Finafloxacin

Last updated
Finafloxacin
Finafloxacin.svg
Clinical data
Trade names Xtoro
Routes of
administration 		otic, oral, intavenous
Legal status
Legal status
Pharmacokinetic data
Elimination half-life 10 hours
Identifiers
  • 8-Cyano-1-cyclopropyl-6-fluoro-7-[(4aS,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl]-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C20H19FN4O4
Molar mass 398.394 g·mol−1
3D model (JSmol)
  • O=C(O)C1=CN(C2CC2)c3c(C1=O)cc(F)c(c3C#N)N4C[C@H]5[C@H](C4)NCCO5
  • InChI=1S/C20H19FN4O4/c21-14-5-11-17(25(10-1-2-10)7-13(19(11)26)20(27)28)12(6-22)18(14)24-8-15-16(9-24)29-4-3-23-15/h5,7,10,15-16,23H,1-4,8-9H2,(H,27,28)/t15-,16-/m0/s1
  • Key:FYMHQCNFKNMJAV-HOTGVXAUSA-N

Finafloxacin (Xtoro) is a fluoroquinolone antibiotic. In the United States, it is approved by the Food and Drug Administration to treat acute otitis externa (swimmer's ear) caused by the bacteria Pseudomonas aeruginosa and Staphylococcus aureus . [1]

Contents

Medical uses

Finafloxacin is used to treat a type of ear infection called acute otitis externa caused by Pseudomonas aeruginosa and Staphylococcus aureus bacteria. [2] In the clinical trial that led to the drug's approval, finafloxacin shortened the time to cessation of ear pain from an average of 6.8 days in patients taking a placebo to 3.5 days. [2]

Finafloxacin cannot be purchased over-the-counter, and is available by prescription only. [3]

Available forms

Finafloxacin is commercially available as a 0.3% otic (meaning "for the ear") suspension for topical administration in the United States. [2] The suspension should be warmed gently in the hands for 1–2 minutes before administration to prevent dizziness, and shaken before use. [2] It is necessary to remain still for 1 minute, with the affected ear facing up while lying on one's side, after administration to allow finafloxacin to penetrate the ear canal and reach the site of infection. [2]

Specific populations

Pregnancy

Finafloxacin is classified as pregnancy category C, meaning that the risk for harming a developing fetus has not been ruled out. [4]

Pediatrics

The efficacy and safety profile of finafloxacin ear drops are unknown in children younger than the age of 1 years old. [3]

Geriatrics

There are no limitations against using finafloxacin ear drops in the elderly. [3]

Adverse effects

The spectrum of adverse effects caused by finafloxacin vary by the method of administration. People that have administered finafloxacin into their ears in the form of drops have experienced ear itching and nausea (<1% for both). [5] People that have administered finafloxacin by mouth or intravenously (IV) have experienced gastrointestinal side effects (including diarrhea, flatulence, and nausea), fatigue, headaches, musculoskeletal problems, and injection site reactions (if IV). [5] Respiratory disorders, including rhinitis and nasopharyngitis, have also been associated with the use of finafloxacin. [6]

People that are allergic to other quinolones may be allergic to finafloxacin as well, and use may result in an allergic reaction in that population. [2] Adverse effects consistent with an allergic reaction to finafloxacin may include swelling of the lips, tongue, or throat, difficulty swallowing, and shortness of breath. [3]

Overdose

It is not thought that an overdose of the otic suspension is likely to cause severe or life-threatening symptoms. [7]

Interactions

Owing to the local effect of administering finafloxacin into the ears, it is unlikely that it will affect or be affected by other medications that are administered into the systemic circulation (e.g. drugs taken by mouth, or by injection). [7]

