How long does Diflucan (fluconazole) stay in the system?

How Long Does Fluconazole Stay in Your System?

Fluconazole has a half-life of approximately 30 hours (range 20-50 hours) in adults with normal kidney function, meaning it takes about 5-10 days to be completely eliminated from your body after stopping treatment. 1

Elimination Timeline

• The terminal plasma elimination half-life is approximately 30 hours after oral administration in normal volunteers, though this can range from 20 to 50 hours 1
• Steady-state concentrations are reached within 5 to 10 days following once-daily dosing, which also reflects the time needed for complete elimination after stopping 1
• Approximately 80% of fluconazole is excreted unchanged in the urine, with only about 11% appearing as metabolites 1, 2
• The drug remains detectable in toenails for up to 6 months after therapy discontinuation, which is why it can be effective for fungal nail infections even after treatment ends 3

Key Pharmacokinetic Properties

• Peak plasma concentrations occur between 1-2 hours after oral administration 1
• Oral bioavailability exceeds 90%, making oral and IV formulations essentially equivalent 1, 4
• Plasma protein binding is very low (11-12%), meaning most of the drug circulates freely and is pharmacologically active 1, 4
• The apparent volume of distribution approximates total body water (0.7 L/kg), allowing extensive tissue penetration 1, 4

Factors That Prolong Elimination

• Renal impairment significantly extends the half-life because fluconazole is primarily eliminated by the kidneys 1, 5
• Neonates have a prolonged half-life of 55-90 hours compared to the 30-hour half-life in adults 3
• Premature newborns (26-29 weeks gestation) have even longer elimination, with a mean half-life of 73.6 hours at birth that gradually decreases over the first weeks of life 1

Tissue Persistence

• Fluconazole penetrates extensively into body fluids and tissues, including cerebrospinal fluid (50-90% of plasma levels), saliva (equal to plasma), vaginal tissue (94-114% of plasma), and skin 1, 4
• Urinary concentrations are approximately 10 times higher than plasma concentrations, which is why it's effective for urinary tract candidiasis 1
• The drug accumulates in nails and skin, persisting long after plasma levels become undetectable 3, 2

Clinical Implications

• A loading dose (double the maintenance dose) is recommended because it takes 6-7 days to reach steady-state with once-daily dosing 5, 6
• Hemodialysis removes approximately 50% of fluconazole in a 3-hour session, requiring supplemental dosing after dialysis 1
• Children clear fluconazole more rapidly (half-life ~14-19 hours) than adults, which is why higher or more frequent dosing is needed in pediatric patients 3

Common Pitfall

The most important caveat is that patients with impaired kidney function will retain fluconazole much longer than those with normal renal function, as there is an inverse relationship between elimination half-life and creatinine clearance 1, 5. Dose adjustment is essential in renal impairment to avoid drug accumulation and potential toxicity.