Delafloxacin

Last updated
Delafloxacin
Delafloxacin.svg
Clinical data
Trade names Baxdela, Quofenix, Delabaxi
Other namesABT-492; RX-3341; WQ-3034
AHFS/Drugs.com Monograph
License data
Routes of
administration
By mouth, intravenous injection
ATC code
Legal status
Legal status
Identifiers
  • 1-(6-amino-3,5-difluoro-2-pyridyl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxo-quinoline-3-carboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C18H12ClF3N4O4
Molar mass 440.76 g·mol−1
3D model (JSmol)
  • Fc4cc(F)c(nc4N1\C=C(\C(=O)O)C(=O)c2c1c(Cl)c(c(F)c2)N3CC(O)C3)N

Delafloxacin sold under the brand name Baxdela among others, is a fluoroquinolone antibiotic used to treat acute bacterial skin and skin structure infections. [1]

Contents

Medical use

Delafloxacin is indicated to treat adults with acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible bacteria or adults with community-acquired bacterial pneumonia (CABP) caused by designated susceptible bacteria. [1]

Susceptible bacteria for ABSSSI are: [1]

Susceptible bacteria for CABP are: [1] Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible [MSSA] isolates only), Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus parainfluenzae, Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae.

It has not been tested in pregnant women. [1]

In the European Union, it is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults when it is considered inappropriate to use other antibacterial agents that are commonly recommended for the initial treatment of these infections. [3]

Adverse effects

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 Clostridioides difficile -associated diarrhea. [1]

Adverse effects occurring in more than 2% of clinical trial subjects included nausea, diarrhea, headache, elevated transaminases, and vomiting. [1]

Interactions

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 amounts of delafloxacin. [1]

Pharmacology

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. [4]

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. [4]

Chemistry

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). [1]

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. [1]

History

Delafloxacin was known as ABT-492, RX-3341, and WQ-3034 while it was under development. [5]

Rib-X Pharmaceuticals acquired delafloxacin from Wakunaga Pharmaceutical in 2006. [6] Rib-X was renamed to Melinta Therapeutics in 2013. [7] It was developed and marketed by Melinta Therapeutics (formerly Rib-X Pharmaceuticals), [1] which subsequently merged with Cempra. [8]

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. [9]

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. [10] New Drug Applications (NDA) for delafloxacin (Baxdela) 450 mg tablets and 300 mg injections were approved by the FDA in June 2017. [11]

The FDA obligated Melinta to conduct further studies as follows: [11]

Melinta merged with Cempra in August, 2017. [8]

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. [9]

Related Research Articles

<span class="mw-page-title-main">Methicillin</span> Antibiotic medication

Methicillin (USAN), also known as meticillin (INN), is a narrow-spectrum β-lactam antibiotic of the penicillin class.

<span class="mw-page-title-main">Levofloxacin</span> Antibiotic

Levofloxacin, sold under the brand name Levaquin among others, is a broad-spectrum antibiotic of the fluoroquinolone drug class. It is the left-handed isomer of the medication ofloxacin. It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, H. pylori, urinary tract infections, Legionnaires' disease, chronic bacterial prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis, meningitis, or pelvic inflammatory disease. It is available by mouth, intravenously, and in eye drop form.

<span class="mw-page-title-main">Cefazolin</span> Antibiotic medication

Cefazolin, also known as cefazoline and cephazolin, is a first-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. Specifically it is used to treat cellulitis, urinary tract infections, pneumonia, endocarditis, joint infection, and biliary tract infections. It is also used to prevent group B streptococcal disease around the time of delivery and before surgery. It is typically given by injection into a muscle or vein.

<span class="mw-page-title-main">Tigecycline</span> Chemical compound

Tigecycline, sold under the brand name Tygacil, is a tetracycline antibiotic medication for a number of bacterial infections. It is a glycylcycline class drug that is administered intravenously. It was developed in response to the growing rate of antibiotic resistant bacteria such as Staphylococcus aureus, Acinetobacter baumannii, and E. coli. As a tetracycline derivative antibiotic, its structural modifications has expanded its therapeutic activity to include Gram-positive and Gram-negative organisms, including those of multi-drug resistance.

<span class="mw-page-title-main">Moxifloxacin</span> Antibiotic

Moxifloxacin is an antibiotic, used to treat bacterial infections, including pneumonia, conjunctivitis, endocarditis, tuberculosis, and sinusitis. It can be given by mouth, by injection into a vein, and as an eye drop.

