Posaconazole

Second-generation systemic triazole antifungal

ATC code: J02AC04

Brand names: Noxafil

Updated 4 Jun 2026 · Methodology

Indications

Invasive aspergillosis

First line

Posaconazole is first-line antifungal for invasive aspergillosis and mucormycosis in haematological cancer patients and after solid organ or haematopoietic stem cell transplantation. ESCMID and SEIMC 2022 recommend either posaconazole or voriconazole as first choice. Posaconazole shows lower hepatotoxicity and neurological adverse rates than voriconazole. Use requires blood-level monitoring (target ≥1 mcg/mL) and liver function checks.

Sources

ICD-10: B44.0 · ICD-11: 1F20.0

Refractory systemic mycoses

First line

Treats refractory systemic mycoses including mucormycosis, fusariosis, coccidioidomycosis and chromoblastomycosis. SEIMC positions posaconazole as first-line for mucormycosis after liposomal amphotericin B.

Sources

ICD-10: B49 · ICD-11: 1F2Z

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

Inhibits fungal lanosterol 14-alpha-demethylase (CYP51), blocking ergosterol synthesis and disrupting cell membrane integrity. Active against Aspergillus spp. (including many fluconazole-resistant strains), Candida spp. (including C. glabrata and C. krusei), Mucorales and endemic dimorphic fungi. High lipophilicity supports tissue accumulation. Posaconazole itself strongly inhibits CYP3A4 and P-glycoprotein, raising levels of most co-administered drugs.

Safety

Contraindications

Co-administration with ergotamine, dihydroergotamine and other ergot alkaloids – fatal ergotism
Co-administration with simvastatin, lovastatin – rhabdomyolysis
Co-administration with sirolimus – fatal immunosuppression
Co-administration with pimozide, quinidine, cisapride – torsades de pointes
Hypersensitivity to posaconazole or other azoles

Serious adverse effects

Hepatotoxicity up to acute liver failure
QT prolongation and torsades de pointes
Anaphylaxis
Severe skin reactions (Stevens-Johnson syndrome)

Common adverse effects

Nausea, vomiting, diarrhoea
Liver transaminase rise
Headache
Hypokalaemia
Rash

Pregnancy: can you take Posaconazole?

Pregnancy data are limited. EMA advises use only when benefit outweighs risk; animal studies showed embryotoxicity.

Breastfeeding: can you take Posaconazole?

Passes into breast milk. Breastfeeding during therapy is not recommended.

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Drug–drug interactions

10 pairs found. Sorted from critical to minor.

CriticalAtorvastatinHMG-CoA reductase inhibitors (statins)

Mechanism

Posaconazole is a strong CYP3A4 inhibitor. Atorvastatin rises 3-4 fold.

Symptoms

Myalgia, weakness, dark urine, rising CK within 5-10 days.

Management

The AEMPS label for posaconazole lists the combination with atorvastatin as contraindicated. The label caps atorvastatin at 10 mg/day instead. For the posaconazole course, pause the statin or switch to pravastatin or rosuvastatin, which do not depend on CYP3A4.

Sources

Pair details →Atorvastatin →

CriticalErgotamineErgot alkaloid, 5-HT1B/1D and alpha-adrenoceptor agonist

Mechanism

Posaconazole is a strong CYP3A4 inhibitor. Noxafil Section 4.3 strict contraindication.

Symptoms

Fatal ergotism.

Management

Combination contraindicated.

Sources

Pair details →Ergotamine →

CriticalEverolimusmTOR kinase inhibitor – immunosuppressant and antineoplastic

Mechanism

Strong CYP3A4 inhibitor. Everolimus rises 9-fold.

Symptoms

Immunosuppression, nephrotoxicity.

Management

Combination contraindicated.

Sources

Pair details →Everolimus →

CriticalPimozideFirst-generation antipsychotic, diphenylbutylpiperidine derivative

Mechanism

Posaconazole is a strong CYP3A4 inhibitor. Pimozide rises, torsades risk. Orap Section 4 + Noxafil Section 4.3.

Symptoms

QT prolongation within 5 days.

Management

Combination contraindicated. Hold pimozide for the entire course.

