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)
下面使用GOOGLE中文翻譯
口腔治療
甲真菌病的治療有多種選擇（表 2）。口服特比萘芬是美國食品藥物管理局（FDA）核准的治療甲癬最有效的藥物[ 54 ]。對於手指甲和腳趾甲灰指甲，特比萘芬的治療持續時間通常分別至少為六週和十二週。特比萘芬對趾甲甲真菌病患者的完全治癒率在 35% 至 78% 之間變化 [ 16 , 17 , 18 , 55 ]。特比萘芬在涉及非皮癬菌黴菌或酵母菌的甲真菌病中的敏感性尚未得到充分研究[ 56 ]。
特比萘芬脈衝給藥方案的劑量、持續時間和頻率可能有所不同。常見的治療方案是每日兩次特比萘芬 250 mg 脈衝治療方案，持續 4 週，然後停藥 4 週。
口服特比萘芬的其他衝擊療法包括每天 500 mg，持續一周，然後三週不治療，每月重複一次，持續三個月[59 ]。評估成本[ 60 ]和合規性[ 61]的研究] 沒有發現連續療法和脈衝療法之間的差異。然而，由於患者偏好、副作用、共病以及潛在藥物交互作用的風險，脈衝給藥可能是首選[ 57 , 60 ]。
特比萘芬使用的禁忌症包括其與其他由細胞色素 P-450 酶 2D6 代謝的藥物的相互作用。最值得注意的是，美托洛爾屬於此類 cP450 2D6 代謝藥物，因此不鼓勵服用美托洛爾的患者進行特比萘芬治療。
特比萘芬使用的禁忌症包括其與其他由細胞色素 P-450 酶 2D6 代謝的藥物的相互作用。最值得注意的是，美托洛爾屬於此類 cP450 2D6 代謝藥物，因此不鼓勵服用美托洛爾的患者進行特比萘芬治療。
在這些情況下，甲癬的口服治療選擇包括伊曲康唑，一種替代的廣譜抗真菌藥物。伊曲康唑經 FDA 核准用於治療甲真菌病，可有效對抗皮癬菌、酵母菌和非皮癬菌黴菌。
劑量選擇包括
每日 200 毫克的連續治療方案，持續三個月，
或每日 400 毫克的四脈衝治療方案，持續一周，然後暫停藥物治療三週。
另一種二線治療選擇包括口服抗真菌氟康唑。FDA 未核准氟康唑用於治療甲真菌病。然而，臨床試驗已證實其對皮癬菌指甲感染的功效。
氟康唑的典型給藥方案是每週一次 150–450 mg，治療指甲的療程為 6 個月，治療腳趾甲的療程為 12 個月或更長時間 [ 22 , 62 ]。完全治癒率範圍為 21% 至 48%，取決於劑量和治療持續時間 [ 21 , 22 ]。表 2. 目前的口服抗黴菌療法。
抗真菌抗藥性是選擇治療方案時也應考慮的變數。隨著皮癬菌感染隨著時間的推移而演變，口服抗真菌藥物的功效也可能會改變。在最近的一項臨床試驗中，對常用的抗真菌藥物（包括特比萘芬、伊曲康唑和氟康唑）進行了針對慢性和慢性復發性體癬、股癬和麵癬的測試[ 25]。
抗真菌抗藥性是選擇治療方案時也應考慮的變數。隨著皮癬菌感染隨著時間的推移而演變，口服抗真菌藥物的功效也可能會改變。在最近的一項臨床試驗中，對常用的抗真菌藥物（包括特比萘芬、伊曲康唑和氟康唑）進行了針對慢性和慢性復發性體癬、股癬和麵癬的測試[ 25]。
經過 4 週的治療，所有藥物的治癒率都在 8% 左右或更低。
治療八週後，特比萘芬、伊曲康唑和氟康唑的治癒率分別為 28%、66% 和 42%。
這項研究顯示了抗真菌抗藥性的現實，以及顯示伊曲康唑在特比萘芬抗藥性皮癬菌病中有效的證據。歐洲也有關於毛癬菌屬特比萘芬抗藥性增加的類似報導[ 23 , 24 ]。需要更多的研究來進一步評估多重抗藥性病例的治療方案。
由於口服抗真菌藥物的全身性，在處方這些藥物時應考慮副作用和藥物交互作用。特比萘芬與肝損傷有關。因此，建議在開始治療之前進行肝功能檢查，儘管一些醫生建議在整個特比萘芬治療過程中評估肝功能[ 20 ]。伊曲康唑治療具有很高的藥物交互作用風險，由於其存在心臟衰竭和心律不整的風險，因此在患有心臟病的患者中應謹慎使用[ 63 ]。氟康唑也與高風險交互作用（用作脈衝治療時不多）心血管風險有關，並且據報道可延長 QT 間期 [ 64]。氟康唑的其他副作用包括明顯的先天缺陷，強烈建議在懷孕期間避免使用這種藥物[ 65 ]。
對於沒有預先存在血液學或肝臟異常的成人和兒童，口服抗真菌治療的間隔監測是不必要的[ 66 ]。此後，FDA 取消了在接受口服抗真菌藥物治療時繼續監測肝功能的建議。由於在已有肝臟疾病的患者中藥物性肝損傷的發生率較高，因此劑量調整和持續的間隔監測對這些病例是有益的。
甲下角化症超過 2 毫米且真菌感染涉及外側指甲或超過整個指甲單位 50% 的個體對治療反應較差的比例較高 [15 ]。最近的一些研究表明，艾夫康唑局部治療在這種情況下可能有用[ 51 , 52 ]。鑑於特比萘芬對皮癬菌敏感，混合感染或抗藥性微生物引起的甲癬也與不良預後相關。據報告，在周邊循環減少的情況下，如老年或糖尿病患者，一線口服抗真菌藥物的治療反應不佳。
Onychomycosis: Old and New
Oral Treatments
