How VABOMERE® works

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
  • Meropenem is stable to hydrolysis by extended spectrum β-lactamases (ESBLs), including penicillinases and cephalosporinases produced by gram-negative bacteria, except carbapenem hydrolyzing ß-lactamases such as KPC5
Vaborbactam
  • First in a new class of cyclic boronic acid BLIs4
  • Potent activity against β-lactamases optimized against KPC4
  • Inactivates KPC-2 and KPC-34
  • Covalent bonding to target with extended resident time allowing meropenem to act unhindered1

VABOMERE was designed to address the challenge of resistant Enterobacteriaceae and optimize the utility of meropenem1

WATCH THE VABOMERE MECHANISM OF ACTION

VABOMERE demonstrates a bactericidal effect against designated susceptible gram-negative organisms, including certain ESBL-producing and recently emergent KPC-producing pathogens.5

Meropenem and vaborbactam were designed to work together1,4

The pharmacokinetics (PK) of vaborbactam are well matched for meropenem5

MEROPENEM PK

Meropenem PK

VABORBACTAM PK

Vabobractam 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 vaborbactam5
  • 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 drug1
  • There were no plasma or urine PK drug-drug interactions1

Optimized dosing for increased time above minimum inhibitory concentration (MIC)6-8

Combined with vaborbactam, a high dose of meropenem administered as a prolonged infusion (2 g administered over 3 hours, every 8 hours) provides optimized pharmacokinetic/pharmacodynamic exposures leading to enhanced bacterial killing.6-8

Review the microbiologic data

References: 1. Data on file. Melinta Therapeutics, Inc. 2. Baldwin CM, Lyseng-Williamson KA, Keam SJ. Meropenem: a review of its use in the treatment of serious bacterial infections. Drugs. 2008;68(6). 3. Merrem I.V. [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2014. 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). 5. VABOMERE [package insert]: Melinta Therapeutics, Inc. 6. Grupper M, Kuti JL, Nicolau DP. Continuous and prolonged intravenous β-lactam dosing: implications for the clinical laboratory. Clin Microbiol Rev. 2016; 29(4). 7. Kuti JL, Dandekar PK, Nightingale CH, et al. Use of Monte Carlo simulation to design an optimized pharmacodynamic dosing strategy for meropenem. J Clin Pharmacol. 2003;43. 8. 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.

+ - 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.
  • Clostridium 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.