Efinaconazole Topical Solution

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 to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 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 by: Valeant Pharmaceuticals International Inc. Laval, Quebec H7L 4A8, Canada. Revised: May 2016

No Information Provided

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 C 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

Efinaconazole is an azole antifungal. Efinaconazole inhibits fungal lanosterol 14α-demethylase involved in the biosynthesis of ergosterol, a constituent of fungal cell membranes.

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 mcg/mL or less against most (≥90%) isolates of the following microorganisms:

Trichophyton rubrum
Trichophyton mentagrophytes

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

JUBLIA
(joo-blee-uh)
(efinaconazole) Topical Solution, 10%

Important information: JUBLIA is for use ontoenails and surrounding skin only. Do not use JUBLIA in your mouth, eyes, or vagina.

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 in children.

What s hould I tell my healthcare provider before us ing JUBLIA?

Before you use JUBLIA, tell your healthcare provider about all your medical conditions, including if you:

• are pregnant or plan to become pregnant. It is not known if JUBLIA can harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if JUBLIA passes into your breast milk.

Tell your healthcare provider about all the medicines you take, including prescription and over-thecounter medicines, vitamins, and herbal supplements.

How s hould I us e JUBLIA?

See the “Ins tructions for Us e” at the end of this Patient Information leaflet for detailed information about the right way to us e JUBLIA.

• Use JUBLIA exactly as your healthcare provider tells you to use it. Apply JUBLIA to your affected toenails 1 time each day. Wait for at least 10 minutes after showering, bathing, or washing before applying JUBLIA. JUBLIA is used for 48 weeks.
• It is not known if the use of nail polish or other cosmetic nail products (such as gel nails or acrylic nails) will affect how JUBLIA works.

What s hould I avoid while us ing JUBLIA?

• JUBLIA is flammable. Avoid heat and flame while applying JUBLIA to your toenail.

What are the pos s ible s ide effects of JUBLIA?

JUBLIA may cause irritation at the treated site. The most common side effects include: ingrown toenail, redness, itching, swelling, burning or stinging, blisters, and pain. Tell your healthcare provider if you have any side effects that bother you or that do not go away.

These are not all the possible side effects of JUBLIA.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1- 800-FDA-1088.

How s hould I s tore JUBLIA?

• Store JUBLIA at room temperature, between 68°F to 77°F (20°C to 25°C). Do not freeze JUBLIA.
• Keep the bottle tightly closed and store in an upright position.
• JUBLIA is flammable. Keep away from heat and flame.

Keep JUBLIA and all medicines out of the reach of children.

General information about the s afe and effective us e of JUBLIA

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about JUBLIA that is written for health professionals. Do not use JUBLIA for a condition for which it was not prescribed. Do not give JUBLIA to other people, even if they have the same condition you have. It may harm them.

What are the ingredients in JUBLIA?

Active ingredients : efinaconazole

Inactive ingredients : alcohol, anhydrous citric acid, butylated hydroxytoluene, C12-15 alkyl lactate, cyclomethicone, diisopropyl adipate, disodium edetate, and purified water.

Instructions for Use

JUBLIA (joo-blee-uh)
(efinaconazole) topical solution, 10%

Important information: JUBLIA is for use ontoenails and surrounding skin only. Do not use JUBLIA in your mouth, eyes or vagina.

Read the Instructions for Use that comes with JUBLIA before you start using it. Talk to your healthcare provider if you have any questions.

How to apply JUBLIA:

Your toenails should be clean and dry before you apply JUBLIA.

Step 1: Before you apply JUBLIA to your affected toenail, remove the cap from the JUBLIA bottle. (See Figure A).

Step 2: Hold the bottle upside down directly over the affected toenail and allow the product to moisten the brush. By turning the bottle upside down, the entire brush will become wet with the drug solution. Apply one drop of JUBLIA onto the toenail. Do not squeeze the bottle or press/rub the brush firmly against the toenail while applying JUBLIA (See Figure B).

Step 3: For the big toenail, also apply a second drop to the end of the toenail by touching the tip of the moist brush to the end of the toenail (See Figure C). If needed, repeat step 2 to re-wet brush.

Step 4: Use the brush attached to the bottle to gently apply JUBLIA. The goal is to make sure that the entire toenail including the cuticle, folds of the skin next to the sides of the toenail, and underneath the nail are covered with the drug solution. (See Figure D). Pressing or rubbing firmly against the toenail while applying JUBLIA could cause brush deformation and over application of the drug solution.

Step 5: Repeat Steps 2 to 4 to apply JUBLIA to each affected toenail.

Step 6: Let JUBLIA dry completely.

Step 7: After applying JUBLIA to your affected toenails, place the cap on the bottle and screw it on tightly.

Step 8: Wash your hands with soap and water after applying JUBLIA.

Side effects that you should report to your doctor or health care professional as soon as possible:

• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
• ingrown toenail

Side effects that usually do not require medical attention (Report these to your doctor or health care professional if they continue or are bothersome.):

• mild skin irritation, burning, or itching

This medicine is for external use only. Do not take by mouth. Follow the directions on the label. Wash hands before and after use. Apply this medicine using the provided brush to cover the entire toenail. Do not use your medicine more often than directed. Finish the full course prescribed by your doctor or health care professional even if you think your condition is better. Do not stop using except on the advice of your doctor or health care professional.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

They need to know if you have any of these conditions:

• an unusual or allergic reaction to efinaconazole, other medicines, foods, dyes or preservatives
• pregnant or trying to get pregnant
• breast-feeding

If you miss a dose, use it as soon as you can. If it is almost time for your next dose, use only that dose. Do not use double or extra doses.

Do not get this medicine in your eyes. If you do, rinse out with plenty of cool tap water.

Tell your doctor or healthcare professional if your symptoms do not start to get better or if they get worse

Wait for at least 10 minutes after bathing before applying this medication. After bathing make sure that your feet are very dry. Fungal infections like moist conditions. Do not walk around barefoot. To help prevent reinfection, wear freshly washed cotton, not synthetic, clothing. Tell your doctor or health care professional if you develop sores or blisters that do not heal properly. If your nail infection returns after you stop using this medicine, contact your doctor or health care professional.

Keep out of the reach of children.

Store at room temperature between 20 and 25 degrees C (68 and 77 degrees F). Keep this medicine in the original container. Throw away any unused medicine after the expiration date.

This medicine is flammable. Avoid exposure to heat, fire, flame, and smoking.