These Highlights Do Not Include All The Information Needed To Use Finacea Foam Safely And Effectively. See Full Prescribing Information For Finacea Foam.

Local Tolerability Studies

In a 21-day cumulative irritation study under occlusive conditions, mild-to-moderate irritation was observed for azelaic acid pre-foam emulsion. In a human repeat insult patch test (HRIPT) study, no sensitization potential was observed for azelaic acid pre-foam emulsion.

Storage and Handling

Store at 25^◦C (77^◦F); excursions permitted between 15–30^◦C (59–86^◦F) [See USP Controlled Room Temperature].

Flammable. Avoid fire, flame, or smoking during and immediately following application. Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperatures above 120°F (49°C).

FINACEA (azelaic acid) Foam contains 15% (w/w) azelaic acid, a naturally-occurring saturated dicarboxylic acid and is suspended in an oil-in-water emulsion vehicle. It is for topical use. Chemically, azelaic acid is 1,7-heptanedicarboxylic acid. The structural formula of azelaic acid is:

Azelaic acid has a molecular formula of C₉ H₁₆ O₄ and a molecular weight of 188.22.

The aluminum containers are filled with hydrophilic emulsion, crimped with a continuous spray valve, and pressurized with propellants consisting of propane, butane, and isobutane. Each gram of FINACEA Foam, 15% contains 0.15 g of azelaic acid. FINACEA Foam also contains benzoic acid (as a preservative), cetostearyl alcohol, dimethyl isosorbide, medium-chain triglycerides, methylcellulose, mono- and di-glycerides, polyoxyl 40 stearate, polysorbate 80, propylene glycol, purified water, sodium hydroxide (to adjust pH), and xanthan gum as inactive ingredients.

The propellant in FINACEA Foam is flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following application. Do not puncture and/or incinerate the containers. Do not expose containers to heat and/or store at temperatures above 120°F (49°C).

The safety and efficacy of FINACEA Foam have not been established in pediatric patients.

Of the total number of subjects in clinical studies of FINACEA Foam, 18.8 percent were 65 and over, while 7.2 percent were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

The efficacy and safety of FINACEA Foam was evaluated in two multicenter, randomized, double-blind, vehicle-controlled, 12-week clinical trials (Trials 1 and 2) in subjects with papulopustular rosacea, with a mean lesion count of 21.3 (range 12 to 50) inflammatory papules and pustules. A total of 1362 (active: 681; vehicle: 681) subjects aged 19 to 92 years (mean age = 50.6 years), 95.7% Caucasian, and 73.4% female participated in the trials. The following subjects were excluded: a) those with ocular rosacea, phymatous rosacea or plaque-type rosacea lesions; b) those with rosacea that requires systemic treatment; c) those who are known non-responders to azelaic acid, and d) those with a known hypersensitivity to any ingredients of the study drug. FINACEA Foam or its vehicle were to be applied twice daily for 12 weeks; no other topical or systemic medication affecting the course of rosacea and/or evaluability was to be used during the studies. Subjects were instructed to avoid any food and beverages that, by their own experience, may provoke erythema, flushing and blushing, including spicy food, hot drinks and alcoholic beverages during the study. Subjects were also instructed to avoid use of products which may cause local irritation such as soaps, alcohol-containing cleansers, tinctures and astringents, abrasives and peeling agents during the study.

The efficacy endpoints were 1) nominal change in inflammatory lesion count from baseline and 2) success defined as a score of "clear" or "minimal" with at least 2-step reduction from baseline on a 5-point Investigator's Global Assessment (IGA). Details on IGA are specified below:

FINACEA Foam was superior to its vehicle in the treatment of rosacea in reducing the number of inflammatory papules and pustules and demonstrating success according to IGA at the end of treatment (Table 2).

None.

The following adverse reactions are described elsewhere in the prescribing information:

• Hypopigmentation [see Warnings and Precautions (5.1)].
• Eye and Mucous Membranes Irritation [see Warnings and Precautions (5.2)].

There have been reports of hypopigmentation after use of azelaic acid. Because azelaic acid has not been well studied in patients with dark complexion, monitor these patients for early signs of hypopigmentation.

The efficacy of FINACEA Foam is being driven by local mechanisms of azelaic acid within the skin.

Pharmacokinetics of azelaic acid and its metabolite pimelic acid was assessed in 21 adult subjects with moderate papulopustular rosacea with a minimum of 15 and no more than 50 inflammatory lesions (papules and/or pustules). Endogenous plasma concentrations of azelaic acid (range <1-105 ng/mL) and pimelic acid (range 0.69-27 ng/mL) were measured over various time points over 2 days prior to treatment initiation. The endogenous plasma concentrations varied widely across subjects and the mean ± SD values of endogenous azelaic acid plasma concentrations ranged between 4.5 ± 2.4 ng/mL and 14.6 ± 5.6 ng/mL and pimelic acid plasma concentrations ranged between 2.2 ± 1.1 ng/mL and 3.7 ± 3.1 ng/mL.

