Mediprobe Research Inc, London, ON, Canada.
Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Canada.
Expert Opin Drug Saf. 2023 Jul-Dec;22(12):1169-1178. doi: 10.1080/14740338.2023.2280137. Epub 2023 Dec 18.
Oral antifungals are used for the treatment of moderate-severe onychomycosis. Terbinafine and itraconazole are approved for onychomycosis treatment in North America; additionally, fluconazole is indicated for onychomycosis in Europe. Other oral antifungals such as ketoconazole and griseofulvin are no longer used for the treatment of onychomycosis due to safety concerns and relatively lower efficacy.
On 7 March 2023, we conducted a comprehensive search in PubMed and Google Scholar, while also manually examining selected article bibliographies and package inserts.
Terbinafine, itraconazole, and fluconazole have several interactions with cytochrome-p450, and either alone, or when co-administered with other drugs these interactions can facilitate a multitude of adverse events. This article identifies possible hepatic, renal, cutaneous, cardiovascular, neurological, hemopoietic, and obstetric adverse events. We have also compared the rates of hepatotoxicity, clinically apparent liver injury, and alanine transaminase elevations between oral antifungals, and recommendations for hepatic monitoring.
We recommend laboratory testing of liver function tests prior to the administration of any oral antifungals, especially when clinically indicated. In the event of a first treatment failure, the diagnosis of onychomycosis must be confirmed, and consideration given to antifungal susceptibility testing. Antifungal stewardship will help reduce the incidence of antifungal resistance.
口服抗真菌药物用于治疗中重度甲真菌病。特比萘芬和伊曲康唑已获批准用于北美地区的甲真菌病治疗;此外,氟康唑也适用于欧洲的甲真菌病。酮康唑和灰黄霉素等其他口服抗真菌药物由于安全性问题和相对较低的疗效,不再用于治疗甲真菌病。
2023 年 3 月 7 日,我们在 PubMed 和 Google Scholar 上进行了全面检索,同时还手动检查了选定文章的参考文献和说明书。
特比萘芬、伊曲康唑和氟康唑与细胞色素 P450 有多种相互作用,无论是单独使用还是与其他药物联合使用,这些相互作用都可能导致多种不良事件。本文确定了可能发生的肝、肾、皮肤、心血管、神经、血液和产科不良事件。我们还比较了不同口服抗真菌药物的肝毒性、临床明显肝损伤和丙氨酸转氨酶升高的发生率,并就肝监测提出了建议。
我们建议在使用任何口服抗真菌药物之前进行肝功能测试,特别是在临床指征明显的情况下。如果首次治疗失败,必须确认甲真菌病的诊断,并考虑进行抗真菌药敏试验。抗真菌药物管理有助于降低抗真菌药物耐药性的发生率。