ADAPALENE AND BENZOYL PEROXIDE gel
For Healthcare Providers >

1. Before You Use Adapalene And Benzoyl Peroxide Gel, Tell Your Doctor If You:
2. How Should I Use Adapalene And Benzoyl Peroxide Gel?
3. Applying Adapalene And Benzoyl Peroxide Gel:
4. Local Skin Reactions. Local Skin Reactions Are Most Likely To Happen During The First 4 Weeks Of Treatment And Usually Lessen With Continued Use Of Adapalene And Benzoyl Peroxide Gel. Signs And Symptoms Of Local Skin Reaction Include:
5. Patient Information
6. What Is Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%?
7. Before You Use Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%, Tell Your Doctor If You:
8. How Should I Use Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%?
9. Applying Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%:
10. Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5% Comes In A Tube And A Pump.if You Have Been Prescribed The:
11. What Should I Avoid While Using Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%?
12. Local Skin Reactions. Local Skin Reactions Are Most Likely To Happen During The First 4 Weeks Of Treatment And Usually Lessen With Continued Use Of Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%. Signs And Symptoms Of Local Skin Reaction Include:
13. How Should I Store Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%?
14. What Are The Ingredients In Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%?
15. Important:
16. Before You Use Adapalene And Benzoyl Peroxide Gel 0.1% / 2.5%, Tell Your Doctor If You:
17. Adapalene And Benzoyl Peroxide Gel 0.1% / 2.5% Comes In A Tube And A Pump. If You Have Been Prescribed The:
18. Local Skin Reactions. Local Skin Reactions Are Most Likely To Happen During The First 4 Weeks Of Treatment And Usually Lessen With Continued Use Of Adapalene And Benzoyl Peroxide Gel 0.1% / 2.5%. Signs And Symptoms Of Local Skin Reaction Include:
19. What Is Adapalene And Benzoyl Peroxide Gel?
20. What Should I Avoid While Using Adapalene And Benzoyl Peroxide Gel?
21. How Should I Store Adapalene And Benzoyl Peroxide Gel?
22. What Are The Ingredients In Adapalene And Benzoyl Peroxide Gel?

Before You Use Adapalene And Benzoyl Peroxide Gel, Tell Your Doctor If You: ⮝

• have other skin problems, including cuts or sunburn
• have any other medical conditions
• are pregnant or planning to become pregnant. It is not known if adapalene and benzoyl peroxide gel can harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.
• are breastfeeding or plan to breastfeed. It is not known if adapalene and benzoyl peroxide gel passes into your breast milk and if it can harm your baby. Talk to your doctor about the best way to feed your baby if you use adapalene and benzoyl peroxide gel.

Tell your doctor about all the medicines you take,including prescription and non-prescription medicines, vitamins and herbal supplements.

Especially tell your doctor if you use any other medicine for acne. Using adapalene and benzoyl peroxide gel with topical medicines that contain sulfur, resorcinol or salicylic acid may cause skin irritation.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How Should I Use Adapalene And Benzoyl Peroxide Gel? ⮝

• Use adapalene and benzoyl peroxide gel exactly as your doctor tells you to use it. Adapalene and benzoyl peroxide gel is for skin use only. Do not use adapalene and benzoyl peroxide gel in or on your mouth, eyes, or vagina.
• Apply adapalene and benzoyl peroxide gel 1 time a day.
• Do not use more adapalene and benzoyl peroxide gel than you need to cover the treatment area. Using too much adapalene and benzoyl peroxide gel or using it more than 1 time a day may increase your chance of skin irritation.

Applying Adapalene And Benzoyl Peroxide Gel: ⮝

• Wash the area where the gel will be applied with a mild cleanser and pat dry.
• Adapalene and benzoyl peroxide gel comes in a tube and a pump. If you have been prescribed the:
  • Tube: Squeeze a small amount (about the size of a pea) of adapalene and benzoyl peroxide gel onto your fingertips and spread a thin layer over the affected area.
  • Pump: Depress the pump to dispense a small amount (about the size of a pea) of adapalene and benzoyl peroxide gel and spread a thin layer over the affected area.

Local Skin Reactions. Local Skin Reactions Are Most Likely To Happen During The First 4 Weeks Of Treatment And Usually Lessen With Continued Use Of Adapalene And Benzoyl Peroxide Gel. Signs And Symptoms Of Local Skin Reaction Include: ⮝

Redness

Dryness

Swelling

Scaling

Stinging or burning

Tell your doctor right away if these side effects continue for longer than 4 weeks or get worse, you may have to stop using adapalene and benzoyl peroxide gel.

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of adapalene and benzoyl peroxide gel. For more information, ask your doctor or pharmacist.

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

You may also report side effects to Taro Pharmaceuticals U.S.A., Inc. at 1-866-923-4914.

Patient Information ⮝

[SeeFDA Approved Patient Labeling (Patient Information)]

Information for Patients

• Advise patients to cleanse the area to be treated with a mild or soapless cleanser; pat dry. Apply adapalene and benzoyl peroxide gel as a thin layer, avoiding the eyes, lips and mucous membranes.
• Advise patients not to use more than the recommended amount and not to apply more than once daily as this will not produce faster results, but may increase irritation.
• Adapalene and benzoyl peroxide gel may cause irritation such as erythema, scaling, dryness, stinging or burning.
• Advise patients to minimize exposure to sunlight, including sunlamps. Recommend the use of sunscreen products and protective apparel, (e.g., hat) when exposure cannot be avoided.
• Adapalene and benzoyl peroxide gel may bleach hair and colored fabric.

Made in Canada

Distributed by:
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA

Revised October 2016

2007424

What Is Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%? ⮝

Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% is a prescription medicine for skin use only (topical) used to treat acne vulgaris in people 9 years of age and older.

Acne vulgaris is a condition in which the skin has blackheads, whiteheads and pimples.

It is not known if Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% is safe and effective in children younger than 9 years old.

Before You Use Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%, Tell Your Doctor If You: ⮝

have other skin problems, including cuts or sunburn

have any other medical conditions

are pregnant or planning to become pregnant. It is not known if Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% can harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.

are breastfeeding or plan to breastfeed. It is not known if Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% passes into your breast milk and if it can harm your baby. Talk to your doctor about the best way to feed your baby if you use Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%.

Tell your doctor about all the medicines you take,including prescription and nonprescription medicines, vitamins and herbal supplements.

Especially tell your doctor if you use any other medicine for acne. Using Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% with topical medicines that contain sulfur, resorcinol or salicylic acid may cause skin irritation.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How Should I Use Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%? ⮝

Use Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% exactly as your doctor tells you to use it. Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% is for skin use only. Do not use Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% in or on your mouth, eyes, or vagina.

Apply Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% 1 time a day.

Do not use more Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% than you need to cover the treatment area. Using too much Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% or using it more than 1 time a day may increase your chance of skin irritation.

Applying Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%: ⮝

Wash the area where the gel will be applied with a mild cleanser and pat dry.

Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5% Comes In A Tube And A Pump.if You Have Been Prescribed The: ⮝

o

Tube: Squeeze a small amount (about the size of a pea) of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% onto your fingertips and spread a thin layer over the affected area.

o

Pump: Depress the pump to dispense a small amount (about the size of a pea) of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% and spread a thin layer over the affected area.

What Should I Avoid While Using Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%? ⮝

You should avoid spending time in sunlight or artificial sunlight, such as tanning beds or sunlamps. Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% can make your skin sensitive to sun and the light from tanning beds and sunlamps. You should wear sunscreen and wear a hat and clothes that cover the areas treated with Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% if you have to be in sunlight.

You should avoid weather extremes such as wind and cold as this may cause irritation to your skin.

You should avoid applying Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% to cuts, abrasions and sunburned skin.

You should avoid skin products that may dry or irritate your skin such as harsh soaps, astringents, cosmetics that have strong skin drying effects and products containing high levels of alcohol.

You should avoid the use of waxing as a hair removal method on skin treated with Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%.

Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% may bleach your clothes or hair. Allow Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% to dry completely before dressing to prevent bleaching of your clothes.

Local Skin Reactions. Local Skin Reactions Are Most Likely To Happen During The First 4 Weeks Of Treatment And Usually Lessen With Continued Use Of Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%. Signs And Symptoms Of Local Skin Reaction Include: ⮝

Redness

Dryness

Swelling

Scaling

Stinging or burning

Tell your doctor right away if these side effects continue for longer than 4 weeks or get worse, you may have to stop using Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%. For more information, ask your doctor or pharmacist.

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

You may also report side effects to Perrigo at 1-866-634-9120.

How Should I Store Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%? ⮝

Store Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% at room temperature, 68 77 F (20 25 C)

Keep Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% inside container and out of light and away from heat.

Keep Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% and all medicines out of the reach of children.

