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.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Fluconazole is a triazole antifungal. It is prescribed for mucosal and cutaneous candidiasis, invasive candidiasis, and prophylaxis in immunocompromised patients ( 2024). Fluconazole is prescribed for prophylaxis in patients on antibiotics and for intestinal dysbiosis in immunocompetent adults and children. The concept of post-antibiotic intestinal dysbiosis lacks a clear definition in international medicine; routine antifungal prophylaxis with antibiotics in immunocompetent people is not indicated (IDSA 2024). The drug can cause hepatotoxicity, QT prolongation, and drug interactions via CYP3A4. If fluconazole was prescribed after antibiotics or for dysbiosis, consider seeking a second opinion.
20 pairs found. Sorted from critical to minor.
Mechanism
Fluconazole at 200 mg/day or above blocks CYP3A4 – the main alprazolam metabolic route. Alprazolam plasma levels rise 2- to 3-fold, with stronger and longer effect.
Symptoms
Deep sedation, drowsiness, ataxia. Particularly dangerous in older patients – fall and fracture risk. Symptoms appear within 1–2 days.
Management
During fluconazole therapy, halve the alprazolam dose. Alternative antifungals: terbinafine or echinocandins. Alternative benzodiazepines without CYP3A4 dependence: lorazepam or oxazepam.
Sources
Mechanism
Dual mechanism: fluconazole prolongs QT (additive with amiodarone) and blocks CYP3A4 – a partial amiodarone clearance route. Amiodarone plasma levels rise.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antifungals: echinocandins (micafungin, caspofungin) for systemic mycoses or terbinafine for dermatophytosis. If fluconazole is needed, ECG before start and every 3 days during therapy.
Mechanism
Fluconazole at 200 mg/day or above moderately inhibits CYP3A4; at 400 mg/day, strongly. Atorvastatin plasma levels rise 2- to 4-fold depending on fluconazole dose.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
For short fluconazole courses (up to 7 days), halve atorvastatin or hold it. For prolonged systemic therapy, alternative antifungals: echinocandins (micafungin, caspofungin); or switch to pravastatin/rosuvastatin.
Sources
Mechanism
Dual risk. Fluconazole blocks CYP2C19 (strongly) and CYP3A4 (moderately) and prolongs QT itself. Citalopram plasma levels rise, plus additive QT prolongation.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Cap citalopram at 20 mg/day when combined. ECG before start and every 3 days during therapy. Alternative antifungals: echinocandins for systemic mycoses or terbinafine for dermatophytosis.
Mechanism
Fluconazole inhibits CYP2C19, the key enzyme converting clopidogrel into its active metabolite. Active levels fall by 25–50% and the antiplatelet effect weakens.
Symptoms
The patient feels no symptoms – the weakened antiplatelet effect is silent. Risk of recurrent coronary events and stent thrombosis rises.
Management
For a short fluconazole course, the effect is clinically minor. For prolonged systemic therapy (>14 days), an alternative antiplatelet is ticagrelor (not CYP2C19-dependent). Alternative antifungal: echinocandins for systemic mycoses.
Mechanism
Fluconazole at 200 mg/day or above blocks CYP3A4 – the main colchicine clearance route. Colchicine plasma levels rise; myopathy risk grows with prolonged therapy.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain. With prolonged combination: muscle weakness, peripheral neuropathy, falling leukocytes and platelets.
Management
For short fluconazole courses (up to 7 days), no special measures are needed. For prolonged systemic therapy with preserved renal function, colchicine 0.3 mg every other day. In chronic kidney disease, do not prescribe; alternative for gout: intra-articular glucocorticoid.
Mechanism
Dual mechanism. Fluconazole blocks CYP3A4 (the main dronedarone clearance route) and prolongs QT itself. Dronedarone plasma levels rise; QT effects add up.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination. Alternative antifungals: echinocandins (micafungin, caspofungin) for systemic mycoses or terbinafine for dermatophytosis. If fluconazole is needed: ECG before start and every 3 days during therapy.
Mechanism
Fluconazole at 200 mg/day or above blocks CYP2C9 – the main glibenclamide metabolic route. Glibenclamide plasma levels rise 2- to 3-fold; hypoglycaemic effect intensifies.
Symptoms
Severe hypoglycaemia: sweating, tremor, hunger, tachycardia, confusion; severe cases progress to seizures and coma. Symptoms appear within 1–7 days, especially in older patients and chronic kidney disease.
Management
For short fluconazole courses, monitor glucose 4 times daily; if needed, halve glibenclamide. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses.
Mechanism
Dual mechanism. Fluconazole prolongs QT and blocks CYP3A4 and CYP2D6 – haloperidol metabolic routes. Haloperidol plasma levels rise; QT effects add up.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination. Alternative antifungals: terbinafine or echinocandins. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole.
Mechanism
Fluconazole inhibits CYP3A4 and CYP2B6 – the main methadone metabolism enzymes. Methadone concentration rises by 35% with QT prolongation. Methadone alone prolongs QT above 80 mg/day; fluconazole amplifies this.
Symptoms
Drowsiness, respiratory depression (rate below 12/min), miosis, ECG QTc above 500 ms. Severe cases: fatal arrhythmia.
Management
Reduce methadone by 25% when starting fluconazole, ECG before and after. With methadone above 80 mg/day or QT risk factors, choose an alternative antifungal (isavuconazole, terbinafine for superficial infections).
Mechanism
Fluconazole is a moderate CYP3A4 inhibitor. Pimozide rises 2–3 fold. QT prolongation is clinically significant. recommends avoidance.
