INDICATIONS
JUBLIA (EFINACONAZOLE) TOPICAL SOLUTION, 10% IS AN AZOLE ANTIFUNGAL INDICATED FOR THE TOPICAL TREATMENT OF ONYCHOMYCOSIS OF THE TOENAIL(S) DUE TO TRICHOPHYTON RUBRUM AND TRICHOPHYTON MENTAGROPHYTES.
HOW SUPPLIED
DOSAGE FORMS AND STRENGTHS
JUBLIA (EFINACONAZOLE) TOPICAL SOLUTION, 10% CONTAINS 100 MG OF EFINACONAZOLE IN EACH GRAM OF CLEAR, COLORLESS TO PALE YELLOW SOLUTION.
STORAGE AND HANDLING
JUBLIA (EFINACONAZOLE) TOPICAL SOLUTION, 10% IS A CLEAR, COLORLESS TO PALE YELLOW SOLUTION SUPPLIED IN A WHITE PLASTIC BOTTLE WITH AN INTEGRATED FLOW-THROUGH BRUSH APPLICATOR AS FOLLOWS:
4 ML (NDC 0187-5400-04)
8 ML (NDC 0187-5400-08)
STORAGE AND HANDLING CONDITIONS:
STORE AT 20°C - 25°C (68°F - 77°F); EXCURSIONS PERMITTED TO 15°C - 30°C (59°F - 86°F) [SEE USP CONTROLLED ROOM TEMPERATURE].
" SOLUTION IS FLAMMABLE; KEEP AWAY FROM HEAT OR FLAME
" PROTECT FROM FREEZING
" KEEP OUT OF THE REACH OF CHILDREN
" KEEP BOTTLE TIGHTLY CLOSED
" STORE IN UPRIGHT POSITION
MANUFACTURED FOR: VALEANT PHARMACEUTICALS NORTH AMERICA LLC, BRIDGEWATER, NJ 08807 USA. MANUFACTURED BY: KAKEN PHARMACEUTICAL CO. LTD, SHIZUOKA, JAPAN. PRODUCT OF JAPAN. REVISED: FEB 2015
DOSAGE AND ADMINISTRATION
APPLY JUBLIA TO AFFECTED TOENAILS ONCE DAILY FOR 48 WEEKS, USING THE INTEGRATED FLOW-THROUGH BRUSH APPLICATOR. WHEN APPLYING JUBLIA, ENSURE THE TOENAIL, THE TOENAIL FOLDS, TOENAIL BED, HYPONYCHIUM, AND THE UNDERSURFACE OF THE TOENAIL PLATE, ARE COMPLETELY COVERED.
JUBLIA IS FOR TOPICAL USE ONLY AND NOT FOR ORAL, OPHTHALMIC, OR INTRAVAGINAL USE
SIDE EFFECTS
CLINICAL TRIALS EXPERIENCE
BECAUSE CLINICAL TRIALS ARE CONDUCTED UNDER WIDELY VARYING CONDITIONS, ADVERSE REACTION RATES OBSERVED IN THE CLINICAL TRIALS OF A DRUG CANNOT BE DIRECTLY COMPARED TO RATES IN THE CLINICAL TRIALS OF ANOTHER DRUG AND MAY NOT REFLECT THE RATES OBSERVED IN PRACTICE.
IN TWO CLINICAL TRIALS, 1227 SUBJECTS WERE TREATED WITH JUBLIA, 1161 FOR AT LEAST 24 WEEKS AND 780 FOR 48 WEEKS. ADVERSE REACTIONS REPORTED WITHIN 48 WEEKS OF TREATMENT AND IN AT LEAST 1% OF SUBJECTS TREATED WITH JUBLIA AND THOSE REPORTED IN SUBJECTS TREATED WITH THE VEHICLE ARE PRESENTED IN TABLE 1.
TABLE 1: ADVERSE REACTIONS REPORTED BY AT LEAST 1% OF SUBJECTS TREATED FOR UP TO 48 WEEKS
ADVERSE EVENT, N (%) JUBLIA
N = 1227 VEHICLE
N = 413
INGROWN TOENAIL 28 (2.3%) 3 (0.7%)
APPLICATION SITE DERMATITIS 27 (2.2%) 1 (0.2%)
APPLICATION SITE VESICLES 20 (1.6%) 0 (0.0%)
APPLICATION SITE PAIN 13 (1.1%) 1 (0.2%)
READ THE JUBLIA (EFINACONAZOLE TOPICAL SOLUTION) SIDE EFFECTS CENTER FOR A COMPLETE GUIDE TO POSSIBLE SIDE EFFECTS
CLINICAL PHARMACOLOGY
MECHANISM OF ACTION
JUBLIA TOPICAL SOLUTION IS AN AZOLE ANTIFUNGAL [SEE MICROBIOLOGY].
PHARMACODYNAMICS
THE PHARMACODYNAMICS OF JUBLIA IS UNKNOWN.