General information about Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% for a condition for which it was not prescribed. Do not give Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% to other people, even if they have the same symptoms you have. It may harm them.

This Patient Information leaflet summarizes the most important information about Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%. If you would like more information, talk with your doctor. You can also ask your doctor or pharmacist for information about Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% that is written for health professionals.

What Are The Ingredients In Adapalene And Benzoyl Peroxide Gel, 0.1%/2.5%? ⮝

Active ingredient: adapalene and benzoyl peroxide

Inactive ingredients: acrylamide/sodium acryloyldimethyltaurate copolymer, docusate sodium, edetate disodium, glycerin, isohexadecane, poloxamer 124, polysorbate 80, propylene glycol, purified water and sorbitan oleate.

Made in Israel

Manufactured By Perrigo

Yeruham, Israel

Distributed By

Perrigo

Allegan, MI 49010

www.perrigo.com

Rev 07-18

7T2W8 RC F2

Important: ⮝

For use on the skin only (topical). Do not use adapalene and benzoyl peroxide gel 0.1% / 2.5% in or on your mouth, eyes, or vagina.

Read this Patient Information leaflet about adapalene and benzoyl peroxide gel 0.1% / 2.5% before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your treatment or your medical condition. If you have any questions about adapalene and benzoyl peroxide gel 0.1% / 2.5%, talk with your doctor or pharmacist.

What isadapalene and benzoyl peroxide gel 0.1% / 2.5%?

Adapalene and benzoyl peroxide gel 0.1% / 2.5% is a prescription medicine for skin use only (topical) used to treat acne vulgaris in people 9 years of age and older.

Acne vulgaris is a condition in which the skin has blackheads, whiteheads and pimples.

It is not known if adapalene and benzoyl peroxide gel 0.1% / 2.5% is safe and effective in children younger than 9 years old.

What should I tell my doctor before usingadapalene and benzoyl peroxide gel 0.1% / 2.5%?

Before You Use Adapalene And Benzoyl Peroxide Gel 0.1% / 2.5%, Tell Your Doctor If You: ⮝

• have other skin problems, including cuts or sunburn
• have any other medical conditions
• are pregnant or planning to become pregnant. It is not known if adapalene and benzoyl peroxide gel 0.1% / 2.5% can harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.
• are breastfeeding or plan to breastfeed. It is not known if adapalene and benzoyl peroxide gel 0.1% / 2.5% passes into your breast milk and if it can harm your baby. Talk to your doctor about the best way to feed your baby if you use adapalene and benzoyl peroxide gel 0.1% / 2.5%.

Tell your doctor about all the medicines you take,including prescription and non prescription medicines, vitamins and herbal supplements.

Especially tell your doctor if you use any other medicine for acne. Using adapalene and benzoyl peroxide gel 0.1% / 2.5% with topical medicines that contain sulfur, resorcinol or salicylic acid may cause skin irritation.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I useadapalene and benzoyl peroxide gel 0.1% / 2.5%?

• Use adapalene and benzoyl peroxide gel 0.1% / 2.5% exactly as your doctor tells you to use it. Adapalene and benzoyl peroxide gel 0.1% / 2.5% is for skin use only. Do not use adapalene and benzoyl peroxide gel 0.1% / 2.5% in or on your mouth, eyes, or vagina.
• Apply adapalene and benzoyl peroxide gel 0.1% / 2.5% 1 time a day.
• Do not use more adapalene and benzoyl peroxide gel 0.1% / 2.5% than you need to cover the treatment area. Using too much adapalene and benzoyl peroxide gel 0.1% / 2.5% or using it more than 1 time a day may increase your chance of skin irritation.

Applyingadapalene and benzoyl peroxide gel 0.1% / 2.5%:

• Wash the area where the gel will be applied with a mild cleanser and pat dry.

Adapalene And Benzoyl Peroxide Gel 0.1% / 2.5% Comes In A Tube And A Pump. If You Have Been Prescribed The: ⮝

• Tube:Squeeze a small amount (about the size of a pea) of adapalene and benzoyl peroxide gel 0.1% / 2.5% onto your fingertips and spread a thin layer over the affected area.
• Pump:Depress the pump to dispense a small amount (about the size of a pea) of adapalene and benzoyl peroxide gel 0.1% / 2.5% and spread a thin layer over the affected area.

What should I avoid while usingadapalene and benzoyl peroxide gel 0.1% / 2.5%?

• You should avoid spending time in sunlight or artificial sunlight, such as tanning beds or sunlamps. Adapalene and benzoyl peroxide gel 0.1% / 2.5% can make your skin sensitive to sun and the light from tanning beds and sunlamps. You should wear sunscreen and wear a hat and clothes that cover the areas treated with adapalene and benzoyl peroxide gel 0.1% / 2.5% if you have to be in sunlight.
• You should avoid weather extremes such as wind and cold as this may cause irritation to your skin.
• You should avoid applying adapalene and benzoyl peroxide gel 0.1% / 2.5% to cuts, abrasions and sunburned skin.
• You should avoid skin products that may dry or irritate your skin such as harsh soaps, astringents, cosmetics that have strong skin drying effects and products containing high levels of alcohol.
• You should avoid the use of waxing as a hair removal method on skin treated with adapalene and benzoyl peroxide gel 0.1% / 2.5%.
• Adapalene and benzoyl peroxide gel 0.1% / 2.5% may bleach your clothes or hair. Allow adapalene and benzoyl peroxide gel 0.1% / 2.5% to dry completely before dressing to prevent bleaching of your clothes.

What are the possible side effects ofadapalene and benzoyl peroxide gel 0.1% / 2.5%?

Local Skin Reactions. Local Skin Reactions Are Most Likely To Happen During The First 4 Weeks Of Treatment And Usually Lessen With Continued Use Of Adapalene And Benzoyl Peroxide Gel 0.1% / 2.5%. Signs And Symptoms Of Local Skin Reaction Include: ⮝

• Redness
• Dryness
• Swelling
• Scaling
• Stinging or burning
  

Tell your doctor right away if these side effects continue for longer than 4 weeks or get worse, you may have to stop using adapalene and benzoyl peroxide gel 0.1% / 2.5%.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of adapalene and benzoyl peroxide gel 0.1% / 2.5%. For more information, ask your doctor or pharmacist.

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

You may also report side effects to Sandoz Inc. at 1-800-525-8747.

How should I storeadapalene and benzoyl peroxide gel 0.1% / 2.5%?

• Store adapalene and benzoyl peroxide gel 0.1% / 2.5% at room temperature, 68 77 F (20 25 C)
• Keep adapalene and benzoyl peroxide gel 0.1% / 2.5% inside container and out of light and away from heat.

Keepadapalene and benzoyl peroxide gel 0.1% / 2.5%and all medicines out of the reach of children.

General information aboutadapalene and benzoyl peroxide gel 0.1% / 2.5%

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use adapalene and benzoyl peroxide gel 0.1% / 2.5% for a condition for which it was not prescribed. Do not give adapalene and benzoyl peroxide gel 0.1% / 2.5% to other people, even if they have the same symptoms you have. It may harm them.

This Patient Information leaflet summarizes the most important information about adapalene and benzoyl peroxide gel 0.1% / 2.5%. If you would like more information, talk with your doctor. You can also ask your doctor or pharmacist for information about adapalene and benzoyl peroxide gel 0.1% / 2.5% that is written for health professionals.

What are the ingredients inadapalene and benzoyl peroxide gel 0.1% / 2.5%?

Active ingredient: adapalene and benzoyl peroxide

Inactive ingredients: carbopol 980, d-limonene, docusate sodium solution, edetate disodium, glycerin, poloxamer 182, polysorbate 80, propylene glycol, purified water, sodium hydroxide and sorbitan monooleate.

Manufactured by:
TOLMAR Inc., Fort Collins, CO 80526 for
Sandoz Inc., Princeton NJ 08540

04005028 Rev. 0 03/18

What Is Adapalene And Benzoyl Peroxide Gel? ⮝

Adapalene and benzoyl peroxide gel is a prescription medicine for skin use only (topical) used to treat acne vulgaris in people 9 years of age and older.

Acne vulgaris is a condition in which the skin has blackheads, whiteheads and pimples.

It is not known if adapalene and benzoyl peroxide gel is safe and effective in children younger than 9 years old.

