Azole antifungal (triazole; CYP2C19/CYP2C9/CYP3A4 inhibitor)
Voriconazole is an antifungal used for serious fungal infections, especially invasive aspergillosis in immunocompromised patients. It is very effective, but requires close monitoring: it affects vision, the liver and interacts with many medicines.
Also known as: Vfend, Voriconazol
Carbamazepine (a CYP450 inducer) markedly reduces Voriconazole levels, risking antifungal failure.
The interaction is bidirectional and practically contraindicated: voriconazole inhibits CYP3A4 and can raise carbamazepine to toxic levels, while carbamazepine strongly induces CYP3A4 (and other pathways) and reduces voriconazole concentrations to subtherapeutic levels, with risk of antifungal failure. The combination should be avoided; if unavoidable, consider another antifungal (e.g. amphotericin B, echinocandins) or another antiepileptic, with close monitoring of levels and response.
Voriconazole + carbamazepine: voriconazole raises carbamazepine levels (CYP3A4 inhibition) and carbamazepine markedly reduces voriconazole levels (induction). Avoid the combination.
CYP3A4/CYP2C19 induction by carbamazepine accelerates voriconazole elimination.
Voriconazole levels, mycological response, liver function tests.
Persistent or worsening fungal infection.
Avoid the combination; if unavoidable, monitor voriconazole levels and clinical response, adjusting the dose.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Voriconazole potentiates the effect of Glyburide (Glibenclamide), with a risk of hypoglycaemia.
Glyburide is metabolised by CYP2C9 (and CYP3A4), and voriconazole inhibits CYP2C9 and CYP3A4: the combination raises the sulfonylurea concentrations and the risk of hypoglycaemia — a mechanism analogous to that documented with fluconazole (glyburide AUC +44% and 5 of 20 volunteers requiring oral glucose in the fluconazole label study). Voriconazole also prolongs the QT and can cause hepatotoxicity. Monitor glycaemia closely at the start of the combination and whenever the antifungal dose changes, warn the patient about hypoglycaemia signs (sweating, tremor, palpitations, confusion) and consider reducing the glyburide dose.
Glyburide + voriconazole: voriconazole inhibits CYP2C9 and raises glyburide levels. Monitor glycaemia and adjust the sulfonylurea dose.
CYP2C9 inhibition by voriconazole reduces glibenclamide metabolism.
Capillary glucose, hypoglycaemia symptoms.
Severe hypoglycaemia.
Monitor blood glucose; a sulfonylurea dose reduction may be needed.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Glyburide (Glibenclamide) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Rifampin (a potent inducer) markedly reduces Voriconazole levels, with a high risk of therapeutic failure.
Voriconazole is metabolised by CYP2C19 and CYP3A4; rifampicin, a potent inducer of both pathways, can reduce its concentrations to nearly undetectable values, with loss of antifungal effect. The combination is practically contraindicated; if unavoidable, consider another antifungal (liposomal amphotericin B, echinocandins) and monitor voriconazole levels if available.
Voriconazole + rifampicin: rifampicin markedly reduces voriconazole levels (CYP3A4/CYP2C19 induction), with antifungal failure. Practically contraindicated.
Potent CYP3A4/CYP2C19 induction by rifampin strongly accelerates voriconazole elimination.
Clinical and mycological response; consider level monitoring.
Antifungal treatment failure (invasive fungal infection).
Avoid the combination (considered contraindicated). Use an alternative antifungal when tuberculosis coexists.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Rifampin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Omeprazole raises Voriconazole levels (CYP2C19 inhibition) and voriconazole raises omeprazole levels.
The interaction is bidirectional and mediated by CYP2C19: voriconazole inhibits CYP2C19 and can raise omeprazole concentrations (Cmax ≈2× and AUC ≈4× per the voriconazole label), while omeprazole increases voriconazole exposure by about 15% (Cmax) and 40% (AUC). The voriconazole label recommends halving the omeprazole dose when starting voriconazole in patients on omeprazole ≥40 mg (no voriconazole dose adjustment needed). In practice, monitor the adverse effects of both (headache, diarrhoea, PPI hypomagnesaemia; voriconazole photosensitivity, hepatotoxicity and visual disturbances) and consider voriconazole therapeutic drug monitoring.
