ACANYA

Coria Laboratories
Valeant Pharmaceuticals North America LLC

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use ACANYA Gel safely and effectively. See full prescribing information for ACANYA Gel.   ACANYA (clindamycin phosphate and benzoyl peroxide) Gel, 1.2%/2.5% For topical use Initial U.S. Approval: 2000INDICATIONS AND USAGEACANYA Gel is a lincosamide antibiotic and benzoyl peroxide indicated for the topical treatment of acne vulgaris. (1)DOSAGE AND ADMINISTRATION Apply a pea-sized amount of ACANYA Gel to the face once daily. (2) Not for oral, ophthalmic, or intravaginal use. (2) DOSAGE FORMS AND STRENGTHSACANYA Gel contains clindamycin phosphate 1.2% and benzoyl peroxide 2.5% in a topical gel in 50 gram pumps. (3)CONTRAINDICATIONSACANYA Gel is contraindicated in: Patients who have demonstrated hypersensitivity (e.g., anaphylaxis) to clindamycin, benzoyl peroxide, any components of the formulation, or lincomycin. (4) Patients with a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis. (4) WARNINGS AND PRECAUTIONS Colitis: Orally and parenterally administered clindamycin has been associated with severe colitis, which may result in death. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical and systemic clindamycin. ACANYA Gel should be discontinued if significant diarrhea occurs. (5.1) Ultraviolet Light and Environmental Exposure: Minimize sun exposure following drug application. (5.2) Side EffectsThe following selected adverse reactions occurred in less than 0.2% of patients: application site pain (0.1%); application site exfoliation (0.1%); and application site irritation (0.1%). (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC, at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch DRUG INTERACTIONS ACANYA Gel should not be used in combination with erythromycin-containing products because of its clindamycin component. (7.1)

FULL PRESCRIBING INFORMATION: CONTENTS*

• 1 ACANYA INDICATIONS AND USAGE
• 2 ACANYA DOSAGE AND ADMINISTRATION
• 3 DOSAGE FORMS AND STRENGTHS
• 4 ACANYA CONTRAINDICATIONS
  • 4.1 Hypersensitivity
  • 4.2 Colitis/Enteritis
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Colitis
  • 5.2 Ultraviolet Light and Environmental Exposure
• 6 ACANYA ADVERSE REACTIONS
  • 6.1 Clinical Studies Experience
  • 6.2 Postmarketing Experience
• 7 DRUG INTERACTIONS
  • 7.1 Erythromycin
  • 7.2 Neuromuscular Blocking Agents
• 8 USE IN SPECIFIC POPULATIONS
  • 8.1 Pregnancy
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
  • 8.5 Geriatric Use
• 11 ACANYA DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.1 Mechanisms of Action
  • 12.3 Pharmacokinetics
  • 12.4 Microbiology
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
• 14 CLINICAL STUDIES
• 16 HOW SUPPLIED/STORAGE AND HANDLING
  • 16.1 How Supplied
  • 16.2 Dispensing Instructions for the Pharmacist
  • 16.3 Storage and Handling
• 17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

ACANYA^® Gel is indicated for the topical treatment of acne vulgaris in patients 12 years or older.

2 DOSAGE AND ADMINISTRATION

Apply a pea-sized amount of ACANYA Gel to the face once daily.

Use of ACANYA Gel beyond 12 weeks has not been evaluated.

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.

ACANYA Gel is not for oral, ophthalmic, or intravaginal use.

3 DOSAGE FORMS AND STRENGTHS

Gel, 1.2%/2.5%

Each gram of ACANYA Gel contains 10 mg (1%) clindamycin as phosphate, and 25 mg (2.5%) benzoyl peroxide in a white to off-white, opaque, smooth gel.

4 CONTRAINDICATIONS

4.1 Hypersensitivity

ACANYA Gel is contraindicated in those individuals who have shown hypersensitivity to clindamycin, benzoyl peroxide, any components of the formulation, or lincomycin. Anaphylaxis, as well as allergic reactions leading to hospitalization, has been reported in postmarketing use with ACANYA Gel [see Postmarketing Experience (6.2) ].

4.2 Colitis/Enteritis

ACANYA Gel is contraindicated in patients with a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis [see Warnings and Precautions (5.1) ].