Sources

Pair details →Pimozide →

CriticalQuinidineClass Ia antiarrhythmic (sodium channel blocker with intermediate kinetics)

Mechanism

Posaconazole strongly inhibits the liver enzyme CYP3A4 (posaconazole label), and the liver clears quinidine mainly through this enzyme (US quinidine label). As a result, posaconazole raises quinidine plasma levels, which prolongs the QT interval on the electrocardiogram and can cause torsade de pointes (posaconazole labels). Quinidine itself prolongs the QT interval in a dose-related way, and cases of torsade de pointes have been reported with posaconazole. The posaconazole label also lists quinidine among drugs that inhibit posaconazole clearance and may raise its levels. The documents give no numbers for this pair. The US quinidine label reports that quinidine levels rise with ketoconazole, another azole antifungal.

Symptoms

The main danger is QT interval prolongation on the electrocardiogram, torsade de pointes and other ventricular arrhythmias up to ventricular fibrillation (posaconazole and quinidine labels). The risk is higher with a slow heart rate, low potassium, magnesium or calcium and high quinidine levels, but the arrhythmia can occur without any of these (US quinidine label). Excess quinidine causes low blood pressure, vomiting, diarrhoea, tinnitus, hearing loss, vertigo, blurred or double vision, headache and confusion (US quinidine label). An arrhythmia attack shows as sudden strong palpitations, dizziness or fainting.

Management

The combination is contraindicated (posaconazole label, European Medicines Agency, ; posaconazole label, US Food and Drug Administration, ). Quinidine is named in the contraindications, including in the generic posaconazole label (Spanish Agency of Medicines and Medical Devices, AEMPS). The FDA posaconazole label contraindicates posaconazole with all drugs that are broken down by the enzyme CYP3A4 and prolong the QT interval. Use posaconazole with caution in people with a prolonged QT interval, cardiomyopathy (especially with heart failure), sinus bradycardia or existing symptomatic arrhythmias (posaconazole label, EMA). Check potassium, magnesium and calcium and correct them as needed before and during posaconazole treatment (posaconazole labels, EMA and FDA). The QT interval on the electrocardiogram is a better guide to quinidine safety than its blood level (quinidine label, FDA). In haemodynamically unstable torsade de pointes, stop quinidine and perform immediate cardioversion or overdrive pacing, and actively correct low potassium, magnesium and calcium (quinidine label, FDA).

Sources

Pair details →Quinidine →

CriticalSimvastatinHMG-CoA reductase inhibitors (statins)

Mechanism

Posaconazole is a strong CYP3A4 inhibitor. Simvastatin rises 10+ fold, rhabdomyolysis risk. Noxafil Section 4.3.

Symptoms

Rhabdomyolysis within 5–10 days.

Management

Combination contraindicated. Pravastatin or rosuvastatin.

Sources

Pair details →Simvastatin →

CriticalSirolimusSelective immunosuppressant, mTOR inhibitor

Mechanism

Posaconazole strongly inhibits CYP3A4, the enzyme that clears sirolimus. In the posaconazole SmPC (Noxafil), repeated posaconazole doses raised sirolimus Cmax a mean 6.7-fold and AUC 8.9-fold, with a range of 3.1 to 17.5-fold. The posaconazole label lists sirolimus as a contraindication. The does not recommend the combination and asks to avoid it whenever possible.

Symptoms

Rising creatinine, thrombocytopenia, hepatotoxicity within 5 days.

Management

The combination is not used. If a transplant patient on sirolimus needs posaconazole, a transplant specialist reviews the immunosuppressive regimen. For unavoidable co-administration the posaconazole SmPC advises a large immediate cut in the sirolimus dose and very frequent trough monitoring: at baseline, during co-administration and when posaconazole stops. If the patient is switched to tacrolimus, its dose also depends on posaconazole: per the SmPC it is reduced to about one third of the current dose and then adjusted by blood levels.

Sources

Pair details →Sirolimus →

CriticalVincristineVinca alkaloid, microtubule assembly inhibitor

Mechanism

Same CYP3A4 + P-gp pharmacodynamics. Fatal neurotoxicity.

Symptoms

Severe neuropathy.

Management

Combination contraindicated.