Omeprazole + voriconazole: bidirectional interaction — voriconazole raises omeprazole (2–4×) and omeprazole increases voriconazole (~15–40%). Halve the omeprazole dose.
Bidirectional CYP2C19 interaction: omeprazole inhibits voriconazole metabolism; voriconazole inhibits omeprazole metabolism.
Voriconazole levels (if available), liver function tests, visual effects.
Photophobia, visual disturbances, elevated transaminases.
Monitor voriconazole response and adverse effects; consider reducing the voriconazole dose with long-term use.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37291cab-e350-d8e3-e063-6294a90a9cb1
Voriconazole raises Sildenafil concentrations (CYP3A4 inhibition), with a risk of hypotension and adverse effects.
Sildenafil is metabolised by CYP3A4, and voriconazole is a strong inhibitor of this enzyme: the sildenafil label recommends "considering a starting dose of 25 mg in patients treated with strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, saquinavir) or erythromycin". Voriconazole also prolongs the QT (the label states that "some azoles, including voriconazole, have been associated with prolongation of the QT interval" and recommends correcting potassium, magnesium and calcium before use), and sildenafil at high levels can cause hypotension, headache, flushing and visual disturbances. Use the lowest effective sildenafil dose (not exceeding 25 mg), space the doses, monitor blood pressure and signs of hypotension.
Sildenafil + voriconazole: voriconazole inhibits CYP3A4 and raises sildenafil levels. Consider a 25 mg starting dose; watch hypotension and QT.
CYP3A4 inhibition by voriconazole increases sildenafil exposure.
Blood pressure, headache, flushing, palpitations.
Hypotension, syncope.
Limit the sildenafil dose during voriconazole therapy; monitor blood pressure.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Sildenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00ee09dd-2de0-4dc4-85f6-b51ed6eabd5b
Voriconazole raises Atorvastatin levels, with a risk of myopathy and rhabdomyolysis.
Voriconazole inhibits CYP3A4 and can raise atorvastatin concentrations, increasing the risk of myopathy/rhabdomyolysis, especially in prolonged antifungal courses (e.g., invasive aspergillosis) or with renal impairment. The atorvastatin label recommends considering the risk/benefit of combination with other azole antifungals (including voriconazole), monitoring muscle symptoms and CK, and using the lowest effective statin dose. Instruct the patient to stop in the presence of muscle pain, weakness or dark urine. In patients on prolonged antifungal therapy, periodically reassess the need for and the dose of the statin.
Atorvastatin + voriconazole: the azole inhibits CYP3A4 and can raise statin levels. Monitor for myopathy and consider dose reduction.
CYP3A4 inhibition by voriconazole reduces atorvastatin metabolism.
Creatine kinase (CK), myalgia, weakness.
Severe muscle pain, dark urine.
Watch for muscle symptoms and CK; consider an alternative statin or reduced dose.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86841382-4229-4e03-958e-3ac22639efd4 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Voriconazole plus Amiodarone carries a risk of QT prolongation and ventricular arrhythmias.
Voriconazole is a moderate-to-potent CYP3A4 inhibitor and reduces amiodarone clearance, potentially raising its concentrations; both drugs prolong the QT interval, so the torsades de pointes risk increases additively. The combination should be avoided in patients with AF or other arrhythmias; if unavoidable (invasive aspergillosis in a patient on amiodarone), reduce the amiodarone dose, monitor the ECG and electrolytes and watch for adverse effects during and after antifungal treatment.
Voriconazole + amiodarone: voriconazole inhibits CYP3A4 and may raise amiodarone levels; both prolong the QT. Avoid the combination.
Additive effect on cardiac repolarization.
ECG (QT interval), electrolytes, signs of arrhythmia.
Syncope, palpitations, torsades de pointes.
Use with caution; monitor ECG (QT) and electrolytes (K+, Mg2+).
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Voriconazole plus Quinine carries a risk of QT prolongation and arrhythmias.
