Rx Drugs Info

finacea (azelaic acidgel 
[INTENDIS]

For Dermatologic Use Only-Not for Ophthalmic, Oral, or Intravaginal Use

Rx only

DESCRIPTION

FINACEA® (azelaic acid) Gel, 15%, contains azelaic acid, a naturally occurring saturated dicarboxylic acid. Chemically, azelaic acid is 1,7-heptanedicarboxylic acid, with the molecular formula C9 H16 O4, a molecular weight of 188.22, and the structural formula:

Image from Drug Label Content

Azelaic acid is a white, odorless crystalline solid that is poorly soluble in water at 20°C (0.24%), but freely soluble in boiling water and in ethanol.

Each gram of FINACEA Gel, 15%, contains 0.15 gm azelaic acid (15% w/w) as the active ingredient in an aqueous gel base containing benzoic acid (as a preservative), disodium-EDTA, lecithin, medium-chain triglycerides, polyacrylic acid, polysorbate 80, propylene glycol, purified water, and sodium hydroxide to adjust pH.

CLINICAL PHARMACOLOGY

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

Pharmacokinetics:

The percutaneous absorption of azelaic acid after topical application of FINACEA Gel, 15%, could not be reliably determined. Mean plasma azelaic acid concentrations in rosacea patients treated with FINACEA Gel, 15%, twice daily for at least 8 weeks are in the range of 42 to 63.1 ng/mL. These values are within the maximum concentration range of 24.0 to 90.5 ng/mL observed in rosacea patients treated with vehicle only. This indicates that FINACEA Gel, 15%, does not increase plasma azelaic acid concentration beyond the range derived from nutrition and endogenous metabolism.

In vitro and human data suggest negligible cutaneous metabolism of 3H-azelaic acid 20% cream after topical application. Azelaic acid is mainly excreted unchanged in the urine, but undergoes some ß-oxidation to shorter chain dicarboxylic acids.

CLINICAL STUDIES

FINACEA Gel, 15%, was evaluated for the treatment of mild to moderate papulopustular rosacea in 2 clinical trials comprising a total of 664 (333 active to 331 vehicle) patients. Both trials were multicenter, randomized, double-blind, vehicle-controlled 12-week studies with identical protocols. Overall, 92.5% of patients were Caucasian and 73% of patients were women, and the mean age was 49 (range 21 to 86) years. Enrolled patients had mild to moderate rosacea with a mean lesion count of 18 (range 8 to 60) inflammatory papules and pustules. Subjects without papules and pustules, with nodules, rhinophyma, or ocular involvement, and a history of hypersensitivity to propylene glycol or to any other ingredients of the study drug were excluded. FINACEA Gel, 15%, 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. Patients were instructed to avoid spicy foods, thermally hot foods and drinks, and alcoholic beverages during the study, and to use only very mild soaps or soapless cleansing lotion for facial cleansing.

The primary efficacy endpoints were both

  1. change from baseline in inflammatory lesion counts and
  2. success defined as a score of clear or minimal with at least a 2 step reduction from baseline on the Investigator's Global Assessment (IGA):
CLEAR: No papules and/or pustules; no or residual erythema; no or mild to moderate telangiectasia
MINIMAL: Rare papules and/or pustules; residual to mild erythema; mild to moderate telangiectasia
MILD: Few papules and/or pustules; mild erythema; mild to moderate telangiectasia
MILD TO MODERATE: Distinct number of papules and/or pustules; mild to moderate erythema; mild to moderate telangiectasia
MODERATE: Pronounced number of papules and/or pustules; moderate erythema; mild to moderate telangiectasia
MODERATE TO SEVERE: Many papules and/or pustules, occasionally with large inflamed lesions; moderate erythema; moderate degree of telangiectasia

SEVERE:

Numerous papules and/or pustules, occasionally with confluent areas of inflamed lesions; moderate or severe erythema; moderate or severe telangiectasia

Primary efficacy assessment was based on the intent-to-treat (ITT) population with last observation carried forward (LOCF).

Both studies demonstrated a statistically significant difference in favor of FINACEA Gel, 15%, over its vehicle in reducing the number of inflammatory papules and pustules associated with rosacea (Table 1) and with success on the IGA in the ITT-LOCF population at the end of treatment.

Table 1. Inflammatory Papules and Pustules (ITT population)*
*
ITT population with last observation carried forward (LOCF);

Study One

FINACEA® Gel,15%

N = 164

Study One

VEHICLE

N = 165

Study Two

FINACEA® Gel,15%

N = 167

Study Two

VEHICLE

N = 166

Mean Lesion

Count

Baseline
17.5 17.6 17.9 18.5

End of

Treatment*
6.8 10.5 9.0 12.1

Mean Percent

Reduction

End of

Treatment*
57.9% 39.9% 50.0% 38.2%

Although some reduction of erythema which was present in patients with papules and pustules of rosacea occurred in clinical studies, efficacy for treatment of erythema in rosacea in the absence of papules and pustules has not been evaluated.

FINACEA Gel, 15%, was superior to the vehicle with regard to success based on the investigator's global assessment of rosacea on a 7-point static score at the end of treatment, (ITT population; Table 2).

Table 2. Investigator's Global Assessment at the End of Treatment*
*
ITT population with last observation carried forward (LOCF);

Study One

FINACEA® Gel, 15%

N = 164

Study One

VEHICLE

N = 165

Study Two

FINACEA® Gel, 15%

N = 167

Study Two

VEHICLE

N = 166

CLEAR, MINIMAL

or MILD at End

of Treatment

(%of Patients)
61% 40% 61% 48%

INDICATIONS AND USAGE

FINACEA Gel, 15%, is indicated for topical treatment of inflammatory papules and pustules of mild to moderate rosacea. Although some reduction of erythema which was present in patients with papules and pustules of rosacea occurred in clinical studies, efficacy for treatment of erythema in rosacea in the absence of papules and pustules has not been evaluated. Patients should be instructed to avoid spicy foods, thermally hot foods and drinks, alcoholic beverages and to use only very mild soaps or soapless cleansing lotion for facial cleansing.

CONTRAINDICATIONS

FINACEA Gel, 15%, is contraindicated in individuals with a history of hypersensitivity to propylene glycol or any other component of the formulation.

WARNINGS

FINACEA Gel, 15%, is for dermatologic use only, and not for ophthalmic, oral or intravaginal use.

There have been isolated reports of hypopigmentation after use of azelaic acid. Since azelaic acid has not been well studied in patients with dark complexion, these patients should be monitored for early signs of hypopigmentation.

PRECAUTIONS

General:

Contact with the eyes should be avoided. If sensitivity or severe irritation develops with the use of FINACEA Gel, 15%, treatment should be discontinued and appropriate therapy instituted.

Information For Patients

Patients using FINACEA Gel, 15%, should receive the following information and instructions:

Drug interactions:

There have been no formal studies of the interaction of FINACEA Gel, 15%, with other drugs.

Carcinogenesis, mutagenesis, impairment of fertility:

Long-term animal studies have not been performed to evaluate the carcinogenic potential of FINACEA Gel, 15%. Azelaic acid was not mutagenic or clastogenic in a battery of in vitro (Ames assay, HGPRT 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 maximum recommended human dose based on body surface area) did not affect fertility or reproductive performance in male or female rats.

Pregnancy:

Teratogenic effects

Pregnancy Category B

There are no adequate and well-controlled studies of topically administered azelaic acid in pregnant women. The experience with FINACEA Gel, 15%, when used by pregnant women is too limited to permit assessment of the safety of its use during pregnancy.

Dermal embryofetal developmental toxicology studies have not been performed with azelaic acid, 15%, gel. Oral embryofetal developmental studies were conducted with azelaic acid in rats, rabbits, and cynomolgus monkeys. 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 some maternal toxicity. Embryotoxicity was observed in rats given 2500 mg/kg/day (162 times the maximum recommended human dose based on body surface area), rabbits given 150 or 500 mg/kg/day (19 or 65 times the maximum recommended human dose based on body surface area) and cynomolgus monkeys given 500 mg/kg/day (65 times the maximum recommended human dose based on body surface area) azelaic acid. No teratogenic effects were observed in the oral embryofetal developmental studies conducted in rats, rabbits and cynomolgus monkeys.

An oral peri- and post-natal developmental study was conducted in rats. Azelaic acid was administered from gestational day 15 through day 21 postpartum up to a dose level of 2500 mg/kg/day. Embryotoxicity was observed in rats at an oral dose that generated some maternal toxicity (2500 mg/kg/day; 162 times the maximum recommended human dose based on body surface area). In addition, slight disturbances in the postnatal development of fetuses was noted in rats at oral doses that generated some maternal toxicity (500 and 2500 mg/kg/day; 32 and 162 times the maximum recommended human dose based on body surface area). No effects on sexual maturation of the fetuses were noted in this study.

Because animal reproduction studies are not always predictive of human response, this drug should be used only if clearly needed during pregnancy.

Nursing mothers:

Equilibrium dialysis was used to assess human milk partitioning in vitro. At an azelaic acid concentration of 25 μg/mL, the milk/ plasma distribution coefficient was 0.7 and the milk/buffer distribution was 1.0, indicating that passage of drug into maternal milk may occur. Since less than 4% of a topically applied dose of azelaic acid cream, 20%, is systemically absorbed, the uptake of azelaic acid into maternal milk is not expected to cause a significant change from baseline azelaic acid levels in the milk. However, caution should be exercised when FINACEA Gel, 15%, is administered to a nursing mother.

Pediatric use:

Safety and effectiveness of FINACEA Gel, 15%, in pediatric patients have not been established.