Symptoms
QT prolongation, dizziness within 5–7 days.
Management
If fluconazole is needed, ECG at baseline and every 3 days, reduce pimozide by 50%. Better: terbinafine for superficial infections.
Mechanism
Rifampicin strongly induces CYP3A4, which partly metabolises fluconazole. Fluconazole plasma levels fall by 25%; antifungal efficacy decreases.
Symptoms
Recurrence of mycosis symptoms: ongoing fever, skin or mucosal lesions; in immunocompromised patients, risk of systemic mycosis progression.
Management
When combined, increase fluconazole by 50–100% with efficacy monitoring. Alternative antifungal during anti-TB therapy: echinocandins (micafungin, caspofungin; no CYP3A4 dependence).
Mechanism
Fluconazole at 200 mg/day or above moderately inhibits CYP3A4 – the main simvastatin metabolic route. Simvastatin plasma levels rise 2- to 3-fold, with increased myopathy risk.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
For short fluconazole courses (up to 7 days), hold simvastatin or halve the dose. For prolonged systemic therapy, switch to pravastatin/rosuvastatin or use an alternative antifungal (echinocandins).
Mechanism
Fluconazole at 200 mg/day or above blocks CYP3A4 – the main tacrolimus metabolic route. Tacrolimus plasma levels rise 2- to 3-fold, with nephrotoxicity and neurotoxicity risks.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients: accelerated graft function decline.
Management
For short fluconazole courses (up to 7 days), reduce tacrolimus by 30% and check trough (C0) daily. For prolonged systemic therapy, alternative antifungals (echinocandins) or titrate tacrolimus to level.
Mechanism
Fluconazole inhibits CYP2C9, the main enzyme of S-warfarin (the more active isomer). INR rises to 8–12 with risk of major bleeding: gastrointestinal, intracranial, retroperitoneal.
Symptoms
By days 3–5: gum and nose bleeding, petechiae, haematuria, bloody stool. INR above 6 without clinical bleeding still requires action.
Management
If fluconazole is required, reduce warfarin by 25–50% from day 1 and check INR on days 3 and 7. Short courses (3 single doses) – INR check on day 5. After fluconazole withdrawal, retitrate warfarin upward.
Sources
Mechanism
Fluconazole weakly blocks CYP2C19 and CYP3A4 – amitriptyline metabolic routes. TCA plasma levels may rise with prolonged fluconazole courses.
Symptoms
Worsening anticholinergic symptoms (dry mouth, constipation, urinary retention), drowsiness, tachycardia. QT prolongation on ECG at fluconazole doses ≥200 mg.
Management
For short fluconazole courses (up to 7 days), no special adjustment. For prolonged systemic therapy (>14 days), reduce amitriptyline by 25% temporarily. Alternative antifungals: terbinafine for dermatophytosis or echinocandins.
Mechanism
Fluconazole at high doses (200 mg/day or above) blocks CYP3A4 – the main amlodipine metabolic route. Amlodipine plasma levels may rise. The effect is clinically weak in short courses.
Symptoms
Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.
Management
For short fluconazole courses (up to 7 days), no adjustment is usually needed. For prolonged systemic therapy (>14 days), reduce amlodipine by 25% with blood pressure monitoring.
Mechanism
Fluconazole is a moderate CYP3A4 inhibitor. Apixaban AUC rises moderately (by 30–40%), increasing bleeding risk.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, black or tarry stools, haematuria. Higher risk in older patients, prior peptic ulcer disease, and chronic kidney disease.
Management
For short fluconazole courses (single 150 mg dose or 5–7 days), do not change apixaban. For longer therapy (over 14 days) in older patients and creatinine clearance below 50 mL/min, consider reducing apixaban to 2.5 mg twice daily. Alternatives: nystatin (not systemically absorbed) or clotrimazole for superficial candidiasis.
Mechanism
Additive QT prolongation – both drugs prolong QTc dose-dependently.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short courses of both (azithromycin 3–5 days, fluconazole single dose for candidiasis), the combination is acceptable. For prolonged systemic fluconazole therapy: alternative antibiotics (doxycycline, a cephalosporin) or antifungals (terbinafine, echinocandins).
Mechanism
Fluconazole weakly inhibits CYP3A4 and CYP2C19. Escitalopram levels may rise slightly. Additive QT risk is moderate — both prolong QT.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short fluconazole courses (single 150 mg dose or 5–7 days) in patients without cardiac disease, no adjustment needed. For longer systemic therapy (over 14 days) in older patients, cap escitalopram at 10 mg/day and check ECG at 2 weeks. For superficial mycosis, alternative: topical clotrimazole or nystatin.
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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.
Compatible. Hale L2. RID about 16%, relatively high, with no consistent infant problems documented in clinical reports. AEMPS: a single 150 mg oral dose for vaginal candidiasis is compatible with breastfeeding. Prolonged high-dose use (systemic mycoses) warrants observation of infant liver enzymes.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
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 category D. 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.
Compatible. Hale L2. RID about 16%, relatively high, with no consistent infant problems documented in clinical reports. AEMPS: a single 150 mg oral dose for vaginal candidiasis is compatible with breastfeeding. Prolonged high-dose use (systemic mycoses) warrants observation of infant liver enzymes.
Fluconazole is contraindicated in: Hypersensitivity to fluconazole or other azoles; Concomitant terfenadine, astemizole, cisapride, or pimozide (arrhythmia risk). Full list in the Safety section.