臨床藥物治療學 Therapeutics of Clinical Drugs 評估口服抗黴菌藥治療陰道炎 臺北市立聯合醫院和平婦幼院區藥劑科藥師許勻婷 吳淑娟 摘要 99 6 112 31 ketoconazole fluconazole ketoconazole ketoconazole fluconazole fluconazole ketoconazole fluconazole ketoconazole candida vulvovaginitis medication use evaluation 壹 前言 FDA ketoconazole fluconazole itraconazole 1 ketoconazole CDC fluconazole 2 ketoconazole fluconazole 貳 材料與方法 99 6 112 31 ketoconazole fluconazole ketoconazole fluconazole ( fluconazole itraconazole) 參 研究結果 k e t o c o n a z o l e 7 9 fluconazole 185 61 156 一 病人基本資料 ketoconazole 34.0 9.8 61 19 31-4044.3% fluconazole 32.8 10.1 72 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.4 Dec. 31 2012
6712 31-4032.1% () 表一病人基本資料 - 年齡 ( ) ( ) Ketoconazole Fluconazole <20 5 (8.2%) 16 (10.3%) 21-30 14 (23.0%) 55 (35.3%) 31-40 27 (44.3%) 50 (32.1%) 41-50 11 (18.0%) 29 (18.6%) >50 4 (6.6%) 6 (3.8%) () 10 (14.3%) Isogen VT 100 mg 9 (12.9%) Nystatin VT Mycomb 9 (12.9%) Lomexin VT 200 mg 8 (11.4%) () 二 病人因陰道炎而就診次數分析 f l u c o n a z o l e ketoconazole 21 (13.5%) 15 (24.6%) 2 () 圖一使用 fluconazole 與 ketoconazole 病人就診次數比較三 Ketoconazole 用法用量之分析 ketoconazole 200 mg 1# qd 742 (53.2%) 1# qd 5 14 (17.7%)1# qd 3 11 (13.9%) () 四 併用其他外用藥品品項及人次分析 ketoconazole 7088.6% Nystatin (VT) 100,000 units 圖二醫師開立 ketoconazole 200 mg 之用 表二外用栓劑及藥膏之成分 ( ) Isogen VT isoconazole 100 mg Lomexin VT fenticonazole 200 mg Nystatin VT nystatin 100,000 units Antifungal cream miconazole 20 mg C. B. oint. Dr. PI cream 法用量 Mycomb cream Tricodex cream chlorpheniramine 10 mg lidocaine 30 mg hexachlorophene 1 mg methyl salicylate 10 mg menthol 10 mg camphor 5 mg betamethasone 0.5 mg clotrimazole 10.0 mg gentamycin 1.0 mg nystatin 100,000 units neomycin 2.5 mg gramicidin 0.25 mg triamcinolone 1.0 mg neomycin 3 mg diphenylpyraline 1 mg nylidrin 1 mg hydrocortisone 5 mg 284 Dec. 31 2012 藥學雜誌第 113 冊 73
臨床藥物治療學 Therapeutics of Clinical Drugs 圖三併用其他外用藥品品項及人次肆 討論一 Ketoconazole 使用之適當性 ketoconazole fluconazole 3 fluconazole ketoconazole ketoconazole fluconazole ketoconazole FDA (black box warning) 4 () 2,5 ketoconazole fluconazole 15 (24.6%) 21 (13.5%) 2 ketoconazole 15 2 ketoconazole 2,5 表三念珠菌陰道炎分類 ( ) 二 Ketoconazole 之用法用量 Ketoconazole 200-400 mg qd 4 200 mg bid 5400 mg qd 5 3,6,7 8 200 mg qd 3 80% 9 3 2,5,8,10 三 併用其他外用藥品品項 ( 13 ) 7 53.8% 74 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.4 Dec. 31 2012
2 15.4% 2 15.4% ketoconazole 1 ketoconazole 1 1 ketoconazole 四 治療念珠菌陰道炎 azole 類藥品之比較 11 2,12 10,12 azole CYP450 (ergosterol) Azole imidazoles ( ketoconazole) triazoles (fluconazole, itraconazole) 80-90% 2 imidazoles triazoles triazole fluconazole 150 mg MIC 90 72-96 13 itraconazole 14 ketoconazole ketoconazole fluconazole itraconazole Ketoconazole fluconazole itraconazole 4 表四口服 Ketoconazole Fluconazole 及 Itraconazole 特性之比較 Ketoconazole Fluconazole Itraconazole 200-400 mg qd 200 mg bid 5 400 mg qd 5 150 mg 3 100, 150 100 mg qd 6 7 200 mg () 150 mg 6 CYP3A4 CYP1A2 CYP2C9 CYP2C9 CYP2C19 200 mg bid 1 200 mg qd 3 200 mg bid 6 14 () CYP3A4 Stevens-Johnson syndrome Stevens- Johnson syndrome 4.83 / 50 / 30.6 / 284 Dec. 31 2012 藥學雜誌第 113 冊 75