What Should I Avoid While Using Adapalene And Benzoyl Peroxide Gel? ⮝

• You should avoid spending time in sunlight or artificial sunlight, such as tanning beds or sunlamps. Adapalene and benzoyl peroxide gel can make your skin sensitive to sun and the light from tanning beds and sunlamps. You should wear sunscreen and wear a hat and clothes that cover the areas treated with adapalene and benzoyl peroxide gel if you have to be in sunlight.
• You should avoid weather extremes such as wind and cold as this may cause irritation to your skin.
• You should avoid applying adapalene and benzoyl peroxide gel to cuts, abrasions and sunburned skin.
• You should avoid skin products that may dry or irritate your skin such as harsh soaps, astringents, cosmetics that have strong skin drying effects and products containing high levels of alcohol.
• You should avoid the use of waxing as a hair removal method on skin treated with adapalene and benzoyl peroxide gel.
• Adapalene and benzoyl peroxide gel may bleach your clothes or hair. Allow adapalene and benzoyl peroxide gel to dry completely before dressing to prevent bleaching of your clothes.

How Should I Store Adapalene And Benzoyl Peroxide Gel? ⮝

• Store adapalene and benzoyl peroxide gel at room temperature, 68 to 77 F (20 to 25 C)
• Keep adapalene and benzoyl peroxide gel inside container and out of light and away from heat.

Keep adapalene and benzoyl peroxide gel and all medicines out of the reach of children.

General information about adapalene and benzoyl peroxide gel

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use adapalene and benzoyl peroxide gel for a condition for which it was not prescribed. Do not give adapalene and benzoyl peroxide gel to other people, even if they have the same symptoms you have. It may harm them.

This Patient Information leaflet summarizes the most important information about adapalene and benzoyl peroxide gel. If you would like more information, talk with your doctor. You can also ask your doctor or pharmacist for information about adapalene and benzoyl peroxide gel that is written for health professionals.

What Are The Ingredients In Adapalene And Benzoyl Peroxide Gel? ⮝

Active ingredient: adapalene, USP and benzoyl peroxide, USP

Inactive ingredients: carbomer 980, docusate sodium, edetate disodium, glycerin, poloxamer 182, polysorbate 80, propylene glycol, purified water, sorbitan monooleate and xanthan gum.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Made in Canada

Distributed by:
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA

Revised October 2016

2007424

1. No Title 1572551885
2. 1 Indications And Usage
3. 2 Dosage And Administration
4. 3 Dosage Forms And Strengths
5. 4 Contraindications
6. 5 Warnings And Precautions
7. 6 Adverse Reactions
8. 7 Drug Interactions
9. 8 Use In Specific Populations
10. 11 Description
11. 12 Clinical Pharmacology
12. 13 Nonclinical Toxicology
13. 14 Clinical Studies
14. 16 How Supplied/storage And Handling
15. Package Label.principal Display Panel
16. Principal Display Panel - 45 G Bottle Carton
17. No Title 1572452625
18. Package/label Principal Display Panel- Carton
19. Highlights Of Prescribing Information
20. Indications And Usage
21. Dosage And Administration
22. Dosage Forms And Strengths
23. Contraindications
24. Warnings And Precautions
25. Adverse Reactions
26. 1 Indications And Usage
27. 2 Dosage And Administration
28. 3 Dosage Forms And Strengths
29. 4 Contraindications
30. 5 Warnings And Precautions
31. 6 Adverse Reactions
32. 7 Drug Interactions
33. 8 Use In Specific Populations
34. 11 Description
35. 12 Clinical Pharmacology
36. 13 Nonclinical Toxicology
37. 14 Clinical Studies
38. 16 How Supplied/storage And Handling
39. Package Label Principal Display Panel

No Title 1572551885 ⮝

NDC 66993-869-48

Prasco

Adapalene and Benzoyl Peroxide gel
0.1% / 2.5%

PUMP

FOR TOPICAL USE ONLY

P53623-0

Rx only

NET WT. 45 g

For topical use only. Not for ophthalmic, oral or intravaginal use.

Usual dosage: Apply a thin film once a day to affected areas.

See package insert for complete prescribing information.

Each gram contains Active: adapalene 0.1% and benzoyl peroxide 2.5% in an aqueous gel consisting of Inactive: acrylamide/sodium acryloyldimethyltaurate copolymer, docusate sodium, edetate disodium, glycerin, isohexadecane, poloxamer 124, polysorbate 80, propylene glycol, purified water, and sorbitan oleate.

Storage: Store at controlled room temperature 68 to 77 F (20 to 25 C) with excursions permitted between 59 and 86 F (15 and 30 C).

Marketed by:
Prasco Laboratories, Mason, OH 45040 USA
Manufactured by:
G Production Inc.
Baie d Urf , QC, H9X 3S4 Canada

Made in Canada.

See lot number and expiration date below.

ADAPALENE AND BENZOYL PEROXIDE adapalene and benzoyl peroxide gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:66993-869 Route of Administration TOPICAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ADAPALENE (UNII: 1L4806J2QF) (ADAPALENE - UNII:1L4806J2QF) ADAPALENE 1 mg in 1 g BENZOYL PEROXIDE (UNII: W9WZN9A0GM) (BENZOYL PEROXIDE - UNII:W9WZN9A0GM) BENZOYL PEROXIDE 25 mg in 1 g

Inactive Ingredients Ingredient Name Strength DOCUSATE SODIUM (UNII: F05Q2T2JA0) EDETATE DISODIUM (UNII: 7FLD91C86K) GLYCERIN (UNII: PDC6A3C0OX) ISOHEXADECANE (UNII: 918X1OUF1E) POLOXAMER 124 (UNII: 1S66E28KXA) POLYSORBATE 80 (UNII: 6OZP39ZG8H) PROPYLENE GLYCOL (UNII: 6DC9Q167V3) WATER (UNII: 059QF0KO0R) SORBITAN MONOOLEATE (UNII: 06XEA2VD56)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:66993-869-48 45 g in 1 BOTTLE, PUMP; Type 0: Not a Combination Product 08/03/2017

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA AUTHORIZED GENERIC NDA022320 08/03/2017

Labeler - Prasco Laboratories (065969375)

Revised: 8/2017 Document Id: 0b7e4a98-52af-4f19-9b13-1a9238d9811b 34391-3 Set id: 97d11c85-c5e3-43da-8e6c-205f37b4293c Version: 2 Effective Time: 20170803 Prasco Laboratories

1 Indications And Usage  ⮝

Adapalene and benzoyl peroxide gel 0.1% / 2.5% is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older.

2 Dosage And Administration  ⮝

For topical use only; adapalene and benzoyl peroxide gel is not for oral, ophthalmic, or intravaginal use. Apply a thin film of adapalene and benzoyl peroxide gel to affected areas of the face and/or trunk once daily after washing. Use a pea-sized amount for each area of the face (e.g., forehead, chin, each cheek). Avoid the eyes, lips and mucous membranes.

3 Dosage Forms And Strengths  ⮝

Each gram of adapalene and benzoyl peroxide gel contains 1 mg (0.1%) adapalene, USP and 25 mg (2.5%) benzoyl peroxide, USP in a white to very pale yellow, opaque, aqueous based gel.

4 Contraindications  ⮝

None

5 Warnings And Precautions  ⮝

5.1 Ultraviolet Light and Environmental Exposure

Exposure to sunlight, including sunlamps, should be minimized during the use of adapalene and benzoyl peroxide gel. Patients with high levels of sun exposure and those with inherent sensitivity to sun should exercise particular caution. Use of sunscreen products and protective apparel, (e.g., hat) are recommended when exposure cannot be avoided. Weather extremes, such as wind or cold, may be irritating to patients under treatment with adapalene and benzoyl peroxide gel.

5.2 Local Cutaneous Reactions

Erythema, scaling, dryness, and stinging/burning may be experienced with use of adapalene and benzoyl peroxide gel. These are most likely to occur during the first four weeks of treatment, are mostly mild to moderate in intensity, and usually lessen with continued use of the medication. Irritant and allergic contact dermatitis may occur. Depending upon the severity of these adverse reactions, patients should be instructed to use a moisturizer, reduce the frequency of the application of adapalene and benzoyl peroxide gel, or discontinue use. The product should not be applied to cuts, abrasions, eczematous or sunburned skin. As with other retinoids, use of waxing as a depilatory method should be avoided on skin treated with adapalene and benzoyl peroxide gel. Avoid concomitant use of other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have strong skin-drying effect and products with high concentrations of alcohol, astringents, spices, or limes).