Voriconazole is an azole antifungal associated with QT prolongation (the label states that "some azoles, including voriconazole, have been associated with prolongation of the QT interval on the ECG" and recommends correcting potassium, magnesium and calcium before use) and is a CYP3A4 inhibitor; quinine is predominantly metabolised by CYP3A4 and its label warns that "CYP3A4 inhibitors alter plasma quinine concentration — monitor for lack of efficacy or increased adverse events of quinine" (the class is documented: ketoconazole increased quinine AUC by 45%). The combination adds up the two risks: additive QT (potentially fatal ventricular arrhythmias) and increased quinine levels (cinchonism, cardiotoxicity, hypoglycaemia). Avoid whenever possible; if unavoidable, monitor the ECG, electrolytes and signs of quinine toxicity.
Quinine + voriconazole: additive QT and increased quinine levels (CYP3A4 inhibition). Avoid; if unavoidable, ECG and monitoring.
Additive effect on cardiac repolarization.
ECG (QT interval), electrolytes (K+, Mg2+).
Syncope, palpitations, torsades de pointes.
Use with caution; monitor ECG (QT) and electrolytes.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0
Voriconazole raises Amlodipine levels (CYP3A4 inhibition), with a risk of hypotension and oedema.
Amlodipine is metabolised by CYP3A4 and the label states that "co-administration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction" (with diltiazem, a moderate inhibitor, exposure increased by 60%). Voriconazole is a strong CYP3A4 inhibitor, so the combination raises amlodipine levels and its dose-dependent effects: hypotension, peripheral oedema, flushing, headache and dizziness, especially in the elderly. Monitor blood pressure and signs of relative overdose; if the combination is needed, consider starting with a lower amlodipine dose or reducing it, monitoring the patient in the first weeks.
Amlodipine + voriconazole: voriconazole inhibits CYP3A4 and raises amlodipine levels. Watch hypotension and oedema; consider a dose reduction.
CYP3A4 inhibition by voriconazole reduces amlodipine metabolism.
Blood pressure, peripheral oedema.
Symptomatic hypotension, significant oedema.
Monitor blood pressure and oedema; consider a reduced amlodipine dose.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Amlodipine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=58a67272-c4c7-4e2c-85a5-9d39034d12c3 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Voriconazole potentiates the anticoagulant effect of Warfarin, raising the INR and the bleeding risk.
Voriconazole inhibits CYP2C9 (which metabolises active S-warfarin) and CYP3A4, with a clinically relevant documented effect: studies at therapeutic doses showed substantial increases in the INR and warfarin exposure when voriconazole is added. The voriconazole label recommends INR monitoring and warfarin dose adjustment. The interaction is particularly relevant in patients with invasive aspergillosis, often already in a fragile clinical state. Monitor the INR frequently at voriconazole initiation and discontinuation and watch for bleeding signs.
Voriconazole inhibits CYP2C9/CYP3A4 and can markedly raise the INR. Monitor the INR closely and consider a warfarin dose reduction.
CYP2C9 inhibition by voriconazole reduces warfarin metabolism.
INR, signs of bleeding.
Unexplained bleeding, melena.
Monitor the INR frequently; adjust the warfarin dose as needed.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Voriconazole may raise Digoxin concentrations, with a risk of digitalis toxicity.
Voriconazole inhibits P-glycoprotein and can reduce digoxin elimination, raising its concentrations and the risk of digitalis toxicity. The voriconazole label recommends monitoring digoxin levels when they are co-administered. The interaction is particularly relevant in immunocompromised patients with invasive fungal infections, often on multiple drugs. Monitor digoxin levels when voriconazole is started and stopped, watch the ECG and digitalis toxicity symptoms and adjust the digoxin dose if needed.
Voriconazole inhibits P-gp and can raise digoxin levels. Monitor digoxin levels and toxicity signs.
Possible P-glycoprotein and metabolic inhibition, reducing digoxin elimination.
Digoxin levels, ECG, gastrointestinal and visual symptoms.
Nausea, vomiting, arrhythmias, xanthopsia.
Monitor digoxin levels and clinical signs; reduce the dose if needed.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4
Voriconazole raises Prednisolone levels (CYP3A4 inhibition), with a risk of enhanced corticosteroid effects.