臨床藥物治療學 Therapeutics of Clinical Drugs 五 美國疾病管制局治療準則 我國健保藥品給付規定及 MICROMEDEX 之比較 ( 表五 ) 1,2 fluconazole fluconazole ketoconazole fluconazole itraconazole 3,4,15 fluconazole ketoconazole ketoconazole fluconazole 表五美國疾病管制局治療準則 我國健保藥品給付規定及 MICROMEDEX 治療念珠菌陰 道炎之比較 fluconazole 150 mg 3 fluconazole 100, 150 200 mg fluconazole 150 mg 6 MICROMEDEX Fluconazole itraconazole ( ) 伍 結論 fluconazole fluconazole ketoconazole (colchicine, alprazolam, triazolam) 11 參考資料 : 1. 2. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2010. MMWR Recomm Rep 2010; 55: 61, 62. Retrieved Oct. 18, 2011, from http://www.cdc.gov/ 3. Brammer KW, Feczko JM. Single-dose oral fluconazole in the treatment of vaginal candidosis. Ann N Y Acad Sci 1988; 544: 561-563. 4. MICROMEDEX 2.0. Retrieved Oct. 18, 2011, from http:// www.thomsonhc.com/micromedex2/librarian 5. Sobel JD. Candida vulvovaginitis. UpToDate 2011. 6. Symoens J, Moens M, Dom J, et al: An evaluation of two years of clinical experience with ketoconazole. Rev Infect Dis 1980b; 2: 674-691. 7. Sobel JD. Recurrent vulvovaginal candidiasis: a prospective study of the efficacy of maintenance ketoconazole therapy. N Engl J Med 1986; 315: 1455-1458. 8. Dipiro JT, Talbert RL, Yee GC, et al: Pharmacotherapy: A Pathophysiologic Approach, 7th ed. United States: The McGraw-Hill Companies, 2008; 1958-9. 9. Creatsas G, Zissis NP, & Lolis D. Ketoconazole, a new antifungal agent, in vaginal candidiasis. Curr Ther Res 1980; 28: 121-126. 10. Eckert LO. Acute vulvovaginitis. N Engl J Med 2006; 355: 1244-52. 11. Watson, Grimshaw JM, Bond CM, Ludbrook A. Oral versus intravaginal imidazole and triazole antifungal treatment of uncomplicated vulvovaginal candidiasis. The Cochrane Collaboration. Conchrane Database Syst Rev 2007 Issue 1. 12. Koda-Kimble MA, Young LY, Kradjan WA, et al: Applied Therapeutics: The Clinical Use of Drugs, 9th Edition. New York: Lippincott Williams & Wilkins, 2006: 65. 22-24. 13. Sobel JD, Wiesenfeld HC, Martens M, et al: Maintenance Fluconazole Therapy for Recurrent Vulvovaginal Candidiasis. N Engl J Med 2004; 351: 876-83. 76 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.4 Dec. 31 2012
14. Witt A, Kaufmann U, Bitschnau M, et al: Monthly itraconazole versus classic homeopathy for the treatment of recurrent vulvovaginal candidiasis: a randomised trial. BJOG 2009; 116: 1499. 15. Sobel JD, Brooker D, Stein GE, et al: Single oral dose fluconazole compared with conventional clotrimazole topical therapy of Candida vaginitis. Am J Obstet Gynecol 1995; 172: 1263-1268. Medication Use Evaluation of Oral Ketoconazole Treatment for Candidal Vulvovaginitis Yun-Ting Hsu, Shu-Chuan Wu Taipei City Hospital, Heping and Women and Children Branch Abstract We collected ketoconazole and fluconazole prescriptions from June 2010 to Dec. 2010. Compared the number of OPD patients who using these two drugs during the study period, we discussed the appropriateness of ketoconazole use and the necessity of concurrent using topical medications. Furthermore, we analyzed the reasons why physicians prescribed oral ketoconazole instead of fluconazole for candidal vulvovaginitis. Guidelines nowadays recommend that oral fluconazole is the most optimal medication for candida vulvovaginitis. Compared to fluconazole, ketoconazole has more side effects and drug-drug interactions. We suggest physicians to prescribe fluconazole as the first-line treatment for candidal vulvovaginitis. 284 Dec. 31 2012 藥學雜誌第 113 冊 77