DangerousContraindicated
St. John's Wort
St. John's Wort can induce drug-metabolizing enzymes and transporters and may lower Itraconazole exposure or undermine therapy.
Recommendation: Avoid St. John's Wort with Itraconazole.
Itraconazole
Prescription ·Strong evidence ·Reviewed May 2026
Itraconazole is a broad-spectrum triazole antifungal used to treat a range of systemic and superficial fungal infections, including aspergillosis, blastomycosis, histoplasmosis, onychomycosis (nail fungus), and oropharyngeal/esophageal candidiasis. It is fungistatic against most pathogens and is available as capsules, an oral solution, and a delayed-release/enhanced-bioavailability formulation. Its absorption and many of its drug interactions are clinically important: capsule absorption requires gastric acid, while the oral solution is best taken on an empty stomach.
What it's good for
- Treatment of onychomycosis (fungal nail infection) of the toenails and fingernails4,1
- Treatment of systemic mycoses including blastomycosis and histoplasmosis4
- Treatment of invasive and non-invasive aspergillosis in patients intolerant of or refractory to amphotericin B
- Treatment of oropharyngeal and esophageal candidiasis (oral solution)2
What to watch for
- Nausea, vomiting, diarrhea, and abdominal pain
- Headache and dizziness
- Hepatotoxicity and elevated liver enzymes (rarely serious liver injury)
- Coadministration with drugs that prolong the QT interval and are metabolized by CYP3A4 (e.g., cisapride, pimozide, quinidine, dofetilide), due to risk of serious cardiac arrhythmias4
- Coadministration with certain HMG-CoA reductase inhibitors metabolized by CYP3A4 (lovastatin, simvastatin) due to rhabdomyolysis risk4
The bottom line
Evidence rating strong. Most-documented uses: treatment of onychomycosis (fungal nail infection) of the toenails and fingernails, treatment of systemic mycoses including blastomycosis and histoplasmosis, treatment of invasive and non-invasive aspergillosis in patients intolerant of or refractory to amphotericin b. 4 sources indexed (2000–2018), with 7 interaction records on file.
The science
How it works, mechanistically.
Core mechanism
Itraconazole inhibits the fungal cytochrome P450 enzyme lanosterol 14-alpha-demethylase (encoded by ERG11/CYP51), which is required for the conversion of lanosterol to ergosterol. Blocking this step depletes ergosterol, an essential component of the fungal cell membrane, and causes accumulation of toxic methylated sterol precursors. The result is increased membrane permeability and disruption of membrane-bound enzyme function, inhibiting fungal growth. Itraconazole is also a potent inhibitor of human CYP3A4 and of P-glycoprotein, which underlies its extensive drug-interaction profile.4,1
Class
Triazole antifungal
Absorption
Fat-soluble; take with food
Dosing
Dosing & protocol.
Common range
Capsules: 200 mg once or twice daily for systemic mycoses; onychomycosis of toenails is typically 200 mg once daily for 12 weeks, or pulse dosing of 200 mg twice daily for 1 week per month for 2 (fingernails) to 3-4 (toenails) cycles. Oral solution: 100-200 mg daily for oral/esophageal candidiasis. Doses above 200 mg/day are usually divided twice daily.
Recommended form
Oral capsule (take with food and an acidic beverage) or oral solution (take on an empty stomach); formulation choice depends on indication
Itraconazole is highly lipophilic. Capsule absorption is enhanced by food and requires an acidic gastric environment, so capsules should be taken with a full meal and ideally an acidic beverage (such as a cola); acid-suppressing drugs (proton pump inhibitors, H2 blockers, antacids) markedly reduce capsule absorption. In contrast, the oral solution and certain enhanced-bioavailability capsules (e.g., Tolsura) are best absorbed on an empty stomach. Formulations are not interchangeable on a milligram-per-milligram basis.
Safety
Full safety detail.
Side effects
- Nausea, vomiting, diarrhea, and abdominal pain
- Headache and dizziness
- Hepatotoxicity and elevated liver enzymes (rarely serious liver injury)
- Edema and new or worsening congestive heart failure (negative inotropic effect)
- Hypokalemia
- Rash and pruritus
- Peripheral neuropathy (discontinue if it occurs)
- Transient or permanent hearing loss (reported)
Contraindications
- Coadministration with drugs that prolong the QT interval and are metabolized by CYP3A4 (e.g., cisapride, pimozide, quinidine, dofetilide), due to risk of serious cardiac arrhythmias4
- Coadministration with certain HMG-CoA reductase inhibitors metabolized by CYP3A4 (lovastatin, simvastatin) due to rhabdomyolysis risk4
- Coadministration with oral midazolam, triazolam, and certain ergot alkaloids2,4
- Use for treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure or a history of CHF3,1
- Coadministration with certain other CYP3A4 substrates per labeling (e.g., colchicine, eplerenone, fesoterodine in renal/hepatic impairment, and others)4
- Known hypersensitivity to itraconazole1,2
- Pregnancy when used for onychomycosis1,3
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 Itraconazole.
