-
Voriconazole coadministration
- Resistant fungal strains
- Candida krusei
- Candida glabrata (some strains)
- Aspergillosis
- Fusarium
- Mucorales or Zygomycetes (e.g. Mucor species, Rhizopus species)
-
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
- Oral Tablets: 50, 100, 150, 200 mg
- Suspension 10 mg/ml, 40 mg/ml
- 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
- 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
- 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
- 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
- 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)
- Brachycephaly
- Cleft Palate
- Congenital Heart Disease
- 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%)
-
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
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