NDC 0023-8694 Azelex

Azelaic Acid

NDC Product Information

Azelex with NDC 0023-8694 is a a human prescription drug product labeled by Allergan, Inc.. The generic name of Azelex is azelaic acid. The product's dosage form is cream and is administered via cutaneous form.

Labeler Name: Allergan, Inc.

Dosage Form: Cream - An emulsion, semisolid3 dosage form, usually containing > 20% water and volatiles5 and/or < 50% hydrocarbons, waxes, or polyols as the vehicle. This dosage form is generally for external application to the skin or mucous membranes.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Azelex Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • AZELAIC ACID .2 g/g

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • CETEARYL ETHYLHEXANOATE (UNII: 9M64UO4C25)
  • GLYCERIN (UNII: PDC6A3C0OX)
  • CETOSTEARYL ALCOHOL (UNII: 2DMT128M1S)
  • CETYL PALMITATE (UNII: 5ZA2S6B08X)
  • PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
  • WATER (UNII: 059QF0KO0R)
  • GLYCERYL MONOSTEARATE (UNII: 230OU9XXE4)
  • COCO-GLYCERIDES (UNII: ISE9I7DNUG)
  • BENZOIC ACID (UNII: 8SKN0B0MIM)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Cutaneous - Administration to the skin.
  • Cutaneous - Administration to the skin.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Decreased Protein Synthesis - [PE] (Physiologic Effect)
  • Decreased Sebaceous Gland Activity - [PE] (Physiologic Effect)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Allergan, Inc.
Labeler Code: 0023
FDA Application Number: NDA020428 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 03-21-1996 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

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Information for Patients

Azelaic Acid Topical

Azelaic Acid Topical is pronounced as (ay ze lay' ik)

Why is azelaic acid topical medication prescribed?
Azelaic acid gel and foam is used to clear the bumps, lesions, and swelling caused by rosacea (a skin disease that causes redness, flushing, and pimples on the face). Aze...
[Read More]

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Azelex Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Other

For Dermatologic Use Only Not for Ophthalmic Use

Active Ingredient: Each gram of AZELEX® contains azelaic acid......... 0.2 g (20% w/w).

Inactive Ingredients: cetearyl octanoate; glycerin; glyceryl stearate and cetearyl alcohol and cetyl palmitate and cocoglycerides; PEG-5 glyceryl stearate; propylene glycol; and purified water. Benzoic acid is present as a preservative.

Description

AZELEX® (azelaic acid cream) 20% contains azelaic acid, a naturally occurring saturated dicarboxylic acid.
Structural Formula: HOOC-(CH2)7-COOH
Chemical Name: 1,7-heptanedicarboxylic acid
Empirical Formula: C9H16O4Molecular Weight: 188.22

Clinical Pharmacology

The exact mechanism of action of azelaic acid is not known. The following in vitro data are available, but their clinical significance is unknown. Azelaic acid has been shown to possess antimicrobial activity against Propionibacterium acnes and Staphylococcus epidermidis. The antimicrobial action may be attributable to inhibition of microbial cellular protein synthesis.
A normalization of keratinization leading to an anticomedonal effect of azelaic acid may also contribute to its clinical activity. Electron microscopic and immunohistochemical evaluation of skin biopsies from human subjects treated with AZELEX® cream demonstrated a reduction in the thickness of the stratum corneum, a reduction in number and size of keratohyalin granules, and a reduction in the amount and distribution of filaggrin (a protein component of keratohyalin) in epidermal layers. This is suggestive of the ability to decrease microcomedo formation.

Pharmacokinetics

Following a single application of AZELEX® cream to human skin in vitro, azelaic acid penetrates into the stratum corneum (approximately 3 to 5% of the applied dose) and other viable skin layers (up to 10% of the dose is found in the epidermis and dermis). Negligible cutaneous metabolism occurs after topical application. Approximately 4% of the topically applied azelaic acid is systemically absorbed. Azelaic acid is mainly excreted unchanged in the urine but undergoes some β-oxidation to shorter chain dicarboxylic acids. The observed half-lives in healthy subjects are approximately 45 minutes after oral dosing and 12 hours after topical dosing, indicating percutaneous absorption rate-limited kinetics.
Azelaic acid is a dietary constituent (whole grain cereals and animal products), and can be formed endogenously from longer-chain dicarboxylic acids, metabolism of oleic acid, and ψ-oxidation of monocarboxylic acids. Endogenous plasma concentration (20 to 80 ng/mL) and daily urinary excretion (4 to 28 mg) of azelaic acid are highly dependent on dietary intake. After topical treatment with AZELEX® cream in humans, plasma concentration and urinary excretion of azelaic acid are not significantly different from baseline levels.

Indications And Usage

AZELEX® cream is indicated for the topical treatment of mild-to-moderate inflammatory acne vulgaris.

Contraindications

AZELEX® cream is contraindicated in individuals who have shown hypersensitivity to any of its components.

Warnings

AZELEX® cream is for dermatologic use only and not for ophthalmic 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 complexions, these patients should be monitored for early signs of hypopigmentation.

General

If sensitivity or severe irritation develop with the use of AZELEX® cream, treatment should be discontinued and appropriate therapy instituted.

Information For Patients

  • Patients should be told:
  • To use AZELEX® cream for the full prescribed treatment period.
  • To avoid the use of occlusive dressings or wrappings.
  • To keep AZELEX® cream away from the mouth, eyes and other mucous membranes. If it does come in contact with the eyes, they should wash their eyes with large amounts of water and consult a physician if eye irritation persists.
  • If they have dark complexions, to report abnormal changes in skin color to their physician.
  • Due in part to the low pH of azelaic acid, temporary skin irritation (pruritus, burning, or stinging) may occur when AZELEX® cream is applied to broken or inflamed skin, usually at the start of treatment. However, this irritation commonly subsides if treatment is continued. If it continues, AZELEX® cream should be applied only once-a-day, or the treatment should be stopped until these effects have subsided. If troublesome irritation persists, use should be discontinued, and patients should consult their physician (see ADVERSE REACTIONS).

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Azelaic acid is a human dietary component of a simple molecular structure that does not suggest carcinogenic potential, and it does not belong to a class of drugs for which there is a concern about carcinogenicity. Therefore, animal studies to evaluate carcinogenic potential with AZELEX® cream were not deemed necessary. In a battery of tests (Ames assay, HGPRT test in Chinese hamster ovary cells, human lymphocyte test, dominant lethal assay in mice), azelaic acid was found to be nonmutagenic. Animal studies have shown no adverse effects on fertility.

Teratogenic Effects

Embryotoxic effects were observed in Segment I and Segment II oral studies with rats receiving 2500 mg/kg/day of azelaic acid. Similar effects were observed in Segment II studies in rabbits given 150 to 500 mg/kg/day and in monkeys given 500 mg/kg/day. The doses at which these effects were noted were all within toxic dose ranges for the dams. No teratogenic effects were observed. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Equilibrium dialysis was used to assess human milk partitioning in vitro. At an azelaic acid concentration of 25 mcg/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 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 AZELEX® cream is administered to a nursing mother.

Pediatric Use

Safety and effectiveness in pediatric patients under 12 years of age have not been established.

Geriatric Use

Clinical studies of AZELEX® cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Adverse Reactions

During U.S. clinical trials with AZELEX® cream, adverse reactions were generally mild and transient in nature. The most common adverse reactions occurring in approximately 1-5% of patients were pruritus, burning, stinging and tingling. Other adverse reactions such as erythema, dryness, rash, peeling, irritation, dermatitis, and contact dermatitis were reported in less than 1% of subjects. There is the potential for experiencing allergic reactions with use of AZELEX® cream.
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.

Dosage And Administration

After the skin is thoroughly washed and patted dry, a thin film of AZELEX® cream should be gently but thoroughly massaged into the affected areas twice daily, in the morning and evening. The hands should be washed following application. The duration of use of AZELEX® cream can vary from person to person and depends on the severity of the acne. Improvement of the condition occurs in the majority of patients with inflammatory lesions within four weeks.

How Supplied

AZELEX® cream is supplied in a closed orifice tube with a white, spiked screwcap in the following sizes:
30 g - NDC 0023-8694-3050 g - NDC 0023-8694-50
Storage: Protect from freezing. Store product on its side. Store at 15°-30° C (59°-86° F).
Revised: 09/2015Distributed under license by Allergan, Inc., Irvine, CA 92612, U.S.A.© 2015 Allergan. All right reserved. ® marks owned by Allergan, Inc.
Made in Italy by Bayer HealthCare Manufacturing S.r.l., Segrate (Milan), Italy
70896US17

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