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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 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) Cost Name Manufacturer Quantity/Price Quantity/Price AW Price Retail Price Azelaic Acid Gallipot 500 gm ($156.00) Azelex cream 20% Allergan 30 gm ($48.53) benzoyl peroxide (aqueous) gel 2.5% Glades 60 gm ($17.82) benzoyl peroxide (aqueous) gel 5% Glades 60 gm ($18.22) 90 gm ($23.91) $0.27-0.3 $0.170.32/gm benzoyl peroxide (aqueous) gel 10% Glades 60 gm ($18.68) 90 gm ($25.06) $0.280.31 $0.260.32/gm $0.31 50 gm ($84.88) $1.62$1.70 $1.84 2.26/gm $0.30 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) tretinoin 0.025% Alpharma/USP D 20 gm ($35.50) 45 gm ($67.20) $7.72 $0.38/gm $1.49$1.78 $1.011.06/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 DermatoVenereologica (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.