<span class="mw-page-title-main">Gemifloxacin</span> Medication to treat chronic bronchitis

Gemifloxacin mesylate, sold under the brand name Factive among others, is a broad-spectrum quinolone antibacterial agent used in the treatment of acute bacterial exacerbation of chronic bronchitis and mild-to-moderate pneumonia. It is taken by mouth. Vansen Pharma Inc. licensed the active ingredient from LG Life Sciences of Korea.

<span class="mw-page-title-main">Oritavancin</span> Pharmaceutical drug

Oritavancin, sold under the brand name Orbactiv among others, is a semisynthetic glycopeptide antibiotic medication for the treatment of serious Gram-positive bacterial infections. Its chemical structure as a lipoglycopeptide is similar to vancomycin.

<span class="mw-page-title-main">Cefoxitin</span> Chemical compound

Cefoxitin is a second-generation cephamycin antibiotic developed by Merck & Co., Inc. from Cephamycin C in the year following its discovery, 1972. It was synthesized in order to create an antibiotic with a broader spectrum. It is often grouped with the second-generation cephalosporins. Cefoxitin requires a prescription and as of 2010 is sold under the brand name Mefoxin by Bioniche Pharma, LLC. The generic version of cefoxitin is known as cefoxitin sodium.

<span class="mw-page-title-main">Cefodizime</span> Chemical compound

Cefodizime is a 3rd generation cephalosporin antibiotic with broad spectrum activity against aerobic gram positive and gram negative bacteria. Clinically, it has been shown to be effective against upper and lower respiratory tract infections, urinary tract infections, and gonorrhea. Cefodizime is a bactericidal antibiotic that targets penicillin-binding proteins (PBPs) 1A/B, 2, and 3 resulting in the eventual death of the bacterial cell. In vivo experimental models of infection showed that bacterial clearance by this drug is at least as effective compared with other 3rd generation cephalosporins. It has similar adverse effect profile to other 3rd generation cephalosporins as well, mainly being limited to gastrointestinal or dermatological side effects.

<span class="mw-page-title-main">Ceftobiprole</span> Chemical compound

Ceftobiprole, sold under the brand name Zevtera among others, is a fifth-generation cephalosporin antibacterial used for the treatment of hospital-acquired pneumonia and community-acquired pneumonia. It is marketed by Basilea Pharmaceutica under the brand names Zevtera and Mabelio. Like other cephalosporins, ceftobiprole exerts its antibacterial activity by binding to important penicillin-binding proteins and inhibiting their transpeptidase activity which is essential for the synthesis of bacterial cell walls. Ceftobiprole has high affinity for penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus strains and retains its activity against strains that express divergent mecA gene homologues. Ceftobiprole also binds to penicillin-binding protein 2b in Streptococcus pneumoniae (penicillin-intermediate), to penicillin-binding protein 2x in Streptococcus pneumoniae (penicillin-resistant), and to penicillin-binding protein 5 in Enterococcus faecalis.

<span class="mw-page-title-main">Dalbavancin</span> Antibiotic used to treat MRSA

Dalbavancin, sold under the brand names Dalvance in the US and Xydalba in the EU among others, is a second-generation lipoglycopeptide antibiotic medication. It belongs to the same class as vancomycin, the most widely used and one of the treatments available to people infected with methicillin-resistant Staphylococcus aureus (MRSA).

<span class="mw-page-title-main">Telavancin</span> Pharmaceutical drug

Telavancin is a bactericidal lipoglycopeptide for use in MRSA or other Gram-positive infections. Telavancin is a semi-synthetic derivative of vancomycin.

<span class="mw-page-title-main">Tedizolid</span> Oxazolidinone-class antibiotic

Tedizolid, sold under the brand name Sivextro is an oxazolidinone-class antibiotic. Tedizolid phosphate is a phosphate ester prodrug of the active compound tedizolid. It was developed by Cubist Pharmaceuticals, following acquisition of Trius Therapeutics, and is marketed for the treatment of acute bacterial skin and skin structure infections.

