DangerousContraindicated
St. John's Wort
St. John's Wort can induce drug-metabolizing enzymes and transporters and may lower Voriconazole exposure or undermine therapy.
Recommendation: Avoid St. John's Wort with Voriconazole.
Voriconazole
Prescription ·Strong evidence ·Reviewed May 2026
Voriconazole is a second-generation triazole antifungal used as first-line therapy for invasive aspergillosis and for serious infections caused by Candida, Scedosporium, and Fusarium species. It is available as oral tablets, an oral suspension, and an intravenous formulation, with high oral bioavailability. Because it is extensively metabolized by hepatic cytochrome P450 enzymes and shows nonlinear, saturable pharmacokinetics, drug interactions and interpatient variability are clinically significant and often require therapeutic drug monitoring.
What it's good for
- First-line treatment of invasive aspergillosis2
- Treatment of candidemia in non-neutropenic patients and other deep tissue Candida infections
- Treatment of esophageal candidiasis
- Treatment of serious infections caused by Scedosporium apiospermum and Fusarium species
What to watch for
- Visual disturbances (blurred vision, altered or enhanced visual perception, photophobia, color vision changes)
- Elevated liver enzymes and hepatotoxicity
- Photosensitivity and increased risk of skin cancer with long-term use
- Hypersensitivity to voriconazole or other azole antifungals1,2
- Coadministration with CYP3A4 substrates that can cause QT prolongation (terfenadine, astemizole, cisapride, pimozide, quinidine)
The bottom line
Evidence rating strong. Most-documented uses: first-line treatment of invasive aspergillosis, treatment of candidemia in non-neutropenic patients and other deep tissue candida infections, treatment of esophageal candidiasis. 4 sources indexed (2002–2021), with 5 interaction records on file.
The science
How it works, mechanistically.
Core mechanism
Voriconazole inhibits the fungal cytochrome P450-dependent enzyme lanosterol 14-alpha-demethylase (encoded by ERG11/CYP51), which catalyzes a key step in the biosynthesis of ergosterol, the principal sterol of the fungal cell membrane. Blocking this enzyme depletes ergosterol and causes accumulation of toxic 14-alpha-methylated sterol precursors, disrupting membrane structure and function and inhibiting fungal growth. It is more selective for fungal than mammalian P450 enzymes, though its inhibition of human CYP2C19, CYP2C9, and CYP3A4 underlies many of its drug interactions.4,1
Class
Triazole antifungal
Absorption
Best on an empty stomach
Dosing
Dosing & protocol.
Common range
IV loading dose 6 mg/kg every 12 hours for 2 doses, then 4 mg/kg IV every 12 hours; oral maintenance 200 mg every 12 hours (may increase to 300 mg every 12 hours) for patients 40 kg or more, or 100 mg every 12 hours (up to 150 mg every 12 hours) for patients under 40 kg. Doses are individualized and frequently guided by trough therapeutic drug monitoring (target trough roughly 1 to 5.5 mg/L).
Recommended form
Oral tablet or IV infusion; oral doses taken at least 1 hour before or 1 hour after a meal
Oral bioavailability is high (about 96 percent) but is reduced when taken with food, especially high-fat meals. Voriconazole should be taken at least 1 hour before or 1 hour after a meal to optimize absorption. Absorption is not pH-dependent, so it does not require gastric acid.
Depletions
What it depletes.
Nutrients this medication can lower over time, and what to replace.
Potassium
ModerateHypokalemia is a recognized adverse effect listed in voriconazole prescribing information and reported in clinical use. It commonly arises in the context of seriously ill antifungal-treated patients, frequently alongside concurrent nephrotoxic or potassium-wasting agents (for example amphotericin B or loop diuretics). Low potassium is clinically important because voriconazole prolongs the QT interval, and hypokalemia compounds the risk of torsades de pointes.
Replace Potassium chloride (only under clinician guidance with monitoring; do not self-supplement potassium)Monitor Serum potassiumOnset Days to weeks during a course of therapy; risk is greatest in critically ill patients and those on concomitant potassium-depleting drugs.
Magnesium
MildHypomagnesemia is reported during voriconazole therapy, often co-occurring with hypokalemia and frequently driven by concurrent therapies such as amphotericin B, proton pump inhibitors, or critical illness rather than a direct, well-characterized depletion mechanism of voriconazole itself. Because low magnesium impairs correction of potassium and independently increases QT-prolongation and arrhythmia risk, it is relevant to monitor during treatment.
Replace Magnesium (oral repletion such as magnesium glycinate, or IV magnesium sulfate in the inpatient setting; under clinician guidance)Monitor Serum magnesiumOnset Days to weeks during therapy, particularly with co-administered magnesium-wasting agents.
Safety
Full safety detail.