6 Adverse Reactions  ⮝

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

During clinical trials, 1401 subjects were exposed to adapalene and benzoyl peroxide gel. A total of 1036 subjects with acne vulgaris, 12 years and older, were treated once daily for 12 weeks to 12 months. Related adverse events reported within 12 weeks of treatment and in at least 1% of subjects treated with adapalene and benzoyl peroxide gel and those reported in subjects treated with the vehicle gel are presented in Table 1:

Table 1 Drug Related Adverse Events Reported in Clinical Trials by At Least 1% of Patients Treated For 12 Weeks

System Organ Class/Preferred Term	Adapalene and Benzoyl
	Peroxide gel	Vehicle gel
	N = 564	N = 489
Subjects with AE (s)	14%	4%
Dry Skin	7%	2%
Contact dermatitis	3%	<1%
Application site burning	2%	<1%
Application site irritation	1%	<1%
Skin irritation	1%	0%
Local tolerability evaluations, presented in Table 2, were conducted at each study visit in clinical trials by assessment of erythema, scaling, dryness, burning, and stinging.

Table 2 Incidence of Local Cutaneous Irritation in Controlled Clinical Trials (N = 553)

Treatment Emergent Signs and Symptoms
	Maximum Severity During Treatment			End of Treatment Severity (12 Weeks)
	Mild	Moderate	Severe	Mild	Moderate	Severe
Erythema	27%	13%	1%	8%	2%	1%
Scaling	35%	11%	1%	9%	1%	<1%
Dryness	41%	13%	1%	10%	2%	<1%
Stinging/burning	41%	15%	3%	7%	2%	1%
Analysis over the 12-week period showed that local tolerability scores for erythema, scaling, dryness, and stinging/burning peaked at Week 1 of therapy and decreased thereafter.

During a pediatric clinical trial, 285 children with acne vulgaris, 9 to 11 years of age were treated with adapalene and benzoyl peroxide gel or with the vehicle gel once daily for 12 weeks. Overall, the safety profile of adapalene and benzoyl peroxide gel in these subjects is comparable to the safety profile observed in older subjects 12 years of age and above, both in the nature and frequency of the observed events.

Analysis of local tolerability evaluations shows similar incidence of treatment emergent signs and symptoms as in subjects 12 years of age and above, with local tolerability signs and symptoms peaking during the first week and decreasing over time.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of adapalene and benzoyl peroxide gel: eyelid edema, sunburn, blister, pain of skin, pruritus, swelling face, conjunctivitis, skin discoloration, rash, eczema, throat tightness and allergic contact dermatitis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

7 Drug Interactions  ⮝

Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. No formal drug-drug interaction studies were conducted with adapalene and benzoyl peroxide gel.

8 Use In Specific Populations  ⮝

8.1 Pregnancy

Teratogenic Effects: Pregnancy Category C

There are no well-controlled trials in pregnant women treated with adapalene and benzoyl peroxide gel. Animal reproduction studies have not been conducted with the combination gel or benzoyl peroxide. Furthermore, such studies are not always predictive of human response; therefore, adapalene and benzoyl peroxide gel should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

No teratogenic effects were observed in rats treated with oral doses of 0.15 to 5 mg adapalene/kg/day, up to 25 times (mg/m2/day) the maximum recommended human dose (MRHD) of 2 grams of adapalene and benzoyl peroxide gel. However, teratogenic changes were observed in rats and rabbits when treated with oral doses of greater than or equal to 25 mg adapalene/kg/day representing 123 and 246 times MRHD, respectively. Findings included cleft palate, microphthalmia, encephalocele and skeletal abnormalities in rats; and umbilical hernia, exophthalmos and kidney and skeletal abnormalities in rabbits.

Dermal teratology studies conducted in rats and rabbits at doses of 0.6 to 6 mg adapalene/kg/day [25 to 59 times (mg/m2) the MRHD] exhibited no fetotoxicity and only minimal increases in supernumerary ribs in both species and delayed ossification in rabbits.

8.3 Nursing Mothers

It is not known whether adapalene or benzoyl peroxide is excreted in human milk following use of adapalene and benzoyl peroxide gel. Because many drugs are excreted in human milk, caution should be exercised when adapalene and benzoyl peroxide gel is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of adapalene and benzoyl peroxide gel in pediatric patients under the age of 9 have not been established.

8.5 Geriatric Use

Clinical studies of adapalene and benzoyl peroxide gel did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

11 Description  ⮝

Adapalene and benzoyl peroxide gel, 0.1%/2.5% is a white to very pale yellow, opaque gel for topical use containing adapalene USP, 0.1% and benzoyl peroxide USP, 2.5%.

Adapalene USP, a synthetic retinoid, is a naphthoic acid derivative with retinoid-like properties. The chemical name for adapalene, USP is (6-[3-(1-adamantyl)-4-methoxyphenyl]-2- naphthoic acid). It has the following structural formula:

Adapalene, USP:

Molecular formula: C28H28O3 Molecular weight: 412.5

Benzoyl Peroxide, USP is a highly lipophilic oxidizing agent that localizes in both bacterial and keratinocyte cell membranes.

The chemical name for benzoyl peroxide, USP is dibenzoyl peroxide. It has the following structural formula:

Benzoyl Peroxide, USP:

Molecular formula: C14H10O4 Molecular weight: 242.23

Inactive ingredients: carbomer 980, docusate sodium, edetate disodium, glycerin, poloxamer 182, polysorbate 80, propylene glycol, purified water, sorbitan monooleate and xanthan gum.

12 Clinical Pharmacology  ⮝

12.1 Mechanism of Action

Adapalene

Adapalene binds to specific retinoic acid nuclear receptors but does not bind to cytosolic receptor protein. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of cellular differentiation, keratinization and inflammatory processes. However, the significance of these findings with regard to the mechanism of action of adapalene for the treatment of acne is unknown.

Benzoyl peroxide

Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects.

12.2 Pharmacodynamics

Pharmacodynamics of adapalene and benzoyl peroxide gel is unknown.

12.3 Pharmacokinetics

A pharmacokinetic study was conducted in 10 adult subjects with acne vulgaris who were treated once daily for 30 days with 2 grams/day of adapalene and benzoyl peroxide gel applied to 1000 cm2 of acne involved skin, (face, chest, and upper back). Two subjects (20%) had quantifiable adapalene plasma concentrations above the limit of quantification (LOQ = 0.1ng/mL). The highest adapalene Cmax and AUC0-24h was 0.21 ng/mL and 1.99 ng h/mL, respectively. Excretion of adapalene appears to be primarily by the biliary route. Pharmacokinetics of adapalene and benzoyl peroxide gel in pediatric subjects have not been evaluated.

Benzoyl peroxide is absorbed by the skin where it is converted to benzoic acid and eliminated in the urine.

13 Nonclinical Toxicology  ⮝

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, photocarcinogenicity, genotoxicity, or fertility studies were conducted with adapalene and benzoyl peroxide gel. Carcinogenicity studies with adapalene have been conducted in mice at topical doses of 0.4, 1.3, and 4 mg/kg/day (1.2, 3.9, and 12 mg/m2/day), and in rats at oral doses of 0.15, 0.5, and 1.5 mg/kg/day (0.9, 3, and 9 mg/m2/day). In terms of body surface area, the highest dose levels are 9.8 (mice) and 7.4 times (rats) the MRHD of 2 grams of adapalene and benzoyl peroxide gel. In the rat study, an increased incidence of benign and malignant pheochromcytomas in the adrenal medulla of male rats was observed.

No significant increase in tumor formation was observed in rodents topically treated with 15 to 25% benzoyl peroxide carbopol gel (6 to 10 times the concentration of benzoyl peroxide in adapalene and benzoyl peroxide gel) for two years. Rats received maximum daily applications of 138 (males) and 205 (females) mg benzoyl peroxide/kg. In terms of body surface area, these levels are 27 to 40 times the MRHD. Similar results were obtained in mice topically treated with 25% benzoyl peroxide carbopol gel for 56 weeks followed by intermittent treatment with 15% benzoyl peroxide carbopol gel for rest of the 2 years study period, and in mice topically treated with 5% benzoyl peroxide carbopol gel for two years.

The role of benzoyl peroxide as a tumor promoter has been well established in several animal species. However, the significance of this finding in humans is unknown.

In a photocarcinogenicity study conducted with 5% benzoyl peroxide carbopol gel, no increase in UV-induced tumor formation was observed in hairless mice topically treated for 40 weeks.

No photocarcinogenicity studies were conducted with adapalene. However, animal studies have shown an increased tumorigenic risk with the use of pharmacologically similar drugs (e.g., retinoids) when exposed to UV irradiation in the laboratory or sunlight. Although the significance of these findings to humans is not clear, patients should be advised to avoid or minimize exposure to either sunlight or artificial irradiation sources.

Adapalene did not exhibit mutagenic or genotoxic effects in vitro (Ames test, Chinese hamster ovary cell assay, mouse lymphoma TK assay) or in vivo (mouse micronucleus test).