Sources

Pair details →Vincristine →

MajorCiclosporinImmunosuppressants. Calcineurin inhibitors

Mechanism

Strong CYP3A4 inhibitor. Cyclosporine rises 1.4-fold.

Symptoms

Nephrotoxicity.

Management

Reduce cyclosporine by 25%.

Sources

Pair details →Ciclosporin →

MajorTacrolimusCalcineurin inhibitor (immunosuppressant)

Mechanism

Posaconazole is a strong CYP3A4 inhibitor. Tacrolimus rises 4-5 fold.

Symptoms

Nephrotoxicity, tremor.

Management

Reduce tacrolimus by 67%, check blood level on days 3-5.

Sources

Pair details →Tacrolimus →

Label mentions90 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

CriticalAtorvastatin
«Administración concomitante con los inhibidores de la HMG-CoA reductasa simvastatina, lovastatina y atorvastatina (ver sección 4.5).»
AEMPS, section 4.3 · Open on CIMA
CriticalAtorvastatin
«HMG-CoA Reductase Inhibitors Primarily Metabolized Through CYP3A4: Coadministration with the HMG-CoA reductase inhibitors that are primarily metabolized through CYP3A4 (e.g., atorvastatin…»
FDA, section 4 · Open on DailyMed
CriticalCisapride
«Administración concomitante con los sustratos del CYP3A4 terfenadina, astemizol, cisaprida, pimozida, halofantrina o quinidina, dado que esto puede causar un aumento en las concentraciones…»
AEMPS, section 4.3 · Open on CIMA
CriticalDihydroergotamine
«Alcaloides del ergot: Posaconazol puede aumentar la concentración plasmática de los alcaloides del ergot (ergotamina y dihidroergotamina), que pueden dar lugar a ergotismo. La administración…»
AEMPS, section 4.5 · Open on CIMA
CriticalDihydroergotamine
«Use with Ergot Alkaloids: Posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see Drug Interactions (7.2) ] .»
FDA, section 4 · Open on DailyMed
CriticalErgotamine
«Alcaloides del ergot: Posaconazol puede aumentar la concentración plasmática de los alcaloides del ergot (ergotamina y dihidroergotamina), que pueden dar lugar a ergotismo. La administración…»
AEMPS, section 4.5 · Open on CIMA
CriticalErgotamine
«Use with Ergot Alkaloids: Posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see Drug Interactions (7.2) ] .»
FDA, section 4 · Open on DailyMed
CriticalLovastatin
«Administración concomitante con los inhibidores de la HMG-CoA reductasa simvastatina, lovastatina y atorvastatina (ver sección 4.5).»
AEMPS, section 4.3 · Open on CIMA
CriticalLovastatin
«HMG-CoA Reductase Inhibitors Primarily Metabolized Through CYP3A4: Coadministration with the HMG-CoA reductase inhibitors that are primarily metabolized through CYP3A4 (e.g., atorvastatin…»
FDA, section 4 · Open on DailyMed
CriticalPimozide
«Administración concomitante con los sustratos del CYP3A4 terfenadina, astemizol, cisaprida, pimozida, halofantrina o quinidina, dado que esto puede causar un aumento en las concentraciones…»
AEMPS, section 4.3 · Open on CIMA
CriticalPimozide
«CONTRAINDICATIONS: • CYP3A4 substrates (pimozide, quinidine): can result in QTc interval prolongation and cases of torsades de pointes (TdP) ( 4.3 , 5.2 , 7.2 )»
FDA, section 4 · Open on DailyMed
CriticalQuinidine
«Administración concomitante con los sustratos del CYP3A4 terfenadina, astemizol, cisaprida, pimozida, halofantrina o quinidina, dado que esto puede causar un aumento en las concentraciones…»
AEMPS, section 4.3 · Open on CIMA
CriticalQuinidine
«CONTRAINDICATIONS: • CYP3A4 substrates (pimozide, quinidine): can result in QTc interval prolongation and cases of torsades de pointes (TdP) ( 4.3 , 5.2 , 7.2 )»
