APMA News - May/June 2020 - 10

BRIEF SUMMARY OF PRESCRIBING INFORMATION
This Brief Summary does not include all the information needed to use
JUBLIA safely and effectively. See full prescribing information for JUBLIA.

JUBLIA®(efinaconazole) topical solution, 10%
For topical use
Initial U.S. Approval: 2014
INDICATIONS AND USAGE
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.
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.

Subcutaneous doses of 1, 5, and 10 mg/kg/day efinaconazole were administered
during the period of organogenesis (gestational days 6-19) to pregnant female
rabbits. In the presence of maternal toxicity, there was no embryofetal toxicity or
malformations at 10 mg/kg/day (154 times the MRHD based on AUC comparisons).
In a pre- and post-natal development study in rats, subcutaneous doses of
1, 5 and 25 mg/kg/day efinaconazole were administered from the beginning of
organogenesis (gestation day 6) through the end of lactation (lactation day 20).
In the presence of maternal toxicity, embryofetal toxicity (increased prenatal pup
mortality, reduced live litter sizes and increased postnatal pup mortality) was
noted at 25 mg/kg/day. No embryofetal toxicity was noted at 5 mg/kg/day (17
times the MRHD based on AUC comparisons). No effects on postnatal development
were noted at 25 mg/kg/day (89 times the MRHD based on AUC comparisons).
Nursing Mothers
It is not known whether efinaconazole is excreted in human milk. After repeated
subcutaneous administration, efinaconazole was detected in milk of nursing rats.
Because many drugs are excreted in human milk, caution should be exercised
when JUBLIA is administered to nursing women.
Pediatric Use
Safety and effectiveness of JUBLIA in pediatric subjects have not been established.

CONTRAINDICATIONS

Geriatric Use

None.

Of the total number of subjects in clinical trials of JUBLIA, 11.3% were 65
and over, while none were 75 and over. No overall differences in safety and
effectiveness were observed between these subjects and younger subjects, and
other reported clinical experience has not identified differences in responses
between the elderly and the younger subjects, but greater sensitivity of some
older individuals cannot be ruled out.

ADVERSE REACTIONS
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%)

NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment of Fertility
A 2-year dermal carcinogenicity study in mice was conducted with daily topical
administration of 3%, 10% and 30% efinaconazole solution. Severe irritation was
noted at the treatment site in all dose groups, which was attributed to the vehicle
and confounded the interpretation of skin effects by efinaconazole. The high dose
group was terminated at week 34 due to severe skin reactions. No drug-related
neoplasms were noted at doses up to 10% efinaconazole solution (248 times the
MRHD based on AUC comparisons).
Efinaconazole revealed no evidence of mutagenic or clastogenic potential based
on the results of two in vitro genotoxicity tests (Ames assay and Chinese hamster
lung cell chromosome aberration assay) and one in vivo genotoxicity test (mouse
peripheral reticulocyte micronucleus assay).
No effects on fertility were observed in male and female rats that were
administered subcutaneous doses up to 25 mg/kg/day efinaconazole (279 times
the MRHD based on AUC comparisons) prior to and during early pregnancy.
Efinaconazole delayed the estrous cycle in females at 25 mg/kg/day but not at 5
mg/kg/day (56 times MRHD based on AUC comparisons).
PATIENT COUNSELING INFORMATION

DRUG INTERACTIONS
In vitro studies have shown that JUBLIA, at therapeutic concentrations, neither
inhibits nor induces cytochrome P450 (CYP450) enzymes.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category C
There are no adequate and well-controlled studies with JUBLIA in pregnant
women. JUBLIA should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus.
Systemic embryofetal development studies were conducted in rats and
rabbits. Subcutaneous doses of 2, 10 and 50 mg/kg/day efinaconazole were
administered during the period of organogenesis (gestational days 6-16) to
pregnant female rats. In the presence of maternal toxicity, embryofetal toxicity
(increased embryofetal deaths, decreased number of live fetuses, and placental
effects) was noted at 50 mg/kg/day [559 times the Maximum Recommended
Human Dose (MRHD) based on Area Under the Curve (AUC) comparisons]. No
embryofetal toxicity was noted at 10 mg/kg/day (112 times the MRHD based
on AUC comparisons). No malformations were observed at 50 mg/kg/day
(559 times the MRHD based on AUC comparisons).

See FDA-Approved Patient Labeling (Patient Information).
Manufactured for:
Bausch Health Americas, Inc. Bridgewater, NJ 08807 USA
Manufactured by:
Bausch Health Companies Inc. Laval, Quebec H7L 4A8, Canada
JUBLIA is a trademark of Bausch Health Companies Inc. or its affiliates.
© 2019 Bausch Health Companies Inc. or its affiliates
U.S. Patents 8,039,494; 7,214,506
Based on 9462903

Rev 9/2016

JUB.0070.USA.19
APMA News - May/June 2020

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