VABOMERE®—restoring the power of meropenem against CRE1

VABOMERE® (meropenem and vaborbactam) combines meropenem, a trusted carbapenem, with vaborbactam, a unique β-lactamase inhibitor (BLI)1

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  • Proven to work against a broad spectrum of gram-negative pathogens2,3
  • Well-established efficacy and safety profile2,3
Vaborbactam
  • First in a new class of cyclic boronic acid BLIs4
  • Covalent bonding to target with extended resident time allowing meropenem to act unhindered5

VABOMERE addresses the challenge of resistant Enterobacterales5

WATCH THE VABOMERE MECHANISM OF ACTION

VABOMERE has a bactericidal effect on designated susceptible gram-negative organisms1

Vaborbactam1:

  • Protects meropenem from degradation by a number of serine β-lactamases
  • Does not have any antibacterial activity itself
  • Does not decrease the activity of meropenem against meropenem-susceptible organisms

Meropenem1:

  • Penetrates the cell wall of most gram-positive and gram-negative bacteria
  • Binds with penicillin-binding protein (PBP) targets
  • Initiates bacterial cell wall rupture and destruction

VABOMERE was specifically designed to be effective against key multidrug-resistant organisms, and has demonstrated no cross-resistance with other classes of antimicrobials.1,6

Meropenem and vaborbactam—designed to work together1

The pharmacokinetics (PK) of vaborbactam are well matched for meropenem1

MEROPENEM PK

Meropenem PK

VABORBACTAM PK

Vaborbactam PK
  • The PK of meropenem and vaborbactam are linear across the dose range studied: 1 g-2 g for meropenem and 0.25 g-2 g for vaborbactam1
  • All evaluated PK measures (Cmax, AUC0-t, and AUC0-inf) were similar for meropenem and vaborbactam alone and meropenem-vaborbactam in combination, indicating that concomitant administration of meropenem and vaborbactam did not affect the plasma PK of either drug7
  • There were no plasma or urine PK drug-drug interactions7

The PK profiles of meropenem and vaborbactam are well matched, and the optimized dosing regimen of VABOMERE leads to target attainment against most commonly encountered CRE.5

Review the microbiologic data

VABOMERE dosing is optimized for strong bactericidal activity8-10

A 3-hour infusion provides optimized PK/PD exposures that lead to enhanced bacterial killing regardless of renal function8-11*†

PK/PD Target Attainment, Enterobacterales isolates11

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PK/PD Target Attainment, KPC-Producing Enterobacterales isolates11

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  • The probability of target attainment exceeds 90% for susceptible MIC breakpoint (4 μg/mL) and intermediate breakpoint (8 μg/mL) in all renal function groups11

STUDY DESCRIPTION: Four simulated patient populations (n=1,000 each) varying by estimated glomerular filtration rate (eGFR) were generated using a uniform probability distribution for the following groups: ≥50, ≥30 to 49, ≥15 to 29, and <15 mL/min/1.73 m2. Using meropenem and vaborbactam population PK models, individual post hoc parameter estimates were generated. Using these estimates, total-drug concentration-time profiles were generated for simulated patients. An algorithm to assess PK/PD target attainment at meropenem and corresponding meropenem-vaborbactam MIC values based on worldwide in vitro surveillance data for Enterobacterales and KPC-producing Enterobacterales was followed.11

*In vitro activity does not necessarily correlate with clinical efficacy.

†Based upon meropenem-vaborbactam MIC distribution for 1,331 KPC-producing Enterobacterales isolates.11

MIC=minimum inhibitory concentration; PD=pharmacodynamic; PK=pharmacokinetic.

References: 1. VABOMERE [package insert]: Melinta Therapeutics, LLC. 2. Merrem IV [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2014.
3. Baldwin CM, Lyseng-Williamson KA, Keam SJ. Meropenem: a review of its use in the treatment of serious bacterial infections. Drugs. 2008;68(6):803-838. 4. Hecker SJ, Reddy KR, Totrov M, et al. Discovery of a cyclic boronic acid β-lactamase inhibitor (RPX7009) with utility vs class A serine carbapenemases. J Med Chem. 2015;58(9):3682-3692. 5. Wenzler E, Scoble PJ. An appraisal of the pharmacokinetic and pharmacodynamic properties of meropenem-vaborbactam. Infect Dis Ther. 2020;9:769-784.
6. Bhowmick T, Weinstein MP. Microbiology of meropenem-vaborbactam: a novel carbapenem beta-lactamase inhibitor combination for carbapenem-resistant Enterobacterales infections. Infect Dis Ther. 2020;9(4):757-767. 7. Data on file: Melinta Therapeutics, LLC. 8. Grupper M, Kuti JL, Nicolau DP. Continuous and prolonged intravenous β-lactam dosing: implications for the clinical laboratory. Clin Microbiol Rev. 2016;29(4):759-772. 9. Lee LS, Kinzig-Schippers M, Nafziger AN, et al. Comparison of 30-min and 3-h infusion regimens for imipenem/cilastatin and for meropenem evaluated by Monte Carlo simulation. Diagn Microbiol Infect Dis. 2010;68(3):251-258.
10. Kuti JL, Dandekar PK, Nightingale CH, Nicolau DP. Use of Monte Carlo simulation to design an optimized pharmacodynamic dosing strategy for meropenem. J Clin Pharmacol. 2003;43(10):1116-1123. 11. Bhavnani SM, Trang M, Griffith DC, et al. Meropenem-vaborbactam pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses as support for dose selection in patients with normal renal function and varying degrees of renal impairment. Presented at: ID Week; October 4-8, 2017; San Diego, CA. Poster 1852.

+ - INDICATIONS AND USAGE

VABOMERE® (meropenem and vaborbactam) is indicated for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTI) including pyelonephritis caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae species complex.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of VABOMERE and other antibacterial drugs, VABOMERE should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

IMPORTANT SAFETY INFORMATION

Contraindications

VABOMERE is contraindicated in patients with known hypersensitivity to any components of VABOMERE (meropenem and vaborbactam), or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to beta-lactam antibacterial drugs.

Warnings and Precautions

  • Hypersensitivity reactions were reported in patients treated with VABOMERE in the clinical trials. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving therapy with beta-lactam antibacterial drugs. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another beta-lactam antibacterial drug. If an allergic reaction to VABOMERE occurs, discontinue the drug immediately.
  • Seizures and other adverse Central Nervous System (CNS) experiences have been reported during treatment with meropenem, which is a component of VABOMERE. Close adherence to the recommended dosage regimens is urged, especially in patients with known factors that predispose to convulsive activity.
  • Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including VABOMERE, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued.
  • The concomitant use of VABOMERE and valproic acid or divalproex sodium is generally not recommended. Case reports in the literature have shown that co-administration of carbapenems, including meropenem, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. If administration of VABOMERE is necessary, consider supplemental anticonvulsant therapy.
  • In patients with renal impairment, thrombocytopenia has been observed in patients treated with meropenem, but no clinical bleeding has been reported.
  • Alert patients receiving VABOMERE on an outpatient basis regarding adverse reactions such as seizures, delirium, headaches and/or paresthesias that could interfere with mental alertness and/or cause motor impairment.
  • Prescribing VABOMERE in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of drug-resistant bacteria.
  • As with other antibacterial drugs, prolonged use of VABOMERE may result in overgrowth of nonsusceptible organisms.

Adverse Reactions

The most frequently reported adverse reactions occurring in ≥3% of patients treated with VABOMERE were headache, phlebitis/infusion site reactions, and diarrhea.

Please see full Prescribing Information.