FDA, section 4 · Open on DailyMed
CriticalSimvastatin
«Administración concomitante con los inhibidores de la HMG-CoA reductasa simvastatina, lovastatina y atorvastatina (ver sección 4.5).»
AEMPS, section 4.3 · Open on CIMA
CriticalSimvastatin
«HMG-CoA Reductase Inhibitors Primarily Metabolized Through CYP3A4: Coadministration with the HMG-CoA reductase inhibitors that are primarily metabolized through CYP3A4 (e.g., atorvastatin…»
FDA, section 4 · Open on DailyMed
CriticalSirolimus
«CONTRAINDICATIONS: • Coadministration of posaconazole with the following drugs is contraindicated; posaconazole increases concentrations and toxicities of: • Sirolimus: ( 4.2 , 7.2 )»
FDA, section 4 · Open on DailyMed
MajorAtazanavir
«Posaconazol es un potente inhibidor del CYP3A4. La administración concomitante de posaconazol con sustratos de CYP3A4 puede causar aumentos importantes en la exposición a sustratos de CYP3A4 tal y…»
AEMPS, section 4.5 · Open on CIMA
MajorCarbamazepine
«Fenitoína: Fenitoína (200 mg una vez al día) disminuyó la C máx y el AUC de posaconazol en un 41 % y un 50 %, respectivamente. Se debe evitar el uso concomitante de posaconazol con fenitoína e…»
AEMPS, section 4.5 · Open on CIMA
MajorCiclosporin
«Ciclosporina: En pacientes con trasplante cardíaco con dosis estables de ciclosporina, 200 mg de posaconazol suspensión oral una vez al día aumentaron las concentraciones de ciclosporina, lo que…»
AEMPS, section 4.5 · Open on CIMA
MajorEfavirenz
«Efavirenz: Efavirenz (400 mg una vez al día) disminuyó la C máx y el AUC de posaconazol en un 45 % y un 50 %, respectivamente. Se debe evitar el uso concomitante de posaconazol con efavirenz salvo…»
AEMPS, section 4.5 · Open on CIMA
MajorEfavirenz
«DRUG INTERACTIONS: Rifabutin, phenytoin, efavirenz Avoid coadministration unless the benefit outweighs the risks ( 7.1 , 7.2 )»
FDA, section 7 · Open on DailyMed
Majorestatinasclass named in the label
«Administración concomitante con los inhibidores de la HMG-CoA reductasa simvastatina, lovastatina y atorvastatina (ver sección 4.5).»
AEMPS, section 4.3 · Open on CIMA
Majormedicamentos que prolongan el QTclass named in the label
«Administración concomitante con los sustratos del CYP3A4 terfenadina, astemizol, cisaprida, pimozida, halofantrina o quinidina, dado que esto puede causar un aumento en las concentraciones…»
AEMPS, section 4.3 · Open on CIMA
MajorPhenobarbital
«Fenitoína: Fenitoína (200 mg una vez al día) disminuyó la C máx y el AUC de posaconazol en un 41 % y un 50 %, respectivamente. Se debe evitar el uso concomitante de posaconazol con fenitoína e…»
AEMPS, section 4.5 · Open on CIMA
MajorPhenytoin
«Fenitoína: Fenitoína (200 mg una vez al día) disminuyó la C máx y el AUC de posaconazol en un 41 % y un 50 %, respectivamente. Se debe evitar el uso concomitante de posaconazol con fenitoína e…»
AEMPS, section 4.5 · Open on CIMA
MajorPhenytoin
«DRUG INTERACTIONS: Rifabutin, phenytoin, efavirenz Avoid coadministration unless the benefit outweighs the risks ( 7.1 , 7.2 )»
FDA, section 7 · Open on DailyMed
MajorRifabutin
«Rifabutina: Rifabutina (300 mg una vez al día) disminuyó la C máx (concentración plasmática máxima) y el AUC (área bajo la curva temporal de concentración plasmática) de posaconazol al 57 % y 51 %…»
AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