<span class="mw-page-title-main">Ceftaroline fosamil</span> Chemical compound

Ceftaroline fosamil (INN), brand name Teflaro in the US and Zinforo in Europe, is a cephalosporin antibiotic with anti-MRSA activity. Ceftaroline fosamil is a prodrug of ceftaroline. It is active against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive bacteria. It retains some activity of later-generation cephalosporins having broad-spectrum activity against Gram-negative bacteria, but its effectiveness is relatively much weaker. It is currently being investigated for community-acquired pneumonia and complicated skin and skin structure infection.

<span class="mw-page-title-main">Lipoglycopeptide</span> Class of chemical compounds

Lipoglycopeptides are a class of antibiotic that have lipophilic side-chains linked to glycopeptides. The class includes oritavancin, telavancin and dalbavancin.

Taksta is a front-loaded oral dosing regimen of sodium fusidate under development in the U.S. as an antibiotic for gram-positive infections including drug-resistant strains such as methicillin-resistant Staphylococcus aureus.

<span class="mw-page-title-main">JNJ-Q2</span> Chemical compound

JNJ-Q2 is a broad-spectrum fluoroquinolone antibacterial drug being developed for the treatment of acute bacterial skin and skin-structure infections and community-acquired pneumonia. Specifically, JNJ-Q2 is being actively studied for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections.

<span class="mw-page-title-main">Omadacycline</span> Chemical compound

Omadacycline, sold under the brand name Nuzyra, is a broad spectrum antibiotic medication belonging to the aminomethylcycline subclass of tetracycline antibiotics. In the United States, it was approved in October 2018, for the treatment of community-acquired bacterial pneumonia and acute skin and skin structure infections.

<span class="mw-page-title-main">Eravacycline</span> Chemical compound

Eravacycline is a synthetic halogenated tetracycline class antibiotic by Tetraphase Pharmaceuticals. It is closely related to tigecycline. It has a broad spectrum of activity including many multi-drug resistant strains of bacteria. Phase III studies in complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI) were recently completed with mixed results. Eravacycline was granted fast track designation by the FDA and is currently available in USA.

<span class="mw-page-title-main">Lefamulin</span> Chemical compound

Lefamulin, sold under the brand name Xenleta, is an antibiotic medication used it to treat adults with community-acquired bacterial pneumonia. It is taken by mouth or by injection into a vein.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 "Baxdela- delafloxacin meglumine tablet Baxdela- delafloxacin meglumine injection, powder, lyophilized, for solution". DailyMed. 12 February 2020. Retrieved 12 May 2020.
  2. "Quofenix EPAR". European Medicines Agency (EMA). 16 December 2019. Retrieved 17 October 2024.
  3. "Quofenix EPAR". European Medicines Agency (EMA). 16 October 2019. Retrieved 12 May 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  4. 1 2 Candel FJ, Peñuelas M (2017). "Delafloxacin: design, development and potential place in therapy". Drug Design, Development and Therapy. 11: 881–891. doi: 10.2147/DDDT.S106071 . PMC   5367733 . PMID   28356714.
  5. "Delafloxacin". AdisInsight. Retrieved 10 July 2017.
  6. Cartwright H (12 July 2011). "Rib-X Pharmaceuticals Signs Global Antibiotic Research Collaboration with Sanofi". PharmaDeals Review. No. 7. doi:10.3833/pdr.v2011i7.1494 (inactive 2024-09-13). Archived from the original on 25 April 2012.{{cite news}}: CS1 maint: DOI inactive as of September 2024 (link)
  7. Stearns J (August 1, 2016). "Melinta Therapeutics takes aim at deadly drug-resistant bacteria". Hartford Business Journal.
  8. 1 2 "Cempra and Melinta Announce Merger to Form Leading, Vertically Integrated Commercial-Stage Anti-Infectives Company" (Press release). Melinta Therapeutics. 9 August 2017. Retrieved 24 November 2022 via GlobeNewswire.
  9. 1 2 Markham A (September 2017). "Delafloxacin: First Global Approval". Drugs. 77 (13): 1481–1486. doi:10.1007/s40265-017-0790-5. PMC   6208769 . PMID   28748399.
  10. Osborne R (20 June 2017). "Melinta's I.V., oral delafloxacin wins FDA nod in skin infections". BioWorld. Archived from the original on 3 August 2019. Retrieved 10 July 2017.
  11. 1 2 "NDA Approval Letter: NDA 208610 and NDA 208611" (PDF). FDA. June 19, 2017.