Geriatric use:

Clinical studies of FINACEA Gel, 15%, did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

ADVERSE REACTIONS

Overall, treatment related adverse events, including burning, stinging/ tingling, dryness/tightness/scaling, itching, and erythema/irritation/redness, were 19.4% (24/124) for FINACEA Gel, 15%, and 7.1% (9/127) for the active comparator gel at 15 weeks.

In two vehicle controlled, and one active controlled U.S. clinical studies, treatment safety was monitored in 788 patients who used twice daily FINACEA Gel, 15%, for 12 weeks (N=333) or for 15 weeks (N=124), or the gel vehicle (N=331) for 12 weeks

Table 3. Cutaneous Adverse Events Occurring in ≥1% of Subjects in the Rosacea Trials by Treatment Group and Maximum Intensity*
*
Subjects may have >1 cutaneous adverse event; thus, the sum of the frequencies of preferred terms may exceed the number of subjects with at least 1 cutaneous adverse event.

FINACEA® Gel, 15%

N=457 (100%)

Vehicle

N=331 (100%)

Mild

n=99

(22%)

Moderate

n=61

(13%)

Severe

n=27

(6%)

Mild

n=46

(14%)

Moderate

n=30

(9%)

Severe

n=5

(2%)

Burning/

stinging/

tingling
71 (16%) 42 (9%) 17 (4%) 8 (2%) 6 (2%) 2 (1%)
Pruritus 29 (6%) 18 (4%) 5 (1%) 9 (3%) 6 (2%) 0 (0%)

Scaling/dry

skin/xerosis
21 (5%) 10 (2%) 5 (1%) 31 (9%) 14 (4%) 1 (<1%)

Erythema/

irritation
6 (1%) 7 (2%) 2 (<1%) 8 (2%) 4 (1%) 2 (1%)

Contact

dermatitis
2 (<1%) 3 (1%) 0 (0%) 1 (<1%) 0 (0%) 0 (0%)
Edema 3 (1%) 2 (<1%) 0 (0%) 3 (1%) 0 (0%) 0 (0%)
Acne 3 (1%) 1 (<1%) 0 (0%) 1 (<1%) 0 (0%) 0 (0%)

FINACEA Gel, 15%, and its vehicle caused irritant reactions at the application site in human dermal safety studies. FINACEA Gel, 15%, caused significantly more irritation than its vehicle in a cumulative irritation study. Some improvement in irritation was demonstrated over the course of the clinical studies, but this improvement might be attributed to subject dropouts. No phototoxicity or photoallergenicity were reported in human dermal safety studies.

In patients using azelaic acid formulations, the following additional adverse experiences have been reported rarely: worsening of asthma, vitiligo depigmentation, small depigmented spots, hypertrichosis, reddening (signs of keratosis pilaris), and exacerbation of recurrent herpes labialis.

Post-marketing safety-Skin: facial burning and irritation; Eyes: iridocyclitis on accidental exposure with FINACEA Gel, 15%, to the eye (see PRECAUTIONS).

OVERDOSAGE

FINACEA Gel, 15%, is intended for cutaneous use only. If pronounced local irritation occurs, patients should be directed to discontinue use and appropriate therapy should be instituted (See PRECAUTIONS).

DOSAGE AND ADMINISTRATION

A thin layer of FINACEA Gel, 15%, should be gently massaged into the affected areas on the face twice daily, in the morning and evening. Patients should be reassessed if no improvement is observed upon completing 12 weeks of therapy.

HOW SUPPLIED

FINACEA® Gel, 15%, is supplied in tubes in the following size:

50 g - NDC 10922-825-02

Storage

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

Distributed under license; U.S. Patent No 4,713,394

© 2005, Intendis, Inc. All rights reserved.

May 2005

Manufactured by Intendis Manufacturing S.p.A., Segrate, Milan, Italy

Distributed by: INTENDIS Pine Brook, NJ 07058

6058301 2540870


Finacea (azelaic acid)
PRODUCT INFO
Product Code 10922-825 Dosage Form GEL
Route Of Administration TOPICAL DEA Schedule
INGREDIENTS
Name (Active Moiety) Type Strength
azelaic acid (azelaic acid) Active 0.15 GRAM  In 1 GRAM
benzoic acid Inactive  
disodium-EDTA Inactive  
lecithin Inactive  
medium-chain triglycerides Inactive  
polyacrylic acid Inactive  
polysorbate 80 Inactive  
propylene glycol Inactive  
water Inactive  
sodium hydroxide Inactive  
IMPRINT INFORMATION
Characteristic Appearance Characteristic Appearance
Color Score
Shape Symbol
Imprint Code Coating
Size
PACKAGING
# NDC Package Description Multilevel Packaging
1 10922-825-02 1 TUBE In 1 CARTON contains a TUBE
1 50 GRAM In 1 TUBE This package is contained within the CARTON (10922-825-02)

Revised: 03/2007INTENDIS

Data are from FDA and U.S. National Library of Medicine.