5 WARNINGS AND PRECAUTIONS

5.1 Colitis

Systemic absorption of clindamycin has been demonstrated following topical use of clindamycin. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical and systemic clindamycin. When significant diarrhea occurs, ACANYA Gel should be discontinued.

Severe colitis has occurred following oral and parenteral administration of clindamycin with an onset of up to several weeks following cessation of therapy. Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen severe colitis. Severe colitis may result in death.

Studies indicate toxin(s) produced by Clostridia is one primary cause of antibiotic-associated colitis. The colitis is usually characterized by severe persistent diarrhea and severe abdominal cramps and may be associated with the passage of blood and mucus. Stool cultures for Clostridium difficile and stool assay for C. difficile toxin may be helpful diagnostically.

5.2 Ultraviolet Light and Environmental Exposure

Minimize sun exposure including use of tanning beds or sun lamps following drug application [see Nonclinical Toxicology (13.1) ].

6 ADVERSE REACTIONS

6.1 Clinical Studies Experience

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

The following selected adverse reactions occurred in less than 0.2% of patients treated with ACANYA Gel: application site pain (0.1%); application site exfoliation (0.1%); and application site irritation (0.1%).

During clinical trials, subjects were assessed for local cutaneous signs and symptoms of erythema, scaling, itching, burning and stinging. Most local skin reactions increased and peaked around week 4 and continually decreased over time reaching near baseline levels by week 12. The percentage of subjects that had symptoms present before treatment, the maximum value recorded during treatment, and the percent with symptoms present at week 12 are shown in Table 1.

Table 1: Local Skin Reactions - Percent of Subjects with Symptoms Present. Combined Results from the Two Phase 3 Trials (N = 773)

	Before Treatment (Baseline)			Maximum During Treatment			End of Treatment (Week 12)
	Mild	Mod.Mod. = Moderate	Severe	Mild	Mod.Mod. = Moderate	Severe	Mild	Mod.Mod. = Moderate	Severe
Erythema	22	4	0	25	5	< 1	15	2	0
Scaling	8	< 1	0	18	3	0	8	1	0
Itching	10	2	0	15	2	0	6	< 1	0
Burning	3	< 1	0	8	2	0	2	< 1	0
Stinging	2	< 1	0	6	1	0	1	< 1	0

6.2 Postmarketing Experience

Anaphylaxis, as well as allergic reactions leading to hospitalizations, has been reported in postmarketing use of products containing clindamycin/benzoyl peroxide.

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

7.1 Erythromycin

ACANYA Gel should not be used in combination with topical or oral erythromycin-containing products due to its clindamycin component. In vitro studies have shown antagonism between erythromycin and clindamycin. The clinical significance of this in vitro antagonism is not known.

7.2 Neuromuscular Blocking Agents

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, ACANYA Gel should be used with caution in patients receiving such agents.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C.

There are no adequate and well-controlled studies in pregnant women treated with ACANYA Gel. ACANYA Gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Animal reproductive/developmental toxicity studies have not been conducted with ACANYA Gel or benzoyl peroxide. Developmental toxicity studies of clindamycin performed in rats and mice using oral doses of up to 600 mg/kg/day (240 and 120 times amount of clindamycin in the highest recommended adult human dose based on mg/m², respectively) or subcutaneous doses of up to 200 mg/kg/day (80 and 40 times the amount of clindamycin in the highest recommended adult human dose based on mg/m², respectively) revealed no evidence of teratogenicity.

8.3 Nursing Mothers

It is not known whether clindamycin is excreted in human milk after topical application of ACANYA Gel. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to use ACANYA Gel while nursing, taking into account the importance of the drug to the mother.

8.4 Pediatric Use

Safety and effectiveness of ACANYA Gel in pediatric patients under the age of 12 have not been evaluated.

8.5 Geriatric Use

Clinical trials of ACANYA Gel did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects.

11 DESCRIPTION

ACANYA (clindamycin phosphate and benzoyl peroxide) Gel, 1.2%/2.5% is a combination product with two active ingredients in an aqueous gel formulation intended for topical use. Clindamycin phosphate is a water-soluble ester of the semi-synthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin.