Following topical dermal applications of a mean dose of 0.94 g of FINACEA Foam (141 mg azelaic acid) twice daily for 7 consecutive days, systemic concentrations of azelaic acid were at steady state by Day 5. On Day 7, a wide range of maximum azelaic acid (22.2 to 90.1 ng/mL) and pimelic acid (2.3-16.9 ng/mL) plasma concentrations (C_max) was also observed after treatment with FINACEA Foam. The mean ± SD C_max for azelaic acid and pimelic acid were 51.8 ± 18.5 ng/mL and 5.0 ± 3.0 ng/mL, respectively. The mean ± SD systemic exposure of azelaic acid and pimelic acid within a dosing interval (AUC_0-12h) were 442.0 ± 177.6 ng.h/mL and 43.4 ± 15.4 ng.h/mL, respectively.

Azelaic acid is mainly excreted unchanged in the urine, but undergoes some ß-oxidation to shorter chain dicarboxylic acids.

FINACEA Foam, 15% is indicated for topical treatment of the inflammatory papules and pustules of mild to moderate rosacea.

The mechanism(s) by which azelaic acid interferes with the pathogenic events in rosacea are unknown.

• Hypopigmentation: Isolated cases of hypopigmentation occurred after azelaic acid use. Monitor patients with dark complexion for early signs of hypopigmentation (5.1)
• Eye and Mucous Membrane Irritation: Azelaic acid has been reported to cause irritation of the eyes. Avoid contact with the eyes and mucous membranes. (5.2)
• Flammability: Contents are flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following application. (5.3)

• Shake well before use.
• Cleanse affected area(s) using only very mild soaps or soapless cleansing lotion and pat dry with a soft towel before application of FINACEA Foam.
• Apply FINACEA Foam twice daily (morning and evening) to the entire facial area (cheeks, chin, forehead, and nose). For a single application, dispense the smallest amount of foam necessary to adequately cover the affected area(s) with a thin layer.
• Use FINACEA Foam continuously over 12 weeks.
• Wash hands immediately following application of FINACEA Foam.
• Cosmetics may be applied after the application of FINACEA Foam has dried.
• Reassess the diagnosis if no improvement is observed upon completing 12 weeks of therapy.
• Avoid the use of occlusive dressings or wrappings.
• Instruct patients to avoid use of alcoholic cleansers, tinctures and astringents, abrasives and peeling agents.
• For topical use.
• Not for oral, ophthalmic or intravaginal use.

Each gram of FINACEA (azelaic acid) Foam contains 0.15 g of azelaic acid (15% w/w) in a white to off-white foam.

Hypersensitivity, rash and worsening of asthma have been reported from the postmarketing experience of azelaic acid-containing formulations. 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.

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

FINACEA Foam was evaluated for the treatment of papulopustular rosacea in two multicenter, randomized, double-blind, vehicle-controlled, 12-week clinical trials involving a total of 1362 (FINACEA Foam, 15%: 681; vehicle: 681) subjects. Overall, 95.7% of subjects were White, 73.4% were female, and the mean age was 50.6 years.

Inform patients using FINACEA Foam of the following:

Azelaic acid has been reported to cause irritation of the eyes. Avoid contact with the eyes, mouth and other mucous membranes. If FINACEA Foam does come in contact with the eyes, wash the eyes with large amounts of water and consult a physician if eye irritation persists.

NDC 50222-303-91

Finacea^®

(azelaic acid)

Foam, 15%

For Topical Use Only

Not for ophthalmic,

oral or intravaginal

use

Sample - Not For Sale

Rx only

Net Wt. 15 g

LEO^®

NDC 50222-303-50

Finacea^®

(azelaic acid)

Foam, 15%

For Topical Use Only

Not for ophthalmic,

oral or intravaginal use

Rx only

Net Wt. 50 g

LEO^®

In a 2-year dermal mouse carcinogenicity study, azelaic acid pre-foam emulsion was administered twice daily to CD-1 mice at topical doses of 5%, 15%, and 30% (500, 1500, and 3000 mg/kg/day azelaic acid). No drug-related tumors were noted at concentrations up to 30% azelaic acid (527 times the MRHD based on AUC comparison).

Azelaic acid was not mutagenic or clastogenic in a battery of in vitro [Ames assay, HGPRT assay in V79 cells (Chinese hamster lung cells), and chromosomal aberration assay in human lymphocytes] and in vivo (dominant lethal assay in mice and mouse micronucleus assay) genotoxicity tests.

Oral administration of azelaic acid at dose levels up to 2500 mg/kg/day (162 times the MRHD based on BSA comparison) did not affect fertility or reproductive performance in male or female rats.

