PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Other Topical Anti-Acne Agents
    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

    HOW SUPPLIED

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

    Before applying, the affected areas should be thoroughly washed (using mild soap or soapless cleansing lotion) and patted dry.
    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 immediately after applying.

    Cream/Ointment/Lotion Formulations

    Apply cream and massage gently into the affected areas.

    Other Topical Formulations

    Gel Formulation
    Apply gel and massage gently into the affected areas
    Cosmetics may be applied after gel has dried.
    Instruct patients to avoid use of alcoholic cleansers, tinctures and astringents, abrasives and peeling agents.
     
    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.
    Instruct patients to avoid use of alcoholic cleansers, tinctures and astringents, abrasives and peeling agents.
    This product is flammable; avoid heat, flame, or smoking during and immediately following application of the foam.

    STORAGE

    Azelex:
    - Protect from freezing
    - Store at room temperature (between 59 to 86 degrees F)
    Finacea:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    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

    Avoid the use of an occlusive dressing or wrap with azelaic acid. Ocular exposure to the drug may cause irritation to the eyes; avoid accidental contact with the eyes, mouth, or 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

    There are no adequate and well-controlled studies regarding the use of azelaic acid during human pregnancy; however, the drug is minimally absorbed systemically following topical administration, and maternal use is not expected to result in fetal drug exposure. In animal reproduction studies, embryofetal toxicity was noted when azelaic acid was administered orally during organogenesis at doses 162-, 19-, and 65-times the maximum recommended human dose in rats, rabbits, and monkeys, respectively. Maternal toxicity was noted at these doses but no malformations were observed in these embryofetal developmental studies.

    Breast-feeding

    Azelaic acid is naturally present in human milk. When used as prescribed, the drug is unlikely to be absorbed through the skin in clinically relevant amounts to cause a change in azelaic acid concentrations in milk or affect milk production; therefore, breast-feeding is not expected to result in infant drug exposure. 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 administered drug, health care 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.

    Tobacco smoking

    The propellant in azelaic acid topical foam is flammable. Instruct patients to avoid fire, flame, and tobacco smoking during and immediately following application.

    ADVERSE REACTIONS

    Severe

    angioedema / Rapid / Incidence not known

    Moderate

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

    Mild

    paresthesias / Delayed / 1.0-6.2
    pruritus / Rapid / 1.0-6.0
    xerosis / Delayed / 0-5.0
    skin irritation / Early / 0-2.0
    acne vulgaris / Delayed / 0-1.0
    rash / Early / 0-1.0
    skin hypopigmentation / Delayed / Incidence not known
    hypertrichosis / Delayed / Incidence not known
    application site reaction / Early / Incidence not known
    urticaria / Rapid / Incidence not known

    DRUG INTERACTIONS

    There are no drug interactions associated with Azelaic Acid products.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies regarding the use of azelaic acid during human pregnancy; however, the drug is minimally absorbed systemically following topical administration, and maternal use is not expected to result in fetal drug exposure. In animal reproduction studies, embryofetal toxicity was noted when azelaic acid was administered orally during organogenesis at doses 162-, 19-, and 65-times the maximum recommended human dose in rats, rabbits, and monkeys, respectively. Maternal toxicity was noted at these doses but no malformations were observed in these embryofetal developmental studies.

    Azelaic acid is naturally present in human milk. When used as prescribed, the drug is unlikely to be absorbed through the skin in clinically relevant amounts to cause a change in azelaic acid concentrations in milk or affect milk production; therefore, breast-feeding is not expected to result in infant drug exposure. 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 administered drug, health care 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.