The chemical name for clindamycin phosphate is Methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo- α -D-galacto-octopyranoside 2-(dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below:

Clindamycin phosphate:

Molecular Formula: C₁₈H₃₄ClN₂O₈PS          Molecular Weight: 504.97

Benzoyl peroxide is an antibacterial and keratolytic agent. The structural formula for benzoyl peroxide is represented below:

Benzoyl peroxide:

Molecular Formula: C₁₄H₁₀O₄          Molecular Weight: 242.23

ACANYA Gel contains the following inactive ingredients: purified water, carbomer 980, propylene glycol, and potassium hydroxide. Each gram of ACANYA Gel contains 1.2% of clindamycin phosphate which is equivalent to 1% clindamycin.

12 CLINICAL PHARMACOLOGY

12.1 Mechanisms of Action

Clindamycin: Clindamycin is a lincosamide antibacterial [see Microbiology (12.4) ].

Benzoyl Peroxide: Benzoyl peroxide is an oxidizing agent with bacteriocidal and keratolytic effects but the precise mechanism of action is unknown.

12.3 Pharmacokinetics

The systemic absorption of clindamycin was investigated in an open-label, multiple-dose trial in 16 adult subjects with moderate to severe acne vulgaris treated with 1 gram of ACANYA Gel applied to the face once daily for 30 days. Twelve subjects (75%) had at least one quantifiable clindamycin plasma concentration above the lower limit of quantification (LOQ = 0.5 ng/mL) on Day 1 or Day 30. On Day 1, the mean (± standard deviation) peak plasma concentrations (C_max) was 0.78 ± 0.22 ng/mL (n=9 with measurable concentrations), and the mean AUC_0-t was 5.29 ± 0.81 h.ng/mL (n=4). On Day 30, the mean C_max was 1.22 ± 0.88 ng/mL (n=10), and the mean AUC_0-t was 8.42 ± 6.01 h.ng/mL (n=6). Clindamycin plasma concentrations were below LOQ in all subjects at 24 hours post-dose on the three tested days (Day 1, 15, and 30).

Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid.

12.4 Microbiology

Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing bacterial protein synthesis.

Clindamycin and benzoyl peroxide individually have been shown to have in vitro activity against Propionibacterium acnes, an organism which has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes is not known.

P. acnes resistance to clindamycin has been documented. Resistance to clindamycin is often associated with resistance to erythromycin.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, mutagenicity and impairment of fertility testing of ACANYA Gel have not been performed.

Benzoyl peroxide has been shown to be a tumor promoter and progression agent in a number of animal studies. Benzoyl peroxide in acetone at doses of 5 and 10 mg administered topically twice per week for 20 weeks induced skin tumors in transgenic Tg.AC mice. The clinical significance of this is unknown.

Carcinogenicity studies have been conducted with a gel formulation containing 1% clindamycin and 5% benzoyl peroxide. In a 2-year dermal carcinogenicity study in mice, treatment with the gel formulation at doses of 900, 2700, and 15000 mg/kg/day (1.8, 5.4, and 30 times amount of clindamycin and 3.6, 10.8, and 60 times amount of benzoyl peroxide in the highest recommended adult human dose of 2.5 g ACANYA Gel based on mg/m², respectively) did not cause any increase in tumors. However, topical treatment with a different gel formulation containing 1% clindamycin and 5% benzoyl peroxide at doses of 100, 500, and 2000 mg/kg/day caused a dose-dependent increase in the incidence of keratoacanthoma at the treated skin site of male rats in a 2-year dermal carcinogenicity study in rats. In an oral (gavage) carcinogenicity study in rats, treatment with the gel formulation at doses of 300, 900 and 3000 mg/kg/day (1.2, 3.6, and 12 times amount of clindamycin and 2.4, 7.2, and 24 times amount of benzoyl peroxide in the highest recommended adult human dose of 2.5 g ACANYA Gel based on mg/m², respectively) for up to 97 weeks did not cause any increase in tumors. In a 52-week dermal photocarcinogenicity study in hairless mice, (40 weeks of treatment followed by 12 weeks of observation), the median time to onset of skin tumor formation decreased and the number of tumors per mouse increased relative to controls following chronic concurrent topical administration of the higher concentration benzoyl peroxide formulation (5000 and 10000 mg/kg/day, 5 days/week) and exposure to ultraviolet radiation.

Clindamycin phosphate was not genotoxic in the human lymphocyte chromosome aberration assay. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in S. typhimurium tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells.