Voriconazole inhibits CYP3A4, the enzyme that metabolises corticosteroids, and the voriconazole label states that this inhibition can lead to corticosteroid excess and adrenal suppression, with Cushing syndrome (with or without subsequent adrenal insufficiency) reported in patients receiving voriconazole concomitantly with corticosteroids; careful monitoring for adrenal dysfunction during and after voriconazole treatment is recommended, and patients should be instructed to seek immediate medical care if signs of Cushing or adrenal insufficiency appear (fatigue, hypotension, hyperpigmentation, weight loss). Consider reducing the corticosteroid dose and monitor metabolic effects (glycaemia, fluid retention).
Prednisolone + voriconazole: the azole inhibits CYP3A4 and can cause corticosteroid excess, Cushing and adrenal suppression. Monitor closely.
CYP3A4 inhibition by voriconazole reduces prednisolone metabolism.
Blood glucose, blood pressure, signs of iatrogenic Cushing.
Oedema, hyperglycaemia, Cushingoid facies.
Watch for corticosteroid effects; adjust the steroid dose if overdosage signs occur.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Prednisolone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52e6e21d-94b8-41a0-8d13-371c0e66bcee — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Alcohol increases the risk of voriconazole hepatotoxicity.
Avoid alcohol during treatment.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c620b2d7-3c2b-4252-8cfc-2f322d624435
Grapefruit inhibits CYP3A4 and can raise voriconazole concentrations, increasing the risk of hepatotoxicity and visual effects.
Avoid grapefruit juice during treatment.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c620b2d7-3c2b-4252-8cfc-2f322d624435
Voriconazole causes severe photosensitivity, with risk of skin lesions and squamous cell carcinoma on prolonged exposure.
Avoid sun exposure and use protection (clothing and sunscreen) during and after treatment.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c620b2d7-3c2b-4252-8cfc-2f322d624435
Voriconazole is hepatotoxic and levels rise in hepatic impairment; requires monitoring and dose adjustment.
Monitor transaminases; adjust the dose in mild-to-moderate hepatic impairment.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c620b2d7-3c2b-4252-8cfc-2f322d624435
Voriconazole is teratogenic and embryotoxic in animals; contraindicated in pregnancy.
Contraindicated in pregnancy; use effective contraception during treatment.
Excreted into breast milk; avoid while breastfeeding.
Advise effective contraception during treatment.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c620b2d7-3c2b-4252-8cfc-2f322d624435
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Broad-spectrum triazole antifungal. Non-linear pharmacokinetics with high inter-individual variability: increasing the oral dose from 200 mg every 12 hours to 300 mg every 12 hours increases exposure (AUC) about 2.5-fold. Median average and maximum plasma concentrations of 2.51 and 3.79 mcg/mL in clinical trials; pharmacokinetic-pharmacodynamic analyses identified positive associations between concentrations and liver function test abnormalities and visual disturbances. QTc prolongation below 10 ms at doses up to 1600 mg.
It inhibits the synthesis of ergosterol, an essential component of the fungal cell membrane, by blocking the cytochrome P450-dependent enzyme (lanosterol 14α-demethylase). The main metabolite, voriconazole N-oxide, has minimal antifungal activity and does not contribute to efficacy.
Oral bioavailability of about 96%; peak plasma concentrations occur 1 to 2 hours after dosing. High-fat meals reduce Cmax and AUC by 34% and 24% (tablet). Absorption is not affected by ranitidine, cimetidine or omeprazole. Without a loading dose, steady state is reached by day 6 in most patients.
Metabolised in the liver by CYP2C19, CYP2C9 and CYP3A4, with relevant genetic polymorphism of CYP2C19 (poor metabolisers reach higher exposures). Less than 2% of the dose is excreted unchanged in the urine; 80 to 83% of the radioactivity is recovered in the urine, more than 94% within the first 96 hours. Systemic exposure increases about 3.2-fold in mild to moderate hepatic impairment.
The terminal half-life is dose-dependent (non-linear pharmacokinetics), so it is not useful for predicting accumulation or elimination; the volume of distribution is about 4.6 L/kg and plasma protein binding about 58%.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
