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  • CLASSES

    Other Topical Anti-Acne Products
    Topical Rosacea Agents

    DEA CLASS

    Rx

    DESCRIPTION

    Treatment for acne vulgaris and rosacea associated with inflammatory pustules and papules
    Only topical formulations (cream, gel, foam) are marketed in the United States
    Azelaic acid is a naturally occurring dietary constituent and can be formed endogenously

    COMMON BRAND NAMES

    Azelex, Finacea, Finacea Plus

    HOW SUPPLIED

    Azelex Topical Cream: 20%
    Finacea Plus Topical Lotion
    Finacea Plus Topical Susp
    Finacea Topical Foam: 15%
    Finacea/Finacea Plus Topical Gel: 15%

    DOSAGE & INDICATIONS

    For the treatment of mild-to-moderate inflammatory acne vulgaris.
    Topical dosage (20% cream)
    Adults

    Apply cream in a thin film to the affected area twice daily, morning and evening. Clinical improvement may not be evident for several weeks (usually 4 weeks). The duration of treatment can vary among individuals and depend on the severity of the acne. Patients with dark complexions should be monitored for early signs of hypopigmentation during treatment.

    For the treatment of inflammatory pustules and papules of mild-to-moderate acne rosacea.
    Topical dosage (20% skin cream† and 15% gel or foam)
    Adults

    Apply 15% gel, foam, or 20% cream in a thin film to the affected area twice daily, morning and evening. Reassess patient if no improvement occurs after 12 weeks of treatment.

    For the treatment of melasma†.
    Topical dosage (20% cream)
    Adults

    Limited clinical data exist on the use of azelaic acid in treating melasma. Several studies suggest that azelaic acid 20% cream applied in a thin film to the affected area twice daily in combination with a broad spectrum sunscreen was either more effective than or equally effective as hydroquinone 2% or 4%, respectively.

    For the treatment of lentigo maligna† in which surgery is contraindicated.
    Topical dosage (cream or ointment 15—35%)
    Adults

    Application of azelaic acid cream or ointment (15% to 35%) 2 to 4 times per day for 3 to 16 months was used in preliminary uncontrolled studies of lentigo maligna. Response rates were variable with complete resolution in 27 patients (n = 50) in one study to only partial improvement in 2 patients (n = 15) in another study. Since surgery is the primary treatment modality for lentigo maligna it has been suggested that azelaic acid be limited to treating lentigo maligna in patients who are not candidates for surgery.

    For the treatment of cutaneous malignant melanoma†.
    Topical and Oral† dosage
    Adults

    In a preliminary uncontrolled study of patients (n = 23) with cutaneous malignant melanoma, oral therapy (10 to 15 g/day) was combined with topical therapy (15% cream applied twice daily) for 2 to 12 weeks prior to surgical excision. Beneficial clinical effects were noted in all patients and included a progressive reduction in the intensity of lesion pigmentation, arrest and subsequent regression of the advancing edge of the lesion, and flattening of nodular areas. Six patients with single local lesions had clinical remission after approximately 10 years of follow-up. Oral doses of up to 4,000 mg/kg have been administered with no apparent toxicity.

    †Indicates off-label use

    MAXIMUM DOSAGE

    No maximum dosage information is available.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    For storage information, see specific product information within the How Supplied section.

    Topical Administration

    Do not apply to the eye; avoid contact with the mouth, eyes, and other mucous membranes. If contact with the eye(s) occur, the eye(s) should be washed with large amounts of water; contact prescriber if ocular irritation persists.
    Occlusive dressings or wrappings should not be used. Wash hands after applying.

    Cream/Ointment/Lotion Formulations

    Before applying, the affected areas should be thoroughly washed (using mild soap or soapless cleansing lotion) and patted dry.
    Apply cream and massage gently into the affected areas.

    Other Topical Formulations

    Gel Formulation
    Before applying, the affected areas should be thoroughly washed (using mild soap or soapless cleansing lotion) and patted dry.
    The gel is available in a tube and a pump. With the first use, the pump may need to be repeatedly depressed before any gel is dispensed. Discard the pump 8 weeks after opening.
    Apply gel and massage gently into the affected areas
    Cosmetics may be applied after gel has dried.
     
    Foam Formulation
    Shake well before use.
    Dispense the smallest amount of foam required to cover the area to be treated (entire face) with a thin layer.
    Instruct patient to avoid flame, fire, or smoking during an immediately after application. The propellant in the foam is flammable. Do not puncture or incinerate the container.
    Cosmetics may be applied after foam has dried.

    STORAGE

    Azelex:
    - Protect from freezing
    - Store at room temperature (between 59 to 86 degrees F)
    Finacea:
    - Do Not Store at Temperatures Above 120 degrees F (49 degrees C)
    - Flammable, keep away from heat and flame
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    - Use within 8 weeks of first opening
    Finacea Plus:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Azelaic acid products that contain propylene glycol should be avoided in patients with a known propylene glycol hypersensitivity; avoid use in patients hypersensitive to any other ingredients of the particular formulation prescribed.
    Azelaic acid has not been well-studied in patients with dark complexions and should be used cautiously in these patients to avoid hypopigmentation.

    Occlusive dressing, ocular exposure

    An occlusive dressing should not be used with azelaic acid. Avoid ocular exposure and accidental exposure/contact with the mouth and other mucous membranes. If contact with the eye(s) occur, the eye(s) should be washed with large amounts of water; patients should contact their physician if ocular irritation persists.

