Evaluation of Azelaic Acid for Non-Prescription Use

Michelle Brown Andy Reynolds Ted Williams Pharm. D candidates OSU College of Pharmacy

Project Methodology

• • Divide and Conquer TM RCS Methodology – Research – Collaborate – Synthesize

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

• Azelaic acid

Drug Requested

• 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)

Name

Azelaic Acid Azelex cream 20%

Manufacturer

Gallipot Allergan benzoyl peroxide (aqueous) gel 2.5% benzoyl peroxide (aqueous) gel 5% benzoyl peroxide (aqueous) gel 10% erythromycin 2% gel clindamycin Pi 1% gel sulfacetamide sodium and sulfur 10% ointment tretinoin 0.025% Glades Glades Glades Allscripts Alpharma/USP D

Cost

Quantity/Price

500 gm ($156.00) 30 gm ($48.53) 60 gm ($17.82) 60 gm ($18.22) 60 gm ($18.68)

Quantity/Price

50 gm ($84.88) 90 gm ($23.91) 90 gm ($25.06) 2.5 gm ($19.31) 20 gm ($35.50) 45 gm ($67.20)

AW Price

$0.31 $1.62 $1.70

$0.30 $0.27-0.3

$0.28 0.31

$7.72 $1.49 $1.78

Retail Price

$1.84 2.26/gm $0.17 0.32/gm $0.26 0.32/gm $0.70/gm $0.95/gm $0.38/gm $1.01 1.06/gm

Conclusions

• • • • • • Effective Safe Low Interactions Low Pregnancy Risk Elevated Cost Recommended for OTC Use

• • • • • • • • • • • • • • • • •

References

Facts and Comparisons 4.0 Available from URL:Online http://online.factsandcomparisons.com/ Goulden, V. Guidelines for the Management of Acne Vulgaris in Adolescents. Pediatric Drugs 2003;5(5):301-313 Feldman, S, Careccia R, Barham K, Hancox J. Diagnosis and Treatment of Acne.. American Family Physician 2004;69:2123-30 Thiboutot D. New Treatments and Therapeutic Strategies for Acne Treatment. Archives of Family Medicine 2000;9:179-187. Berardi R, McDermott J, Newton G, Oszko M, Popovich N, Rollims C, et al. Handbook of Nonprescription Drugs 2004;913-927.

The Red Book, (2003).

Arash Akhaven and Susan Bershad, “Topical Acne Drugs; Review of Clinical Properties, Systemic Exposure, and Safety,” Am J Clin Dermatol 2003, 4(7): 473-492.

Mackrides, P S, Shaughnessy A F, “Azelaic Acid Therapy for Acne,” American Family Physician 1996, 54(8): 2457-2459.

Spellman M.C. and Pincus, S.H., “Efficacy and Safety of Azelaic Acid and Glycolic Acid Combination Therapy Compared with Tretinoin Therapy for Acne,” Clinical Therapeutics 1998, 20(4): 711-720.

Physician’s Desk Reference 2005, 59th ed.: 907-908.

Drug Information Handbook 2005, 13th ed: 165-166.

RxList The Internet Drug Index on the web at http://www.rxlist.com/cgi/pharmclips.cgi?keyword=AZELEX (last accessed Nov. 28, 2005).

Nazzaro-Porro, M., Passai, S., Picardo, M., Breathnach, A., Clayton, R. Zina, G., Beneficial effect of 15% azelaic acid cream on acne vulgaris. British Journal of Dermatology (1983) 109:45-48 Cavicchini, S., Caputo, R. Long-term Treatment of Acne with 20% Azelaic Acid Cream. Acta Dermato Venereologica (1989) Suppliment 143:40-44 Hjorth, N., Graupe, K. Azelaic Acid for the Treatment of Acne: A Clinical comparison with Oral Tetracycline. Acta Derm Venereologica (1989) Suppliment 143:45-48 Spellmajn, M.C., Pincus, S. H. Efficacy and Safety of Azelaic Acid and Glycolic Acid Combination Therapy Compared with Tretinoin Therapy for Acne. Clinical Therapeutics (1998) 20:4 711-720 Gollinick, H. P. M., Graupe, K., Zaumseil. Comparison of combined azelaic acid cream plus oral minocycline with oral isotretinoin in severe acne. European Journal Dermatology (2001) 11:538-44.

Gass, S. Expert opinion of a practicing dermatologist.