PHARMACOKINETICS
SYSTEMIC ABSORPTION OF EFINACONAZOLE IN 18 ADULT SUBJECTS WITH SEVERE ONYCHOMYCOSIS WAS DETERMINED AFTER APPLICATION OF JUBLIA ONCE DAILY FOR 28 DAYS TO PATIENTS 10 TOENAILS AND 0.5 CM ADJACENT SKIN. THE CONCENTRATION OF EFINACONAZOLE IN PLASMA WAS DETERMINED AT MULTIPLE TIME POINTS OVER THE COURSE OF 24-HOUR PERIODS ON DAYS 1, 14, AND 28. EFINACONAZOLE MEAN ± SD PLASMA CMAX ON DAY 28 WAS 0.67 ± 0.37 NG/ML AND THE MEAN ± SD AUC WAS 12.15 ± 6.91 NG*H/ML. THE PLASMA CONCENTRATION VERSUS TIME PROFILE AT STEADY STATE WAS GENERALLY FLAT OVER A 24-HOUR DOSING INTERVAL. IN A SEPARATE STUDY OF HEALTHY VOLUNTEERS, THE PLASMA HALF-LIFE OF EFINACONAZOLE FOLLOWING DAILY APPLICATIONS WHEN APPLIED TO ALL 10 TOENAILS FOR 7 DAYS WAS 29.9 HOURS.
DRUG INTERACTIONS
JUBLIA IS CONSIDERED A NON-INHIBITOR OF THE CYP450 ENZYME FAMILY. IN IN VITRO STUDIES USING HUMAN LIVER MICROSOMES, EFINACONAZOLE DID NOT INHIBIT CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2PE1 AND CYP3A4 ENZYME ACTIVITIES AT EXPECTED CLINICAL SYSTEMIC CONCENTRATIONS. IN VITRO STUDIES IN HUMAN PRIMARY HEPATOCYTES SHOWED THAT EFINACONAZOLE DID NOT INDUCE CYP1A2 OR CYP3A4 ACTIVITIES.
MICROBIOLOGY
MECHANISM OF ACTION
EFINACONAZOLE IS AN AZOLE ANTIFUNGAL. EFINACONAZOLE INHIBITS FUNGAL LANOSTEROL 14?-DEMETHYLASE INVOLVED IN THE BIOSYNTHESIS OF ERGOSTEROL, A CONSTITUENT OF FUNGAL CELL MEMBRANES.
ACTIVITY IN VITRO AND IN VIVO
EFINACONAZOLE HAS BEEN SHOWN TO BE ACTIVE AGAINST ISOLATES OF THE FOLLOWING MICROORGANISMS, BOTH IN VITRO AND IN CLINICAL INFECTIONS. EFINACONAZOLE EXHIBITS IN VITRO MINIMUM INHIBITORY CONCENTRATIONS (MICS) OF 0.06 ?G/ML OR LESS AGAINST MOST ( ? 90%) ISOLATES OF THE FOLLOWING MICROORGANISMS:
TRICHOPHYTON RUBRUM
TRICHOPHYTON MENTAGROPHYTES
MECHANISM OF RESISTANCE
EFINACONAZOLE DRUG RESISTANCE DEVELOPMENT WAS STUDIED IN VITRO AGAINST T. MENTAGROPHYTES, T. RUBRUM AND C. ALBICANS. SERIAL PASSAGE OF FUNGAL CULTURES IN THE PRESENCE OF SUB-GROWTH INHIBITORY CONCENTRATIONS OF EFINACONAZOLE INCREASED THE MIC BY UP TO 4-FOLD. THE CLINICAL SIGNIFICANCE OF THESE IN VITRO RESULTS IS UNKNOWN.
CLINICAL STUDIES
THE SAFETY AND EFFICACY OF ONCE DAILY USE OF JUBLIA FOR THE TREATMENT OF ONYCHOMYCOSIS OF THE TOENAIL WERE ASSESSED IN TWO 52-WEEK PROSPECTIVE, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND CLINICAL TRIALS IN PATIENTS 18 YEARS AND OLDER (18 TO 70 YEARS OF AGE) WITH 20% TO 50% CLINICAL INVOLVEMENT OF THE TARGET TOENAIL, WITHOUT DERMATOPHYTOMAS OR LUNULA (MATRIX) INVOLVEMENT. THE TRIALS COMPARED 48-WEEKS OF TREATMENT WITH JUBLIA TO THE VEHICLE SOLUTION. THE COMPLETE CURE RATE WAS ASSESSED AT WEEK 52 (4-WEEKS AFTER COMPLETION OF THERAPY). COMPLETE CURE WAS DEFINED AS 0% INVOLVEMENT OF THE TARGET TOENAIL (NO CLINICAL EVIDENCE OF ONYCHOMYCOSIS OF THE TARGET TOENAIL) IN ADDITION TO MYCOLOGIC CURE, DEFINED AS BOTH NEGATIVE FUNGAL CULTURE AND NEGATIVE KOH. TABLE 2 LISTS THE EFFICACY RESULTS FOR TRIALS 1 AND 2.
TABLE 2: EFFICACY ENDPOINTS
TRIAL 1 TRIAL 2
JUBLIA
N = 656 VEHICLE
N = 214 JUBLIA
N = 580 VEHICLE
N = 201
COMPLETE 117 7 88 11
CUREA 17.8% 3.3% 15.2% 5.5%
COMPLETE OR 173 15 136 15
ALMOST COMPLETE CUREB 26.4% 7.0% 23.4% 7.5%
MYCOLOGIC CUREC 362 36 310 34
55.2% 16.8% 53.4% 16.9%
A COMPLETE CURE DEFINED AS 0% CLINICAL INVOLVEMENT OF THE TARGET TOENAIL PLUS NEGATIVE KOH AND NEGATIVE CULTURE.
B COMPLETE OR ALMOST COMPLETE CURE DEFINED AS ? 5% AFFECTED TARGET TOENAIL AREA INVOLVED AND NEGATIVE KOH AND CULTURE.
C MYCOLOGIC CURE DEFINED AS NEGATIVE KOH AND NEGATIVE CULTURE.