Fertility studies have not been performed with ACANYA Gel or benzoyl peroxide, but fertility and mating ability have been studied with clindamycin. Fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 120 times the amount of clindamycin in the highest recommended adult human dose of 2.5 g ACANYA Gel, based on mg/m²) revealed no effects on fertility or mating ability.

14 CLINICAL STUDIES

The safety and efficacy of once daily use of ACANYA Gel were assessed in two 12-week multi-center, randomized, blinded trials in subjects 12 years and older with moderate to severe acne vulgaris. The two trials were identical in design and compared ACANYA Gel to clindamycin in the vehicle gel, benzoyl peroxide in the vehicle gel, and the vehicle gel alone.

The co-primary efficacy variables were:

• (1) Mean absolute change from baseline at week 12 in
  • Inflammatory lesion counts
  • Non-inflammatory lesion counts
• (2) Percent of subjects who had a two grade improvement from baseline on an Evaluator's Global Severity (EGS) score.

The EGS scoring scale used in all of the clinical trials for ACANYA Gel is as follows:

The results of Trial 1 at week 12 are presented in Table 2:

The results of Trial 2 at week 12 are presented in Table 3:

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

ACANYA Gel is supplied as a 50 g pump (NDC 13548-132-50).

16.2 Dispensing Instructions for the Pharmacist

• Dispense ACANYA Gel with a 10 week expiration date.
• Specify "Store at room temperature up to 25°C (77°F). Do not freeze."

16.3 Storage and Handling

• PHARMACIST: Prior to Dispensing: Store in a refrigerator, 2°C to 8°C (36°F to 46°F).
• PATIENT: Store at room temperature at or below 25°C (77°F).
• Protect from freezing.
• Keep out of the reach of children.
• Keep container tightly closed.

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling (Patient Information)

• Patients who develop allergic reactions such as severe swelling or shortness of breath should discontinue use and contact their physician immediately.
• ACANYA Gel may cause irritation such as erythema, scaling, itching, or burning, especially when used in combination with other topical acne therapies.
• Excessive or prolonged exposure to sunlight should be limited. To minimize exposure to sunlight, a hat or other clothing should be worn. Sunscreen may also be used.
• ACANYA Gel may bleach hair or colored fabric.

PATIENT INFORMATION
ACANYA^® (AH-CAN΄-YAH)
(clindamycin phosphate and benzoyl peroxide) Gel, 1.2%/2.5%

Read the Patient Information that comes with ACANYA Gel 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 medical condition or your treatment.

What is ACANYA Gel?

ACANYA Gel is a prescription medicine used on the skin (topical) to treat acne vulgaris in people 12 years and older. ACANYA Gel contains clindamycin phosphate and benzoyl peroxide.

It is not known if ACANYA Gel is safe and effective for use longer than 12 weeks.

It is not known if ACANYA Gel is safe and effective in children under 12 years of age.

Who should not use ACANYA Gel?

Do not use ACANYA Gel if you have:

• Crohn's disease
• ulcerative colitis
• had inflammation of the colon (colitis), or severe diarrhea with past antibiotic use

Talk with your doctor if you are not sure if you have one of these conditions.

What should I tell my doctor before using ACANYA Gel?

Before using ACANYA Gel, tell your doctor about all of your medical conditions, including if you:

• have any allergies.
• have any other medical conditions.
• are pregnant or planning to become pregnant. It is not known if ACANYA Gel will harm your unborn baby.
• are breastfeeding or plan to breast-feed. It is not known if ACANYA Gel passes into your breast milk. One of the medicines in ACANYA Gel contains clindamycin. Clindamycin when taken by mouth or by injection has been reported to appear in breast milk. You and your doctor should decide whether you will use ACANYA Gel while breast-feeding.

Tell your doctor about all the medicines and skin products you use. Especially tell your doctor if you will have surgery with general anesthesia. One of the medicines in ACANYA Gel (clindamycin) can affect how certain medicines work when used in general anesthesia.

• ACANYA Gel should not be used with products that contain erythromycin.
• Other skin and topical acne products may increase the irritation of your skin when used with ACANYA Gel.

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

How should I use ACANYA Gel?

• Use ACANYA Gel exactly as prescribed.
• Your doctor will tell you how long to use ACANYA Gel.
• Throw away (discard) any unused ACANYA Gel.

Instructions for applying ACANYA Gel

• Apply ACANYA Gel to your face one time each day as prescribed.
   
