Finafloxacin (Xtoro) is a

fluoroquinolone antibiotic A quinolone antibiotic is a member of 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 ...

. In the United States, it is approved by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

to treat acute

otitis externa Otitis externa, also called swimmer's ear, is inflammation of the ear canal. It often presents with ear pain, swelling of the ear canal, and occasionally decreased hearing. Typically there is pain with movement of the outer ear. A high fever is ...

(swimmer's ear) caused by the bacteria ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerug ...

'' and '' Staphylococcus aureus''.

Medical uses

Finafloxacin is used to treat a type of ear infection called acute otitis externa caused by ''

'' and '' Staphylococcus aureus'' bacteria. 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 A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...

to 3.5 days. Finafloxacin cannot be purchased

over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...

, and is available by prescription only.

Available forms

Finafloxacin is commercially available as a 0.3% otic (meaning "for the ear")

suspension Suspension or suspended may refer to: Science and engineering * Suspension (topology), in mathematics * Suspension (dynamical systems), in mathematics * Suspension of a ring, in mathematics * Suspension (chemistry), small solid particles suspende ...

for

topical administration A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

in the United States. The suspension should be warmed gently in the hands for 1–2 minutes before administration to prevent dizziness, and shaken before use. 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.

Specific populations

Pregnancy

Finafloxacin is classified as

pregnancy category The pregnancy category of a medication is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does ''not'' include any risks conferred by pharmaceutical agents or their ...

C, meaning that the risk for harming a developing fetus has not been ruled out.

Pediatrics

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

Geriatrics

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

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 Itch (also known as pruritus) is a Wikt:sensation, sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of Sensory system, sensory experience. Itch has many similarities to pain, ...

and

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

(<1% for both). People that have administered finafloxacin by mouth or

intravenously Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

(IV) have experienced gastrointestinal side effects (including

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

, flatulence, and nausea), fatigue,

headaches Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

, musculoskeletal problems, and injection site reactions (if IV). Respiratory disorders, including

rhinitis Rhinitis, also known as coryza, is irritation and inflammation of the mucous membrane inside the nose. Common symptoms are a stuffy nose, runny nose, sneezing, and post-nasal drip. The inflammation is caused by viruses, bacteria, irrita ...

and

nasopharyngitis The common cold or the cold is a viral infectious disease of the upper respiratory tract that primarily affects the respiratory mucosa of the nose, throat, sinuses, and larynx. Signs and symptoms may appear fewer than two days after exposu ...

, have also been associated with the use of finafloxacin. People that are allergic to other quinolones may be allergic to finafloxacin as well, and use may result in an

allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

in that population. Adverse effects consistent with an allergic reaction to finafloxacin may include swelling of the lips, tongue, or throat, difficulty swallowing, and shortness of breath.

Overdose

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

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).

Pharmacology

Mechanism of action

Finafloxacin is a

fluoroquinolone A quinolone antibiotic is a member of 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 wel ...

class antibiotic of the 8-

cyano Cyanide is a naturally occurring, rapidly acting, toxic chemical that can exist in many different forms. In chemistry, a cyanide () is a chemical compound that contains a functional group. This group, known as the cyano group, consists of a ...

subclass (referring to the CN substituent at the 8th position). 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. However, unlike other fluoroquinolones, finafloxacin is highly active under acidic ( pH 5.0–6.0) conditions, where certain bacteria (like ''

Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is thoug ...

'', a bacterium that is known to infect the human

stomach The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...

, despite the harsh acidity) thrive. 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. Finafloxacin has demonstrated bactericidal activity against a range of bacterial pathogens, especially at acidic pH, with a post-antibiotic effect. Owing to its activity against both

Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

and

Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...

bacteria, finafloxacin is classified as a

broad-spectrum antibiotic A broad-spectrum antibiotic is an antibiotic that acts on the two major bacterial groups, Gram-positive and Gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are used when a bacterial ...

Pharmacokinetics

Finafloxacin has good oral

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...

, meaning that a substantial portion of a dose taken by mouth reaches a person's systemic circulation. Some people have experienced unintentional, quantifiable absorption of finafloxacin into systemic circulation after administering the drug via the ear. The

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

of finafloxacin is approximately 10 hours in humans.

Chemistry

The chemical structure of finafloxacin has been described as a "fluorinated quinolone derivative with 8-

-substituent and 7-pyrrolo-oxazinyl moiety." Its low isoelectric point (pH 6.7) is lower than the isoelectric point of another fluoroquinolone class antibiotic called

ciprofloxacin 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 diarrhea, respiratory tract infections, skin inf ...

(pH 7.4), which accounts for finafloxacin's superior activity at low pH (5.0–6.0). 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 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. Common side effects in ...

has an 8-

methoxy In organic chemistry, a methoxy group is the functional group consisting of a methyl group bound to oxygen. This alkoxy group has the formula . On a benzene ring, the Hammett equation classifies a methoxy substituent at the ''para'' position a ...

-substituent instead. The oxygen atom in the ring structure of finafloxacin makes the molecule more

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are ...

than ciprofloxacin. 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. An example of its synthesis is provided below:

History

Finafloxacin is the first

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

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

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 A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidne ...

in the future. Finafloxacin's manufacturer, MerLion, has invested money in studying the use of finafloxacin for this indication.

References

{{QuinoloneAntiBiotics Fluoroquinolone antibiotics Carboxylic acids Cyclopropyl compounds Nitriles