Pharmacology

Mechanism of action

Finafloxacin is a fluoroquinolone class antibiotic of the 8-cyano subclass (referring to the CN substituent at the 8th position). [5] Like other fluoroquinolones, its antibiotic activity is derived from its pharmacological mechanism of action as a type II topoisomerase poison, preventing bacteria from replicating and performing other vital, cellular functions. [5] However, unlike other fluoroquinolones, finafloxacin is highly active under acidic (pH 5.0–6.0) conditions, where certain bacteria (like Helicobacter pylori , a bacterium that is known to infect the human stomach, despite the harsh acidity) [8] thrive. [5] Other acidic conditions found on the human body include the vagina, urinary tract, and skin, though finafloxacin is currently not used to treat infections in these areas either. [6]

Finafloxacin has demonstrated bactericidal activity against a range of bacterial pathogens, especially at acidic pH, with a post-antibiotic effect. [5] Owing to its activity against both Gram-positive and Gram-negative bacteria, finafloxacin is classified as a broad-spectrum antibiotic. [5]

Pharmacokinetics

Finafloxacin has good oral bioavailability, meaning that a substantial portion of a dose taken by mouth reaches a person's systemic circulation. [5] Some people have experienced unintentional, quantifiable absorption of finafloxacin into systemic circulation after administering the drug via the ear. [5]

The elimination half-life of finafloxacin is approximately 10 hours in humans. [6]

Chemistry

The chemical structure of finafloxacin has been described as a "fluorinated quinolone derivative with 8-cyano-substituent and 7-pyrrolo-oxazinyl moiety." [6] Its low isoelectric point (pH 6.7) is lower than the isoelectric point of another fluoroquinolone class antibiotic called ciprofloxacin (pH 7.4), which accounts for finafloxacin's superior activity at low pH (5.0–6.0). [6]

There are some notable differences between the chemistry of finafloxacin and related fluoroquinolones. For example, the 8-cyano-substituent is not found in ciprofloxacin, and moxifloxacin has an 8-methoxy-substituent instead. The oxygen atom in the ring structure of finafloxacin makes the molecule more hydrophilic than ciprofloxacin. [9]

The chemical structure of finafloxacin is nearly identical to that of pradofloxacin.

Synthesis

The synthesis of finafloxacin has been described in detail in its patents. [10] An example of its synthesis is provided below: [10]

FinafloxacinSynthesis.jpg

History

Finafloxacin is the first FDA approved medication in the United States that was first developed by a Singaporean drug company. [11] Finafloxacin was officially approved by the FDA on December 17, 2014. [12] The company, MerLion Pharmaceuticals, partnered with the North American company Alcon to produce the drug commercially in the United States. [13]

Research

Owing to its high bactericidal activity in acidic environments, Bartoletti et al have speculated that finafloxacin may be useful in the treatment of urinary tract infections in the future. [14] Finafloxacin's manufacturer, MerLion, has invested money in studying the use of finafloxacin for this indication. [13]

Related Research Articles

<span class="mw-page-title-main">Ciprofloxacin</span> Fluoroquinolone antibiotic

Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhoea, respiratory tract infections, skin infections, typhoid fever, and urinary tract infections, among others. For some infections it is used in addition to other antibiotics. It can be taken by mouth, as eye drops, as ear drops, or intravenously.

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

Levofloxacin

<span class="mw-page-title-main">Ofloxacin</span> Antibiotic to treat bacterial infections

Ofloxacin is a quinolone antibiotic useful for the treatment of a number of bacterial infections. When taken by mouth or injection into a vein, these include pneumonia, cellulitis, urinary tract infections, prostatitis, plague, and certain types of infectious diarrhea. Other uses, along with other medications, include treating multidrug resistant tuberculosis. An eye drop may be used for a superficial bacterial infection of the eye and an ear drop may be used for otitis media when a hole in the ear drum is present.

