II. Indications
- Onychomycosis
- Candida Infections
- Yeast Vaginitis
- Systemic Candidiasis
- Oropharyngeal Candidiasis (Thrush)
- Candida Esophagitis
- Candida Pyelonephritis
- Systemic fungal infections (esp. Immunocompromised patients, Neutropenia, HIV Infection)
- Coccidioidomycosis
- Cryptococcosis
- Other Fluconazole activity
- Histoplasmosis (variable activity)
- Blastomycosis
- Sporotrichosis
III. Contraindications
- Voriconazole coadministration
- Resistant fungal strains
- Candida krusei
- Candida glabrata (some strains)
- Aspergillosis
- Fusarium
- Mucorales or Zygomycetes (e.g. Mucor species, Rhizopus species)
IV. Mechanism
- Azole Antifungal (triazole)
- Inhibits fungal CYP450 enzymes
- Inhibits sterol demethylation
- Blocks the synthesis of plasma membrane steroids (conversion from lanosterol to ergosterol)
- Results in plasma membrane damage
V. Medications
- Oral Tablets: 50, 100, 150, 200 mg
- Suspension 10 mg/ml, 40 mg/ml
VI. Dosing: Common Indications in Immunocompetent Patients
- See below for Thrush dosing in infants
-
Tinea Versicolor
- Adult: 400 mg orally for one dose (or 300 mg orally once weekly for 2 weeks)
-
Yeast Vaginitis
- Adult: 150 mg orally for one dose
- Recurrent in Adults
- Start: 150 mg orally every third day for 3 doses
- Next: 150 mg orally weekly for up to 6 months
VII. Dosing: Indications in Immunocompromised Patients
- See Cryptococcal Meningitis
- Oropharyngeal Candidiasis (Thrush)
- Adult: 200 mg orally on Day 1, then 100 mg orally/IV daily for 14 days
- 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
- Start: 6 mg/kg (up to 200 mg) orally/IV on Day 1
- Next: 3 mg/kg (up to 100 mg) orally/IV daily for 21 days (and at least 2 weeks after resolution)
- May require increased dose up to 12 mg/kg (up to 200 to 400 mg) daily
- Systemic Candidiasis
- Start: 12 mg/kg (up to 800 mg) orally/IV on day 1
- Next: 6 to 12 mg/kg (up to 400 mg) orally/IV daily
- Continue for 14 days after Blood Culture negative AND symptoms resolved
- Candida Pyelonephritis
- Dose: 3 to 6 mg/kg (up to 200 to 400 mg) IV or orally daily for 14 days
- Candida prophylaxis in severe Neutropenia
- Adult: 400 mg orally/IV daily until severe Neutropenia resolves
-
Coccidioidomycosis Treatment and Prophylaxis in HIV Infection
- Adult: 400 mg orally/IV daily
VIII. Dosing: Renal
- GFR <50 ml/min
- Give initial loading dose (up to 400 mg)
- Decrease maintenance dose to 50% of recommended dose
-
Hemodialysis
- Give 100% of recommended dose after each Hemodialysis run
- Give 50% of recommended dose on non-Hemodialysis days
IX. Dosing: Other Historic Indications
- Largely replaced by other systemic Antifungals
-
Tinea Capitis
- Daily: 6 mg/kg/day (up to 150 mg to 300 mg) daily for 3 to 6 weeks OR
- Weekly: 6 mg/kg/day (up to 150 mg to 300 mg) weekly for 8 to 12 weeks
-
Onychomycosis
- Adult: 150 to 300 mg (up to 450 mg) orally once per week
- Child: 3 to 6 mg/kg once weekly
- Course
- Fingernail: 3-6 months
- Toenail: 6-12 months
X. Adverse Effects
- Common (5% of patients)
- Serious (uncommon to rare)
- Stevens Johnson Syndrome
- Anaphylaxis
- Leukopenia
- Hypokalemia
