Second-generation systemic triazole antifungal
ATC code: J02AC04 (Posaconazole)
Brand names
Noxafil
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.
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.
First line
Treats refractory systemic mycoses including mucormycosis, fusariosis, coccidioidomycosis and chromoblastomycosis. SEIMC positions posaconazole as first-line for mucormycosis after liposomal amphotericin B.
9 pairs found. Sorted from critical to minor.
Mechanism
Posaconazole is a strong CYP3A4 inhibitor. Noxafil Section 4.3 strict contraindication.
Symptoms
Fatal ergotism.
Management
Combination contraindicated.
Mechanism
Strong CYP3A4 inhibitor. Everolimus rises 9-fold.
Symptoms
Immunosuppression, nephrotoxicity.
Management
Combination contraindicated.
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.
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.
Mechanism
Posaconazole is a strong CYP3A4 inhibitor. Sirolimus rises 9-fold with severe immunosuppression. Noxafil Section 4.3 strict contraindication.
Symptoms
Rising creatinine, thrombocytopenia, hepatotoxicity within 5 days.
Management
Combination contraindicated. For invasive mycosis in transplant patient, switch sirolimus to tacrolimus with 75% dose reduction and frequent monitoring.
Mechanism
Same CYP3A4 + P-gp pharmacodynamics. Fatal neurotoxicity.
Symptoms
Severe neuropathy.
Management
Combination contraindicated.
Mechanism
Posaconazole is a strong CYP3A4 inhibitor. Atorvastatin rises 3-4 fold.
Symptoms
Myalgia, weakness, dark urine, rising CK within 5-10 days.
Management
Cap atorvastatin at 10 mg/day.
Sources
Mechanism
Strong CYP3A4 inhibitor. Cyclosporine rises 1.4-fold.
Symptoms
Nephrotoxicity.
Management
Reduce cyclosporine by 25%.
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.
Opens the checker prefilled with this drug. Pick the second one from your regimen.
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Pregnancy data are limited. EMA advises use only when benefit outweighs risk; animal studies showed embryotoxicity.
Passes into breast milk. Breastfeeding during therapy is not recommended.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
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.
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.
FDA category C. Pregnancy data are limited. EMA advises use only when benefit outweighs risk; animal studies showed embryotoxicity.
Passes into breast milk. Breastfeeding during therapy is not recommended.
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.