Bacterial mutagenicity assays (Ames test) with benzoyl peroxide has provided mixed results, mutagenic potential was observed in a few but not in a majority of investigations. Benzoyl peroxide has been shown to produce single-strand DNA breaks in human bronchial epithelial and mouse epidermal cells, it has caused DNA-protein cross-links in the human cells, and has also induced a dose-dependent increase in sister chromatid exchanges in Chinese hamster ovary cells.

In rat oral studies, 20 mg adapalene/kg/day (120 mg/m2/day; 98 times the MRHD based on mg/m2/day comparison) did not affect the reproductive performance and fertility of F0 males and females, or growth, development and reproductive function of F1 offspring.

No fertility studies were conducted with benzoyl peroxide.

14 Clinical Studies  ⮝

The safety and efficacy of adapalene and benzoyl peroxide gel applied once daily for the treatment of acne vulgaris were assessed in two 12-week, multicenter, controlled clinical studies of similar design, comparing adapalene and benzoyl peroxide gel to the gel vehicle in acne subjects. Treatment response was defined as the percent of subjects who had a two grade improvement and rated Clear and Almost Clear at Week 12 based on the Investigator s Global Assessment (IGA) and mean absolute change from baseline at Week 12 in both inflammatory and non-inflammatory lesion counts. An IGA score of Clear corresponded to residual hyperpigmentation and erythema may be present. An IGA score of Almost Clear corresponded to a few scattered comedones and a few small papules.

In Study 1, 517 subjects were randomized to adapalene and benzoyl peroxide gel, adapalene 0.1% in vehicle gel, benzoyl peroxide 2.5% in vehicle gel, or vehicle gel. The median age of these 517 subjects was 15 years old and 60% were males.

At baseline subjects had between 20 to 50 inflammatory lesions and 30 to 100 non-inflammatory lesions. The majority of subjects had a baseline IGA score of Moderate which corresponded to more than half of the face is involved, many comedones, papules and pustules. The efficacy results at week 12 are presented in Table 3.

In Study 2, 1668 subjects were randomized to adapalene and benzoyl peroxide gel, adapalene 0.1% in vehicle gel, benzoyl peroxide 2.5% in vehicle gel, or vehicle gel. The median age of subjects was 16 years old and 49% were males. At baseline subjects had between 20 to 50 inflammatory lesions and 30 to 100 non-inflammatory lesions as well as an Investigator Global Assessment score of Moderate . The efficacy results at week 12 are presented in Table 3.

In study 3, 285 pediatric subjects 9 to 11 years of age were randomized to adapalene and benzoyl peroxide gel or vehicle gel. The median age of subjects was 11 years and 24% were males. At baseline, subjects had a minimum of 20 but not more than 100 total lesions (inflammatory and/or non-inflammatory) with an Investigator Global Assessment score of Moderate . The efficacy results at week 12 are presented in Table 3.

Table 3: Clinical Efficacy of Adapalene and Benzoyl Peroxide Gel at Week 12

Study 1
	Adapalene and	Adapalene 0.1% in	Benzoyl Peroxide 2.5% in	Vehicle gel
	Benzoyl Peroxide gel	Vehicle gel	Vehicle gel
	(N = 149)	(N = 148)	(N = 149)	(N = 71)
IGA: Two Grade
Improvement and Clear	32	18	18	4
or Almost Clear	(21.5%)	(12.2%)	(12.1%)	(5.6%)
Inflammatory Lesions:
Mean Absolute	16.0	11.4	10.5	9.5
(Percent) Change	(52.4%)	(39.9%)	(35.8%)	(31.8%)
Non-inflammatory
Lesions: Mean Absolute	23.4	15.2	13.7	13.2
(Percent) Change	(45.9%)	(29.6%)	(32.2%)	(27.8%)

Study 2
	Adapalene and	Adapalene 0.1% in	Benzoyl Peroxide 2.5%	Vehicle gel
	Benzoyl Peroxide gel	Vehicle gel	in Vehicle gel
	(N = 415)	(N = 420)	(N = 415)	(N = 418)
IGA: Two Grade
Improvement and Clear	125	83	92	47
or Almost Clear	(30.1%)	(19.8%)	(22.2%)	(11.3%)
Inflammatory Lesions:
Mean Absolute	15.4	12.3	13.7	8.7
(Percent) Change	(53.4%)	(41.7%)	(47.6%)	(30.2%)
Non-inflammatory
Lesions: Mean
Absolute (Percent)	24.6	21.0	19.2	11.3
Change	(48.1%)	(40.8%)	(37.2%)	(23.2%)
In both Studies 1 and 2 the treatment effect was smaller in subjects with a small number of baseline lesions than in subjects with a large number of baseline lesions.

Study 3
	Adapalene and Benzoyl Peroxide Gel	Vehicle Gel
	N=142	N=143
IGA: Two Grade Improvement and Clear or Almost Clear	67 (47.2%)	22 (15.4%)
Inflammatory Lesions: Mean Absolute (Percent) Change	7.4 (36.0%)	0.7 (-13.2%)*
Non-inflammatory Lesions: Mean Absolute (Percent) Change	20.2 (54.7%)	2.9 (2.3%)
** - That is, a mean percent increase of 13.2%

16 How Supplied/storage And Handling  ⮝

Adapalene and benzoyl peroxide gel 0.1% / 2.5% is white to very pale yellow in color and opaque in appearance, and is supplied as follows:

45 gram tube NDC 0472-0310-45
45 gram pump NDC 0472-0310-38

STORAGE AND HANDLING

Store at 25 C (77 F); excursions permitted to 15 to 30 C (59 to 86 F) [See USP Controlled Room Temperature]. Protect from light and keep away from heat. Keep tube tightly closed.

Keep out of reach of children.

Package Label.principal Display Panel  ⮝

Actavis

Rx Only

NDC 0472-0310-38

Adapalene

and Benzoyl

Peroxide Gel

0.1%/2.5%

For Topical Use Only

Not for Ophthalmic, Oral or Intravaginal Use

Net Wt. 45 g Pump

ADAPALENE AND BENZOYL PEROXIDE adapalene and benzoyl peroxide gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0472-0310 Route of Administration TOPICAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ADAPALENE (UNII: 1L4806J2QF) (ADAPALENE - UNII:1L4806J2QF) ADAPALENE 1 mg in 1 g BENZOYL PEROXIDE (UNII: W9WZN9A0GM) (BENZOYL PEROXIDE - UNII:W9WZN9A0GM) BENZOYL PEROXIDE 25 mg in 1 g

Inactive Ingredients Ingredient Name Strength CARBOMER HOMOPOLYMER TYPE C (UNII: 4Q93RCW27E) DOCUSATE SODIUM (UNII: F05Q2T2JA0) EDETATE DISODIUM (UNII: 7FLD91C86K) GLYCERIN (UNII: PDC6A3C0OX) POLOXAMER 182 (UNII: JX0HIX6OAG) POLYSORBATE 80 (UNII: 6OZP39ZG8H) PROPYLENE GLYCOL (UNII: 6DC9Q167V3) WATER (UNII: 059QF0KO0R) SORBITAN MONOOLEATE (UNII: 06XEA2VD56) XANTHAN GUM (UNII: TTV12P4NEE)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0472-0310-38 1 in 1 CARTON 07/27/2017 1 45 g in 1 BOTTLE, PUMP; Type 0: Not a Combination Product 2 NDC:0472-0310-45 1 in 1 CARTON 07/27/2017 2 45 g in 1 TUBE; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA203790 07/27/2017

Labeler - Actavis Pharma, Inc. (119723554)

Revised: 7/2017 Document Id: 7621bbb4-7449-47d8-bdf3-b103bc7335e8 34391-3 Set id: c385ad61-ee7e-4f16-8aa8-0357b14ea3bb Version: 21 Effective Time: 20170727 Actavis Pharma, Inc.

Principal Display Panel - 45 G Bottle Carton ⮝

NDC 51672-1364-3

45 g

Adapalene and Benzoyl
Peroxide Gel

0.1% / 2.5%

PUMP

FOR TOPICAL USE ONLY. NOT FOR OPHTHALMIC, ORAL OR INTRAVAGINAL USE.

Rx only

Keep this and all medications out of the reach of children.