  • Before you apply ACANYA Gel, wash your face gently with a mild soap, rinse with warm water, and pat your skin dry.
  • To apply ACANYA Gel to your face, use the pump to dispense one pea-sized amount of ACANYA Gel onto your fingertip. See Figure 1. One pea-sized amount of ACANYA Gel should be enough to cover your entire face.

    Figure 1

  • Dot the one pea-sized amount of ACANYA Gel onto six areas of your face (chin, left cheek, right cheek, nose, left forehead, right forehead). See Figure 2.

    Figure 2

  • After applying the ACANYA Gel this way, spread the gel over your face and gently rub it in. It is important to spread the gel over your whole face.
  • Wash your hands with soap and water after applying ACANYA Gel.
  • If your doctor tells you to put ACANYA Gel on other areas of your skin with acne, be sure to ask how much you should use.
  • Do not get ACANYA Gel in your mouth, eyes, or nose, or on your lips. If this occurs, rinse the affected area with warm water and call your doctor right away if the area becomes very red, itchy, tender, or swollen.
  • Do not get ACANYA Gel on cuts or open wounds.
  • Do not use more ACANYA Gel than prescribed.

What should I avoid while using ACANYA Gel?

• Limit your time in sunlight. Avoid using tanning beds or sun lamps. If you have to be in sunlight, wear a wide-brimmed hat or other protective clothing, and a sunscreen with SPF 15 rating or higher. Your doctor can give you more information about why this is important.
• Do not wash your face more than 2 to 3 times a day. Washing your face too often or scrubbing it may make your acne worse.
• Avoid getting ACANYA Gel in your hair or on colored fabric. ACANYA Gel may bleach hair or colored fabric.

What are possible side effects with ACANYA Gel?

ACANYA Gel can cause serious side effects including:

• Inflammation of the colon (colitis). Stop using ACANYA Gel and call your doctor right away if you have severe watery diarrhea, or bloody diarrhea.
• Allergic reactions. Stop using ACANYA Gel, call your doctor and get help right away if you have any of the following symptoms:
  • severe itching
  • swelling of your face, eyes, lips, tongue or throat
  • trouble breathing

Common side effects with ACANYA Gel include:

• Skin irritation. Stop using ACANYA Gel and call your doctor if you have a skin rash or your skin becomes very red, itchy or swollen.

Talk to your doctor about any side effect that bothers you or that does not go away.

These are not all the possible side effects with ACANYA Gel. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

You may also report side effects to Valeant Pharmaceuticals North America LLC at 1-800-321-4576.

How should I store ACANYA Gel?

• Store ACANYA Gel at room temperature at or below 25°C (77°F).
• The expiration date of ACANYA Gel is 10 weeks from the date you fill your prescription.
• Safely throw away expired ACANYA Gel.
• Do not freeze.
• Keep the container tightly closed.

Keep ACANYA Gel and all medicines out of the reach of children.

General information about ACANYA Gel

Medicines are sometimes prescribed for conditions that are not mentioned in Patient Information leaflets. Do not use ACANYA Gel for a condition for which it was not prescribed. Do not give ACANYA Gel to other people, even if they have the same condition you have. It may harm them.

This leaflet summarizes the most important information about ACANYA Gel. If you would like more information, talk with your doctor. You can also ask your doctor or pharmacist for information about ACANYA Gel that is written for healthcare professionals.

For more information about ACANYA Gel, call 1-800-321-4576.

What are the ingredients in ACANYA Gel?

Active Ingredients: clindamycin phosphate 1.2% and benzoyl peroxide 2.5%

Inactive Ingredients: purified water, carbomer 980, propylene glycol, and potassium hydroxide

Marketed by:
Valeant Pharmaceuticals North America LLC, Bridgewater, NJ 08807

Manufactured by:
Contract Pharmaceuticals Limited Mississauga, Ontario Canada L5N 6L6

U.S. Patents 5,733,886 and 8,288,434

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

Rev. 02/2014
2006787
9379500

PRINCIPAL DISPLAY PANEL - 50 gram Carton

NDC 13548-132-50

Acanya ^®
(Clindamycin Phosphate and
Benzoyl Peroxide) Gel, 1.2%/2.5%

Rx ONLY

FOR TOPICAL USE ONLY

One premixed 50-gram pump dispenser