Xtoro

XTORO* (finafloxacin otic suspension), 0.3% is indicated for the treatment of acute otitis externa (AOE) with or without an otowick, caused by susceptible strains of Pseudomonas aeruginosa and Staphylococcus aureus in patients age 1 year and older.

Mechanism Of Action

Finafloxacin is a fluoroquinolone antimicrobial [see Microbiology].

Pharmacokinetics

Finafloxacin plasma concentrations were evaluated following single or repeated ototopical doses of XTORO (finafloxacin otic suspension), 0.3%. In healthy subjects administered 4 drops in each ear twice daily for seven days, quantifiable finafloxacin concentrations were observed in 2 of 14 subjects; and these concentrations were just above the quantitation limit (0.05 ng/mL). Similarly, in AOE patients administered a single dose of 4 or 8 drops in each ear, quantifiable finafloxacin concentrations of up to 0.234 ng/mL were observed in plasma samples from 2 of 36 AOE patients.

Microbiology

Finafloxacinbelongs to the fluoroquinolone class of antibacterials which involves the inhibition of bacterial type II topoisomerase enzymes, DNA gyrase and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair and recombination.

Finafloxacin has been shown to be active against most isolates of the following bacteria, both in vitro and clinical studies as described in the INDICATIONS AND USAGE section of the package insert for XTORO

Pseudomonas aeruginosa
Staphylococcus aureus.

Resistance to fluoroquinolones occurs primarily by mutations in the chromosomal DNA that encode for DNA gyrase and DNA topoisomerase enzymes, decreased outer membrane permeability or drug efflux mechanisms. In vitro resistance to finafloxacin due to spontaneous mutation is rare.

Cross-resistance has been observed between finafloxacin and other fluoroquinolones. No cross-resistance has been observed between finafloxacin and other classes of antibacterial agents.

Clinical Studies

In two randomized multicenter, vehicle controlled clinical trials, XTORO dosed four drops twice daily for 7 days was superior to its vehicle for both clinical and microbiological outcomes as well as in time to cessation of ear pain in patients with acute otitis externa (AOE).

Among 560 patients (161 with an otowick) that were pathogen positive (baseline microbiological specimen that contained Staphylococcus aureus and/or Pseudomonas aeruginosa), clinical cure on Day 11 was 71% in XTORO versus 37% in Vehicle. Among 1234 patients who received study treatment (Intent to Treat population (ITT)), aged 6 months to 85 years, clinical cures were 71% for XTORO and 50% in Vehicle.

Clinical Curesa at Day 11 (Pathogen Positive Subset, and ITT)

The median time to cessation of ear pain in pathogen positive patients treated with XTORO was
3.5 days compared to 6.8 days in Vehicle. The median time to cessation of ear pain in ITT patients treated with XTORO was 3.5 days compared to 5.3 days in Vehicle.

Median Time (in Days) to Cessation of Ear Pain (Pathogen Positive Subset and ITT)

Among the pathogen positive patients, microbiological success (eradication of all baseline organisms) was achieved on Day 11 in 67% in XTORO versus 13% in the Vehicle treated patients.

Microbiological Successb at Day 11 (Pathogen Positive Subset)

In clinically cured pathogen positive patients, XTORO demonstrated eradication rates of 89% in both Staphylococcus aureus and Pseudomonas aeruginosa. Vehicle eradication rates were 33% for Staphylococcus aureus and 20% for Pseudomonas aeruginosa.

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of finafloxacin ear drops in the elderly.

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Keep the bottle closed when you are not using it. You may store it in the refrigerator or at room temperature, away from light and heat. Do not freeze.

Serious side effects have been reported with Xtoro including the following:

• Itching of the ear
• Nausea

Xtoro can cause dizziness. Do not drive or operate heavy machinery until you know how Xtoro  affects you.

Do not take Xtoro if you:

• are allergic to Xtoro or to any of its ingredients

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Xtoro, there are no specific foods that you must exclude from your diet when receiving this medication.

Take Xtoro exactly as prescribed.

This medication comes in a suspension form and is instilled into the ear twice daily for 7 days.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of Xtoro at the same time.

Use this medicine exactly as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

This medicine should be used only in the ear. Do not put it in the eyes or nose, and do not take it by mouth. If this medicine is swallowed by accident or gets in your eyes, call your doctor right away.

It is important that the infected ear remain clean and dry. When bathing, avoid getting the infected ear wet. Avoid swimming unless your doctor has instructed you otherwise.

To use the ear drops:

• Wash your hands thoroughly with soap and water.
• Hold the bottle in your hands for 1 or 2 minutes to warm the suspension. Cold drops could cause you to become dizzy.
• Shake the bottle well before using it.
• Lie down on your side with the infected ear facing up.
• Drop the prescribed number of drops into the ear. Keep the ear tilted up for 60 seconds.
• Repeat the above steps if both ears are infected.

Keep using this medicine for the full treatment time, even if you or your child feel better after the first few doses. The infection may not clear up if you stop using the medicine too soon. Do not miss any doses.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For otic dosage form (suspension):
  • For ear infections:
    • Adults and children 1 year of age and older—4 drops into the affected ear(s) two times a day for 7 days. For patients who need to use an otowick, use a starting dose of 8 drops followed by 4 drops into the affected ear(s) two times a day for 7 days.
    • Children younger than 1 year of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Keep the bottle closed when you are not using it. You may store it in the refrigerator or at room temperature, away from light and heat. Do not freeze.

Use the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up the missed dose.