Antifungals, triazole derivatives
ATC code: J02AC01 (Fluconazole)
Inhibits the fungal CYP450-dependent enzyme lanosterol 14-alpha-demethylase. Disrupts ergosterol synthesis – a component of the fungal cell membrane. The membrane loses integrity and the fungal cell dies. Excellent CSF penetration – CSF/plasma ratio is 60–80 %.
First line
First-line for consolidation and maintenance phases of cryptococcal meningitis. Induction with amphotericin B plus flucytosine for 2 weeks. Then consolidation with fluconazole 400–800 mg/day for 8 weeks. Maintenance 200 mg/day until immune reconstitution. Excellent CNS penetration makes fluconazole the optimal choice.
First line
First-line systemic therapy for moderate to severe oropharyngeal candidiasis. Dose 100–200 mg/day for 7–14 days. Mild cases can be managed topically with nystatin or clotrimazole. In HIV-infected patients, systemic fluconazole is preferred due to higher efficacy.
First line
First-line for uncomplicated vulvovaginal candidiasis. Single oral dose of 150 mg. Efficacy comparable to topical azoles but with greater convenience. For recurrent candidiasis (4 or more episodes per year), 150 mg once weekly for 6 months.
1 pair found. Sorted from critical to minor.
Mechanism
Флуконазол ингибирует CYP2C9 – основной фермент метаболизма варфарина. МНО может удвоиться за 3–7 дней.
Management
Снизить дозу варфарина на 25–50% или временно отменить. Контроль МНО через 3 и 7 дней.
FDA pregnancy categories were retired in 2015 (historically high doses were category D). High doses (400–800 mg/day) in the first trimester are linked to craniofacial and skeletal anomalies. Even a single 150 mg dose during the first trimester is associated with increased risk of spontaneous abortion and stillbirth (Mølgaard-Nielsen D et al. JAMA. 2016;315(1):58–67, n = 1.4 million). The current position of CDC and most guidelines is to avoid systemic fluconazole in the first trimester; candidiasis is treated with topical azoles (clotrimazole, miconazole) for at least 7 days. From the second trimester, a single 150 mg dose is acceptable when topical therapy fails.
fluconazole is evaluated for the following indications with varying evidence strength: Oropharyngeal candidiasis (evidence tier A), Vulvovaginal candidiasis (evidence tier A), Cryptococcal meningitis (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of fluconazole (≥ 1 in 100): Headache, Nausea, Abdominal pain, Diarrhea, Rash. See the Safety section for uncommon and serious reactions.
FDA pregnancy categories were retired in 2015 (historically high doses were category D). High doses (400–800 mg/day) in the first trimester are linked to craniofacial and skeletal anomalies. Even a single 150 mg dose during the first trimester is associated with increased risk of spontaneous abortion and stillbirth (Mølgaard-Nielsen D et al. JAMA. 2016;315(1):58–67, n = 1.4 million). The current position of CDC and most guidelines is to avoid systemic fluconazole in the first trimester; candidiasis is treated with topical azoles (clotrimazole, miconazole) for at least 7 days. From the second trimester, a single 150 mg dose is acceptable when topical therapy fails.
fluconazole is contraindicated in: Hypersensitivity to fluconazole or other azoles; Concomitant terfenadine, astemizole, cisapride, or pimozide (arrhythmia risk). Full list in the Safety section.