Version May 2024
Dosage guidance:
Dosing: Dosage recommendations are expressed as grams of meropenem/vaborbactam combination.
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms): Note: Reserve for patients with or at risk for extensively drug-resistant pathogens (nonsusceptible to ≥1 agent in all but 2 or fewer antimicrobial classes) (eg, carbapenem-resistant Enterobacterales) (Ref).
IV: 4 g every 8 hours. Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days and depends on clinical response and the antimicrobial chosen to complete the regimen (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Estimation of renal function for the purpose of meropenem/vaborbactam dosing may be done using the Modification of Diet in Renal Disease (MDRD) formula (manufacturer's labeling). Dosage recommendations are expressed as grams of meropenem/vaborbactam combination.
Altered kidney function:
eGFR ≥50 to 130 mL/minute/1.73 m2: IV: No dosage adjustment necessary.
eGFR 30 to 49 mL/minute/1.73 m2: IV: 2 g every 8 hours.
eGFR 15 to 29 mL/minute/1.73 m2: IV: 2 g every 12 hours.
eGFR <15 mL/minute/1.73 m2: IV: 1 g every 12 hours.
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV: 4 g every 8 hours (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (meropenem: 38%; vaborbactam: 53%) (Ref):
IV: 1 g every 12 hours; when scheduled doses fall on dialysis days, administer one of the two doses after the hemodialysis session (Ref).
Peritoneal dialysis: Likely to be dialyzable (low Vd, low protein binding) (Ref):
IV: 1 g every 12 hours (Ref).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions (eg, CNS effects including seizures) due to drug accumulation is important.
IV: 2 g every 8 hours (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions (eg, CNS effects including seizures) due to drug accumulation is important.
IV: 2 g every 12 hours; when scheduled doses fall on PIRRT days, administer one of the two doses after PIRRT session (Ref).
There are no dosage adjustments provided in the manufacturer's labeling. However, dosage adjustment unlikely because hepatic disease does not affect pharmacokinetics of meropenem and vaborbactam does not undergo hepatic elimination.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reactions may not be exclusive to meropenem and vaborbactam. Some patients in this study were switched to levofloxacin after 15 doses of meropenem and vaborbactam.
Also see Meropenem.
1% to 10%:
Cardiovascular: Phlebitis (≤4%)
Central nervous system: Headache (9%)
Endocrine & metabolic: Hypokalemia (1%)
Gastrointestinal: Diarrhea (3%), nausea (2%)
Hepatic: Increased serum ALT (2%), increased serum AST (2%)
Hypersensitivity: Hypersensitivity (2%)
Local: Infusion site reaction (≤4%)
Miscellaneous: Fever (2%)
Frequency not defined: Gastrointestinal: Clostridioides difficile-associated diarrhea
<1%, postmarketing, and/or case reports: Azotemia, chest discomfort, decreased appetite, deep vein thrombosis, dizziness, hallucination, hyperglycemia, hyperkalemia, hypoglycemia, hypotension, increased creatine phosphokinase, insomnia, lethargy, leukopenia, oral candidiasis, paresthesia, pharyngitis, renal impairment, tremor, vulvovaginal candidiasis
Hypersensitivity to meropenem, vaborbactam, other carbapenems or beta-lactamase inhibitors, or any component of the formulation; patients who have demonstrated anaphylactic reactions to beta-lactam antibacterial agents
Concerns related to adverse effects:
• Hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis and serious skin reactions, have been reported with beta-lactam antibacterial agents. Risk may be increased in patients with history of sensitivity to multiple allergens; inquire about previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactam antibacterials, and other allergens prior to treatment initiation. Discontinue use if an allergic reaction occurs.
• CNS effects: Associated with CNS adverse effects, including seizures; use with caution in patients with CNS disorders (eg, brain lesions, history of seizures) or with bacterial meningitis and/or compromised renal function. Closely adhere to recommended dosing, especially in patients with risk factors for seizures. Patients who develop focal tremors, myoclonus, or seizures should undergo neurological evaluation and may require dosage adjustment or discontinuation of treatment. Outpatient use may result in paresthesias, seizures, delirium and/or headaches that can impair neuromotor function and alertness; patients should not operate machinery or drive until it is established that meropenem and vaborbactam is well tolerated.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required in patients with creatinine clearance <50 mL/minute. Increased seizure risk and thrombocytopenia have been reported in patients with renal impairment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Vabomere: 2 g: Meropenem 1 g and vaborbactam 1 g (1 ea)
No
Solution (reconstituted) (Vabomere Intravenous)
2 (1-1) g (per each): $259.20
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IV: Administer by IV infusion over 3 hours.
