Vaborbactam

Approved Uses

Vaborbactam is a medication used in combination with the antibiotic meropenem. This combination is specifically approved for use in adults to treat the following conditions:

• Complicated urinary tract infections (cUTI): These are severe infections of the urinary system that are often more difficult to manage than simple infections.
• Pyelonephritis: This is a serious bacterial infection that affects the kidneys.

How It Is Administered

This medication is intended for infections caused by specific susceptible bacteria. It is administered by a healthcare professional as an intravenous (IV) infusion, typically in a hospital or clinical setting. It is generally used for serious infections when a doctor determines this specific combination of medicines is the appropriate treatment option.

Mechanism of Action

Vaborbactam belongs to a class of drugs known as beta-lactamase inhibitors. While it does not kill bacteria on its own, it plays a critical role in treating infections by protecting the antibiotic it is paired with, such as meropenem.

Some bacteria produce specific enzymes called beta-lactamases. These enzymes act like a defense mechanism for the bacteria, breaking down and deactivating antibiotics before they can work. This process is a common cause of antibiotic resistance.

Vaborbactam works by:

• Inhibiting enzymes: It binds to and blocks the action of certain beta-lactamase enzymes produced by the bacteria.
• Restoring antibiotic activity: By neutralizing these enzymes, vaborbactam prevents the antibiotic from being destroyed.
• Enhancing effectiveness: This allows the antibiotic to successfully enter the bacterial cells and kill them.

This medication is specifically designed to target bacteria that have become resistant to other treatments, helping to ensure the accompanying antibiotic remains effective against tough-to-treat infections.

Common Side Effects

Some individuals may experience mild side effects during treatment. These often include:

• Headache
• Diarrhea
• Nausea or vomiting
• Pain, redness, or swelling at the injection site
• Inflammation of the vein (phlebitis)

Serious Side Effects

Contact a healthcare provider immediately if you experience any of the following serious symptoms:

• Signs of a severe allergic reaction, such as hives, skin rash, or swelling of the face, lips, or tongue
• Severe stomach cramps and watery or bloody diarrhea, which may occur during treatment or several months after the last dose
• Seizures, tremors, or involuntary muscle movements
• Confusion or significant changes in mood or behavior
• Tingling or numbness in the hands or feet
• Severe skin reactions, including blistering, peeling, or red skin rashes

Allergic Reactions

Serious and occasionally fatal hypersensitivity (allergic) reactions have been reported in patients receiving beta-lactam antibiotics. This medication is contraindicated in patients with a known history of severe hypersensitivity to vaborbactam, meropenem, or other beta-lactam drugs, such as penicillins and cephalosporins. If an allergic reaction occurs, the medication must be discontinued immediately.

Seizures and Central Nervous System Effects

Seizures and other central nervous system (CNS) adverse reactions, including tremors and confusion, have occurred during treatment. These events are most commonly reported in patients with pre-existing CNS disorders, such as brain lesions or a history of seizures, and in those with impaired kidney function. Healthcare providers typically monitor patients with known neurological disorders closely during therapy.

Clostridium Difficile-Associated Diarrhea

Nearly all antibacterial agents can cause Clostridium difficile-associated diarrhea (CDAD), which ranges in severity from mild diarrhea to fatal colitis. This condition occurs because the antibiotic alters the normal bacteria in the colon, allowing C. difficile to grow. CDAD has been reported to occur more than two months after the completion of antibiotic treatment. If CDAD is suspected or confirmed, the antibiotic may need to be stopped.

Development of Drug-Resistant Bacteria

Using this medication in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit and increases the risk that bacteria will develop resistance to the drug. This makes future infections harder to treat.

Overgrowth of Non-Susceptible Organisms

As with other antibiotics, prolonged use of vaborbactam and meropenem may result in the overgrowth of organisms that are not sensitive to the medication, including fungi. If a secondary infection occurs during treatment, appropriate medical action is required.

Pregnancy

There are no well-controlled studies on the use of vaborbactam in pregnant women to inform drug-associated risks. In animal reproduction studies, vaborbactam alone did not cause fetal harm even at high doses. However, vaborbactam is used in combination with meropenem, and animal studies of meropenem have shown some evidence of adverse developmental effects, such as fetal loss.

Pregnant individuals should discuss their medical history and the necessity of the treatment with their doctor to determine if the benefits to the mother outweigh the potential risks to the fetus.

Breastfeeding

It is currently unknown if vaborbactam is excreted in human breast milk. Research indicates that meropenem, which is administered alongside vaborbactam, does pass into breast milk in small quantities. The effects of vaborbactam on a breastfed infant or on milk production are not yet established.

Decisions regarding the use of this medication while breastfeeding should involve a discussion with a healthcare professional, considering the following factors:

• The importance of the drug to the mother's health.
• The potential risks to the nursing infant from the medication or the mother's underlying condition.
• The developmental and health benefits of breastfeeding.

Dosage Forms

Vaborbactam is supplied as a sterile, preservative-free powder in single-dose vials. It is only available as a combination product with the antibiotic meropenem.

Administration

This medication is administered by a healthcare professional in a hospital or clinic setting. The process involves the following steps:

• Reconstitution: The powder is mixed with a compatible liquid to create a solution.
• Dilution: The solution is further diluted into an intravenous (IV) bag.
• Infusion: The medicine is delivered slowly into a vein, typically over a period of several hours.

FDA Approval History

The U.S. Food and Drug Administration (FDA) approved the combination of meropenem and vaborbactam in August 2017. Vaborbactam is a beta-lactamase inhibitor that is not available as a standalone medication; it is only administered in combination with the carbapenem antibiotic meropenem.

Approved Indications

This combination therapy is indicated for the treatment of patients 18 years of age and older with the following conditions caused by susceptible bacteria:

• Complicated urinary tract infections (cUTI)
• Pyelonephritis (a type of kidney infection)

The FDA approval was based on clinical trials showing the drug's effectiveness against specific microorganisms, including Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae species complex.

Regulatory Status and Safety

The medication is available by prescription only and is administered via intravenous infusion. There are currently no boxed warnings or Risk Evaluation and Mitigation Strategies (REMS) associated with this drug combination. To maintain the effectiveness of the drug and prevent the development of drug-resistant bacteria, the FDA recommends that it be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.

FDA Approval and Indications

The U.S. Food and Drug Administration (FDA) approved the combination of meropenem and vaborbactam in August 2017. It is specifically indicated for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTI), including a type of kidney infection known as pyelonephritis.

The approval was based on clinical trials demonstrating that the combination was effective against specific susceptible microorganisms. To maintain the effectiveness of the drug and reduce the development of drug-resistant bacteria, the FDA recommends that it only be used to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.

Regulatory Designations

During its development, the FDA granted this drug combination several special designations to expedite its availability:

• Qualified Infectious Disease Product (QIDP): A status given to antibacterial or antifungal human drugs intended to treat serious or life-threatening infections.
• Fast Track: A process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.
• Priority Review: An FDA designation that directs overall attention and resources to the evaluation of applications for drugs that would, if approved, be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions.