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: C₉H₁₆O₄
Molecular Weight: 188.22

Active Ingredient: Each gram of AZELEX contains azelaic acid..........0.2 gm (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.

Last updated on RxList: 11/11/2008

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

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.

AZELEX Cream is supplied in a closed orifice tube with a white, spiked screwcap in the following sizes:

30 g - NDC 0023-8694-30
50 g - NDC 0023-8694-50

Note: Protect from freezing. Store product on its side.

Store between 15° - 30° C (59° - 86° F).

Distributed by: Allergan, Inc., Irvine, California 92612, U.S.A. Made in Italy. FDA Rev date: 6/10/2003

Last updated on RxList: 11/11/2008

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.

No information provided.

Last updated on RxList: 11/11/2008

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.

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.

Pregnancy

Teratogenic Effects: Pregnancy Category B.

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 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 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.

Last updated on RxList: 11/11/2008

No information provided.

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

Last updated on RxList: 11/11/2008

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.

Last updated on RxList: 11/11/2008

Patients should be told:

1. To use AZELEX Cream for the full prescribed treatment period.
2. To avoid the use of occlusive dressings or wrappings.
3. 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.
4. If they have dark complexions, to report abnormal changes in skin color to their physician.
5. 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.)

Last updated on RxList: 11/11/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

AZELAIC ACID CREAM - TOPICAL

(ay-zeh-LAY-ick)

COMMON BRAND NAME(S): Azelex

USES: This medication is used for the treatment of mild to moderate acne. Azelaic acid belongs to a class of drugs known as dicarboxylic acids. It works by stopping the growth of bacteria on the skin and by reducing the amount of a natural skin substance (keratin) that can cause acne.

HOW TO USE: This medication is applied to the skin twice daily, or as directed by your doctor. To apply, clean the affected area with a mild soap or soap-free cleanser and pat dry. Apply a thin layer on the skin and massage in gently. Wash hands well after use.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same time(s) each day.

Avoid contact in or near the eyes or inside the nose and mouth. If it gets in your eyes wash out immediately with plenty of water and call your doctor if irritation persists. Do not apply any type of dressing or covering over the cream unless told to do so by your doctor.

Do not use large amounts or apply this more often than directed. Your condition will not clear faster, but the chance for side effects may be increased. Use for the full course of treatment as directed by your doctor. Improvement is usually seen within 4 weeks, but the full effects of this medication may take longer.

Inform your doctor if your condition persists or worsens after 4 weeks.

SIDE EFFECTS: Stinging, burning, itching, tingling, redness or drying of the skin may occur, usually at the beginning of treatment.

These side effects may be controlled by using this medication once daily instead of twice daily. Consult your doctor for more details.

If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: changes in skin color (hypopigmentation), worsening of cold sores or fever blisters (oral herpes).

Dark-skinned individuals may notice a lightening in skin color. Consult your doctor or pharmacist for advice and report these changes if they occur.

Tell your doctor immediately if any of these rare but very serious side effects occur: worsening of asthma symptoms (shortness of breath, wheezing, increased use of quick-relief inhalers).

A very serious allergic reaction to this drug is unlikely but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using this medication, tell your doctor or pharmacist if you are allergic to it; to propylene glycol or benzoic acid; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: asthma, repeat episodes of cold sores or fever blisters (oral herpes).

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This medication passes into breast milk. Though there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Avoid use of skin care products that can cause further irritation (e.g., cleansers that contain alcohol, tinctures, astringents, abrasives and peeling agents). Consult your doctor or pharmacist for details.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. This medicine may be harmful if swallowed.

NOTES: Do not share this medication with others.

MISSED DOSE: If you miss a dose, apply it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C). Do not freeze. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.