Evaluation of Azelaic Acid for Non-Prescription Use

Michelle BrownAndy ReynoldsTed Williams

Pharm. D candidates OSU College of Pharmacy

Project Methodology

• Divide and Conquer

• RCS Methodology– Research– Collaborate– Synthesize

TM

Search Strategy

• Relied primarily on MedLine search

• Used tertiary resources at the discretion of the author

• One dermatologist interview

Disease State

• Definition

• Causes

• Progression

• Classification

Diseases

• Mild to Moderate Acne Vulgaris

• Rosacea

• Melasma

Disease State Definition

• Acne– chronic inflammatory disease

of the pilosebaceous units in

the dermis

– Pilosebaceous unit location– Mainly face, back and chest

– Also neck and upper arms

Disease State Causes

• Causes of Acne– Exact causes unknown

– 4 factors involved• Excessive Sebum produced

• Hyperkeratinization of the hair follicle– Prevents shedding of the follicular keratinocytes

– Leads to the formation of microscopic lesions microcomedo

• Accumulation of lipids and cellular debris

• Colonization by Propionibacterium acnes

Disease State Progression

• Normal Follicle

Disease State Progression

• Microcomedo

Disease State Progression

• Open Comedo– “Blackhead”

Disease State Progression

• Closed Comedo– “Whitehead”

Disease State Progression

• Papule– Enflamed lesion

Disease State Progression

• Pustule– Enlarged papule

• Pus filled

• Raised

• Reddened

Disease State Progression

• Nodule (or Cyst)– Inflammation penetrates

deeper into skin– May lead to scarring

or pitting

Disease State Classification

• Defined by American Academy of Dermatology – Mild Acne

• A few to several papules or pustules

– Moderate Acne• Several to many papules and pustules along with several

nodules

– Severe Acne• Numerous or extensive papules and pustules as well as many

nodules

Drug Information

• Drug Requested/Indications

• Pharmacokinetics

• Pharmacology

• Dose

• Adverse Effects

Drug Requested

• Azelaic acid

• 20% Azelaic acid cream= Azelex (Allergan)

• Skin and Mucus Membrane Agent

• Acne Medication

• FDA approved for tx. Mild to moderate acne

Pharmacokinetics

• Chemical structure of Azelaic acid:

straight chain, saturated dicarboxylic acid• Some undergoes ß-oxidation• Most excreted unchanged in urine• 10% cream is found in dermis and epidermis• 3-5% penetrates outermost layer of epidermis• 4% systemically absorbed• 12 hour half-life

Pharmacology

• Antimicrobial ex. tetracycline, clindamycin, erythromycin, benzoyl peroxide

• Anti-keratinizing agent ex. Retinol

• Antioxidant? (result = anti-inflammatory properties) ex. Retinol

• Reduces size of acne lesions, prevents recurrence

Dose

• Wash face with mild soap or soapless cleanser • Pat dry• Cover affected area with thin layer of Azelaic acid

20% cream• Massage into skin• Do this twice daily, once in morning and once in

the evening• In case of missed dose . . .

Adverse Effects

• Common Effects: – Itching – Burning – Stinging– Tingling– Scaling – Dry skin– Irritation at application site– Depigmentation of skin

Adverse Effects

• Rare Effects (<1%):

• Worsening of asthma

• Hypertrichosis

• Reddening of skin

• Exacerbation of recurrent herpes labialis

Safety

• Low systemic absorption– FDA Pregnancy category B– Not passed in lactation in above baseline levels– Good option for pregnant patients vs. oral

treatments

• No known drug interactions

Efficacy

• Demonstrated effective vs. no treatment• Demonstrated effective vs. other topicals

(benzoyl peroxide)• Demonstrated effective vs. oral treatments

(tetracycline)• Effective in combinations with other

topicals (Glycolic Acid) and oral treatments (minocycline)

CostName Manufacturer Quantity/Price Quantity/Price AW Price Retail Price

Azelaic Acid Gallipot 500 gm ($156.00)

  $0.31  

Azelex cream 20% Allergan 30 gm ($48.53)

50 gm ($84.88)

$1.62-$1.70

$1.84 -2.26/gm

benzoyl peroxide (aqueous) gel 2.5%

Glades 60 gm ($17.82)

  $0.30  

benzoyl peroxide (aqueous) gel 5%

Glades 60 gm ($18.22)

90 gm ($23.91)

$0.27-0.3 $0.17-0.32/gm

benzoyl peroxide (aqueous) gel 10%

Glades 60 gm ($18.68)

90 gm ($25.06)

$0.28-0.31

$0.26-0.32/gm

erythromycin 2% gel

        $0.70/gm

clindamycin Pi 1% gel

        $0.95/gm

sulfacetamide sodium and sulfur

10% ointment

Allscripts 2.5 gm ($19.31)

  $7.72 $0.38/gm

tretinoin 0.025% Alpharma/USPD

20 gm ($35.50)

45 gm ($67.20)

$1.49-$1.78

$1.01-1.06/gm

Conclusions

• Effective

• Safe

• Low Interactions

• Low Pregnancy Risk

• Elevated Cost

• Recommended for OTC Use

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