<span class="mw-page-title-main">Cefixime</span> A third generation cephalosporin antibiotic

Cefixime, sold under the brand name Suprax among others, is an antibiotic medication used to treat a number of bacterial infections. These infections include otitis media, strep throat, pneumonia, urinary tract infections, gonorrhea, and Lyme disease. For gonorrhea typically only one dose is required. In the United States it is a second-line treatment to ceftriaxone for gonorrhea. It is taken by mouth.

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

Ceftazidime, sold under the brand name Fortaz among others, is a third-generation cephalosporin antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for joint infections, meningitis, pneumonia, sepsis, urinary tract infections, malignant otitis externa, Pseudomonas aeruginosa infection, and vibrio infection. It is given by injection into a vein, muscle, or eye.

<span class="mw-page-title-main">Norfloxacin</span> Chemical compound, antibiotic

Norfloxacin, sold under the brand name Noroxin among others, is an antibiotic that belongs to the class of fluoroquinolone antibiotics. It is used to treat urinary tract infections, gynecological infections, inflammation of the prostate gland, gonorrhea and bladder infection. Eye drops were approved for use in children older than one year of age.

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

Amikacin is an antibiotic medication used for a number of bacterial infections. This includes joint infections, intra-abdominal infections, meningitis, pneumonia, sepsis, and urinary tract infections. It is also used for the treatment of multidrug-resistant tuberculosis. It is used by injection into a vein using an IV or into a muscle.

<span class="mw-page-title-main">Ciprofloxacin/dexamethasone</span> Pharmaceutical product

Ciprofloxacin/dexamethasone (Ciprodex) is an antibiotic/steroid combination medication. It contains the synthetic broad-spectrum antibacterial agent, ciprofloxacin hydrochloride (0.3%), combined with the anti-inflammatory corticosteroid, dexamethasone (0.1%), in a sterile, preserved suspension for otic use.

<span class="mw-page-title-main">Ear drop</span> Form of medication placed in ears

Ear drops are a form of topical medication for the ears used to treat infection, inflammation, impacted ear wax and local anesthesia. They are commonly used for short-term treatment and can be purchased with or without a prescription. Before using ear drops, refer to the package insert or consult a health professional for the amount of drops to use and the duration of treatment.

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

Enoxacin is an oral broad-spectrum fluoroquinolone antibacterial agent used in the treatment of urinary tract infections and gonorrhea. Insomnia is a common adverse effect. It is no longer available in the United States.

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

Cinoxacin is a quinolone antibiotic that has been discontinued in the U.K. as well the United States, both as a branded drug or a generic. The marketing authorization of cinoxacin has been suspended throughout the EU.

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

Enrofloxacin, sold under the brand name Baytril, among others, is a fluoroquinolone antibiotic used for the treatment of animals. It is a bactericidal agent.

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

Fleroxacin is a quinolone antibiotic. It is sold under the brand names Quinodis and Megalocin.

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

Flumequine is a synthetic fluoroquinolone antibiotic used to treat bacterial infections. It is a first-generation fluoroquinolone antibacterial that has been removed from clinical use and is no longer being marketed. The marketing authorization of flumequine has been suspended throughout the EU. It kills bacteria by interfering with the enzymes that cause DNA to unwind and duplicate. Flumequine was used in veterinarian medicine for the treatment of enteric infections, as well as to treat cattle, swine, chickens, and fish, but only in a limited number of countries. It was occasionally used in France to treat urinary tract infections under the trade name Apurone. However this was a limited indication because only minimal serum levels were achieved.

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

Prulifloxacin is an older synthetic antibiotic of the fluoroquinolone class undergoing clinical trials prior to a possible NDA submission to the U.S. Food and Drug Administration (FDA). It is a prodrug which is metabolized in the body to the active compound ulifloxacin. It was developed over two decades ago by Nippon Shinyaku Co. and was patented in Japan in 1987 and in the United States in 1989.

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

Nadifloxacin is a topical fluoroquinolone antibiotic for the treatment of acne vulgaris. It is also used to treat bacterial skin infections.

