Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

JUBLIA (NDA-203567)

(EFINACONAZOLE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

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03/31/2022 (SUPPL-10)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

New subsection added

The following adverse reactions have been identified during post-approval use of JUBLIA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.

General Disorders and Administration Site Conditions: Application site erythema and exfoliation

Skin and Subcutaneous Tissue Disorders: Onychomadesis, Nail discoloration

04/26/2020 (SUPPL-9)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

There are no available human data for the use of JUBLIA during pregnancy to inform any drug associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

In animal reproduction studies, efinaconazole did not cause malformations or any harm to the fetus when administered to pregnant rabbits and rats during the period of organogenesis at subcutaneous doses up to 112 and 154 times, respectively, the Maximum Recommended Human Dose (MRHD) based on Area Under the Curve (AUC) comparisons.

Embryolethality was observed only in rats in the presence of maternal toxicity at systemic exposures 559 times the MRHD based on AUC comparisons. Subcutaneous efinaconazole administration to pregnant rats from the beginning of organogenesis through the end of lactation did not cause embryofetal toxicity or developmental effects at systemic exposures 17 times the MRHD based on AUC comparisons (see Data).

The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies.

Data

Animal Data

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 MRHD based on 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).

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 postnatal 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).

8.2 Lactation

(PLLR conversion)

Risk Summary

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.

The developmental and health benefits of breastfeeding should be considered, along with the mother’s clinical need for JUBLIA, and any potential adverse effects on the breastfed infant from JUBLIA.

8.4 Pediatric Use

(additions underlined)

The safety and effectiveness of JUBLIA were established in patients 6 years and older. Use of JUBLIA in these age groups is supported by evidence from well-controlled trials in adults with additional data from an open-label safety study in 60 pediatric subject ages 6 to 17 (including a pharmacokinetic study in 17 subjects 12 years to less than 17 years old) [see Clinical Pharmacology (12.3)]. Safety and effectiveness of JUBLIA in pediatric subjects under 6 years of age have not been established.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT INFORMATION

(additions underlined)

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What is JUBLIA?

JUBLIA is a prescription medicine used to treat fungal infections of the toenails.

It is not known if JUBLIA is safe and effective for use in children under 6 years of age.

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