Azelaic Acid

Class: Skin and Mucous Membrane Agents, Miscellaneous
ATC Class: D10AX03
VA Class: DE752
Chemical Name: Nonanedioic acid
Molecular Formula: C₉H₁₆O₄
CAS Number: 123-99-9
Brands: Azelex, Finacea

Introduction

Antibacterial and antiproliferative agent; naturally occurring aliphatic dicarboxylic acid.^{1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 19 20 22 26}

Uses for Azelaic Acid

Acne

Treatment of mild to moderate inflammatory acne vulgaris.^{1 2 4 5 6 7 8 10 11 12 13 14 15 19 20 26}

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Not for the treatment of noninflammatory acne vulgaris.²¹

Rosacea

Treatment of inflammatory lesions (papules and pustules) associated with mild to moderate rosacea.²²

Treatment of erythema in rosacea without papules and pustules has not been evaluated.^b

Azelaic Acid Dosage and Administration

Administration

Topical Administration

Apply topically to the skin as a 20% cream or 15% gel.^{1 2 3 5 7 8 10 11 12 13 14 15 17 22 26}

For dermatologic use only; avoid contact with eyes, mouth, or other mucous membranes.^{1 22 26} If contact with the eye(s) occurs, wash with large amounts of water; consult clinician if ocular irritation persists.^{1 22 26}

Wash skin and pat dry before applying cream or gel to affected areas.^{1 22 26} Use only very mild soaps or soapless cleansing lotions before applying gel for treatment of rosacea.^{22 b}

Apply in a thin layer of cream or gel and rub gently into affected areas.^{1 22 26} Wash hands after application.^{1 22 26}

If irritation is excessive or persists in patients with acne, decrease frequency of application to once daily or discontinue until manifestations subside.^{1 22 26 a}

If irritation is excessive or persists in patients with rosacea, discontinue therapy.^{1 22 26 b}

Do not use occlusive dressings or wrappings.^{1 22 26}

Allow gel to dry before applying cosmetics to skin.^{22 26}

Dosage

Pediatric Patients

Acne

Topical

Adolescents ≥12 years of age: Apply 20% cream in a thin film to affected areas twice daily (morning and evening).^{1 26}

Improvement usually is detectable within 1–2 months of initiating therapy;^{1 2 11 14 15 16 19} however, maximum benefit generally requires more prolonged treatment.^{2 13}

Usual duration of therapy is ≤6 months;^{2 19} however, therapy for ≥1 year has been required for control of individual lesions^{2 19} and repeat courses have been used for recurrences.¹⁹

Adults

Acne

Topical

Apply 20% cream in a thin film to affected areas twice daily (morning and evening).^{1 26}

Improvement usually is detectable within 1–2 months of initiating therapy;^{1 2 11 14 15 16 19} however, maximum benefit generally requires more prolonged treatment.^{2 13}

Usual duration of therapy is ≤6 months;^{2 19} however, therapy for ≥1 year has been required for control of individual lesions^{2 19} and repeat courses have been used for recurrences.¹⁹

Rosacea

Topical

Apply 15% gel in a thin film to affected area twice daily (morning and evening).²²

Safety and efficacy of therapy with gel for >12 weeks not established.²²

Prescribing Limits

Pediatric Patients

Acne

Topical

Adolescents ≥12 years of age: Some clinicians suggest maximum 6 months of therapy;^{2 19} however, ≥1 year of therapy has been used in for control of individual lesions.¹⁹

Adults

Acne

Topical

Some clinicians suggest maximum 6 months of therapy;^{2 19} however, ≥1 year of therapy has been used in for control of individual lesions.¹⁹

Rosacea

Topical

Safety and efficacy of therapy with gel for >12 weeks not established.²²

Special Populations

No special population dosage recommendations at this time.¹

Cautions for Azelaic Acid

Contraindications

• Known hypersensitivity to azelaic acid or any of its components.^{a b}

• Known hypersensitivity to propylene glycol (for gel formulation).^b

Warnings/Precautions

Warnings

Hypopigmentation

Hypopigmentation reported rarely;^{a b} monitor patients with dark complexions for early signs of hypopigmentation during therapy.^{1 22 26}

General Precautions

Dermatologic Effects

Possible skin irritation (e.g., pruritus, burning, stinging) during initial weeks of therapy.^{1 22 26} If sensitivity or severe irritation develops, discontinue therapy, contact clinician, and institute appropriate therapy.^{1 22 26 a}

Specific Populations

Pregnancy

Category B.^{a b}

Lactation

Minimally distributed into milk following topical application.^{a b} Caution if used in nursing women.^{a b}

Pediatric Use

Safety and efficacy of 20% cream not established in children <12 years of age.^a

Safety and efficacy of 15% gel not established.^b

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^{a b}

Common Adverse Effects

20% cream: Pruritus, burning, stinging, tingling.^a

15% gel: Pruritus, burning, stinging, tingling, scaling, dryness.^b

Interactions for Azelaic Acid

No formal interaction studies to date.^b

Azelaic Acid Pharmacokinetics

Absorption

Minimally absorbed following topical administration.^{a b}

Elimination

Metabolism

Minimally metabolized following topical application; undergoes some β-oxidation to shorter chain dicarboxylic acids.^{a b}

Elimination Route

Excreted principally in urine as unchanged drug.^{a b}

Half-life

12 hours following topical application.^a

Stability

Storage

Topical

Cream

15–30°C; do not freeze.^a Keep container on its side.^a

Gel

25°C (may be exposed to 15–30°C).^b

Actions

• Exact mechanism of action for treatment of acne vulgaris not fully elucidated; however, effect appears to result partially from antibacterial activity.^{1 2 3 4 5 6 7 9 10 11 12 13 14 15 17 19 20}

• Inhibits growth of susceptible organisms (principally Propionibacterium acnes)^{1 2 4 5 7 10 11 13 14 16 17 19 20} on skin by inhibiting protein synthesis.^{1 2 7 10 11 19 20}

• Usually bacteriostatic; may be bactericidal in high concentrations against P. acnes and Staphylococcus epidermidis^{2 5 7 19}

• May inhibit follicular keratinization,²⁰ which may prevent development or maintenance of comedones.^{1 2 12 14 19}

• Exhibits antiproliferative effects against hyperactive and abnormal melanocytes but does not exhibit an appreciable depigmenting effect on normally pigmented skin.⁹

• Exact mechanism of action for treatment of rosacea is unknown.²²

Advice to Patients

• Importance of using for full prescribed treatment period.^a

• Importance of avoiding contact with eyes, mouth, or other mucous membranes.^{1 22 26 a} If contact with eyes occurs, wash eyes with large amounts of water and contact clinician if eye irritation persists.^{1 22 26 a}

• Importance of discontinuing therapy and consulting clinician if severe local irritation, severe itching, and/or rash occurs.^{1 22 26 a}

• Importance of washing hands following application.^{1 22 26 a}

• Importance of avoiding occlusive dressings.^{1 22 26 a}

• Importance of reporting abnormal changes in skin color to a clinician.^{a b}

• Importance of patients being treated for rosacea avoiding foods or beverages that may cause flushing or blushing, such as spicy foods, alcoholic beverages, and thermally hot drinks.^{22 b}

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^{a b}

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{a b}

• Importance of informing patients of other important precautionary information.^{a b} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Azelex 20% Cream (ALLERGAN DERMATOLOGICS): 30/$196.00 or 90/$557.95

Azelex 20% Cream (ALLERGAN DERMATOLOGICS): 50/$292.98 or 150/$833.94

Finacea 15% Gel (INTENDIS): 50/$178.49 or 150/$499.96