VFEND
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VFEND (VFEND).
Inhibits fungal cytochrome P450 14α-demethylase (CYP51), blocking ergosterol synthesis and disrupting fungal cell membrane integrity.
| Metabolism | Hepatic via CYP2C19 (major), CYP3A4, and CYP2C9 (minor); major metabolite is voriconazole N-oxide. |
| Excretion | Primarily hepatic metabolism; <2% excreted unchanged in urine. Fecal excretion accounts for ~80% of metabolites. Renal excretion of unchanged drug is negligible. |
| Half-life | Terminal half-life is approximately 24 hours (range 12–30 h) in adults. Prolonged in hepatic impairment (Child-Pugh A: 48 h; B: 72 h). |
| Protein binding | Approximately 58% bound to serum albumin. |
| Volume of Distribution | Volume of distribution at steady state is 4.6 L/kg (range 3–7 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 96% (fasting). Reduced to 65% with high-fat meal, but still >90% in most patients. |
| Onset of Action | IV: Rapid distribution, but clinical response typically seen within 24–48 hours. Oral: Peak concentrations reached in 1–2 hours; clinical effect onset similar to IV after loading doses. |
| Duration of Action | Dosing interval is 12 hours after loading. Clinical effect persists throughout the dosing interval with twice-daily dosing. |
| Molecular Weight | 349.3 |
| Action Class | Fungal ergosterol synthesis inhibitor |
| Brand Substitutes | Voriways Tablet, Verz 200mg Tablet, Voritrol 200 Tablet, Vorilong 200mg Tablet, Vosicaz Tablet, Vorific 200mg Injection, Voritrop 200mg Injection, Rextro 200mg Injection, Verz 200 Injection, Vorzu 200mg Injection, Voritek 50mg Tablet, Vorizef 50mg Tablet, Voritrol 50mg Tablet, Rextro 50mg Tablet, Verz 50mg Tablet |
IV: Loading dose of 6 mg/kg every 12 hours for 2 doses, then 4 mg/kg every 12 hours. Oral: Weight ≥40 kg: Loading dose of 400 mg every 12 hours for 2 doses, then 200 mg every 12 hours; weight <40 kg: Loading dose of 200 mg every 12 hours for 2 doses, then 100 mg every 12 hours.
| Dosage form | FOR SUSPENSION |
| Renal impairment | IV formulation: Avoid in patients with CrCl <50 mL/min due to accumulation of sulfobutyl ether beta-cyclodextrin (SBECD). Oral: No adjustment needed for renal impairment. |
| Liver impairment | Child-Pugh Class A and B: Standard loading dose, then reduce maintenance dose by 50%. Child-Pugh Class C: Use with caution; data insufficient for specific recommendation. |
| Pediatric use | IV: Age ≥2 years: Loading dose of 9 mg/kg every 12 hours for 2 doses, then 8 mg/kg every 12 hours. Oral: Age ≥2 years: Loading dose of weight-based regimen (varies), then 9 mg/kg every 12 hours (maximum 350 mg every 12 hours). |
| Geriatric use | No specific dose adjustment; monitor renal function as elderly often have decreased CrCl. Consider avoiding IV if CrCl <50 mL/min. |
| 1st trimester | Teratogenic in animal studies; associated with skeletal and cardiovascular malformations. Avoid use unless no alternative. |
| 2nd trimester | Known teratogen; risk of fetal harm outweighs benefits in most cases. Use only for life-threatening infections. |
| 3rd trimester | Continued risk; monitor for fetal effects. Use only if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for VFEND (VFEND).
| Placental transfer | Crosses placenta in animals; likely in humans. Associated with fetal malformations. |
| Breastfeeding | Excreted into breast milk in animal studies; unknown in humans. Due to potential for serious adverse reactions (hepatotoxicity, visual disturbances), avoid breastfeeding or discontinue drug. |
■ FDA Black Box Warning
QT prolongation and torsades de pointes: Voriconazole is contraindicated with drugs that prolong QT interval and with potent CYP3A4 inducers (rifampin, carbamazepine, phenytoin, barbiturates). Visual hallucinations, hepatotoxicity, and severe photosensitivity have been reported.
| Serious Effects |
Hypersensitivity to voriconazole or any excipientCoadministration with CYP3A4 substrates that prolong QT interval (e.g., terfenadine, astemizole, cisapride, pimozide, quinidine)Coadministration with sirolimusCoadministration with rifampin, carbamazepine, long-acting barbiturates, efavirenz (if voriconazole dose not adjusted)Coadministration with ergot alkaloids
| Precautions | Hepatotoxicity (monitor LFTs), visual disturbances (including photophobia and blurred vision; monitor visual function), QT prolongation, severe cutaneous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), photosensitivity (UV exposure risk), pancreatitis, renal effects (cumulative exposure with IV vehicle SBECD), adrenal insufficiency, drug interactions (potent CYP inducers/inhibitors), and teratogenicity (pregnancy category D). |
| Food/Dietary |
Loading safety data…
| Lactation Rating |
| L5 - Contraindicated |
| Teratogenic Risk | Pregnancy Category D. First trimester: skeletal abnormalities, cleft palate; second and third trimester: potential fetal harm due to placental transfer. |
| Fetal Monitoring | Monitor LFTs, renal function, electrolytes (K, Mg, Ca), and ECG for QT prolongation. Assess fetal growth and development via ultrasound. |
| Fertility Effects | No adequate human data; animal studies show reduced fertility at high doses. Potential for reversible hormonal disturbances. |
| Avoid high-fat meals when taking oral voriconazole as they decrease absorption. Grapefruit and grapefruit juice should be avoided as they can increase voriconazole levels and toxicity. No other specific food restrictions. |
| Clinical Pearls | Voriconazole (VFEND) distributes extensively into tissues, including the central nervous system and vitreous humor. Monitor liver function tests regularly due to hepatotoxicity risk; consider therapeutic drug monitoring (target trough 1-5.5 mg/L). Note non-linear pharmacokinetics: dose adjustment between oral and intravenous forms is not 1:1. Avoid in patients with CYP2C19 poor metabolizers (especially Asian populations) due to elevated exposure. Administer IV formulation without a filter (or use a 0.2-micron filter if necessary). |
| Patient Advice | Take voriconazole exactly as prescribed; do not skip doses or stop without consulting your doctor. · Take each dose at least 1 hour before or 1 hour after a meal to ensure proper absorption. · Avoid direct sunlight and use sun protection; this medication can make your skin sensitive to UV light and increase risk of sunburn or skin cancer. · Report any signs of liver problems (yellowing of skin or eyes, dark urine, pale stools, severe nausea, vomiting, abdominal pain) or visual disturbances (blurred vision, sensitivity to light, changes in color vision) immediately. · Do not drive at night or perform hazardous activities if you experience visual changes; avoid driving altogether during nighttime. · Inform your doctor of all other medications you take, including over-the-counter drugs and supplements, as many interactions exist. · Do not take with St. John's wort, rifampin, carbamazepine, or long-acting barbiturates. |