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 CYP3A4 or P-glycoprotein and could increase itraconazole intolerance in susceptible patients.
Recommendation: Avoid high-dose berberine unless the prescriber has reviewed the full medication list.
ModerateTiming Sensitive
Calcium
Calcium supplements, particularly calcium carbonate, raise gastric pH and can substantially reduce the dissolution and absorption of itraconazole capsules, which require an acidic stomach environment to dissolve. This may lead to subtherapeutic antifungal concentrations and treatment failure.
Recommendation: Separate calcium supplements from itraconazole capsules by at least 2 hours. Take itraconazole capsules with food and an acidic beverage (such as a cola) when possible. The oral solution and SUBA formulation are less pH-dependent and may be preferred if frequent calcium use is required. Discuss persistent infections with the prescriber.
ModerateTiming Sensitive
Iron
Oral iron salts are best absorbed in an acidic environment and are sometimes taken with antacids or co-administered with acid-reducing agents; more importantly, conditions and products that raise gastric pH impair itraconazole capsule absorption. Co-timing iron-containing multivitamin/antacid combinations with itraconazole can lower antifungal exposure.
Recommendation: Take itraconazole capsules with an acidic beverage and food, and separate from iron supplements (especially those formulated with calcium or buffering agents) by at least 2 hours. Monitor for signs of inadequate antifungal response.
SeriousConflict
St. John's Wort
St. John's Wort is a potent inducer of CYP3A4 and P-glycoprotein. Itraconazole is extensively metabolized by CYP3A4, so concomitant use markedly increases itraconazole clearance and can reduce plasma concentrations to subtherapeutic levels, risking antifungal treatment failure.
Recommendation: Avoid combining St. John's Wort with itraconazole. If an antidepressant or mood supplement was being used, discuss alternatives with the prescriber. Because enzyme induction persists for one to two weeks after stopping St. John's Wort, do not assume immediate normalization of itraconazole levels.
InfoCaution
Milk Thistle
Milk thistle (silymarin) has shown weak and inconsistent effects on CYP3A4 and P-glycoprotein in laboratory studies. While clinically significant interaction with itraconazole is unlikely at typical doses, milk thistle is often used by people with liver concerns, and itraconazole carries a risk of hepatotoxicity, so liver status warrants attention.
Recommendation: Routine concurrent use is generally acceptable, but monitor for symptoms of liver stress (nausea, dark urine, jaundice, right-upper-quadrant pain) during itraconazole therapy and report them promptly. Do not rely on milk thistle to prevent drug-induced liver injury.
Sources
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Randomized controlled trials
1- 1Continuous versus intermittent (pulse) itraconazole for the treatment of toenail onychomycosisNeeds reviewNo linkGupta AK, et al · Journal of the American Academy of Dermatology · 2000
Both continuous and pulse itraconazole regimens achieved clinical and mycological cure in dermatophyte toenail onychomycosis, with pulse dosing reducing total drug exposure.
Reviews & position papers
2- 2Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction and oral bioavailability of itraconazole formulationsNeeds reviewNo linkLindsay J, Mudge S, Thompson GR · Clinical Pharmacokinetics / Antimicrobial Agents and Chemotherapy · 2018
Itraconazole capsule bioavailability depends on an acidic gastric environment and food, while the cyclodextrin oral solution achieves higher and more reliable exposure when taken fasting.
- 3Itraconazole and congestive heart failure: a review of safety signalsNeeds reviewNo linkAhmad SR, Singer SJ, Leissa BG · Mayo Clinic Proceedings · 2001
Cases of congestive heart failure were associated with itraconazole, supporting a boxed warning and contraindication of itraconazole for onychomycosis in patients with ventricular dysfunction or CHF.
Reference material
1- 4Sporanox (itraconazole) Capsules US Prescribing InformationNeeds reviewNo linkJanssen Pharmaceuticals · FDA Label · 2018
Itraconazole is a triazole antifungal that inhibits ergosterol synthesis; capsule absorption requires gastric acidity and is enhanced by food, and the drug is a potent CYP3A4 inhibitor with multiple contraindicated coadministrations.
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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