VFEND

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VFEND (VFEND).

How it works

Inhibits fungal cytochrome P450 14α-demethylase (CYP51), blocking ergosterol synthesis and disrupting fungal cell membrane integrity.

What the body does with it

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.

Classification & Brands

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

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VFEND (VFEND).

Breastfeeding	Excreted in human milk; M/P ratio not determined. Avoid breastfeeding due to potential adverse effects (QT prolongation, hepatotoxicity).
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to voriconazole or excipients, coadministration with CYP3A4 substrates that prolong QT (e.g., terfenadine, astemizole, cisapride, pimozide, quinidine, ivabradine), potent CYP3A4 inducers (rifampin, rifabutin, carbamazepine, long-acting barbiturates, efavirenz, ritonavir, ranolazine, ergot alkaloids, St. John's wort). Coadministration with sirolimus is contraindicated.

Clinical Precautions

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).

Clinical Tips & Counseling

Drug interactions

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VFEND

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VFEND (VFEND).

How it works

Inhibits fungal cytochrome P450 14α-demethylase (CYP51), blocking ergosterol synthesis and disrupting fungal cell membrane integrity.

What the body does with it

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.

Classification & Brands

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

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VFEND (VFEND).

Breastfeeding	Excreted in human milk; M/P ratio not determined. Avoid breastfeeding due to potential adverse effects (QT prolongation, hepatotoxicity).
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.