    Pregnancy

    Azelaic acid is classified FDA pregnancy risk category B. Animal data suggests embryotoxic effects when administered orally; 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, azelaic acid should be used during pregnancy only if clearly needed.

    Breast-feeding

    According to the manufacturer, caution should be exercised when azelaic acid is administered to breast-feeding women. In vitro studies assessing human milk partitioning suggests that azelaic acid may be distributed into breast milk. However, 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 concentrations in the milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Children, infants, neonates

    The safety and effectiveness of azelaic acid cream and gel formulations in neonates, infants, and children under 12 years of age have not been established. The foam formulation is not approved for use in pediatric patients less than 18 years of age.

    Herpes infection

    Do not apply azelaic acid to areas affected by herpes labialis; exacerbations of herpes infection have been reported.

    Asthma, deterioration of asthma

    Worsening or deterioration of asthma has been observed in patients treated with azelaic acid. Instruct drug recipients to contact their physician if signs of an asthma exacerbation (i.e., dyspnea, wheezing) develop during therapy.

    ADVERSE REACTIONS

    Severe

    angioedema / Rapid / Incidence not known

    Moderate

    erythema / Early / 0-2.0
    edema / Delayed / 0-1.0
    contact dermatitis / Delayed / 0-1.0
    wheezing / Rapid / Incidence not known
    dyspnea / Early / Incidence not known
    ocular inflammation / Early / Incidence not known

    Mild

    paresthesias / Delayed / 1.0-6.2
    pruritus / Rapid / 0-6.0
    xerosis / Delayed / 0-5.0
    skin irritation / Early / 0-2.0
    rash (unspecified) / Early / 0-1.0
    skin hypopigmentation / Delayed / Incidence not known
    hypertrichosis / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known

    DRUG INTERACTIONS

    There are no drug interactions associated with Azelaic Acid products.

    PREGNANCY AND LACTATION

    Pregnancy

    Azelaic acid is classified FDA pregnancy risk category B. Animal data suggests embryotoxic effects when administered orally; 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, azelaic acid should be used during pregnancy only if clearly needed.

    According to the manufacturer, caution should be exercised when azelaic acid is administered to breast-feeding women. In vitro studies assessing human milk partitioning suggests that azelaic acid may be distributed into breast milk. However, 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 concentrations in the milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    The efficacy of azelaic acid in acne vulgaris is due to an antimicrobial effect and an antikeratinizing effect on the follicular epidermis. The antimicrobial effects of azelaic acid involves inhibition of synthesis of microbial cellular proteins; the exact mechanism of action is unknown. Azelaic acid possesses bacteriostatic properties against a variety of aerobic microorganisms, especially Staphylococcus epidermidis and Propionibacterium acnes which are known to be elevated in acne-bearing skin; at high concentrations, azelaic acid is bactericidal against S. epidermidis and P. acnes. By reducing the concentration of bacteria present on the skin, azelaic acid decreases the inflammation associated with acne lesions. Azelaic acid may also possess a direct antiinflammatory effect by scavenging oxygen radicals. The antikeratinizing effects of azelaic acid may be due to decreased synthesis of filaggrin (keratin filament aggregating protein). By inhibiting filaggrin, azelaic acid may normalize the keratinization of the follicle and produce a reduction in noninflamed acne lesions. Azelaic acid does not affect sebum excretion.
     
    The mechanism of action that results in the efficacy of azelaic acid in acne rosacea is not clear; clinical studies suggest interference with the pathogenic effects in rosacea. Anti-inflammatory effects have been noted in vitro.
     
    The antiproliferative and cytotoxic actions of azelaic acid may be due to reversible inhibition of a variety of oxidoreductive enzymes including DNA polymerase, tyrosinase, and mitochondrial enzymes of the respiratory chain. At the cellular level, azelaic acid causes mitochondrial swelling and accumulation of cytoplasmic lipid droplets. Azelaic acid has shown efficacy in treating such conditions as lentigo maligna, cutaneous malignant melanoma, and melasma (chloasma). When azelaic acid is applied topically in these conditions, there is a reduction in epidermal melanogenesis and replacement of abnormal melanocytes by normal cells; flattening of nodular areas may also occur. Hyperactive and malignant melanocytes are much more susceptible to the effects of azelaic acid than are normal melanocytes.

    PHARMACOKINETICS

    Azelaic acid is applied topically to the skin. Azelaic acid is mainly excreted unchanged in the urine but does undergo some beta-oxidation to shorter chain dicarboxylic acids. Plasma concentrations and daily urinary excretion of azelaic acid are highly dependent on dietary intake.

    Oral Route

    The observed half-lives in healthy subjects are approximately 45 minutes after oral dosing, indicating percutaneous absorption rate-limited kinetics.

    Topical Route

    Following a single application to human skin in vitro, the drug penetrates into the stratum corneum (approximately 3—5% of the applied dose) and other viable skin layers (up to 10% of the dose is found in the epidermis and dermis). Approximately 4% of the topically applied dose is absorbed systemically. Negligible cutaneous metabolism occurs after topical administration. The observed half-lives in healthy subjects are approximately 12 hours after topical dosing, indicating percutaneous absorption rate-limited kinetics. Following topical administration, plasma concentrations and urinary excretion of azelaic acid are not significantly different from baseline levels.