- QTc Prolongation (Torsades de Pointes risk)
- Hepatotoxicity
- Liver Function Test abnormalities
XI. Safety
- Considered safe in Lactation
- Pregnancy Category D
- Pregnancy Category C only at low dose (150 mg once) for Vaginal Candidiasis
- As of 2016, evidence of Miscarriage risk, with even 1-2 doses
- Previously thought safe in pregnancy if limited to occassional single dose
- Mølgaard-Nielsen (2016) JAMA 315(1):58-67 +PMID:26746458 [PubMed]
- Congenital abnormalities reported after higher dose first trimester exposure (400 to 800 mg/day)
- Pregnancy Category C only at low dose (150 mg once) for Vaginal Candidiasis
XII. Pharmacokinetics
- Excellent oral Bioavailability
- Not significantly affected by Antacid-induced higher gastric pH
- Peak oral concentrations at 1-2 hours are similar to IV administration
- Long Elimination Half-Life: 30 hours
- Distribution
- Penetrates cerebrospinal fluid (CSF) with concentrations reaching 50 to 90% of serum concentrations
- Also penetrates eye and urine
- Metabolism and excretion
- Hepatic metabolism
- Excreted unchanged in urine (80%)
XIII. Drug Interactions
-
General
- Absorption not affected by gastric pH
- CYP2C9 Inhibitor (strong)
- CYP2C19 Inhibitor (strong)
- CYP3A4 Inhibitor (moderate)
- Avoid with drugs that Drugs That Prolong the QTc Interval
- INCREASES levels of other agents
- Alfentanil
- Benzodiazepines (significant sedation)
- Calcium Channel Blockers
- Celecoxib
- Cyclosporine
- Fentanyl
- Florbiprofen
- Fluvastatin (limit to max of 20 mg/day)
- Losartan
- Lovastatin
- Methadone
- Phenytoin
- Rifabutin
- Simvastatin
- Sirolimus
- Sulfonylureas (e.g. Glyburide, Glipizide, Hypoglycemia risk)
- Tacrolimus
- Theophylline
- Tofacitinib (limit to max of 5 mg)
- Tolbutamide
- Warfarin (bleeding risk)
- Fluconazole levels DECREASED by other agents
- Fluconazole levels INCREASED by other agents
XIV. Monitoring
-
Onychomycosis or Yeast Vaginitis
- No routine lab tests recommended
- Some guidelines have recommended baseline labs
- Complete Blood Count (CBC)
- Liver transaminases (AST, ALT)
- Serum Creatinine
XV. Resources
- Fluconazole Tablet or Suspension (DailyMed)
- Fluconazole IV Solution (DailyMed)
XVI. References
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
- Olson (2020) Clinical Pharmacology, Medmaster, Miami, Fl, p. 120-1
- (2012) Med Lett Drugs Ther 10(120): 61-8 [PubMed]
- (1990) Med Lett Drugs Ther 32(818): 50 to 52 [PubMed]
- Desai (1996) Am Fam Physician 54(4):1337-46 [PubMed]
- Ely (2014) Am Fam Physician 90(10): 702-10 [PubMed]
- Gupta (1999) J Am Acad Dermatol 41:237-49 [PubMed]
- Friedlander (1999) Pediatr Infect Dis J 18(2):205-10 [PubMed]
- Wildfeuer (1997) Mycoses 40:259-65 [PubMed]
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fluconazole (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
FLUCONAZOLE 10 MG/ML SUSP | Generic | $0.27 per ml |
FLUCONAZOLE 100 MG TABLET | Generic | $0.28 each |
FLUCONAZOLE 150 MG TABLET | Generic | $0.55 each |
FLUCONAZOLE 200 MG TABLET | Generic | $0.46 each |
FLUCONAZOLE 40 MG/ML SUSP | Generic | $0.49 per ml |
FLUCONAZOLE 50 MG TABLET | Generic | $0.29 each |