Local Tolerability Studies

In a 21-day cumulative irritation study under occlusive conditions, mild-to-moderate irritation was observed for azelaic acid pre-foam emulsion. In a human repeat insult patch test (HRIPT) study, no sensitization potential was observed for azelaic acid pre-foam emulsion.

Storage and Handling

Store at 25^◦C (77^◦F); excursions permitted between 15–30^◦C (59–86^◦F) [See USP Controlled Room Temperature].

Flammable. Avoid fire, flame, or smoking during and immediately following application. Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperatures above 120°F (49°C).

FINACEA (azelaic acid) Foam contains 15% (w/w) azelaic acid, a naturally-occurring saturated dicarboxylic acid and is suspended in an oil-in-water emulsion vehicle. It is for topical use. Chemically, azelaic acid is 1,7-heptanedicarboxylic acid. The structural formula of azelaic acid is:

Azelaic acid has a molecular formula of C₉ H₁₆ O₄ and a molecular weight of 188.22.

The aluminum containers are filled with hydrophilic emulsion, crimped with a continuous spray valve, and pressurized with propellants consisting of propane, butane, and isobutane. Each gram of FINACEA Foam, 15% contains 0.15 g of azelaic acid. FINACEA Foam also contains benzoic acid (as a preservative), cetostearyl alcohol, dimethyl isosorbide, medium-chain triglycerides, methylcellulose, mono- and di-glycerides, polyoxyl 40 stearate, polysorbate 80, propylene glycol, purified water, sodium hydroxide (to adjust pH), and xanthan gum as inactive ingredients.

The propellant in FINACEA Foam is flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following application. Do not puncture and/or incinerate the containers. Do not expose containers to heat and/or store at temperatures above 120°F (49°C).

The safety and efficacy of FINACEA Foam have not been established in pediatric patients.

Of the total number of subjects in clinical studies of FINACEA Foam, 18.8 percent were 65 and over, while 7.2 percent were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

The efficacy and safety of FINACEA Foam was evaluated in two multicenter, randomized, double-blind, vehicle-controlled, 12-week clinical trials (Trials 1 and 2) in subjects with papulopustular rosacea, with a mean lesion count of 21.3 (range 12 to 50) inflammatory papules and pustules. A total of 1362 (active: 681; vehicle: 681) subjects aged 19 to 92 years (mean age = 50.6 years), 95.7% Caucasian, and 73.4% female participated in the trials. The following subjects were excluded: a) those with ocular rosacea, phymatous rosacea or plaque-type rosacea lesions; b) those with rosacea that requires systemic treatment; c) those who are known non-responders to azelaic acid, and d) those with a known hypersensitivity to any ingredients of the study drug. FINACEA Foam or its vehicle were to be applied twice daily for 12 weeks; no other topical or systemic medication affecting the course of rosacea and/or evaluability was to be used during the studies. Subjects were instructed to avoid any food and beverages that, by their own experience, may provoke erythema, flushing and blushing, including spicy food, hot drinks and alcoholic beverages during the study. Subjects were also instructed to avoid use of products which may cause local irritation such as soaps, alcohol-containing cleansers, tinctures and astringents, abrasives and peeling agents during the study.

The efficacy endpoints were 1) nominal change in inflammatory lesion count from baseline and 2) success defined as a score of "clear" or "minimal" with at least 2-step reduction from baseline on a 5-point Investigator's Global Assessment (IGA). Details on IGA are specified below:

FINACEA Foam was superior to its vehicle in the treatment of rosacea in reducing the number of inflammatory papules and pustules and demonstrating success according to IGA at the end of treatment (Table 2).

None.

The following adverse reactions are described elsewhere in the prescribing information:

• Hypopigmentation [see Warnings and Precautions (5.1)].
• Eye and Mucous Membranes Irritation [see Warnings and Precautions (5.2)].

There have been reports of hypopigmentation after use of azelaic acid. Because azelaic acid has not been well studied in patients with dark complexion, monitor these patients for early signs of hypopigmentation.

The efficacy of FINACEA Foam is being driven by local mechanisms of azelaic acid within the skin.

Pharmacokinetics of azelaic acid and its metabolite pimelic acid was assessed in 21 adult subjects with moderate papulopustular rosacea with a minimum of 15 and no more than 50 inflammatory lesions (papules and/or pustules). Endogenous plasma concentrations of azelaic acid (range <1-105 ng/mL) and pimelic acid (range 0.69-27 ng/mL) were measured over various time points over 2 days prior to treatment initiation. The endogenous plasma concentrations varied widely across subjects and the mean ± SD values of endogenous azelaic acid plasma concentrations ranged between 4.5 ± 2.4 ng/mL and 14.6 ± 5.6 ng/mL and pimelic acid plasma concentrations ranged between 2.2 ± 1.1 ng/mL and 3.7 ± 3.1 ng/mL.

Following topical dermal applications of a mean dose of 0.94 g of FINACEA Foam (141 mg azelaic acid) twice daily for 7 consecutive days, systemic concentrations of azelaic acid were at steady state by Day 5. On Day 7, a wide range of maximum azelaic acid (22.2 to 90.1 ng/mL) and pimelic acid (2.3-16.9 ng/mL) plasma concentrations (C_max) was also observed after treatment with FINACEA Foam. The mean ± SD C_max for azelaic acid and pimelic acid were 51.8 ± 18.5 ng/mL and 5.0 ± 3.0 ng/mL, respectively. The mean ± SD systemic exposure of azelaic acid and pimelic acid within a dosing interval (AUC_0-12h) were 442.0 ± 177.6 ng.h/mL and 43.4 ± 15.4 ng.h/mL, respectively.

Azelaic acid is mainly excreted unchanged in the urine, but undergoes some ß-oxidation to shorter chain dicarboxylic acids.

FINACEA Foam, 15% is indicated for topical treatment of the inflammatory papules and pustules of mild to moderate rosacea.

The mechanism(s) by which azelaic acid interferes with the pathogenic events in rosacea are unknown.

• Hypopigmentation: Isolated cases of hypopigmentation occurred after azelaic acid use. Monitor patients with dark complexion for early signs of hypopigmentation (5.1)
• Eye and Mucous Membrane Irritation: Azelaic acid has been reported to cause irritation of the eyes. Avoid contact with the eyes and mucous membranes. (5.2)
• Flammability: Contents are flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following application. (5.3)

• Shake well before use.
• Cleanse affected area(s) using only very mild soaps or soapless cleansing lotion and pat dry with a soft towel before application of FINACEA Foam.
• Apply FINACEA Foam twice daily (morning and evening) to the entire facial area (cheeks, chin, forehead, and nose). For a single application, dispense the smallest amount of foam necessary to adequately cover the affected area(s) with a thin layer.
• Use FINACEA Foam continuously over 12 weeks.
• Wash hands immediately following application of FINACEA Foam.
• Cosmetics may be applied after the application of FINACEA Foam has dried.
• Reassess the diagnosis if no improvement is observed upon completing 12 weeks of therapy.
• Avoid the use of occlusive dressings or wrappings.
• Instruct patients to avoid use of alcoholic cleansers, tinctures and astringents, abrasives and peeling agents.
• For topical use.
• Not for oral, ophthalmic or intravaginal use.

Each gram of FINACEA (azelaic acid) Foam contains 0.15 g of azelaic acid (15% w/w) in a white to off-white foam.

Hypersensitivity, rash and worsening of asthma have been reported from the postmarketing experience of azelaic acid-containing formulations. 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.

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

FINACEA Foam was evaluated for the treatment of papulopustular rosacea in two multicenter, randomized, double-blind, vehicle-controlled, 12-week clinical trials involving a total of 1362 (FINACEA Foam, 15%: 681; vehicle: 681) subjects. Overall, 95.7% of subjects were White, 73.4% were female, and the mean age was 50.6 years.

Inform patients using FINACEA Foam of the following:

Azelaic acid has been reported to cause irritation of the eyes. Avoid contact with the eyes, mouth and other mucous membranes. If FINACEA Foam does come in contact with the eyes, wash the eyes with large amounts of water and consult a physician if eye irritation persists.

NDC 50222-303-91

Finacea^®

(azelaic acid)

Foam, 15%

For Topical Use Only

Not for ophthalmic,

oral or intravaginal

use

Sample - Not For Sale

Rx only

Net Wt. 15 g

LEO^®

NDC 50222-303-50

Finacea^®

(azelaic acid)

Foam, 15%

For Topical Use Only

Not for ophthalmic,

oral or intravaginal use

Rx only

Net Wt. 50 g

LEO^®

In a 2-year dermal mouse carcinogenicity study, azelaic acid pre-foam emulsion was administered twice daily to CD-1 mice at topical doses of 5%, 15%, and 30% (500, 1500, and 3000 mg/kg/day azelaic acid). No drug-related tumors were noted at concentrations up to 30% azelaic acid (527 times the MRHD based on AUC comparison).

Azelaic acid was not mutagenic or clastogenic in a battery of in vitro [Ames assay, HGPRT assay in V79 cells (Chinese hamster lung cells), and chromosomal aberration assay in human lymphocytes] and in vivo (dominant lethal assay in mice and mouse micronucleus assay) genotoxicity tests.

Oral administration of azelaic acid at dose levels up to 2500 mg/kg/day (162 times the MRHD based on BSA comparison) did not affect fertility or reproductive performance in male or female rats.