Several treatment options exist for the treatment of onychomycosis (Table 2). Oral terbinafine is the most effective Food and Drug Administration (FDA)-approved treatment for onychomycosis [54]. Terbinafine treatment duration is typically a minimum of six weeks and twelve weeks for fingernail and toenail onychomycosis, respectively. Terbinafine complete cure rates vary between 35% and 78% in patients with toenail onychomycosis [16,17,18,55]. Terbinafine sensitivity is not well studied in onychomycosis involving non-dermatophyte molds or yeast [56].
Terbinafine pulse dosing regimens can vary in dose, duration, and frequency. A common regimen is two pulse regimens of terbinafine 250 mg daily for four weeks, followed by four weeks off. A meta-analysis by Gupta et al. determined that continuous terbinafine regimen is generally superior to pulse dosing for mycologic cure. However, both continuous and pulse dosing had similar complete cure rates [57,58]. Other pulse regimens for oral terbinafine include 500 mg daily for one week, followed by three weeks of no treatment, repeated every month for three months [59]. Studies assessing cost [60] and compliance [61] did not identify a difference between continuous and pulse regimens. However, pulse dosing may be preferred due to patient preference, side effects, comorbidities, and risk of potential drug–drug interactions [57,60].
Contraindications to terbinafine use include its interaction with other pharmaceuticals that are metabolized by cytochrome P-450 enzyme 2D6. Most notably, metoprolol is among this category of cP450 2D6 metabolized drugs, making terbinafine treatment discouraged in patients taking metoprolol. In these cases, oral treatment options for onychomycosis include itraconazole, an alternative broad-spectrum antifungal. Itraconazole is FDA-approved for the treatment of onychomycosis and is effective against dermatophytes, yeasts, and non-dermatophyte molds. Dosing options include a continuous treatment regimen of 200 mg daily for three months or a four-pulse treatment regimen of 400 mg daily for one week, followed by a three-week pause in drug treatment. Complete cure rate with itraconazole treatment ranges between 14–43% [16,17,18,19,20].
