Evaluating Eravacycline's Place in Therapy

The US Food and Drug Administration (FDA) approved eravacycline (Xerava) for the treatment of complicated intra-abdominal infections in adults 18 years and older in August 2018.

Eravacycline is a tetracycline-class antibacterial that has demonstrated potent activity against multidrug-resistant pathogens.

The FDA’s decision to approve eravacycline was based on 2 double-blind, multicenter phase 3 clinical trials. In these studies, the therapy was found to be noninferior in clinical response when compared with ertapenem and meropenem. The study drug was well-tolerated with commonly reported adverse reactions consisting of nausea, vomiting, and infusion site reactions.

Now, with a sampling of real-world data to pull from, a team of investigators has compiled a review of the therapeutic, published recently in Pharmacotherapy.

“Clinicians now have [eravacycline] as a novel therapeutic option for the treatment of adults with intra-abdominal infections, allergies to β-lactam agents, Clostridioides difficile-associated diarrhea, or if tolerability to other agents is a concern,” the investigators wrote.

As part of their review, the authors focused on eravacycline’s place in therapy.

First, the authors acknowledged that eravacycline is a potential competitor to tigecycline, as eravacycline has a strong gastrointestinal safety profile, no FDA boxed warnings related to an increase in mortality levels, and higher serum levels. Despite this, it has not been proven if a patient with a tigecycline allergy could tolerate eravacycline or if tigecycline-resistant isolates are also resistant to eravacycline.

The authors pointed that it would be interesting to assess eravacycline’s clinical performance among patients with pneumonia, sepsis, and bacteremia, as tigecycline has been associated with increased mortality in this patient population.

Eravacycline is also a strong option for patients who are at a high risk of C diff, as it is associated with a low risk of C diff infection, similar to other tetracyclines. Additionally, it should be well-tolerated among patients with β-lactam allergies or intolerance to fluroquinolones.

The agent can also limit the use of β-lactams for patients with seizure disorders and limit the use of quinolones, carbapenems, and β-lactam inhibitors among patients with multidrug-resistant infections and patients at risk for carbapenem-resistant Enterobacteriaceae, which is a priority for stewardship efforts.

Challenges associated with eravacycline include an unfavorable response to Enterococcus faecalis that was documented in 1 of the phase 3 trials, which the investigators noted as “concerning, particularly for a drug with relatively good gram-positive bacterial activity.” There are also limited data to support use in urgent threats such as Acinetobacter.

The authors wrote that future research should investigate the therapeutic in non-FDA-approved indications such as Neisseria gonorrhea and nontuberculous mycobacterium. Research should also revisit the possibility for oral eravacycline, which could impact the agent’s place in therapy. More data is also needed on real-world use of the agent.

“The launching wholesale acquisition cost of [eravacycline] is $44 per vial or $702-$2464 for a 4 to 24-day course, which is at least 3 times less than the least expensive branded antimicrobial with similar spectrum,” the investigators noted.

Based on the agent’s place in therapy, the authors note that it is a valuable empiric therapy especially when broad coverage is needed and for patients with allergies or intolerance to β-lactams or fluroquinolones. However, more real-world data is needed to fully evaluate the agent’s potential place in therapy.