Azelex

Other Topical Agents for Acne
Topical Rosacea Agents

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

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.

Apply cream and massage gently into the affected areas.

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.

angioedema / Rapid / Incidence not known

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

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

Azelex, Finacea

Rx

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

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.

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.

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.

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.

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

No dosage adjustments are needed.

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

There are no drug interactions associated with Azelaic Acid products.

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

No maximum dosage information is available.

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.

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.

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

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.

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.