Drug reference

Fluconazole

Antifungal

Also known as Diflucan, Flucostat, Flucon, Zocon

START

Confirm fungal infection (KOH prep, culture, or clinical diagnosis for OPC). Baseline LFTs, serum creatinine, ECG if high-dose or cardiac risk.

TYPICAL MAX

400 mg/day (standard); 800 mg/day (severe infections, cryptococcal meningitis — specialist only). Do not exceed 400 mg/day in patients with QT prolongation risk.

STOP IF

Signs of hepatotoxicity (jaundice, dark urine, RUQ pain, ALT >3x ULN), QTc >500 ms, severe rash (SJS/TEN suspected), anaphylaxis

WATCH

LFTs at baseline and weekly during prolonged therapy (>2 weeks), serum creatinine (renal dose adjustment), ECG if high-dose or on other QT drugs, drug interactions (CYP2C9, CYP2C19, CYP3A4 inhibition)

CDSCO approvedJan AushadhiATC D01AC15

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 23min · absorption onset
PEAK: 1.5h · 1-2 h (oral)
t½: 1.3d · 30 h (normal); 50-100 h (renal impairment)
DURATION: 1d · 24 h (daily dosing)

EXCRETION

~80% renal unchanged; minimal hepatic metabolism

route + CYP

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

FDA PLLR: Low-dose fluconazole (150 mg single dose) for vulvovaginal candidiasis is generally considered acceptable in pregnancy. High-dose fluconazole (400-800 mg/day) in first trimester is associated with teratogenic effects (craniofacial, skeletal, cardiac defects). Avoid high-dose in first trimester; use only if benefit clearly outweighs risk with informed consent.

FDA category + note

Top interactionssee all 12 →

AstemizoleContraindicatedTextbook-citedKDT 7e · p948
CisaprideContraindicatedTextbook-citedKDT 7e · p948
TerfenadineContraindicatedTextbook-citedKDT 7e · p948
CilostazoleContraindicatedTextbookKDT 7e · p555

Available in India

1,350 branded formulations and 12 fixed-dose combinations. Look up specific brands in the Drugs workspace.

Jan Aushadhi — generic available at GoI pharmacies

Mechanism

Fluconazole is a synthetic triazole antifungal agent that selectively inhibits fungal cytochrome P450-dependent enzyme lanosterol 14-α-demethylase. This inhibition prevents conversion of lanosterol to ergosterol, an essential component of the fungal cell membrane. The accumulation of 14-α-methyl sterols disrupts membrane fluidity and function, increasing membrane permeability and leading to impaired fungal growth and cell death. Fluconazole is fungistatic at therapeutic concentrations but may be fungicidal against Cryptococcus and some Candida species at higher concentrations.

Indications

Oropharyngeal candidiasis (OPC)Esophageal candidiasisVulvovaginal candidiasis (single-dose therapy)Cryptococcal meningitis (induction and maintenance, in combination with amphotericin B)Prevention of cryptococcal meningitis relapse in AIDS patients (maintenance)Prevention of candidiasis in bone marrow transplant patientsSystemic candidiasis (candidemia, disseminated candidiasis)Coccidioidomycosis (meningitis and disseminated disease)

Dosing

Adult: Oropharyngeal candidiasis: 200 mg PO/IV day 1, then 100 mg daily x 7-14 days. Esophageal candidiasis: 200-400 mg PO/IV day 1, then 100-200 mg daily x 14-21 days (min 14 days). Vulvovaginal candidiasis: 150 mg PO single dose. Cryptococcal meningitis: 400 mg day 1, then 200-400 mg daily x 10-12 weeks (with amphotericin B for induction). Maintenance: 200 mg daily. Systemic candidiasis: 400-800 mg daily.
Pediatric: 3-13 years: 3-6 mg/kg/day PO/IV (max 200-400 mg/day). 13-18 years: adult dosing. Neonates (0-14 days): same mg/kg dose q72h (immature metabolism); 15-27 days: q48h.
Renal adjustment: CrCl >50: full dose. CrCl ≤50 (no dialysis): 50% of recommended dose. HD: give usual dose after each dialysis session. CRRT: 200-400 mg daily (dose based on effluent rate).
Hepatic adjustment: No adjustment for mild-moderate hepatic impairment. Use with caution in severe hepatic disease; monitor liver function.
Geriatric: No specific adjustment for age alone. Adjust based on renal function. Elderly may have reduced clearance.
Max dose: 400 mg/day (most indications); 800 mg/day (systemic candidiasis, cryptococcal meningitis, severe infections)

Pharmacokinetics

Onset

Rapid absorption after oral administration; clinical improvement typically within 24-72 hours for mucocutaneous candidiasis.

Peak effect

Oral: peak plasma at 1-2 hours. IV: immediate peak at end of infusion.

Duration

Long half-life allows once-daily dosing. Steady state by day 7-10.

Half-life

20-50 hours (mean ~30 hours); prolonged in renal impairment (up to 98 hours). Terminal t½ 88-111 hours.

Bioavailability

>90% (oral bioavailability approaches IV; food does not significantly affect absorption).

Protein binding

Low: 11-12% (primarily to albumin).

Metabolism

Minimally metabolized in the liver (<11% of dose). Major route: renal excretion of unchanged drug.

Excretion

Primarily renal: ~80% excreted unchanged in urine within 96 hours. 11% as metabolites. Fecal: ~2% of dose.

Contraindications

Hypersensitivity to fluconazole or other azole antifungals
Concomitant administration with cisapride (QT prolongation risk)
Concomitant administration with terfenadine or astemizole (QT prolongation, arrhythmia risk)
Concomitant administration with pimozide (QT prolongation)
Concomitant administration with quinidine (QT prolongation)
Concomitant administration with erythromycin (QT prolongation)
Relative: pregnancy (high-dose, first trimester — teratogenic risk)

Side effects

Common

HeadacheNausea, vomiting, abdominal painDiarrheaRashElevated liver enzymes (transient, usually asymptomatic)

Serious

Hepatotoxicity (hepatitis, hepatic necrosis, fulminant hepatic failure — rare but fatal cases reported)
QT prolongation and torsades de pointes (dose-dependent, especially at high doses >400 mg/day)
Severe cutaneous adverse reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
Anaphylaxis and angioedema
Teratogenicity (high-dose in first trimester: craniofacial, skeletal, cardiac anomalies — embryopathy similar to warfarin embryopathy)
Adrenal insufficiency (at high doses, via inhibition of CYP450 in adrenal cortex)

Pregnancy & lactation

Pregnancy

Lactation

Excreted in breast milk at concentrations similar to plasma. Compatible with breastfeeding per AAP. No adverse effects reported in breastfed infants at standard doses.