Fluconazole

Fluconazole (triazole)

  • Pregnancy Category D but single dose 150 mg for vaginal candidiasis is Category C
  • Not routinely recommended during lactation

Formulations

  • IV, tablets (50, 100, 150, 200 mg) or oral suspension (50 mg / 5 mL or 200 mg / 5 mL)

Dosing 

Tinea unguium

  • 150-300 mg q week until normal nail growth (approx. 3-12 months)

Tinea capitis (children):

  • 6mg/kg daily x 4-8 weeks

Tinea corporis:

  • 150-300 mg q week x 2-4 weeks

Tinea pedis

  • 150 mg q week 2-6 week

Candida

  • 150 mg / week for 2-4 weeks (single dose of 150 mg for Vaginal Candidiasis)

Pityriasis Versicolor

  • Single dose of 400 mg or 200-300 mg weekly for 2-3 weeks

  • Triazoles inhibit lanosterol 14α demethylase leading to decreased ergosterol synthesis (impaired cell wall & arrested cell growth) “fungistatic”

  • Skin: through sweat & direct diffusion & accumulates in stratum corneum (half-life 60-90 hours 🡪 explains why we can give as weekly doses)
  • Nails: through nail bed
  • Hair: unclear but detectable in hair
  • Bioavailability: > 90%
  • Half-life > 30 hours
  • Crosses blood-brain-barrier
  • Not affected by food
  • Minimal first-pass liver metabolism
  • Renal excretion (80%)

FDA

  • Mucosal (vaginal, esophageal & oropharyngeal)
  • Prophylaxis for systemic candida (e.g. in transplant patients)
  • Cryptococcal meningitis

Off-label

  • Other candida (cutaneous, mucocutaneous, & onychomycosis), dermatophyte onychomycosis, tinea (cruris, pedis an&d capitis), pityriasis versicolor, Pityrosporum folliculitis, sporotrichosis

Absolute

  • Hypersensitivity
  • Drugs that prolong QT

Relative

  • Any risk factors for QT prolongation
  • Liver disease, transaminitis, prior liver insult
  • Renal failure (caution)

Common

  • Headache, nausea, vomiting, abdominal pain, diarrhea, transaminitis, elevated liver enzymes (especially AST)

Dermatologic

  • Steven Johnson/Toxic epidermal necrolysis, angioedema, erythema multiforme

Rare

  • Hepatotoxicity

Inhibits CYP2C9 (potent)

  • Increasing levels of: warfarin, antidepressants, anticonvulsants, statins

Inhibits CYP3A4 (moderate)

  • Increasing levels of:
    • cyclosporine, statins, benzos, dapsone, antipsychotics, warfarin, colchicine

  • Liver function tests before starting treatment (ALT, AST)
  • Symptoms to monitor include nausea, anorexia, fatigue, vomiting, abdominal pain: discontinue & do complete liver profile