Meropenem and Vaborbactam

• It is used to treat a urinary tract infection (UTI).

• Tell all of your health care providers that you take meropenem and vaborbactam. This includes your doctors, nurses, pharmacists, and dentists.
• Very bad and sometimes deadly allergic side effects have rarely happened with drugs like this one. Talk with the doctor.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• Do not use longer than you have been told. A second infection may happen.
• If you are 65 or older, use meropenem and vaborbactam with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Irritation where this medicine is given.
• Loose stools (diarrhea).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• Vabomere
• Vaborbactam and Meropenem

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

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. Although the mechanism of this interaction is unknown, data from in vitro and animal studies suggest that carbapenems may inhibit the hydrolysis of valproic acid’s glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing the serum concentrations of valproic acid. If administration of meropenem and vaborbactam is necessary, then supplemental anti-convulsant therapy should be considered.1

Probenecid competes with meropenem for active tubular secretion, resulting in increased plasma concentrations of meropenem. Co-administration of probenecid with meropenem and vaborbactam is not recommended.1

Mechanism of Action

The meropenem component of meropenem and vaborbactam is a penem antibacterial drug. The bactericidal action of meropenem results from the inhibition of cell wall synthesis. Meropenem penetrates the cell wall of most gram-positive and gram-negative bacteria to bind penicillin-binding protein (PBP) targets. Meropenem is stable to hydrolysis by most beta-lactamases, including penicillinases and cephalosporinases produced by gram-negative and gram-positive bacteria, with the exception of carbapenem hydrolyzing beta-lactamases.1

The vaborbactam component of meropenem and vaborbactam is a non-suicidal beta-lactamase inhibitor that protects meropenem from degradation by certain serine beta-lactamases such as Klebsiella pneumoniae carbapenemase (KPC). Vaborbactam does not have any antibacterial activity. Vaborbactam does not decrease the activity of meropenem against meropenem-susceptible organisms.1

Spectrum

Meropenem and vaborbactam has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections.1

Gram-negative Bacteria

• Enterobacter cloacae species complex1

• Escherichia coli1

• Klebsiella pneumoniae1

The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following bacteria exhibit an in vitro MIC less than or equal to the susceptible breakpoint for meropenem and vaborbactam against isolates of a similar genus or organism group. However, the efficacy of meropenem and vaborbactam in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials.1

Gram-negative Bacteria

• Citrobacter freundii1

• Citrobacter koseri1

• Enterobacter aerogenes1

• Klebsiella oxytoca1

• Morganella morganii1

• Proteus mirabilis1

• Providencia spp.1

• Pseudomonas aeruginosa1

• Serratia marcescens1

In vitro synergy studies have not demonstrated antagonism between meropenem and vaborbactam and levofloxacin, tigecycline, polymyxin, amikacin, vancomycin, azithromycin, daptomycin, or linezolid.1

Resistance

Mechanisms of beta-lactam resistance may include the production of beta-lactamases, modification of PBPs by gene acquisition or target alteration, up-regulation of efflux pumps, and loss of outer membrane porin. Meropenem and vaborbactam may not have activity against gram-negative bacteria that have porin mutations combined with overexpression of efflux pumps.1

Clinical isolates may produce multiple beta-lactamases, express varying levels of beta-lactamases, or have amino acid sequence variations, and other resistance mechanisms that have not been identified.1

Culture and susceptibility information and local epidemiology should be considered in selecting or modifying antibacterial therapy.1

Meropenem and vaborbactam demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and extended-spectrum beta-lactamases (ESBLs) of the following groups: KPC, SME, TEM, SHV, CTX-M, CMY, and ACT.1

Meropenem and vaborbactam is not active against bacteria that produce metallo-beta lactamases or oxacillinases with carbapenemase activity.1

In the Phase 3 cUTI trial with meropenem and vaborbactam, some isolates of E. coli, K. pneumoniae, E. cloacae, C. freundii, P. mirabilis, and P. stuartii that produced beta-lactamases were susceptible to meropenem and vaborbactam (minimum inhibitory concentration ≤4 mcg /mL). These isolates produced one or more beta-lactamases of the following enzyme groups: OXA (non-carbapenemases), KPC, CTX-M, TEM, SHV, CMY, and ACT.1

Some beta-lactamases were also produced by an isolate of K. pneumoniae that was not susceptible to meropenem and vaborbactam (minimum inhibitory concentration ≥32 mcg/mL). This isolate produced beta-lactamases of the following enzyme groups: CTX-M, TEM, SHV, and OXA.1

No cross-resistance with other classes of antimicrobials has been identified. Some isolates resistant to carbapenems (including meropenem) and to cephalosporins may be susceptible to meropenem and vaborbactam.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.