Fluconazole

Azole Antifungal (triazole)
Inhibits fungal CYP450 enzymes
Inhibits sterol demethylation
1. Blocks the synthesis of plasma membrane steroids (conversion from lanosterol to ergosterol)
2. Results in plasma membrane damage

See below for Thrush dosing in infants
Tinea Versicolor
1. Adult: 400 mg orally for one dose (or 300 mg orally once weekly for 2 weeks)
Yeast Vaginitis
1. Adult: 150 mg orally for one dose
2. Recurrent in Adults
  1. Start: 150 mg orally every third day for 3 doses
  2. Next: 150 mg orally weekly for up to 6 months

See Cryptococcal Meningitis
Oropharyngeal Candidiasis (Thrush)
1. Adult: 200 mg orally on Day 1, then 100 mg orally/IV daily for 14 days
2. Child: 6 mg/kg (up to 200 mg) orally/IV on Day 1, then 3 mg/kg (up to 100 mg) orally daily for 14 days
Esophageal Candidiasis
1. Start: 6 mg/kg (up to 200 mg) orally/IV on Day 1
2. Next: 3 mg/kg (up to 100 mg) orally/IV daily for 21 days (and at least 2 weeks after resolution)
3. May require increased dose up to 12 mg/kg (up to 200 to 400 mg) daily
Systemic Candidiasis
1. Start: 12 mg/kg (up to 800 mg) orally/IV on day 1
2. Next: 6 to 12 mg/kg (up to 400 mg) orally/IV daily
3. Continue for 14 days after Blood Culture negative AND symptoms resolved
Candida Pyelonephritis
1. Dose: 3 to 6 mg/kg (up to 200 to 400 mg) IV or orally daily for 14 days
Candida prophylaxis in severe Neutropenia
1. Adult: 400 mg orally/IV daily until severe Neutropenia resolves
Coccidioidomycosis Treatment and Prophylaxis in HIV Infection
1. Adult: 400 mg orally/IV daily

GFR <50 ml/min
1. Give initial loading dose (up to 400 mg)
2. Decrease maintenance dose to 50% of recommended dose
Hemodialysis
1. Give 100% of recommended dose after each Hemodialysis run
2. Give 50% of recommended dose on non-Hemodialysis days

Largely replaced by other systemic Antifungals
Tinea Capitis
1. Daily: 6 mg/kg/day (up to 150 mg to 300 mg) daily for 3 to 6 weeks OR
2. Weekly: 6 mg/kg/day (up to 150 mg to 300 mg) weekly for 8 to 12 weeks
Onychomycosis
1. Adult: 150 to 300 mg (up to 450 mg) orally once per week
2. Child: 3 to 6 mg/kg once weekly
3. Course
  1. Fingernail: 3-6 months
  2. Toenail: 6-12 months

Excellent oral Bioavailability
1. Not significantly affected by Antacid-induced higher gastric pH
2. Peak oral concentrations at 1-2 hours are similar to IV administration
Long Elimination Half-Life: 30 hours
Distribution
1. Penetrates cerebrospinal fluid (CSF) with concentrations reaching 50 to 90% of serum concentrations
2. Also penetrates eye and urine
Metabolism and excretion
1. Hepatic metabolism
2. Excreted unchanged in urine (80%)

General
1. Absorption not affected by gastric pH
2. CYP2C9 Inhibitor (strong)
3. CYP2C19 Inhibitor (strong)
4. CYP3A4 Inhibitor (moderate)
Avoid with drugs that Drugs That Prolong the QTc Interval
INCREASES levels of other agents
1. Alfentanil
2. Benzodiazepines (significant sedation)
3. Calcium Channel Blockers
4. Celecoxib
5. Cyclosporine
6. Fentanyl
7. Florbiprofen
8. Fluvastatin (limit to max of 20 mg/day)
9. Losartan
10. Lovastatin
11. Methadone
12. Phenytoin
13. Rifabutin
14. Simvastatin
15. Sirolimus
16. Sulfonylureas (e.g. Glyburide, Glipizide, Hypoglycemia risk)
17. Tacrolimus
18. Theophylline
19. Tofacitinib (limit to max of 5 mg)
20. Tolbutamide
21. Warfarin (bleeding risk)
Fluconazole levels DECREASED by other agents
1. Cimetidine
2. Rifampin
Fluconazole levels INCREASED by other agents
1. Hydrochlorothiazide

Onychomycosis or Yeast Vaginitis
1. No routine lab tests recommended
Some guidelines have recommended baseline labs
1. Complete Blood Count (CBC)
2. Liver transaminases (AST, ALT)
3. Serum Creatinine