CriticalDronedarone
«Administración conjunta con inhibidores potentes del citocromo P 450 (CYP) 3A4 como ketoconazol, itraconazol, voriconazol, posaconazol, telitromicina, claritromicina, nefazodona y ritonavir (ver…»
AEMPS, section 4.3 · Open on CIMA
CriticalLovastatin
«CONTRAINDICATIONS: Concomitant administration with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir…»
FDA, section 4 · Open on DailyMed
CriticalRanolazine
«Administración concomitante de inhibidores potentes del CYP3A4 (p.ej. itraconazol, ketoconazol, voriconazol, posaconazol, inhibidores de la proteasa del VIH, claritromicina, telitromicina…»
AEMPS, section 4.3 · Open on CIMA
CriticalSimvastatin
«posaconazol, voriconazol, inhibidores de la proteasa del VIH (p. ej. nelfinavir), boceprevir,»
AEMPS, section 4.3 · Open on CIMA
MajorAlprazolam
«No se recomienda la administración de alprazolam junto con ketoconazol, itraconazol, posaconazol, voriconazol y otros antifúngicos azólicos.»
AEMPS, section 4.5 · Open on CIMA
MajorApixaban
«Inhibidores del CYP3A4 y de la P ‑ gp: No se recomienda el uso de apixabán en los pacientes que reciban tratamiento sistémico concomitante con inhibidores potentes del CYP3A4 y de la P ‑ gp como los…»
AEMPS, section 4.5 · Open on CIMA
MajorAtorvastatin
«Inhibidores de la CYP3A4: Los inhibidores potentes de la CYP3A4 han demostrado que producen concentraciones notablemente elevadas de atorvastatina (ver Tabla 1 y la información específica a…»
AEMPS, section 4.5 · Open on CIMA
MajorBudesonide/formoterol
«Los inhibidores potentes del CYP3A4 (p. ej., ketoconazol, itraconazol, voriconazol, posaconazol, claritromicina, telitromicina, nefazodona e inhibidores de la proteasa del VIH) pueden incrementar…»
AEMPS, section 4.5 · Open on CIMA
MajorDarunavir
«Established and Other Potentially Significant Drug Interactions: Antifungals : itraconazole, isavuconazole, ketoconazole, posaconazole voriconazole  darunavir  itraconazole  isavuconazole …»
FDA, section 7 · Open on DailyMed
MajorEfavirenz
«Established and Other Potentially Significant Drug Interactions: Posaconazole ↓ posaconazole* Avoid concomitant use unless the benefit outweighs the risks.»
FDA, section 7 · Open on DailyMed
MajorFamotidine
«Si es posible, debe evitarse la administración conjunta de posaconazol en suspensión oral y famotidina, ya que la famotidina puede reducir la absorción de la suspensión oral de posaconazol durante el…»
AEMPS, section 4.5 · Open on CIMA
MajorOmeprazole
«Otros principios activos: La absorción de posaconazol, erlotinib, ketoconazol e itraconazol se reduce de forma significativa, por lo que pueden perder eficacia clínica. Se recomienda evitar la…»
AEMPS, section 4.5 · Open on CIMA
MajorOxycodone
«Los inhibidores de la CYP3A4, como los antibióticos macrólidos (p. ej., claritromicina, eritromicina y telitromicina), los antifúngicos azólicos (p. ej., ketoconazol, voriconazol, itraconazol y…»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Posaconazole used for?

Posaconazole is evaluated for the following indications with varying evidence strength: Refractory systemic mycoses (evidence tier A), Invasive aspergillosis (evidence tier A). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Posaconazole?

Common side effects of Posaconazole (≥ 1 in 100): Nausea, vomiting, diarrhoea, Liver transaminase rise, Headache, Hypokalaemia, Rash. See the Safety section for uncommon and serious reactions.

Is Posaconazole safe during pregnancy?

Pregnancy data are limited. EMA advises use only when benefit outweighs risk; animal studies showed embryotoxicity.

Is Posaconazole compatible with breastfeeding?

Passes into breast milk. Breastfeeding during therapy is not recommended.

Who should not take Posaconazole?

Posaconazole is contraindicated in: Co-administration with ergotamine, dihydroergotamine and other ergot alkaloids – fatal ergotism; Co-administration with simvastatin, lovastatin – rhabdomyolysis; Co-administration with sirolimus – fatal immunosuppression; Co-administration with pimozide, quinidine, cisapride – torsades de pointes; Hypersensitivity to posaconazole or other azoles. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 04/14/2025
FDA / DailyMedLabel dated 07/15/2026

Other drugs in this group

Amphotericin B, Fluconazole, Isavuconazole, Itraconazole, Ketoconazole, Voriconazole