門診處方討論 -Spironolactone for Acne Vulgaris

王繼正 藥師98.01.13

門診處方

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.

Severity and type of acne

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, retinoids 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

Third-line therapies high-dose systemic antibiotics and systemic isotretinoin

First CONSULT 2007

Mechanism of actionAntiandrogenic 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.

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

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.

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

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

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

英國英國 Oxford CenterOxford Center證據應用等證據應用等級級

Level Therapy/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。

Strength Of EvidenceStrength 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.

Guidelines of care for acne vulgaris management J Am Acad Dermatol 2007

RecommendationStrength of recommendation

Level of evidence

Topical theapy

Retinoids A I

Benzoyl peroxide A I

Antibiotics A I

other agent A I

Systemic antibiotics

Tetracyclines A I

Macrolides A I

Trimethoprim-sulfamethoxazole A I

Hormonal agents

Spironolactone B II

Contraceptive agent A I

　 Oral corticosteroids B II

Conclusion Dose : spironolactone 25 mg BID Indication ： acne vulgaris Evidence base: Category B

處方合理性

Thanks for your attention !!