1. 門診處方討論 - Spironolactone for Acne Vulgaris 王繼正 藥師 98.01.13

2. 門診處方

3. Definitions  Acne vulgaris is a chronic inflammatory dermatosis which is notable for open and/or closed comedones (blackheads and whiteheads) and inflammatory lesions including papules, pustules, or nodules.

4. Severity and type of acne

5. Summary of therapies for acne  The appropriate choice of pharmacotherapy depends upon the type of acne (comedonal or inflammatory) and its severity (mild, moderate, or severe)  First-line therapies (topical) benzoyl peroxide, antibiotics, retinoidsbenzoyl peroxide  Second-line therapies consist of oral antibiotics including tetracyclines (tetracycline, minocycline, doxycycline, and trimethoprim/sulfamethoxazole in order of preference), combined antiandrogen estrogen contraceptives, and spironolactone trimethoprim/sulfamethoxazole spironolactone  Third-line therapies high-dose systemic antibiotics and systemic isotretinoinisotretinoin First CONSULT 2007

6. Mechanism of action Antiandrogenic agent-- Spironolactone  interferes with testosterone biosynthesis by reducing 17-hydroxylase activity, and thus lowers plasma testosterone loves.  inhibit dihydrotestosterone's binding to cytosol protein receptor.

7. Spironolactone Indications  Acne vulgaris non-FDA labeled indications  衛生署核准適應症 利尿高血壓、原發性醛類脂醇過多症

8. Dose  50-200 mg/day have been shown to effective in acne.  Higher doses of the drug (200 mg/day) were associated with higher rates of adverse effects.  Hormonal treatment for acne are tolerated in women only.

9. Adverse effects  menstrual irregularities  gynecomastia  breast tenderness  hyperkalemia  hyponatremia  headache, nausea, vomiting, constipation

10. Evidence  A systematic review found no good-quality evidence on the treatment of acne vulgaris with spironolactone (Level A) Cochrane Database of Systematic Reviews 2003, Issue 4  Strength of Recommendation: Class II b Strength of Evidence: Category B J Am Acad Dermatol 2007 、 Micromedex

11. Evidence  Best evidence for the use of spironolactone in acne comesfrom 4 studies in which spironolacton alone or as an adjunct in doses 50 to 200 mg/day showed 50% to 70% improvement of acne. Treatment of Acne Vulgaris. JAMA 2004

12. 英國 Oxford Center 證據應用等級 LevelTherapy/Prevention, Aetilogy/Harm 1 a 將隨機對照臨床研究 (Randomized Clinical Trial, RCT) 以系統性評論 (systemic review, SR) 後的結果。 b 具有嚴格的信賴區間的個別 RCT 研究。 c 無論使用何種研究方法，但其研究結果為完全正面、完全負面或完全無效果 (all or none) 的研究結果。 2 a 將同質性的世代研究 (cohort studies) 以系統性評論的結果。 b 個別世代研究或是質量較不足的 RCT 研究。 c 以多數結果為基礎的研究，及生態學的研究 ("Outcomes" research; ecological studies) 。 3 a 將同質的個案對照研究 (case control studies) 以系統性評論後的結果。 b 個別的個案對照研究 (individual case control study) 。 4 病例統計報告，以及質量較不足的個案對照研究。 5 未經嚴謹評估的意見，或者基礎生理學、一般實驗室研究及必要原則。

13. Strength Of Evidence Category Strength Of Evidence A Meta-analyses of RCT with homogeneity with regard to the directions and degrees of results between individual studies. Multiple, well-done randomized clinical trials involving large numbers of patients. B Meta-analyses of RCT with conflicting conclusions with regard to the directions and degrees of results between individual studies. Randomized controlled trials that involved small numbers of patients or had significant methodological flaws (e.g., bias, drop-out rate, flawed analysis, etc.). Nonrandomized studies (e.g., cohort studies, case- control studies, observational studies). C Expert opinion or consensus, case reports or case series.

14. Guidelines of care for acne vulgaris management J Am Acad Dermatol 2007 Recommendation Strength of recommendation Level of evidence Topical theapy RetinoidsAI Benzoyl peroxideAI AntibioticsAI other agentAI Systemic antibiotics TetracyclinesAI MacrolidesAI Trimethoprim- sulfamethoxazole AI Hormonal agents SpironolactoneBII Contraceptive agentAI Oral corticosteroidsBII

15. Conclusion  Dose : spironolactone 25 mg BID  Indication ： acne vulgaris  Evidence base: Category B  處方合理性

16. Thanks for your attention !!