TARO

ADAPALENE AND BENZOYL PEROXIDE adapalene and benzoyl peroxide gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:51672-1364 Route of Administration TOPICAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ADAPALENE (UNII: 1L4806J2QF) (ADAPALENE - UNII:1L4806J2QF) ADAPALENE 1 mg in 1 g BENZOYL PEROXIDE (UNII: W9WZN9A0GM) (BENZOYL PEROXIDE - UNII:W9WZN9A0GM) BENZOYL PEROXIDE 25 mg in 1 g

Inactive Ingredients Ingredient Name Strength docusate sodium (UNII: F05Q2T2JA0) edetate disodium (UNII: 7FLD91C86K) glycerin (UNII: PDC6A3C0OX) poloxamer 124 (UNII: 1S66E28KXA) SODIUM ACRYLOYLDIMETHYLTAURATE-ACRYLAMIDE COPOLYMER (1:1; 90000-150000 MPA.S) (UNII: 5F4963KLHS) propylene glycol (UNII: 6DC9Q167V3) water (UNII: 059QF0KO0R)

Product Characteristics Color WHITE (white to pale yellow) Score Shape Size Flavor Imprint Code Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:51672-1364-6 1 in 1 CARTON 01/24/2018 1 45 g in 1 TUBE; Type 0: Not a Combination Product 2 NDC:51672-1364-3 1 in 1 CARTON 01/24/2018 2 45 g in 1 BOTTLE, PUMP; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA206959 01/24/2018

Labeler - Taro Pharmaceuticals U.S.A., Inc. (145186370)

Establishment
Name	Address	ID/FEI	Business Operations
Taro Pharmaceuticals Inc.		206263295	MANUFACTURE(51672-1364)

Revised: 9/2017 Document Id: c8d13d7d-b67b-46c2-a56b-8a95c6f2f92b 34391-3 Set id: a53f1aa5-d3d1-45af-8728-8f36090f49da Version: 1 Effective Time: 20170929 Taro Pharmaceuticals U.S.A., Inc.

No Title 1572452625 ⮝

NDC 66993-869-48

Prasco

Adapalene and Benzoyl Peroxide gel
0.1% / 2.5%

PUMP

FOR TOPICAL USE ONLY

P53623-0

Rx only

NET WT. 45 g

For topical use only. Not for ophthalmic, oral or intravaginal use.

Usual dosage: Apply a thin film once a day to affected areas.

See package insert for complete prescribing information.

Each gram contains Active: adapalene 0.1% and benzoyl peroxide 2.5% in an aqueous gel consisting of Inactive: acrylamide/sodium acryloyldimethyltaurate copolymer, docusate sodium, edetate disodium, glycerin, isohexadecane, poloxamer 124, polysorbate 80, propylene glycol, purified water, and sorbitan oleate.

Storage: Store at controlled room temperature 68 to 77 F (20 to 25 C) with excursions permitted between 59 and 86 F (15 and 30 C).

Marketed by:
Prasco Laboratories, Mason, OH 45040 USA
Manufactured by:
G Production Inc.
Baie d Urf , QC, H9X 3S4 Canada

Made in Canada.

See lot number and expiration date below.

ADAPALENE AND BENZOYL PEROXIDE adapalene and benzoyl peroxide gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:66993-869 Route of Administration TOPICAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ADAPALENE (UNII: 1L4806J2QF) (ADAPALENE - UNII:1L4806J2QF) ADAPALENE 1 mg in 1 g BENZOYL PEROXIDE (UNII: W9WZN9A0GM) (BENZOYL PEROXIDE - UNII:W9WZN9A0GM) BENZOYL PEROXIDE 25 mg in 1 g

Inactive Ingredients Ingredient Name Strength DOCUSATE SODIUM (UNII: F05Q2T2JA0) EDETATE DISODIUM (UNII: 7FLD91C86K) GLYCERIN (UNII: PDC6A3C0OX) ISOHEXADECANE (UNII: 918X1OUF1E) POLOXAMER 124 (UNII: 1S66E28KXA) POLYSORBATE 80 (UNII: 6OZP39ZG8H) PROPYLENE GLYCOL (UNII: 6DC9Q167V3) WATER (UNII: 059QF0KO0R) SORBITAN MONOOLEATE (UNII: 06XEA2VD56)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:66993-869-48 45 g in 1 BOTTLE, PUMP; Type 0: Not a Combination Product 08/03/2017

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA AUTHORIZED GENERIC NDA022320 08/03/2017

Labeler - Prasco Laboratories (065969375)

Revised: 8/2017 Document Id: 0b7e4a98-52af-4f19-9b13-1a9238d9811b 34391-3 Set id: 97d11c85-c5e3-43da-8e6c-205f37b4293c Version: 2 Effective Time: 20170803 Prasco Laboratories

Package/label Principal Display Panel- Carton ⮝

Rx Only

NDC 45802-846-01

Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%

Pump

For Topical Use Only

NET WT 45 g

The following image is a placeholder representing the product identifier that is either affixed or imprinted on the drug package label during the packaging operation.

ADAPALENE AND BENZOYL PEROXIDE adapalene and benzoyl peroxide gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:45802-846 Route of Administration TOPICAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ADAPALENE (UNII: 1L4806J2QF) (ADAPALENE - UNII:1L4806J2QF) ADAPALENE 0.1 g in 100 g BENZOYL PEROXIDE (UNII: W9WZN9A0GM) (BENZOYL PEROXIDE - UNII:W9WZN9A0GM) BENZOYL PEROXIDE 2.5 g in 100 g

Inactive Ingredients Ingredient Name Strength DOCUSATE SODIUM (UNII: F05Q2T2JA0) EDETATE DISODIUM (UNII: 7FLD91C86K) GLYCERIN (UNII: PDC6A3C0OX) ISOHEXADECANE (UNII: 918X1OUF1E) POLYSORBATE 80 (UNII: 6OZP39ZG8H) PROPYLENE GLYCOL (UNII: 6DC9Q167V3) WATER (UNII: 059QF0KO0R) SORBITAN MONOOLEATE (UNII: 06XEA2VD56) POLOXAMER 124 (UNII: 1S66E28KXA)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:45802-846-01 1 in 1 CARTON 01/24/2018 1 45 g in 1 BOTTLE, PUMP; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA205033 01/24/2018

Labeler - Perrigo New York Inc (078846912)

Revised: 2/2019 Document Id: 67eb2377-843f-4238-b7bf-e30cf11245a1 34391-3 Set id: e50e3ef9-3a9b-4172-a908-71c973a7fb5c Version: 4 Effective Time: 20190212 Perrigo New York Inc

Highlights Of Prescribing Information ⮝

These highlights do not include all the information needed to use ADAPALENE and BENZOYL PEROXIDE GEL, 0.1%/2.5% safely and effectively. See full prescribing information for ADAPALENE and BENZOYL PEROXIDE GEL, 0.1%/2.5%.
ADAPALENE and BENZOYL PEROXIDE GEL, 0.1%/2.5% for topical use
Initial U.S. Approval: 2008

Indications And Usage ⮝

Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% is a combination of adapalene, a retinoid, and benzoyl peroxide, and is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older. (1)

Dosage And Administration ⮝

Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% is not for oral, ophthalmic, or intravaginal use. (2)

Apply a thin film of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% to affected areas of the face and/or trunk once daily after washing. Use a pea-sized amount for each area of the face (e.g., forehead, chin, each cheek). Avoid the eyes, lips and mucous membranes. (2)

Dosage Forms And Strengths ⮝

Each gram of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% contains 1 mg (0.1%) adapalene and 25 mg (2.5%) benzoyl peroxide. (3)

Contraindications ⮝

None. (4)

Warnings And Precautions ⮝

Ultraviolet Light and Environmental Exposure: Avoid exposure to sunlight and sunlamps. Wear sunscreen when sun exposure cannot be avoided. (5.1) (5)

Erythema, scaling, dryness, stinging/burning, irritant and allergic contact dermatitis may occur with use of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% and may necessitate discontinuation. (5.2) (5)

Adverse Reactions ⮝

Most commonly reported adverse events ( 1%) in patients treated with Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% were dry skin, contact dermatitis, application site burning, application site irritation and skin irritation.

To report SUSPECTED ADVERSE REACTIONS, contact Perrigo at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 2/2019

1 Indications And Usage ⮝

Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older.

2 Dosage And Administration ⮝

For topical use only; Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% is not for oral, ophthalmic, or intravaginal use. Apply a thin film of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% to affected areas of the face and/or trunk once daily after washing. Use a pea-sized amount for each area of the face (e.g., forehead, chin, each cheek). Avoid the eyes, lips and mucous membranes.

3 Dosage Forms And Strengths ⮝

Each gram of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% contains 1 mg (0.1%) adapalene and 25 mg (2.5%) benzoyl peroxide in a white to very pale yellow, opaque, aqueous based gel.

4 Contraindications ⮝

None

5 Warnings And Precautions ⮝

5.1 Ultraviolet Light and Environmental Exposure

Exposure to sunlight, including sunlamps, should be minimized during the use of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%. Patients with high levels of sun exposure and those with inherent sensitivity to sun should exercise particular caution. Use of sunscreen products and protective apparel, (e.g., hat) are recommended when exposure cannot be avoided. Weather extremes, such as wind or cold, may be irritating to patients under treatment with Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%.