An additional second-line treatment option includes the oral antifungal fluconazole. Fluconazole is not FDA approved for the treatment of onychomycosis. However, clinical trials have established its efficacy in dermatophyte nail infections. Typical dosing regimen of fluconazole is 150–450 mg once weekly for a duration of six months for fingernails and 12 months or more for toenails [22,62]. Complete cure rates range from 21% to 48%, depending on dosage and treatment duration [21,22].
Table 2. Current oral antifungal therapies.
Antifungal resistance is a variable that also should be considered when choosing treatment options. As dermatophytic infections evolve over time, the efficacy of oral antifungals may change, as well. In a recent clinical trial, commonly prescribed antifungals, including terbinafine, itraconazole, and fluconazole, were tested against chronic and chronic relapsing tinea corporis, cruris, and faciei [25]. After four weeks of treatment, all drugs demonstrated a cure rate around 8% or less. After eight weeks of treatment, cure rates with terbinafine, itraconazole, and fluconazole were reported as 28%, 66%, and 42%, respectively. This study indicates the reality of antifungal resistance, as well as evidence suggesting the effectiveness of itraconazole in terbinafine-resistant dermatophytosis. Similar reports of increasing terbinafine resistance in Trichophyton species have been reported in Europe [23,24]. More studies are needed to further assess treatment regimens in multi-drug resistant cases.
Due to the systemic nature of oral antifungal medications, side effects and drug–drug interactions should be considered when prescribing each of these medications. Terbinafine has been associated with hepatic injury. Therefore, liver function tests are recommended prior to starting treatment, although some doctors recommend evaluating liver function throughout the course of terbinafine treatment [20]. Itraconazole therapy carries a high risk of drug interactions and should be used cautiously in patients with cardiac conditions due to its risk of heart failure and arrythmias [63]. Fluconazole is also associated with high risk of interactions (not much when used as pulse treatment) cardiovascular risk and has been reported to prolong the QT interval [64]. Additional side effects with fluconazole include significant congenital defects, and avoidance of this medication during pregnancy is strongly advised [65].
Interval monitoring in oral antifungal treatment is unnecessary in adults and children without preexisting hematologic or hepatic abnormalities [66]. The recommendation for continued hepatic function monitoring while receiving treatment with an oral antifungal has since been removed by the FDA. Due to higher incidence rates of drug-induced liver injury seen in patients with preexisting hepatic conditions, dosing adjustments and continued interval monitoring is beneficial in these cases.
Poor response to treatment is seen at higher rates in individuals with subungual keratosis measuring more than 2 mm and fungal infection involving the lateral nail or over 50% of the entire nail unit [15]. Recently a few studies showed that topical treatment with efinaconazole can be useful in this setting [51,52]. Given the terbinafine sensitivity to dermatophytes, onychomycosis caused by mixed infection or resistant organisms are also associated with poor prognostic outcomes. In the setting of decreased peripheral circulation, as in elderly or diabetic patients, poor treatment response to first-line oral antifungals has been reported.
Oral Treatments
Several treatment options exist for the treatment of onychomycosis (Table 2). Oral terbinafine is the most effective Food and Drug Administration (FDA)-approved treatment for onychomycosis [54]. Terbinafine treatment duration is typically a minimum of six weeks and twelve weeks for fingernail and toenail onychomycosis, respectively. Terbinafine complete cure rates vary between 35% and 78% in patients with toenail onychomycosis [16,17,18,55]. Terbinafine sensitivity is not well studied in onychomycosis involving non-dermatophyte molds or yeast [56].
Terbinafine pulse dosing regimens can vary in dose, duration, and frequency. A common regimen is two pulse regimens of terbinafine 250 mg daily for four weeks, followed by four weeks off. A meta-analysis by Gupta et al. determined that continuous terbinafine regimen is generally superior to pulse dosing for mycologic cure. However, both continuous and pulse dosing had similar complete cure rates [57,58]. Other pulse regimens for oral terbinafine include 500 mg daily for one week, followed by three weeks of no treatment, repeated every month for three months [59]. Studies assessing cost [60] and compliance [61] did not identify a difference between continuous and pulse regimens. However, pulse dosing may be preferred due to patient preference, side effects, comorbidities, and risk of potential drug–drug interactions [57,60].
