Fluconazole

Aka: Fluconazole, Diflucan

advertisement

II. Indications

  1. Onychomycosis
  2. Candida Infections
    1. Yeast Vaginitis
    2. Systemic Candidiasis
    3. Oropharyngeal Candidiasis (Thrush)
    4. Candida Esophagitis
    5. Candida Pyelonephritis
  3. Systemic fungal infections (esp. Immunocompromised patients, Neutropenia, HIV Infection)
    1. Coccidioidomycosis
    2. Cryptococcosis
  4. Other Fluconazole activity
    1. Histoplasmosis (variable activity)
    2. Blastomycosis
    3. Sporotrichosis

III. Contraindications

  1. Voriconazole coadministration
  2. Resistant fungal strains
    1. Candida krusei
    2. Candida glabrata (some strains)
    3. Aspergillosis
    4. Fusarium
    5. Mucorales or Zygomycetes (e.g. Mucor species, Rhizopus species)

IV. Mechanism

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

V. Medications

  1. Oral Tablets: 50, 100, 150, 200 mg
  2. Suspension 10 mg/ml, 40 mg/ml

VI. Dosing: Common Indications in Immunocompetent Patients

  1. See below for Thrush dosing in infants
  2. Tinea Versicolor
    1. Adult: 400 mg orally for one dose (or 300 mg orally once weekly for 2 weeks)
  3. 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

VII. Dosing: Indications in Immunocompromised Patients

  1. See Cryptococcal Meningitis
  2. 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
  3. 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
  4. 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
  5. Candida Pyelonephritis
    1. Dose: 3 to 6 mg/kg (up to 200 to 400 mg) IV or orally daily for 14 days
  6. Candida prophylaxis in severe Neutropenia
    1. Adult: 400 mg orally/IV daily until severe Neutropenia resolves
  7. Coccidioidomycosis Treatment and Prophylaxis in HIV Infection
    1. Adult: 400 mg orally/IV daily

VIII. Dosing: Renal

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

IX. Dosing: Other Historic Indications

  1. Largely replaced by other systemic Antifungals
  2. 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
  3. 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

X. Adverse Effects

  1. Common (5% of patients)
    1. Nausea
    2. Headache
    3. Pruritus
    4. Facial Edema
  2. Serious (uncommon to rare)
    1. Stevens Johnson Syndrome
    2. Anaphylaxis
    3. Leukopenia
    4. Hypokalemia
    5. QTc Prolongation (Torsades de Pointes risk)
    6. Hepatotoxicity
      1. Liver Function Test abnormalities

XI. Safety

  1. Considered safe in Lactation
  2. Pregnancy Category D
    1. Pregnancy Category C only at low dose (150 mg once) for Vaginal Candidiasis
      1. As of 2016, evidence of Miscarriage risk, with even 1-2 doses
      2. Previously thought safe in pregnancy if limited to occassional single dose
      3. Mølgaard-Nielsen (2016) JAMA 315(1):58-67 +PMID:26746458 [PubMed]
    2. Congenital abnormalities reported after higher dose first trimester exposure (400 to 800 mg/day)
      1. Brachycephaly
      2. Cleft Palate
      3. Congenital Heart Disease

XII. Pharmacokinetics

  1. 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
  2. Long Elimination Half-Life: 30 hours
  3. Distribution
    1. Penetrates cerebrospinal fluid (CSF) with concentrations reaching 50 to 90% of serum concentrations
    2. Also penetrates eye and urine
  4. Metabolism and excretion
    1. Hepatic metabolism
    2. Excreted unchanged in urine (80%)

XIII. Drug Interactions

  1. General
    1. Absorption not affected by gastric pH
    2. CYP2C9 Inhibitor (strong)
    3. CYP2C19 Inhibitor (strong)
    4. CYP3A4 Inhibitor (moderate)
  2. Avoid with drugs that Drugs That Prolong the QTc Interval
    1. Erythromycin
    2. Pimozide
    3. Quinidine
  3. 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)
  4. Fluconazole levels DECREASED by other agents
    1. Cimetidine
    2. Rifampin
  5. Fluconazole levels INCREASED by other agents
    1. Hydrochlorothiazide

XIV. Monitoring

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

XV. Resources

  1. Fluconazole Tablet or Suspension (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f694c617-3383-416c-91b6-b94fda371204
  2. Fluconazole IV Solution (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cd24a261-9c15-42b4-8040-89d2dbda174e

XVI. References

  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  2. Olson (2020) Clinical Pharmacology, Medmaster, Miami, Fl, p. 120-1
  3. (2012) Med Lett Drugs Ther 10(120): 61-8 [PubMed]
  4. (1990) Med Lett Drugs Ther 32(818): 50 to 52 [PubMed]
  5. Desai (1996) Am Fam Physician 54(4):1337-46 [PubMed]
  6. Ely (2014) Am Fam Physician 90(10): 702-10 [PubMed]
  7. Gupta (1999) J Am Acad Dermatol 41:237-49 [PubMed]
  8. Friedlander (1999) Pediatr Infect Dis J 18(2):205-10 [PubMed]
  9. Wildfeuer (1997) Mycoses 40:259-65 [PubMed]

Images: Related links to external sites (from Bing)

These images are a random sampling from a Bing search on the term "Fluconazole." Click on the image (or right click) to open the source website in a new browser window. Search Bing for all related images

Related Studies

Cost: Medications

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
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

Related Topics in Pharmacology

advertisement