Side effects
- Visual disturbances (blurred vision, altered or enhanced visual perception, photophobia, color vision changes)
- Elevated liver enzymes and hepatotoxicity
- Photosensitivity and increased risk of skin cancer with long-term use
- Skin rash, including rare severe reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
- QT interval prolongation
- Visual and auditory hallucinations
- Nausea, vomiting, and headache
- Peripheral neuropathy with prolonged therapy
- Fluoride excess and periostitis with long-term use
- Infusion-related reactions with IV administration
Contraindications
- Hypersensitivity to voriconazole or other azole antifungals1,2
- Coadministration with CYP3A4 substrates that can cause QT prolongation (terfenadine, astemizole, cisapride, pimozide, quinidine)
- Coadministration with potent CYP3A4 inducers (rifampin, rifabutin, carbamazepine, long-acting barbiturates, St. John's wort) that markedly lower voriconazole levels
- Coadministration with sirolimus, efavirenz (standard doses), ergot alkaloids, ritonavir (high dose), or naloxegol
- IV formulation use in moderate to severe renal impairment due to accumulation of the cyclodextrin vehicle (use caution)2
Interactions
Interaction records.
ModerateCaution
Green Tea Extract
Concentrated green tea extract has been associated with liver injury, which can complicate use of hepatotoxic drugs such as Voriconazole.
Recommendation: Avoid high-dose green tea extract during therapy or use only with clinician review, especially if liver enzymes are abnormal or symptoms of hepatitis occur.
ModerateCaution
Berberine
Berberine may inhibit CYP enzymes or P-glycoprotein and could increase voriconazole adverse effects in susceptible patients.
Recommendation: Avoid high-dose berberine unless the prescriber is monitoring voriconazole response and toxicity.
ModerateCaution
Milk Thistle
Milk thistle (silymarin) has been reported to modulate CYP3A4 and CYP2C9 activity in some experimental settings, and these enzymes contribute to voriconazole metabolism. Although clinical pharmacokinetic effects are modest and inconsistent, patients sometimes take milk thistle for liver support precisely when voriconazole, a drug associated with hepatotoxicity, is in use. Combining a marginally active herbal CYP modulator with a narrow-therapeutic-window antifungal warrants attention, especially since voriconazole levels are highly variable and routinely monitored.
Recommendation: Tell your prescriber if you take milk thistle while on voriconazole. It is not strictly prohibited, but voriconazole already requires therapeutic drug monitoring and liver function testing, so disclose the supplement so trough levels and LFTs can be interpreted correctly. Do not start or stop milk thistle abruptly during therapy without informing the team.
ModerateCaution
Ginkgo Biloba
Ginkgo biloba has been reported to modestly induce CYP2C19 in some pharmacokinetic studies, and CYP2C19 is a major pathway for voriconazole metabolism (with large genetic variability among individuals). Concurrent ginkgo could lower voriconazole concentrations in some patients, contributing to subtherapeutic antifungal exposure. Ginkgo also has antiplatelet activity, which is a separate consideration in patients who may be thrombocytopenic from infection or chemotherapy.
Recommendation: Avoid ginkgo biloba during voriconazole therapy unless your prescriber approves it. If it cannot be avoided, ensure voriconazole trough levels are monitored, since reduced concentrations risk antifungal failure. Report any unusual bruising or bleeding.
Sources
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Randomized controlled trials
2- 1Therapeutic drug monitoring of voriconazole: a prospective randomized controlled trialNeeds reviewPMIDPark WB, Kim NH, Kim KH, et al. · Clinical Infectious Diseases · 2012
Routine therapeutic drug monitoring reduced drug discontinuation due to adverse events and improved treatment response compared with no monitoring.
- 2Voriconazole versus amphotericin B for primary therapy of invasive aspergillosisNeeds reviewPMIDHerbrecht R, Denning DW, Patterson TF, et al. · New England Journal of Medicine · 2002
Initial therapy with voriconazole led to better responses (52.8 percent vs 31.6 percent) and improved survival compared with amphotericin B in invasive aspergillosis.
Reviews & position papers
1- 3Clinical pharmacokinetics and pharmacodynamics of voriconazoleNeeds reviewPMIDTheuretzbacher U, Ihle F, Derendorf H · Clinical Pharmacokinetics · 2006
Voriconazole shows nonlinear pharmacokinetics due to saturable metabolism, with CYP2C19 polymorphisms contributing to large interpatient exposure variability.
Reference material
1- 4VFEND (voriconazole) US Prescribing InformationNeeds reviewNo linkPfizer Inc. · FDA Label · 2021
Voriconazole acts primarily by inhibiting fungal cytochrome P450-mediated 14-alpha-lanosterol demethylation, an essential step in ergosterol biosynthesis.
Keep exploring
Deep dives & adjacent profiles.
This page is educational. Do not start, stop, or change a supplement or medication based on it without checking with a qualified healthcare professional.
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