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

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

<span class="mw-page-title-main">Quinolone antibiotic</span> Class of antibacterial drugs, subgroup of quinolones

Quinolone antibiotics constitute a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as well as in animal husbandry, specifically poultry production.

Staphylococcus schleiferi is a Gram-positive, cocci-shaped bacterium of the family Staphylococcaceae. It is facultatively anaerobic, coagulase-variable, and can be readily cultured on blood agar where the bacterium tends to form opaque, non-pigmented colonies and beta (β) hemolysis. There exists two subspecies under the species S. schleiferi: Staphylococcus schleiferi subsp. schleiferi and Staphylococcus schleiferi subsp. coagulans.

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

Plazomicin, sold under the brand name Zemdri, is an aminoglycoside antibiotic used to treat complicated urinary tract infections. As of 2019 it is recommended only for those in whom alternatives are not an option. It is given by injection into a vein.

References

  1. ↑ "FDA approves Xtoro to treat swimmer's ear". Food and Drug Administration. December 17, 2014.
  2. 1 2 3 4 5 6 "Finafloxacin: New fluoroquinolone for acute otitis externa". pharmacist.com. American Pharmacists Association. February 1, 2015. Retrieved 14 August 2017.
  3. 1 2 3 4 "finafloxacin (Otic route)". drugs.com. Drugs.com. Retrieved 15 August 2017.
  4. ↑ "Rx Update: Xtoro (Finafloxacin Otic Suspension)". contemporaryclinic.pharmacytimes.com. Contemporary Clinic 2017 Pharmacy & Healthcare Communications, LLC. Retrieved 14 August 2017.
  5. 1 2 3 4 5 6 7 8 9 McKeage K (April 2015). "Finafloxacin: first global approval". Drugs. 75 (6): 687–93. doi:10.1007/s40265-015-0384-z. PMID   25808831. S2CID   207488603.
  6. 1 2 3 4 5 Kocsis B, Domokos J, Szabo D (May 2016). "Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin". Annals of Clinical Microbiology and Antimicrobials. 15 (1): 34. doi:10.1186/s12941-016-0150-4. PMC   4878067 . PMID   27215369.
  7. 1 2 "Xtoro". drugs.com. Drugs.com. Retrieved 15 August 2017.
  8. ↑ Blaser MJ (October 2006). "Who are we? Indigenous microbes and the ecology of human diseases". EMBO Reports. 7 (10): 956–60. doi:10.1038/sj.embor.7400812. PMC   1618379 . PMID   17016449.
  9. ↑ Lemaire S, Van Bambeke F, Tulkens PM (July 2011). "Activity of finafloxacin, a novel fluoroquinolone with increased activity at acid pH, towards extracellular and intracellular Staphylococcus aureus, Listeria monocytogenes and Legionella pneumophila" (PDF). International Journal of Antimicrobial Agents. 38 (1): 52–9. doi:10.1016/j.ijantimicag.2011.03.002. PMID   21596526.
  10. 1 2 "Finafloxacin". pharmacodia.com. Retrieved 14 August 2017.
  11. ↑ Poh LC (July 29, 2017). "Biotech sector poised to deliver more health and wealth". SPH Digital News. The Straits Times. Retrieved 15 August 2017.
  12. ↑ "Xtoro Approval History". drugs.com. Drugs.com. Retrieved 15 August 2017.
  13. 1 2 Lane EJ (January 27, 2015). "Singapore's MerLion eyes partner for Phase III of Finafloxacin urinary infection trials". Questex LLC. FierceBiotech. Retrieved 15 August 2017.
  14. ↑ Bartoletti R, Cai T, Perletti G, Wagenlehner FM, Bjerklund Johansen TE (2015). "Finafloxacin for the treatment of urinary tract infections". Expert Opinion on Investigational Drugs. 24 (7): 957–63. doi:10.1517/13543784.2015.1052401. PMID   26068714. S2CID   27148906.
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