 6 hours; CrCl 15-29: 500 mg IV every 8 hours; CrCl <15 not on hemodialysis: not recommended; hemodialysis: 500 mg IV every 12 hours, on dialysis days administer after session. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); use with caution. |
| Pediatric use | Safety and efficacy not established in pediatric patients <18 years. |
| Geriatric use | No specific dose adjustment beyond renal function; monitor renal function closely and adjust dose based on creatinine clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RECARBRIO (RECARBRIO).
| Breastfeeding | Unknown if distributed in human milk; no M/P ratio available. Consider benefits of breastfeeding and mother's need for drug. |
| Teratogenic Risk | No adequate human data; animal studies show no fetal harm at clinically relevant exposures. Risk cannot be ruled out; use only if maternal benefit justifies potential fetal risk. |
| Fetal Monitoring | Standard monitoring for infection resolution; no specific fetal monitoring required. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to imipenem, cilastatin, relebactam, or any component of the formulation","History of anaphylactic reaction to beta-lactam antibiotics (penicillins, cephalosporins, carbapenems)"]
| Precautions | ["Hypersensitivity reactions including anaphylaxis in patients with beta-lactam allergy","Seizures and other CNS adverse reactions, including confusional states and myoclonus, especially in patients with renal impairment or pre-existing CNS disorders","Clostridioides difficile-associated diarrhea (CDAD)","Development of drug-resistant bacteria","Reduced efficacy in patients with renal impairment; dose adjustment required"] |
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| Fertility Effects | No human data on fertility; animal studies show no impairment of fertility at clinically relevant doses. |