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Jublia

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Jublia

CLINICAL PHARMACOLOGY

Mechanism Of Action

JUBLIA topical solution is an azole antifungal.

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 14α-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 μg/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 Curea 117 7 88 11
17.8% 3.3% 15.2% 5.5%
Complete or Almost Complete Cureb 173 15 136 15
26.4% 7.0% 23.4% 7.5%
Mycologic Curec 362 36 310 34
55.2% 16.8% 53.4% 16.9%
aComplete cure defined as 0% clinical involvement of the target toenail plus negative KOH and negative culture.
bComplete or almost complete cure defined as ≤ 5% affected target toenail area involved and negative KOH and culture.
cMycologic cure defined as negative KOH and negative culture.

Last reviewed on RxList: 6/19/2014
This monograph has been modified to include the generic and brand name in many instances.

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