Delafloxacin

440.76000

440.76

6315412YVF

DTXSID40172331

J01MA23|J - Antiinfectives for systemic use

121.68000

2.56390

1.796 g/cm3

238-241 °C @ Solvent: Water

698.5ºC at 760 mmHg

376.2ºC

The most common adverse reactions noted with Delafloxacin were nausea (8%), diarrhea (8%), headache (3%), transaminase elevations (3%), and vomiting (2%). Fluoroquinolones are associated with increased frequency of tendon rupture and tendonitis, increased risk of peipheral neuropathy, excacerbation of myasthenia gravis, and development of Clostridium difficile-associated diarrhea. Fluoroquinolones are also associated with an increased risk of central nervous system reactions (CNS), including: convulsions and increased intracranial pressure (including pseudotumor cerebri) and toxic psychosis. Fluoroquinolones may also cause CNS reactions of nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and suicidal thoughts or acts.

Delafloxacin, like other fluoroquinolones, is associated with a low rate (3% to 4%) of serum enzyme elevations during therapy. These abnormalities are generally mild, asymptomatic and transient, resolving even with continuation of therapy. ALT elevations above 5 times the upper limit of normal occur in 1% or less of subjects. Although delafloxacin may not have been clearly linked to cases of clinically apparent liver injury, the other fluoroquinolones, such as ciprofloxacin, levofloxacin and moxifloxacin, rank among the 25 most common causes of drug induced liver injury in many case series. Estimates of the frequency of liver injury from fluoroquinolones have been 1:15,000 to 1:25,000 exposed persons. Delafloxacin has been in clinical use for a short time only, but is likely to have a similar frequency and pattern of liver injury as the other fluoroquinolones.

Delafloxacin is 84% bound to human plasma proteins. It primarily binds to serum albumin.

Delafloxacin is indicated for the treatment of acute bacterial skin and skin structure infections caused by the Gram-positive organisms Staphylococcus aureus (including methicillin-resistant and methicillin-susceptible isolates), Staphylococcus haemolyticus, Staphylococcus lugdunensis, Streptococcus agalactiae, Streptococcus anginosus Group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), Streptococcus pyogenes, and Enterococcus faecalis as well as the Gram-negative organisms Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.|FDA Label|Quofenix 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 (see sections 4.4 and 5.1).Consideration should be given to official guidance on the appropriate use of antibacterial agents.|Treatment of community-acquired pneumonia|Treatment of local infections of skin and subcutaneous tissues

Delafloxacin is a fourth generation fluoroquinolone with expanded activity against gram-positive bacteria as well as atypical pathogens. Delafloxacin has been linked to mild ALT elevations during therapy, but has yet to be linked to instances of idiosyncratic acute liver injury with symptoms and jaundice as have been described with other fluoroquinolones.

Antiinfective Agents

Delafloxacin is a fluoroquinolone antibacterial drug which kills bacterial cells.

The median time to peak plasma concentration for orally administered Delafloxacin is 0.75 (0.5-4.0) hours after a single dose and 1.00 (0.5-6.0) hours for steady state dosing. The median time to peak plasma concentration for intravenously administered Delafloxacin is 1.00 (1.0-1.2) hours for a single dose and 1.0 (1.0-1.0) hour for steady state dosing. The absolute bioavailability for orally administed Delafloxacin is 58.8%.|After a single intravenous dose, 65% of Delafloxacin was excreted in the urine either unchanged or as glucuronide metabolites with 28% excreted unchanged in the feces. After a single oral dose, 50% of Delafloxacin was excreted in the urine either unchanged or as glucuronide metabolites with 48% excreted unchanged in the feces.|The steady sate volume of distrubution of Delafloxacin is 30-48 liters.|The mean total clearance of Delafloxacin is 16.3 liters per hour. Renal clearance accounts for 35-45% of total clearance.

Delafoxacin is primarily metabolized via glucuronidation mediated by UDP glucuronosyltransferase 1-1, UDP-glucuronosyltransferase 1-3, and UDP-glucuronosyltransferase 2B15. Less than 1% is metabolized via oxidation.

The mean half life of elimination of Delafloxacin is 3.7 hours after a single intravenous administration. The mean half life of elimination for multple oral administrations is 4.2-8.5 hours.

Delafloxacin inhibits the activity of bacterial DNA topoisomerase IV and DNA gyrase (topoisomerase II). This interferes with bacterial DNA replication by preventing the relaxation of positive supercoils introduced as part of the elongation process. The resultant strain inhibits further elongation. Delafloxacin exerts concentration-dependent bacteriocidal activity.

1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Human drugs -> Quofenix -> EMA Drug Category|Antibacterials for systemic use -> Human pharmacotherapeutic group|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients