Finacea Foam

Patient Information

Inform patients using Finacea Foam of the following information and instructions:

• For external use only.
• Cleanse affected area(s) with a very mild soap or a soapless cleansing lotion and pat dry with a soft towel.
• Shake well before use.
• Avoid use of alcoholic cleansers, tinctures and astringents, abrasives and peeling agents.
• Avoid contact with the eyes, mouth and other mucous membranes. If Finacea Foam does come in contactwith the eyes, wash the eyes with large amounts of water and consult your physician if eye irritationpersists.
• If allergic reactions occur, discontinue use and consult your physician.
• Wash hands immediately following application of Finacea Foam.
• Cosmetics may be applied after the application of Finacea Foam has dried.
• Avoid the use of occlusive dressings and wrappings.
• To help manage rosacea, avoid any triggers that may provoke erythema, flushing, and blushing. Thesetriggers can include spicy and thermally hot food and drinks such as hot coffee, tea, or alcoholicbeverages.
• The propellant in Finacea Foam is flammable. Avoid fire, flame, or smoking during and immediatelyfollowing application.
• Discard product 8 weeks after opening.

Description

Finacea (azelaic acid) Foam contains 15% (w/w) azelaic acid, a naturally-occurring saturated dicarboxylic acidand is suspended in an oil-in-water emulsion vehicle for topical administration to affected skin area.Chemically, azelaic acid is 1,7-heptanedicarboxylic acid. The structural formula of azelaic acid is:

Azelaic acid has a molecular formula of C₉H₁₆O₄ and a molecular weight of 188.22.

The aluminum containers are filled with hydrophilic emulsion, crimped with a continuous spray valve, andpressurized with propellants consisting of propane, butane, and isobutane. Each gram of Finacea Foam contains0.15 g of azelaic acid. Finacea Foam also contains benzoic acid, cetostearyl alcohol, dimethyl isosorbide,medium-chain triglycerides, methylcellulose, mono- and di-glycerides, polyoxyl 40 stearate, polysorbate 80,propylene glycol, purified water, sodium hydroxide, and xanthan gum as inactive ingredients.

Finacea(azelaic acid) Foam, 15% is indicated for topical treatment of the inflammatory papules and pustules ofmild to moderate rosacea.

Dosage And Administration

• Apply a thin layer of Finacea Foam twice daily (morning andevening) to the entire facial area (cheeks, chin, forehead, andnose). For a single application, dispense the smallest amount of foam necessary to adequately coverthe affected area(s) with a thin layer.
• Shake well before use.
• Cosmetics may be applied after the application of FinaceaFoam has dried.
• Avoid the use of occlusive dressings or wrappings.
• Finacea Foam should be used continuously over 12 weeks.
• Reassess patients if no improvement is observed upon completing 12 weeks of therapy.
• Not for oral, ophthalmic or intravaginal use.

How Supplied

Dosage Forms And Strengths

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

Finacea (azelaic acid) Foam 15% is a white to off-white emulsion supplied in a pressurized 50 g (NDC 50419-829-01) aluminum can.

Storage And Handling

Store at 25° C (77° F); excursions permitted between 15–30° C (59–86° F) [See USP Controlled RoomTemperature].

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

Manufactured for: Bayer HealthCare Pharmaceuticals Inc. Whippany, NJ 07981. Revised: Jul 2019.

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

• Hypopigmentation [see WARNINGS AND PRECAUTIONS].
• Eye and Mucous Membranes Irritation [see WARNINGS AND PRECAUTIONS].

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in theclinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may notreflect 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 50.6years.

Table 1: Adverse Reactions Occurring in ≥ 0.5% of Subjects Treated with Finacea Foam Compared withSubjects Treated with Vehicle

Post-Marketing Experience

Hypersensitivity, rash and worsening of asthma have been reported from the postmarketing experience ofazelaic acid-containing formulations. Because these reactions are reported voluntarily from a population ofuncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship todrug exposure.

Local Tolerability Studies

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

Drug Interactions

No Information Provided

Included as part of the “PRECAUTIONS” Section

Precautions

Skin Reactions

There have been isolated reports of hypopigmentation after use of azelaic acid. Because azelaic acid has notbeen well studied in patients with dark complexion, monitor these patients for early signs of hypopigmentation.

Eye And Mucous Membranes Irritation

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

Flammability

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

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Systemic long-term animal studies have not been performed to evaluate the carcinogenic potential of azelaicacid. In a 26-week dermal carcinogenicity study using transgenic (Tg.AC) mice, Finacea Gel and the gelvehicle, when applied once or twice daily, did not increase the number of female Tg.AC animals withpapillomas at the treatment site. No statistically significant increase in the number of animals with papillomas atthe treatment site was observed in male Tg.AC animals after once daily application. After twice dailyapplication, Finacea Gel and the gel vehicle induced a statistically significant increase in the number of maleanimals with papillomas at the treatment site when compared to untreated males. This suggests that the positiveeffect may be associated with the vehicle application. The clinical relevance of the findings in animals tohumans is not clear.

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 (dominantlethal 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)did not affect fertility or reproductive performance in male or female rats.

Use In Specific Populations

Pregnancy

Teratogenic Effects

Pregnancy Category B

There are no adequate and well-controlled studies in pregnant women. Therefore, Finacea Foam should be usedduring pregnancy only if the potential benefit justifies the potential risk to the fetus.

Dermal embryofetal developmental toxicology studies have not been performed with azelaic acid, 15% foam.Oral embryofetal developmental studies were conducted with azelaic acid in rats, rabbits, and cynomolgusmonkeys. Azelaic acid was administered during the period of organogenesis in all three animal species.Embryotoxicity was observed in rats, rabbits, and monkeys at oral doses of azelaic acid that generated somematernal toxicity. Embryotoxicity was observed in rats given 2500 mg/kg/day [162 times the maximumrecommended human dose (MRHD) based on body surface area (BSA)], rabbits given 150 or 500 mg/kg/day(19 or 65 times the MRHD based on BSA) and cynomolgus monkeys given 500 mg/kg/day (65 times theMRHD based on BSA) azelaic acid. No teratogenic effects were observed in the oral embryofetaldevelopmental studies conducted in rats, rabbits and cynomolgus monkeys.

An oral peri- and post-natal developmental study was conducted in rats. Azelaic acid was administered fromgestational day 15 through day 21 postpartum up to a dose level of 2500 mg/kg/day. Embryotoxicity was “Application site pain” is a term used to describe disagreeable skin sensations, including burning,stinging, paraesthesia and tenderness. observed in rats at an oral dose of 2500 mg/kg/day (162 times the MRHD based on BSA) that generated somematernal toxicity. In addition, slight disturbances in the post-natal development of fetuses was noted in rats atoral doses that generated some maternal toxicity (500 and 2500 mg/kg/day; 32 and 162 times the MRHD basedon BSA). No effects on sexual maturation of the fetuses were noted in this study.

Nursing Mothers

It is not known if azelaic acid is secreted into human milk in vivo . No well-controlled studies of topicallyadministered azelaic acid in nursing women are available. Nevertheless, the decision to discontinue nursing orto discontinue the drug should take into account the importance of the drug to the mother.

Pediatric Use

The safety and efficacy of FinaceaFoam in children below the age of 18 years have not been established.

Geriatric Use

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

No Information Provided.

Contraindications

None.

Mechanism Of Action

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

Pharmacodynamics

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

Pharmacokinetics

Pharmacokinetics of azelaic acid and its metabolite pimelic acid was assessed in 21 adult subjects withmoderate papulopustular rosacea with a minimum of 15 and no more than 50 inflammatory lesions (papulesand/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. Theendogenous plasma concentrations varied widely across subjects and the mean ± SD values of endogenousazelaic acid plasma concentrations ranged between 4.5 ± 2.4 ng/mL and 14.6 ± 5.6 ng/mL and pimelic acidplasma 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) twicedaily for 7 consecutive days, systemic concentrations of azelaic acid were at steady state by Day 5. On Day 7, awide range of maximum azelaic acid (22.2 to 90.1 ng/mL) and pimelic acid (2.3-16.9 ng/mL) plasmaconcentrations (Cmax) was also observed after treatment with Finacea Foam. The mean ± SD Cmax for azelaicacid and pimelic acid were 51.8 ± 18.5 ng/mL and 5.0 ± 3.0 ng/mL, respectively. The mean ± SD systemicexposure of azelaic acid and pimelic acid within a dosing interval (AUC0-12h) were 442.0 ± 177.6 ng.h/mL and43.4 ± 15.4 ng.h/mL, respectively.

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

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Systemic long-term animal studies have not been performed to evaluate the carcinogenic potential of azelaicacid. In a 26-week dermal carcinogenicity study using transgenic (Tg.AC) mice, Finacea Gel and the gelvehicle, when applied once or twice daily, did not increase the number of female Tg.AC animals withpapillomas at the treatment site. No statistically significant increase in the number of animals with papillomas atthe treatment site was observed in male Tg.AC animals after once daily application. After twice dailyapplication, Finacea Gel and the gel vehicle induced a statistically significant increase in the number of maleanimals with papillomas at the treatment site when compared to untreated males. This suggests that the positiveeffect may be associated with the vehicle application. The clinical relevance of the findings in animals tohumans is not clear.

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 (dominantlethal 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)did not affect fertility or reproductive performance in male or female rats.

Clinical Studies

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 lesioncount 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 thetrials. The following subjects were excluded: a) those with ocular rosacea, phymatous rosacea or plaque-typerosacea lesions; b) those with rosacea that requires systemic treatment; c) those who are known non-respondersto azelaic acid, and d) those with a known hypersensitivity to any ingredients of the study drug. Finacea Foamor its vehicle were to be applied twice daily for 12 weeks; no other topical or systemic medication affecting thecourse of rosacea and/or evaluability was to be used during the studies. Subjects were instructed to avoid anyfood and beverages that, by their own experience, may provoke erythema, flushing and blushing, includingspicy 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) successdefined as a score of “clear” or “minimal” with at least 2-step reduction from baseline on a 5-pointInvestigator’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 inflammatorypapules and pustules and demonstrating success according to IGA at the end of treatment (Table 2).

Table 2: IGA Success Rate and Nominal Change in Inflammatory Lesion Count from Baseline to End ofthe 12-Week Treatment Period