INDICATIONS
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.
HOW SUPPLIED
DOSAGE FORMS AND STRENGTHS
5 ML OF A 0.3% TOPICAL OTIC SUSPENSION IN AN EIGHT (8) ML BOTTLE.
XTORO (FINAFLOXACIN OTIC SUSPENSION) 0.3% IS A STERILE, PRESERVED, AQUEOUS, OTIC SUSPENSION SUPPLIED IN AN OPAQUE PLASTIC BOTTLE WITH A CONTROLLED DROP TIP AND A WHITE CAP:
5 ML FILL IN AN 8 ML BOTTLE (NDC 0065-XXXX-XX)
STORAGE AND HANDLING
STORE AT 2-25Β°C (36-77Β°F). DO NOT FREEZE.
MANUFACTURED BY: ALCON LABORATORIES, INC. 6201 SOUTH FREEWAY FORT WORTH, TEXAS 76134 USA 1-800-757-9785. REVISED: DECEMBER 2014.
DOSAGE AND ADMINISTRATION
INSTILL FOUR DROPS INTO THE AFFECTED EAR(S) TWICE DAILY FOR SEVEN DAYS. FOR PATIENTS REQUIRING USE OF AN OTOWICK, THE INITIAL DOSE CAN BE DOUBLED (TO 8 DROPS), FOLLOWED BY 4 DROPS INSTILLED INTO THE AFFECTED EAR TWICE DAILY FOR SEVEN DAYS.
IMPORTANT ADMINISTRATION INSTRUCTIONS INCLUDE:
" WARM THE SUSPENSION BY HOLDING THE BOTTLE IN THE HAND FOR ONE OR TWO MINUTES PRIOR TO DOSING IN ORDER TO AVOID DIZZINESS WHICH MAY RESULT FROM THE INSTILLATION OF A COLD SUSPENSION. SHAKE BOTTLE WELL BEFORE USE.
" LIE WITH THE AFFECTED EAR UPWARD, INSTILL THE DROPS, AND MAINTAIN THE POSITION FOR 60 SECONDS TO FACILITATE PENETRATION OF THE DROPS INTO THE EAR CANAL.
" REPEAT IF NECESSARY FOR THE OPPOSITE EAR.
SIDE EFFECTS
CLINICAL STUDIES EXPERIENCE
BECAUSE CLINICAL STUDIES ARE CONDUCTED UNDER WIDELY VARYING CONDITIONS, ADVERSE REACTION RATES OBSERVED IN THE CLINICAL STUDIES OF A DRUG CANNOT BE DIRECTLY COMPARED TO RATES IN THE CLINICAL STUDIES OF ANOTHER DRUG AND MAY NOT REFLECT THE RATES OBSERVED IN PRACTICE.
A TOTAL OF 618 PATIENTS WERE TREATED WITH XTORO IN TWO PHASE 3 CLINICAL TRIALS. THE MOST FREQUENTLY REPORTED ADVERSE REACTIONS OF THOSE EXPOSED TO XTORO OCCURRING AT AN INCIDENCE OF 1% INCLUDED EAR PRURITUS AND NAUSEA.
READ THE XTORO (FINAFLOXACIN OTIC SUSPENSION) SIDE EFFECTS CENTER FOR A COMPLETE GUIDE TO POSSIBLE SIDE EFFECTS
CLINICAL PHARMACOLOGY
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.
MECHANISM OF RESISTANCE
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
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)
STUDY 1 STUDY 2
XTORO VEHICLE XTORO VS. VEHICLE DIFFERENCE
(95% CI) XTORO VEHICLE XTORO VS. VEHICLE DIFFERENCE
(95% CI)
PATHOGEN + SUBSET 104/145
(71.7%) 46/138
(33.3%) 38.4%
(27.6%, 49.1%) 101/147
(68.7%) 52/130
(40.0%) 28.7%
(17.4%, 40.0%)
ITT 245/344
(71.2%) 173/342
(50.6%) 20.6%
(13.5%, 27.8%) 194/274
(70.8%) 134/274
(48.9%) 21.9%
(13.9%, 29.9%)
A A CLINICAL CURE WAS ATTAINED IF THE SUM OF THE NUMERICAL SCORES OF THE 3 SIGNS AND SYMPTOMS OF AOE (TENDERNESS, ERYTHEMA, AND EDEMA) WAS 0 AT DAY 11
(TOC).
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)
STUDY 1 STUDY 2
XTORO VEHICLE XTORO VS. VEHICLE DIFFERENCE (95% CI) XTORO VEHICLE XTORO VS. VEHICLE DIFFERENCE (95% CI)
PATHOGEN + SUBSET 4.0 7.0 -3.0
(-5.0, -0.8) 3.0 6.5 -3.6
(-5.0, -2.0)
ITT 4.0 5.0 -1.0
(-2.0, -0.5) 3.0 5.5 -2.2
(-3.0, -1.0)
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)
STUDY 1 STUDY 2
XTORO VEHICLE XTORO VS. VEHICLE DIFFERENCE (95% CI) XTORO VEHICLE XTORO VS. VEHICLE DIFFERENCE (95% CI)
PATHOGEN + SUBSET 97/145 (66.9%) 18/138 (13.0%) 53.9% (44.4%, 63.4%) 97/147 (66.0%) 15/130 (11.5%) 54.4% (45.0%, 63.9%)
B MICROBIOLOGICAL SUCCESS WAS ATTAINED IF ALL PRE-THERAPY BACTERIA WERE ABSENT FROM THE EXIT OTIC SPECIMEN. THE PRESENCE OF FUNGI AND/OR YEAST WAS NOT CONSIDERED IN THE DETERMINATION OF MICROBIOLOGICAL SUCCESS.
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.