Voriconazole
VFEND
What it isTriazole inhibiting fungal CYP51; invasive aspergillosis.
Why this oneIt is first-line for invasive aspergillosis and penetrates the CNS and eye.
What limits itNon-linear kinetics with CYP2C19 variation demanding level monitoring. Visual disturbance, photosensitivity with skin cancer, and periostitis.
FDA-approved for
- aspergillosis (2002)
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Invasive aspergillosis | adult | 6 mg/kg IV q12h x24h (load) | 4 mg/kg IV q12h or 200 mg PO BID | 4 mg/kg IV q12h |
| Candidemia / deep-tissue Candida | adult | 3-4 mg/kg IV q12h | 3-4 mg/kg IV q12h or 200 mg PO BID | 4 mg/kg IV q12h |
| Scedosporiosis and Fusariosis | adult | 4 mg/kg IV q12h | 4 mg/kg IV q12h or 200 mg PO BID | 4 mg/kg IV q12h |
| Esophageal candidiasis | adult | 200 mg PO BID | 200 mg PO BID | 200 mg PO BID |
| Invasive fungal infections | pediatric 2-<12y | 9 mg/kg IV q12h x24h (load) | 8 mg/kg IV q12h or 9 mg/kg PO BID (max 350 mg) | 9 mg/kg PO BID (max 350 mg) |
Renal Avoid IV formulation if CrCl <50 mL/min (moderate-severe) due to vehicle accumulation
Hepatic Use half the maintenance dose in mild-moderate impairment (Child-Pugh A/B)
Instructions
- Correct potassium, magnesium, and calcium before treatment
- Evaluate liver function at start of and during therapy
- Avoid direct sunlight (photosensitivity)
Contraindications
- CYP3A4-substrate drugs with serious/life-threatening toxicity at elevated levels (e.g., pimozide, quinidine, ergot alkaloids, sirolimus, lurasidone, ivabradine, naloxegol, tolvaptan, eplerenone, finerenone, venetoclax [CLL/SLL ramp-up], voclosporin)
- Strong CYP450 inducers that reduce voriconazole levels (rifampin, rifabutin, carbamazepine, long-acting barbiturates, St. John's Wort, high-dose efavirenz, high-dose ritonavir)
Cautions
- Hepatic toxicity
- Arrhythmias and QT prolongation
- Infusion-related reactions (incl. anaphylaxis)
- Visual disturbances (incl. optic neuritis, papilledema)
- Severe cutaneous adverse reactions
- Photosensitivity
- Adrenal dysfunction
- Renal toxicity
Adverse reactions
- Visual disturbances
- Fever
- Nausea
- Rash
- Vomiting
- Chills
- Headache
- Abnormal liver function tests
- Tachycardia
- Hallucinations
Pregnancy Can cause fetal harm (animal malformations)
Lactation Undefined
NO BOXED WARNINGS
Principal riskNon-linear kinetics needing level monitoring; visual disturbance
Cost, est. cash$20–$1,500/dose or month
Generic entry2010
Classes and tags
Clinical profile
Legacy pregnancy categoryD
Defining liabilityHepatotoxicity, visual/neuropsychiatric effects, QT risk and extensive CYP interactions.
Mechanism of action: Voriconazole ballicule
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Multi-CYP inhibitor
