Meropenem + Vaborbactam

Indications

Meropenem + Vaborbactam is used for: Urinary Tract Infections

Adult Dose

Urinary Tract Infections Indicated for complicated urinary tract infections (cUTIs), including pyelonephritis caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae species complex in adults ?18 years 4 g (meropenem [2g]/vaborbactam [2g]) IV q8hr for up to 14 days; infuse over 3 hr

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Renal impairment Treatment duration for all doses: Up to 14 days eCrCl >50 mL/min/1.73²: No dosage adjustment necessary eCrCl 30-49 mL/min/1.73²: 2 g (meropenem [1g]/vaborbactam [1g]) IV q8hr eCrCl 15-29 mL/min/1.73²: 2 g (meropenem [1g]/vaborbactam [1g]) IV q12hr eCrCl <15 mL/min/1.73²: 1 g (meropenem [0.5g]/vaborbactam [0.5g]) IV q12hr Dose adjustments for renal impairment should be administered after hemodialysis session

Administration

IV Preparation Reconstitute with 20 mL of 0.9% NaCl per vial; and then further dilute Mixed gently to dissolve; reconstituted solution concentration equals 0.05 g/mL (meropenem) and 0.05 g/mL (vaborbactam) Reconstituted solution must be immediately diluted further in a 0.9% NaCl infusion bag After dilution, final infusion concentration of meropenem/vaborbactam should be 2-8 mg/mL Visually inspect the diluted solution for particulate matter and discoloration prior to administration (the infusion solution for administration should appear colorless to light yellow); discard unused portion after use See prescribing information for further information IV Administration Infuse diluted solution IV over 3 hr Infusion must be completed within 4 hr if stored at room temperature or 22 hr if stored refrigerated at 2-8°C (36-46°F)

Contra Indications

Hypersensitivity to any components of meropenem/vaborbactam, other carbapenem drugs, or patients who have demonstrated anaphylactic reactions to beta-lactam antibacterial drugs

Precautions

Hypersensitivity reactions reported; inquire about previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactam antibacterial drugs, and other allergens prior initiating treatment; if an allergic reaction occurs, discontinue meropenem/vaborbactam immediately; see Contraindications Thrombocytopenia may occur in renally impaired patients; no clinical bleeding has been reported Potential for neuromotor impairment; alert outpatients regarding possible adverse reactions (eg, seizures, delirium, headaches, paresthesias) that could interfere with mental alertness and/or cause motor impairment; advise patients not to operate machinery or motorized vehicles To reduce the development of drug-resistant bacteria and to maintain the effectiveness, only prescribe to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria Prolonged use may result in overgrowth of nonsusceptible organisms; repeat evaluation; if superinfection does occur during therapy, appropriate measures should be taken

Pregnancy-Lactation

Pregnancy Human data are insufficient to establish a drug-associated risk of major birth defects or miscarriages with meropenem/vaborbactam in pregnant women Malformations (supernumerary lung lobes, interventricular septal defect) were observed in offspring from pregnant rabbits administered vaborbactam IV during the organogenesis period at doses approximately equivalent to or above the maximum recommended human dose (MRHD) based on plasma AUC comparison; uncertain whether malformations are clinically relevant; no similar malformations or fetal toxicity were observed in offspring from pregnant rats administered vaborbactam IV during organogenesis or from late pregnancy through lactation at a dose equivalent to ~1.6 times the MRHD based on body surface area (BSA) comparison Lactation Meropenem reported to be excreted in human milk; unknown whether vaborbactam is excreted in human milk No information is available on the effects of meropenem/vaborbactam on the breastfed child or on milk production The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for meropenem/vaborbactam and any potential adverse effects on the breastfed child from meropenem/vaborbactam or from underlying maternal condition

Interactions

Probenecid competes with meropenem for active tubular secretion, resulting in increased plasma concentrations of meropenem; coadministration with probenecid is not recommended Concomitant use of meropenem/vaborbactam with valproic acid and divalproex sodium is generally not recommended; case reports have shown that coadministration of carbapenems (eg, meropenem) to patients receiving valproic acid or divalproex sodium results in decreased valproic acid concentrations

Adverse Effects

Side effects of Meropenem + Vaborbactam : 1-10% Headache (8.8%) Phlebitis/infusion site reactions (4.4%) Diarrhea (3.3%) Hypersensitivity (1.8%) Nausea (1.8%) Increased ALT (1.8%) Increased AST (1.5%) Pyrexia (1.5%) Hypokalemia (1.1%) >1% Leukopenia Chest discomfort Pharyngitis Vulvovaginal candidiasis Oral candidiasis Creatinine phosphokinase increase Decreased appetite Hyperkalemia Hyperglycemia Hypoglycemia Dizziness Tremor Paresthesia Lethargy Hallucination Insomnia Azotemia Renal impairment Deep vein thrombosis Hypotension Vascular pain

Mechanism of Action

Meropenem: Inhibits bacterial cell wall synthesis by binding to several of the penicillin-binding proteins (PBPs), which, in turn, inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis; bacteria eventually lyse as a result of ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested Vaborbactam: Nonsuicidal beta-lactamase inhibitor that protects meropenem from degradation by certain serine beta-lactamases (eg, Klebsiella pneumoniae carbapenemase [KPC]); vaborbactam does not have any antibacterial activity and does not decrease meropenem activity against meropenem-susceptible organisms