5.2 Local Cutaneous Reactions

Erythema, scaling, dryness, and stinging/burning may be experienced with use of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%. These are most likely to occur during the first four weeks of treatment, are mostly mild to moderate in intensity, and usually lessen with continued use of the medication. Irritant and allergic contact dermatitis may occur. Depending upon the severity of these adverse reactions, patients should be instructed to use a moisturizer, reduce the frequency of the application of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%, or discontinue use. The product should not be applied to cuts, abrasions, eczematous or sunburned skin. As with other retinoids, use of waxing as a depilatory method should be avoided on skin treated with Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%.

Avoid concomitant use of other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have strong skin-drying effect and products with high concentrations of alcohol, astringents, spices, or limes).

6 Adverse Reactions ⮝

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

During clinical trials, 1401 subjects were exposed to adapalene and benzoyl peroxide gel, 0.1%/2.5%. A total of 1036 subjects with acne vulgaris, 12 years and older, were treated once daily for 12 weeks to 12 months. Related adverse events reported within 12 weeks of treatment and in at least 1% of subjects treated with adapalene and benzoyl peroxide gel, 0.1%/2.5% and those reported in subjects treated with the vehicle gel are presented in Table 1:

Table 1 Drug Related Adverse Events Reported in Clinical Trials by At Least 1% of Patients Treated For 12 Weeks

System Organ Class/Preferred Term	Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% N=564	Vehicle gel N=489
Subjects with AE (s)	14%	4%
Dry Skin	7%	2%
Contact dermatitis	3%	<1%
Application site burning	2%	<1%
Application site irritation	1%	<1%
Skin irritation	1%	0%

Local tolerability evaluations, presented in Table 2, were conducted at each study visit in clinical trials by assessment of erythema, scaling, dryness, burning, and stinging.

Table 2 Incidence of Local Cutaneous Irritation in Controlled Clinical Trials (N=553) Treatment Emergent Signs and Symptoms

	Maximum Severity During Treatment			End of Treatment Severity (12 Weeks)
	Mild	Moderate	Severe	Mild	Moderate	Severe
Erythema	27%	13%	1%	8%	2%	1%
Scaling	35%	11%	1%	9%	1%	<1%
Dryness	41%	13%	1%	10%	2%	<1%
Stinging/burning	41%	15%	3%	7%	2%	1%

Analysis over the 12-week period showed that local tolerability scores for erythema, scaling, dryness, and stinging/burning peaked at Week 1 of therapy and decreased thereafter.

During a pediatric clinical trial, 285 children with acne vulgaris, 9 to 11 years of age were treated with adapalene and benzoyl peroxide gel, 0.1%/2.5% or with the vehicle gel once daily for 12 weeks. Overall, the safety profile of adapalene and benzoyl peroxide gel, 0.1%/2.5% in these subjects is comparable to the safety profile observed in older subjects 12 years of age and above, both in the nature and frequency of the observed events.

Analysis of local tolerability evaluations shows similar incidence of treatment emergent signs and symptoms as in subjects 12 years of age and above, with local tolerability signs and symptoms peaking during the first week and decreasing over time.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of adapalene and benzoyl peroxide gel, 0.1%/2.5%: eyelid edema, sunburn, blister, pain of skin, pruritus, swelling face, conjunctivitis, skin discoloration, rash, eczema, throat tightness and allergic contact dermatitis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

7 Drug Interactions ⮝

Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents.

No formal drug-drug interaction studies were conducted with Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%.

8 Use In Specific Populations ⮝

8.1 Pregnancy

Pregnancy Category C

There are no well-controlled trials in pregnant women treated with Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%. Animal reproduction studies have not been conducted with the combination gel or benzoyl peroxide. Furthermore, such studies are not always predictive of human response; therefore, Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

No teratogenic effects were observed in rats treated with oral doses of 0.15 to 5.0 mg adapalene/kg/day, up to 25 times (mg/m2/day) the maximum recommended human dose (MRHD) of 2 grams of adapalene and benzoyl peroxide gel, 0.1%/2.5%. However, teratogenic changes were observed in rats and rabbits when treated with oral doses of 25 mg adapalene/kg/day representing 123 and 246 times MRHD, respectively. Findings included cleft palate, microphthalmia, encephalocele and skeletal abnormalities in rats; and umbilical hernia, exophthalmos and kidney and skeletal abnormalities in rabbits.

Dermal teratology studies conducted in rats and rabbits at doses of 0.6-6.0 mg adapalene/kg/day [25-59 times (mg/m2) the MRHD] exhibited no fetotoxicity and only minimal increases in supernumerary ribs in both species and delayed ossification in rabbits.

8.3 Nursing Mothers

It is not known whether adapalene or benzoyl peroxide is excreted in human milk following use of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5%. Because many drugs are excreted in human milk, caution should be exercised when Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% in pediatric patients under the age of 9 have not been established.

8.5 Geriatric Use

Clinical studies of adapalene and benzoyl peroxide gel, 0.1%/2.5% did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

11 Description ⮝

Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% is a white to very pale yellow, opaque gel for topical use containing adapalene 0.1% and benzoyl peroxide 2.5%.

Adapalene, a synthetic retinoid, is a naphthoic acid derivative with retinoid-like properties. The chemical name for adapalene is (6-[3-(1-adamantyl)-4-methoxyphenyl]-2- naphthoic acid). It has the following structural formula:

Adapalene:

Benzoyl Peroxide is a highly lipophilic oxidizing agent that localizes in both bacterial and keratinocyte cell membranes. The chemical name for benzoyl peroxide is dibenzoyl peroxide. It has the following structural formula:

Benzoyl Peroxide:

Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% contains the following inactive ingredients: acrylamide/sodium acryloyldimethyltaurate copolymer, docusate sodium, edetate disodium, glycerin, isohexadecane, poloxamer 124, polysorbate 80, propylene glycol, purified water, and sorbitan oleate.

12 Clinical Pharmacology ⮝

12.1 Mechanism of Action

Adapalene

Adapalene binds to specific retinoic acid nuclear receptors but does not bind to cytosolic receptor protein. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of cellular differentiation, keratinization and inflammatory processes. However, the significance of these findings with regard to the mechanism of action of adapalene for the treatment of acne is unknown.

Benzoyl peroxide

Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects.

12.2 Pharmacodynamics

Pharmacodynamics of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% is unknown.

12.3 Pharmacokinetics

A pharmacokinetic study was conducted in 10 adult subjects with acne vulgaris who were treated once daily for 30 days with 2 grams/day of adapalene and benzoyl peroxide gel, 0.1%/2.5% applied to 1000 cm2 of acne involved skin, (face, chest, and upper back). Two subjects (20%) had quantifiable adapalene plasma concentrations above the limit of quantification (LOQ = 0.1ng/mL). The highest adapalene Cmax and AUC0-24h was 0.21 ng/mL and 1.99 ng h/mL, respectively. Excretion of adapalene appears to be primarily by the biliary route. Pharmacokinetics of adapalene and benzoyl peroxide gel, 0.1%/2.5% in pediatric subjects have not been evaluated. Benzoyl peroxide is absorbed by the skin where it is converted to benzoic acid and eliminated in the urine.

13 Nonclinical Toxicology ⮝

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, photocarcinogenicity, genotoxicity, or fertility studies were conducted with adapalene and benzoyl peroxide gel, 0.1%/2.5%. Carcinogenicity studies with adapalene have been conducted in mice at topical doses of 0.4, 1.3, and 4.0 mg/kg/day (1.2, 3.9, and 12 mg/m2/day), and in rats at oral doses of 0.15, 0.5, and 1.5 mg/kg/day (0.9, 3.0, and 9.0 mg/m2/day). In terms of body surface area, the highest dose levels are 9.8 (mice) and 7.4 times (rats) the MRHD of 2 grams of adapalene and benzoyl peroxide gel, 0.1%/2.5%. In the rat study, an increased incidence of benign and malignant pheochromcytomas in the adrenal medulla of male rats was observed.

No significant increase in tumor formation was observed in rodents topically treated with 15-25% benzoyl peroxide carbopol gel (6-10 times the concentration of benzoyl peroxide in adapalene and benzoyl peroxide gel, 0.1%/2.5%) for two years. Rats received maximum daily applications of 138 (males) and 205 (females) mg benzoyl peroxide/kg. In terms of body surface area, these levels are 27-40 times the MRHD. Similar results were obtained in mice topically treated with 25% benzoyl peroxide carbopol gel for 56 weeks followed by intermittent treatment with 15% benzoyl peroxide carbopol gel for rest of the 2 years study period, and in mice topically treated with 5% benzoyl peroxide carbopol gel for two years.

