|Synonyms||ABT-492; RX-3341; WQ-3034|
|Oral, intravenous injection|
|Chemical and physical data|
|Molar mass||440.76 g/mol|
|3D model (JSmol)|
Delafloxacin (INN) (trade name Baxdela) is a fluoroquinolone antibiotic used to treat acute bacterial skin and skin structure infections. It was developed and marketed by Melinta Therapeutics (formerly Rib-X Pharmaceuticals), which subsequently merged with Cempra.
Delafloxacin is used to treat acute bacterial skin and skin structure infections caused by designated susceptible bacteria.
Susceptible bacteria are:
- Gram-positive organisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Staphylococcus haemolyticus, Staphylococcus lugdunensis, Streptococcus agalactiae, Streptococcus anginosus group, Streptococcus pyogenes, and Enterococcus faecalis
- Gram-negative organisms: Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
It has not been tested in pregnant women.
Like other drugs in the fluoroquinolone class, delafloxacin contains a black box warning about the risk of tendinitis, tendon rupture, peripheral neuropathy, central nervous system effects, and exacerbation of myasthenia gravis. The label also warns against the risk of hypersensitivity reactions and Clostridium difficile-associated diarrhea.
Like other fluoroquinolones, delafloxacin chelates metals including aluminum, magnesium, sucralfate, iron, zinc, and divalent and trivalent cations like didanosine; using this drugs with antacids, some dietary supplements, or drugs buffered with any of these ions will interfere with available amounds of delafloxacin.
The half-life varies in around 8 hours at normal doses. Excretion is 65% through urine, mostly in unmetabolized form, and 28% via feces. Clearance is reduced in people with severe kidney disease.
Delafloxacin is more active (lower MIC90) than other quinolones against Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). In contrast to most approved fluoroquinolones, which are zwitterionic, delafloxacin has an anionic character, which results in a 10-fold increase in delafloxacin accumulation in both bacteria and cells at acidic pH. This property is believed to confer to delafloxacin an advantage for the eradication of Staphylococcus aureus in acidic environments, including intracellular infections and biofilms.
The chemical name is 1-deoxy-1 (methylamino)-D-glucitol, 1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (salt).
The injectable form of delafloxacin is sold as the meglumine salt of the active ingredient and its United States Adopted Name, delafloxacin meglumine, reflects that; the injection formulation also includes EDTA and sulfobutylether-β-cyclodextrin. The tablet is made of delafloxacin, citric acid anhydrous, crospovidone, magnesium stearate, microcrystalline cellulose, povidone, sodium bicarbonate, and sodium phosphate monobasic monohydrate.
Delafloxacin was known as ABT-492, RX-3341, and WQ-3034 while it was under development.
Key clinical trials for delafloxacin have been performed by Melinta regarding indications for skin and skin structure infections as well as complicated bacterial infections and uncomplicated gonorrhea. The trial on gonorrhea was terminated before data was released.
Delafloxacin was approved by the FDA in June 2017, after it was noninferior to vancomycin plus aztreonam in two trials on 1042 patients with acute bacterial skin and skin structure infection. New Drug Applications (NDA) for delafloxacin (Baxdela) 450 mg tablets and 300 mg injections were approved by the FDA in June 2017.
The FDA obligated Melinta to conduct further studies as follows:
- a 5-year surveillance study to determine if resistance emerges, with the final report due in December 2022
- a study of the IV form in pregnant rats to determine distribution to the reproductive tract, due June 2018, with further studies required if there is significant distribution.
Melinta merged with Cempra in August, 2017.
Melinta has entered into commercialization and distribution agreements with both Menarini Therapeutics (March 2017) and Eurofarma Laboratórios (January 2015) for international commercialization of delafloxacin. The agreement with Menarini allows them to commercialize and distribute in 68 countries, including Europe, China, and South Korea among others. A similar agreement with Eurofarma allows for commercialization in Brazil.
- "Delafloxacin tablets US label" (PDF). FDA. June 2017. Retrieved July 9, 2017. This article incorporates text from this source, which is in the public domain. For label updates, see FDA index page for NDA 208610 for tablets, and see FDA index page for NDA 208611 for injectable form.
- "Cempra Press Releases".
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- "Delafloxacin". AdisInsight. Retrieved 10 July 2017.
- Cartwright, Heather (12 July 2011). "Rib-X Pharmaceuticals Signs Global Antibiotic Research Collaboration with Sanofi". PharmaDeals Review (7). doi:10.3833/pdr.v2011i7.1494. Archived from the original on 25 April 2012.
- Stearns, John (August 1, 2016). "Melinta Therapeutics takes aim at deadly drug-resistant bacteria". Hartford Business Journal.
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- Osborne, Randy (20 June 2017). "Melinta's I.V., oral delafloxacin wins FDA nod in skin infections". BioWorld.
- "NDA Approval Letter: NDA 208610 and NDA 208611" (PDF). FDA. June 19, 2017.