Fluconazole
Regulatory sources consulted
Approved indications
- Vaginal candidiasis, acute or recurrent.
- Mucosal candidiasis, including oropharyngeal, esophageal, candiduria, and chronic mucocutaneous candidiasis.
- Systemic candidiasis, including candidemia, disseminated candidiasis, and pneumonia.
- Cryptococcal meningitis (treatment and maintenance therapy to prevent relapse in patients with AIDS).
- Prophylaxis of Candida infections in patients undergoing bone marrow transplantation who receive cytotoxic chemotherapy and/or radiation therapy.
- Onychomycosis (off-label use). · off-label
Contraindications
Absolute
- Hypersensitivity to fluconazole, other azole derivatives, or any of the excipients.
- Co-administration with terfenadine (at fluconazole doses ≥400 mg/day).
- Co-administration of other drugs known to prolong the QT interval and which are metabolized via CYP3A4 (e.g., cisapride, astemizole, pimozide, quinidine, erythromycin).
Clinical warnings
- Major warning · Hepatic injury: Rare cases of serious hepatic toxicity, including fatalities, have been reported. Discontinue if signs/symptoms of liver disease develop. — FDA
- Major warning · Dermatologic reactions: Exfoliative skin disorders (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported. Discontinue if rash progresses. — FDA
- Major warning · Potential for fetal harm: High-dose exposure (400-800 mg/day) during the first trimester is associated with a pattern of congenital anomalies. Avoid in pregnancy unless strictly necessary. — FDA
- Major warning · QT Prolongation: Cases of QT prolongation and torsades de pointes have been reported. Use with caution in patients with proarrhythmic conditions. — ANSM RCP
Drug interactions
- HighQuinidineC01BA01
Mechanism: Fluconazole (a moderate CYP3A4 inhibitor) increases quinidine concentrations. Both drugs prolong the QT interval, significantly increasing the risk of serious ventricular arrhythmias (Torsades de Pointes).
Recommendation: Co-administration is contraindicated.
FDA labelANSM RCP
- HighWarfarinB01AA03
Mechanism: Fluconazole (a moderate CYP2C9 inhibitor) inhibits the metabolism of the more potent S-warfarin isomer, leading to an increased prothrombin time (INR) and risk of bleeding.
Recommendation: Closely monitor INR when starting or stopping fluconazole and adjust warfarin dose as needed.
FDA label
- ModerateClopidogrelB01AC04
Mechanism: Fluconazole (a strong CYP2C19 inhibitor) inhibits the conversion of the prodrug clopidogrel to its active metabolite, reducing its antiplatelet effect and increasing the risk of thrombotic events.
Recommendation: Avoid concomitant use if possible. Consider an alternative antifungal agent that does not strongly inhibit CYP2C19.
FDA label
Adverse events
Common (≥1%)
headache · nausea · abdominal pain · diarrhea · skin rash · elevated transaminases
Rare but serious
severe hepatotoxicity (hepatic failure) · anaphylaxis · Stevens-Johnson syndrome (SJS) · toxic epidermal necrolysis (TEN) · DRESS syndrome · QT prolongation and Torsades de Pointes · agranulocytosis · seizures
Pregnancy and lactation
FDA category: Not applicable (descriptive warning)
Avoid during pregnancy. High doses (400-800 mg/day) in the first trimester are associated with a rare and distinctive pattern of birth defects. Data on low doses (150 mg) suggest a potential increased risk of spontaneous abortion. Use only if the potential benefit justifies the risk to the fetus in severe infections. Excreted in breast milk; breastfeeding is not recommended.
Recent literature (PubMed)
Esta guía global actualizada para el manejo de la candidiasis aborda el aumento de infecciones difíciles de tratar, como las causadas por C. auris y C. parapsilosis resistente al fluconazol. Proporciona recomendaciones basadas en la evidencia para diversas formas de candidiasis, considerando nuevos patógenos y opciones de tratamiento.
Revisión exhaustiva sobre la candidiasis invasiva, destacando su epidemiología, factores de riesgo y desafíos diagnósticos. Se subraya la importancia del tratamiento antifúngico temprano y la retirada del catéter venoso central. Se discute la resistencia al fluconazol en especies como N. glabrata, C. parapsilosis y C. auris como una preocupación creciente.
Revisión sobre el tratamiento de la onicomicosis. Menciona que el fluconazol se utiliza comúnmente fuera de etiqueta para esta indicación, aunque la terbinafina y el itraconazol son los agentes orales aprobados. Destaca las tasas de curación limitadas y la aparición de resistencia a la terbinafina.
Este artículo de revisión sobre onicomicosis posiciona al fluconazol, junto con el itraconazol, como antifúngicos de amplio espectro eficaces contra dermatofitos, levaduras y algunos mohos no dermatofíticos, siendo una alternativa a la terbinafina, el fármaco de primera elección.
Revisión actualizada sobre tinea pedis (pie de atleta). El tratamiento de elección es la terapia tópica con antifúngicos como los azoles. La terapia oral, que podría incluir fluconazol, se reserva para casos graves, fracaso del tratamiento tópico o pacientes inmunocomprometidos.