The role of benzoyl peroxide as a tumor promoter has been well established in several animal species. However, the significance of this finding in humans is unknown.

In a photocarcinogenicity study conducted with 5% benzoyl peroxide carbopol gel, no increase in UV-induced tumor formation was observed in hairless mice topically treated for 40 weeks.

No photocarcinogenicity studies were conducted with adapalene. However, animal studies have shown an increased tumorigenic risk with the use of pharmacologically similar drugs (e.g., retinoids) when exposed to UV irradiation in the laboratory or sunlight. Although the significance of these findings to humans is not clear, patients should be advised to avoid or minimize exposure to either sunlight or artificial irradiation sources.

Adapalene did not exhibit mutagenic or genotoxic effects in vitro (Ames test, Chinese hamster ovary cell assay, mouse lymphoma TK assay) or in vivo (mouse micronucleus test).

Bacterial mutagenicity assays (Ames test) with benzoyl peroxide has provided mixed results, mutagenic potential was observed in a few but not in a majority of investigations. Benzoyl peroxide has been shown to produce single-strand DNA breaks in human bronchial epithelial and mouse epidermal cells, it has caused DNA-protein cross-links in the human cells, and has also induced a dose-dependent increase in sister chromatid exchanges in Chinese hamster ovary cells.

In rat oral studies, 20 mg adapalene/kg/day (120 mg/m2/day; 98 times the MRHD based on mg/m2/day comparison) did not affect the reproductive performance and fertility of F0 males and females, or growth, development and reproductive function of F1 offspring.

No fertility studies were conducted with benzoyl peroxide.

14 Clinical Studies ⮝

The safety and efficacy of adapalene and benzoyl peroxide gel, 0.1%/2.5% applied once daily for the treatment of acne vulgaris were assessed in two 12-week, multicenter, controlled clinical studies of similar design, comparing adapalene and benzoyl peroxide gel, 0.1%/2.5% to the gel vehicle in acne subjects. Treatment response was defined as the percent of subjects who had a two grade improvement and rated Clear and Almost Clear at Week 12 based on the Investigator s Global Assessment (IGA) and mean absolute change from baseline at Week 12 in both inflammatory and non-inflammatory lesion counts.

An IGA score of Clear corresponded to residual hyperpigmentation and erythema may be present. An IGA score of Almost Clear corresponded to a few scattered comedones and a few small papules.

In Study 1, 517 subjects were randomized to adapalene and benzoyl peroxide gel, 0.1%/2.5%, adapalene 0.1% in vehicle gel, benzoyl peroxide 2.5% in vehicle gel, or vehicle gel. The median age of these 517 subjects was 15 years old and 60% were males.

At baseline subjects had between 20 to 50 inflammatory lesions and 30 to 100 non-inflammatory lesions. The majority of subjects had a baseline IGA score of Moderate which corresponded to more than half of the face is involved, many comedones, papules and pustules. The efficacy results at week 12 are presented in Table 3.

In Study 2, 1668 subjects were randomized to adapalene and benzoyl peroxide gel, 0.1%/2.5%, adapalene 0.1% in vehicle gel, benzoyl peroxide 2.5% in vehicle gel, or vehicle gel. The median age of subjects was 16 years old and 49% were males. At baseline subjects had between 20 to 50 inflammatory lesions and 30 to 100 non-inflammatory lesions as well as an Investigator Global Assessment score of Moderate . The efficacy results at week 12 are presented in Table 3.

In Study 3, 285 pediatric subjects 9 to 11 years of age were randomized to adapalene and benzoyl peroxide gel, 0.1%/2.5% or vehicle gel. The median age of subjects was 11 years and 24% were males. At baseline, subjects had a minimum of 20 but not more than 100 total lesions (inflammatory and/or non-inflammatory) with an Investigator Global Assessment score of Moderate . The efficacy results at week 12 are presented in Table 3.

Table 3: Clinical Efficacy of Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% at Week 12

Study 1
	Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% (N=149)	Adapalene 0.1% in Vehicle gel (N=148)	Benzoyl Peroxide 2.5% in Vehicle gel (N=149)	Vehicle gel (N=71)
IGA: Two Grade Improvement and Clear or Almost Clear	32 (21.5%)	18 (12.2%)	18 (12.1%)	4 (5.6%)
Inflammatory Lesions: Mean Absolute (Percent) Change	16.0 (52.4%)	11.4 (39.9%)	10.5 (35.8%)	9.5 (31.8%)
Non-inflammatory Lesions: Mean Absolute (Percent) Change	23.4 (45.9%)	15.2 (29.6%)	13.7 (32.2%)	13.2 (27.8%)

Study 2
	Adapalene and Benzoyl Peroxide Gel, 0.1%/2/5% (N=415)	Adapalene 0.1% in Vehicle gel (N=420)	Benzoyl Peroxide 2.5% in Vehicle gel (N=415)	Vehicle gel (N=418)
IGA: Two Grade Improvement and Clear or Almost Clear	125 (30.1%)	83 (19.8%)	92 (22.2%)	47 (11.3%)
Inflammatory Lesions: Mean Absolute (Percent) Change	15.4 (53.4%)	12.3 (41.7%)	13.7 (47.6%)	8.7 (30.2%)
Non-inflammatory Lesions: Mean Absolute (Percent) Change	24.6 (48.1%)	21.0 (40.8%)	19.2 (37.2%)	11.3 (23.2%)

In both Studies 1 and 2 the treatment effect was smaller in subjects with a small number of baseline lesions than in subjects with a large number of baseline lesions.

Study 3
	Adapalene and Benzoyl Peroxide Gel,0.1%/2.5% (N=142)	Vehicle Gel (N=143)
IGA: Two Grade Improvement and Clear or Almost Clear	67 (47.2%)	22 (15.4%)
Inflammatory Lesions: Mean Absolute (Percent) Change	7.4 (36.0%)	0.7 (-13.2%)*
Non-inflammatory Lesions: Mean Absolute (Percent) Change	20.2 (54.7%)	2.9 (2.3%)

*-That is, a mean percent increase of 13.2%

16 How Supplied/storage And Handling ⮝

Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% is white to very pale yellow in color and opaque in appearance, and is supplied as follows:

45 gram tube NDC 45802-846-84

45 gram pump NDC 45802-846-01

Storage and handling

-

Store at 25 C; excursions permitted to 15 30 C (59 86 F).

-

Protect from light.

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Keep out of reach of children.

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Keep away from heat.

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Keep tube tightly closed.

Package Label Principal Display Panel ⮝

Adapalene and Benzoyl Peroxide Gel 0.1%/2.5% 45g Pump Label

Adapalene and Benzoyl Peroxide Gel, 0.1%/2.5% 45g Pump Carton

ADAPALENE AND BENZOYL PEROXIDE adapalene and benzoyl peroxide gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0781-7182 Route of Administration TOPICAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ADAPALENE (UNII: 1L4806J2QF) (ADAPALENE - UNII:1L4806J2QF) ADAPALENE 1 mg in 1 g BENZOYL PEROXIDE (UNII: W9WZN9A0GM) (BENZOYL PEROXIDE - UNII:W9WZN9A0GM) BENZOYL PEROXIDE 25 mg in 1 g

Inactive Ingredients Ingredient Name Strength CARBOMER HOMOPOLYMER TYPE C (UNII: 4Q93RCW27E) DOCUSATE SODIUM (UNII: F05Q2T2JA0) EDETATE DISODIUM (UNII: 7FLD91C86K) GLYCERIN (UNII: PDC6A3C0OX) LIMONENE, (+)- (UNII: GFD7C86Q1W) POLOXAMER 182 (UNII: JX0HIX6OAG) POLYSORBATE 80 (UNII: 6OZP39ZG8H) PROPYLENE GLYCOL (UNII: 6DC9Q167V3) WATER (UNII: 059QF0KO0R) SODIUM HYDROXIDE (UNII: 55X04QC32I) SORBITAN MONOOLEATE (UNII: 06XEA2VD56)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0781-7182-70 1 in 1 CARTON 05/23/2018 1 45 g in 1 BOTTLE, PUMP; Type 0: Not a Combination Product 2 NDC:0781-7182-19 1 in 1 CARTON 05/23/2018 2 45 g in 1 TUBE; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA206164 05/23/2018

Labeler - Sandoz Inc. (005387188)

Revised: 10/2019 Document Id: 12b7a31c-65a0-46d4-a655-3015c95b6386 34391-3 Set id: 0270be63-492a-4204-b04e-12e41d7d909a Version: 9 Effective Time: 20191028 Sandoz Inc.