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms): Treatment of complicated urinary tract infection, including pyelonephritis, caused by susceptible Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae species complex in patients ≥18 years of age.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Management: Avoid use of fexinidazole with OAT1/3 substrates when possible. If combined, monitor for increased OAT1/3 substrate toxicities. Risk D: Consider therapy modification
Hormonal Contraceptives: Vaborbactam may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing meropenem/vaborbactam to ensure contraceptive reliability. Risk D: Consider therapy modification
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Leflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Nitisinone: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
OAT1/3 Substrates (Clinically Relevant): Vaborbactam may increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Pretomanid: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Meropenem. Risk X: Avoid combination
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Taurursodiol: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk X: Avoid combination
Teriflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vaborbactam: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Valproate Products: Carbapenems may decrease the serum concentration of Valproate Products. Management: Concurrent use of carbapenem antibiotics with valproic acid is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional anti-seizure medication. Risk D: Consider therapy modification
The effectiveness of hormonal contraceptives may be reduced when used with meropenem/vaborbactam. An alternative nonhormonal contraceptive or additional contraceptive method (eg, barrier method) is recommended during treatment. Consult drug interactions database for more detailed information specific to use of meropenem/vaborbactam and specific contraceptives.
Animal reproduction studies have not been conducted with this combination; adverse events were observed in animal reproduction studies following administration of the vaborbactam component.
Also refer to the meropenem monograph for additional information.
Meropenem is present in breast milk; excretion of vaborbactam is not known.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother
Also refer to the meropenem monograph for additional information.
Some products may contain sodium.
Monitor for signs of hypersensitivity reaction, including anaphylaxis and serious skin reactions. Periodically monitor renal function; in patients with changing renal function, monitor serum creatinine and eGFR at least daily.
Meropenem: Inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins, which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis; bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested
Vaborbactam is a beta-lactamase inhibitor that protects meropenem from degradation by certain serine beta-lactamases (eg, K. pneumonia carbapenemase [KPC]). Vaborbactam does not have antibacterial activity.
Distribution: Vd: Meropenem: 20.2 L; Vaborbactam: 18.6 L
Protein binding: Meropenem: ~2%; Vaborbactam: ~33%
Metabolism: Meropenem: Hydrolysis of beta-lactam bond to open lactam form (minor); Vaborbactam: Not metabolized
Half-life elimination: Meropenem: 1.22 hours; Vaborbactam: 1.68 hours
Excretion: Meropenem: Urine (40% to 60% [unchanged]; 22% inactive hydrolysis product); feces (~2%); Vaborbactam: Urine (75% to 95% [unchanged])
Altered kidney function: Meropenem AUC ratios to subjects with normal renal function are 1.28, 2.07, and 4.63 for subjects with mild (eGFR 60 to 89 mL/minute/1.73 m2), moderate (eGFR 30 to 59 mL/minute/1.73 m2), and severe (eGFR <30 mL/minute/1.73 m2) renal impairment, respectively. Vaborbactam AUC ratios to subjects with normal renal function are 1.18, 2.31, and 7.8 for subjects with mild, moderate, and severe renal impairment, respectively. Vaborbactam exposure was high in subjects with end-stage renal disease and higher when administered after dialysis than when administered before.
Anti-infective considerations:
Parameters associated with efficacy:
Meropenem: See Meropenem monograph.
Vaborbactam (in combination with meropenem):
AUC, associated with free 24-hour AUC (fAUC24) of vaborbactam to meropenem-vaborbactam minimum inhibitory concentration (MIC) ratio.
Enterobacterales, including KPC-producing strains (eg, E. coli, K. pneumoniae): Vaborbactam fAUC24/meropenem-vaborbactam MIC: Goal: 18 (1-log kill), 25 (2-log kill), 36 (3-log kill), ≥24 (prevention of resistance) (Griffith 2018).
Expected drug exposure in normal renal function:
Adults: IV (3-hour infusion): Multiple doses (steady state):
Cmax (peak):
Meropenem 2 g/vaborbactam 2 g every 8 hours: Meropenem: 43.4 ± 8.8 to mg/L; vaborbactam: 55.6 ± 11 mg/L.
AUC24:
Meropenem 2 g/vaborbactam 2 g every 8 hours: Meropenem: 414 mg•hour/L; vaborbactam: 588 mg•hour/L.
Postantibiotic effect: See Meropenem monograph.
Parameters associated with toxicity: See Meropenem monograph.
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