由於藥局沒有 terbinafine. 只有 fluconazole. 所以查詢了一下文獻.
找到一些治療建議
Fluconazole在美國FDA並沒有列入治療甲癬的處方
但在歐洲則被列入治療甲癬的處方
台灣健保也沒有將fluconazole 列為甲癬治療選項
所以如果要用 fluconazole 治療甲癬. 似乎只能自費(看其他皮膚科醫師文章也是這樣建議)
全民健康保險藥品新收載品項明細表-附件1
第 10 節 抗微生物劑 Antimicrobial agents20140403 修正規定
10.6.1.Fluconazole oral（如 Diflucan oral）：（85/10/1、87/4/1）
限
1.全身黴菌感染之治療。
2.免疫不全病例，治療或預防黴菌感染時使用。
健保給付規定: 10.6.4. Terbinafine ( 如 Lamisil tab )：(85/1/1、91/4/1、98/8/1)限 1.手指甲癬及足趾甲癬病例使用， 每日 250 mg，手指甲癬限用 42 顆，需於 8 週內使用完畢。足趾 甲癬限用 84 顆，需於 16 週內使 用完畢。治療結束日起算，各在 6 及 12 個月內不得重複使用本品或 其他同類口服藥品。(98/8/1) 2.其他頑固性體癬及股癬病例使 用，每日一次，最長使用 2 週， 治療期間不得併用其他同類藥 品。 3.頭癬病例使用，每日一次，最長使 用 4 週，若確需延長治療時間，須 於病歷詳細載明備查。(98/8/1)
Onychomycosis A Comprehensive Overview 5/6 2023
Oral Antifungals
Terbinafine and itraconazole are the two predominantly used antifungals for onychomycosis, both holding FDA approval for this indication. Fluconazole can also be used but is only available as an off-label option within the United States. These drugs are effective but possess a wide range of interactions and side effects (Gupta & Stec, 2019a). Patient compliance tends to be higher with oral therapy because of the shorter duration of use when compared with topical therapies (Gupta et al., 2018).
As stated above, oral antifungals are generally considered to be more efficacious than topicals in nearly all cases. However, specific indications for oral therapy include a lack of response to a 6-month duration of topical therapy and proximal subungual onychomycosis, specifically, when more than 50% of the nail matrix or nail plate is involved or if there are numerous nails infected (Gupta, Paquet, & Simpson, 2013).
Terbinafine
Terbinafine disrupts the synthesis of sterols by inhibiting the enzyme squalene monooxygenase. Terbinafine has minimal activity against NDMs and yeast but possesses broad-spectrum activity against dermatophytes. The recommended dosage for onychomycosis is 250 mg once a day for 12 weeks for toenails and 6 weeks for fingernails (Gupta, Paquet, Simpson, & Tavakkol, 2013). Clinical cure rates for toenail onychomycosis are reported to be 74% after a 12-week period (Drake et al., 1997).
Common side effects can include gastric upset, altered taste, elevated liver function tests, headache, and rash (Bhatia et al., 2019). It is also important to keep in mind that terbinafine clearance is decreased with renal or hepatic dysfunction (Shear et al., 1991). Terbinafine is considered one of the safest oral antifungals for use in pregnancy but should still be used with caution (Andersson et al., 2020). Drug interactions are possible in patients taking beta-blockers, tricyclic antidepressants, monoamine oxidase inhibitors, Class 1C antiarrhythmics, and selective serotonin reuptake inhibitors, because of its inhibition of the CYP2D6 isozyme (Gupta, Paquet, & Simpson, 2013).
Advantages of terbinafine include its increased efficacy compared with the other antifungals when treating dermatophyte onychomycosis. When compared with pulse dosing or continuous itraconazole, utilizing continuous terbinafine results in the lowest recurrence rate (Yin et al., 2012). Oral terbinafine is considered first-line therapy for the treatment of onychomycosis because of its superior cost-effectiveness ratio when compared with other oral antifungals (Darkes et al., 2003).
Itraconazole
Itraconazole inhibits ergosterol synthesis by inhibiting lanosterol 14α-demethylase. It is effective at treating Candida, dermatophytes, and NDMs (Elewski, 1993). The suggested dose is a pulse regimen utilizing 400 mg of itraconazole daily for 1 week, followed by 3 weeks off and continued for three to four total pulses. Mycologic and clinical cure rates with this regimen are 63% and 70%, respectively (Gupta et al., 2004).
Common side effects include dyspepsia, flatulence, diarrhea, abdominal pain, fatigue, dizziness, pruritus, and elevated transaminases (Gupta et al., 1998). It is recommended that itraconazole be avoided during pregnancy, especially during the first trimester (Pilmis et al., 2015). Itraconazole possesses drug–drug interactions with astemizole, carbamazepine, cisapride, cyclosporine, didanosine, digoxin, H2 receptor blockers, isoniazid, lovastatin, midazolam, phenytoin, oral contraceptives, quinidine, rifampin, tacrolimus, vincristine, and warfarin because of its CYP3A4 inhibition (Leyden, 1998).
Overall, itraconazole can be used for onychomycosis because of mixed infections, NDMs, and Candida spp. However, when treating onychomycosis caused by dermatophytes, the most common cause, terbinafine has consistently been shown to be more effective (Trivedi & Shah, 2010).
Griseofulvin
Griseofulvin inhibits the assembly of microtubules and disrupts the formation of the mitotic spindle, inhibiting mitosis in dermatophytes. It is effective against Epidermophyton, Microsporum, and Trichophyton but is ineffective against Candida. The suggested dosing for onychomycosis is 1000 mg daily for 4 months in toenails and 6 months in fingernails (Olson & Troxell, 2022).
This medication has almost completely been replaced by more efficacious antifungal agents such as terbinafine and itraconazole. Therefore, it should rarely be utilized for treating onychomycosis. Adverse reactions range from diarrhea, vomiting, and nausea to photosensitivity and urticaria. Other side effects include a disulfiram-like reaction, and thus, alcohol should be avoided when taking this medication (Olson & Troxell, 2022).
Off-Label
Fluconazole
Fluconazole, a triazole, interacts with 14α-demethylase, an enzyme responsible for catalyzing the conversion of lanosterol to ergosterol (Govindarajan et al., 2022). It is only available as an off-label option in the United States but is approved in Europe to treat onychomycosis. Treatment is normally continued until the fingernail or toenail is completely grown, which can be as long as 9 and 18 months, respectively. Clinical and mycological cure rates for toenail onychomycosis utilizing a weekly dose of 150 mg are 39% and 57%, respectively (Gupta, Drummond-Main, & Paquet, 2013).
The most common side effects include elevation of transaminases, abdominal pain, headache, nausea, and rash (Muńoz et al., 1991). It is also rarely associated with hepatotoxicity, which occurs more often in immunosuppressed individuals. It should be avoided in pregnancy, particularly the first trimester, because of its association with spontaneous abortions and heart malformations (Zhang et al., 2019). Fluconazole is an inhibitor of fungal cytochrome P450 and thus possesses numerous drug interactions (Kowalsky, 1990).
Overall, fluconazole should be utilized when the use of first-line antifungals is contraindicated or when a patient struggles with compliance or desires an oral medication with less frequent dosing.
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