Contraindications to terbinafine use include its interaction with other pharmaceuticals that are metabolized by cytochrome P-450 enzyme 2D6. Most notably, metoprolol is among this category of cP450 2D6 metabolized drugs, making terbinafine treatment discouraged in patients taking metoprolol. In these cases, oral treatment options for onychomycosis include itraconazole, an alternative broad-spectrum antifungal. Itraconazole is FDA-approved for the treatment of onychomycosis and is effective against dermatophytes, yeasts, and non-dermatophyte molds. Dosing options include a continuous treatment regimen of 200 mg daily for three months or a four-pulse treatment regimen of 400 mg daily for one week, followed by a three-week pause in drug treatment. Complete cure rate with itraconazole treatment ranges between 14–43% [16,17,18,19,20].
An additional second-line treatment option includes the oral antifungal fluconazole. Fluconazole is not FDA approved for the treatment of onychomycosis. However, clinical trials have established its efficacy in dermatophyte nail infections. Typical dosing regimen of fluconazole is 150–450 mg once weekly for a duration of six months for fingernails and 12 months or more for toenails [22,62]. Complete cure rates range from 21% to 48%, depending on dosage and treatment duration [21,22].
Table 2. Current oral antifungal therapies.
Antifungal resistance is a variable that also should be considered when choosing treatment options. As dermatophytic infections evolve over time, the efficacy of oral antifungals may change, as well. In a recent clinical trial, commonly prescribed antifungals, including terbinafine, itraconazole, and fluconazole, were tested against chronic and chronic relapsing tinea corporis, cruris, and faciei [25]. After four weeks of treatment, all drugs demonstrated a cure rate around 8% or less. After eight weeks of treatment, cure rates with terbinafine, itraconazole, and fluconazole were reported as 28%, 66%, and 42%, respectively. This study indicates the reality of antifungal resistance, as well as evidence suggesting the effectiveness of itraconazole in terbinafine-resistant dermatophytosis. Similar reports of increasing terbinafine resistance in Trichophyton species have been reported in Europe [23,24]. More studies are needed to further assess treatment regimens in multi-drug resistant cases.
Due to the systemic nature of oral antifungal medications, side effects and drug–drug interactions should be considered when prescribing each of these medications. Terbinafine has been associated with hepatic injury. Therefore, liver function tests are recommended prior to starting treatment, although some doctors recommend evaluating liver function throughout the course of terbinafine treatment [20]. Itraconazole therapy carries a high risk of drug interactions and should be used cautiously in patients with cardiac conditions due to its risk of heart failure and arrythmias [63]. Fluconazole is also associated with high risk of interactions (not much when used as pulse treatment) cardiovascular risk and has been reported to prolong the QT interval [64]. Additional side effects with fluconazole include significant congenital defects, and avoidance of this medication during pregnancy is strongly advised [65].
Interval monitoring in oral antifungal treatment is unnecessary in adults and children without preexisting hematologic or hepatic abnormalities [66]. The recommendation for continued hepatic function monitoring while receiving treatment with an oral antifungal has since been removed by the FDA. Due to higher incidence rates of drug-induced liver injury seen in patients with preexisting hepatic conditions, dosing adjustments and continued interval monitoring is beneficial in these cases.
Poor response to treatment is seen at higher rates in individuals with subungual keratosis measuring more than 2 mm and fungal infection involving the lateral nail or over 50% of the entire nail unit [15]. Recently a few studies showed that topical treatment with efinaconazole can be useful in this setting [51,52]. Given the terbinafine sensitivity to dermatophytes, onychomycosis caused by mixed infection or resistant organisms are also associated with poor prognostic outcomes. In the setting of decreased peripheral circulation, as in elderly or diabetic patients, poor treatment response to first-line oral antifungals has been reported.
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