1. Evalulation of Azelaic Acid for Non-Prescription Use Michelle Brown Andy Reynolds Ted Williams Pharm. D candidates, OSU College of Pharmacy

2. Search Strategy Relied primarily on MedLine search Used tertiary resources at the discretions of the author One dermatologist interview

3. Diseases Mild to Moderate Acne Vulgaris Rosacea Melasma

4. 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

5. 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

6. Disease State Progression Normal Follicle

7. Disease State Progression Microcomedo

8. Disease State Progression Open Comedo –“Blackhead”

9. Disease State Progression Closed Comedo –“Whitehead”

10. Disease State Progression Papule –Enflamed lesion

11. Disease State Progression Pustule –Enlarged papule Pus filled Raised Reddened

12. Disease State Progression Nodule (or Cyst) –Inflammation penetrates deeper into skin –May lead to scarring or pitting

13. 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

14. Drug Information Drug Requested Pharmacology Dose Indications Pharmacokinetics Side Effects

15. 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)

16. 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

17. Cost NameManufacturerQuantity/Price AW PriceRetail Price Azelaic AcidGallipot500 gm ($156.00) $0.31 Azelex cream 20%Allergan30 gm ($48.53) 50 gm ($84.88) $1.62- $1.70 $2.26/gm benzoyl peroxide (aqueous) gel 2.5% Glades60 gm ($17.82) $0.30 benzoyl peroxide (aqueous) gel 5% Glades60 gm ($18.22) 90 gm ($23.91) $0.27-0.3$0.17- 0.32/gm benzoyl peroxide (aqueous) gel 10% Glades60 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 Allscripts2.5 gm ($19.31) $7.72$0.38/gm tretinoin 0.025%Alpharma/USP D 20 gm ($35.50) 45 gm ($67.20) $1.49- $1.78 $1.01- 1.06/gm

18. Conclusions Effective Safe No known Interactions Low Pregnancy Risk Elevated Cost vs. Benzoyl Peroxide Recommended for OTC Use

19. 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.