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Extended-Spectrum Triazole — Aspergillus / Mucor / Prophylaxis in Immunocompromised Pregnancy: Avoid — teratogenic in animal studies; alternative antifungal in pregnancy

Posaconazole

Brand names: Noxafil

Adult dose

Dose: Prophylaxis (GvHD/AML): 300 mg IV/oral once daily after loading (300 mg BD day 1); Treatment of refractory aspergillosis: 300 mg IV/oral once daily; Mucormycosis: 300 mg once daily (after stabilisation on amphotericin)
Route: Oral tablet, oral suspension, or IV infusion
Frequency: Once daily (modified-release tablets and IV); suspension: 200 mg 3 times daily with food
Max: 300 mg/day (tablet/IV); 600 mg/day (suspension)
IMPORTANT formulation hierarchy: modified-release tablet = IV (preferred) > oral suspension. Oral suspension requires high-fat food and acid for absorption — unreliable in mucositis patients; switch to tablet or IV in high-risk patients. Broadest spectrum triazole — unique Mucor/Rhizopus coverage (Mucormycosis/Zygomycosis).

Paediatric dose

Route:
Seek specialist opinion — modified-release tablet/IV not licensed under 18 years; suspension used off-label in specialist paediatric ID/oncology centres

Dose adjustments

Renal

IV formulation: avoid if CrCl <50 mL/min (sulfobutylether-beta-cyclodextrin vehicle accumulates); oral tablet: no dose adjustment

Hepatic

Use with caution — hepatically metabolised; monitor LFTs

Clinical pearls

  • Mucormycosis (Rhizopus, Mucor): posaconazole is the only azole active against Mucorales — used as step-down from liposomal amphotericin B after stabilisation; not first-line (amphotericin preferred for induction)
  • EORTC MSG trial: posaconazole prophylaxis in AML/MDS patients reduced invasive fungal infections and overall mortality vs fluconazole/itraconazole
  • Modified-release tablet: dramatically improved bioavailability vs suspension — absorption no longer food-dependent; preferred formulation when patient can swallow tablets
  • Sirolimus interaction is absolute — check for sirolimus before prescribing; if concurrent, switch sirolimus or use alternative antifungal

Contraindications

  • Concurrent ergotamine, sirolimus (markedly increases sirolimus to toxic levels)
  • Concurrent rifampicin or other potent CYP3A4 inducers
  • QT prolongation/concurrent QT-prolonging drugs
  • Hypersensitivity to azole antifungals

Side effects

  • Nausea and vomiting
  • Hepatotoxicity (elevated LFTs)
  • QTc prolongation
  • Hypokalaemia
  • Headache
  • Rash
  • Hypertension

Interactions

  • Sirolimus — absolute contraindication (10× increase in sirolimus levels — toxicity)
  • Cyclosporin — increased levels (reduce dose 25%, monitor levels)
  • Rifampicin/rifabutin — significantly reduce posaconazole levels — avoid
  • Statins — increased levels
  • Warfarin — enhanced INR
  • Midazolam — increased benzodiazepine levels (2–6×)

Monitoring

  • Posaconazole trough levels (target >0.7 mg/L prophylaxis; >1 mg/L treatment)
  • LFTs weekly during loading then monthly
  • ECG (QTc)
  • Electrolytes (potassium)
  • Sirolimus/ciclosporin levels if co-prescribed

Reference: BNFc; BNF 90; ESCMID/ECMM Aspergillosis Guidelines; ECMM/ISHAM Mucormycosis Guidelines; EORTC MSG Posaconazole Prophylaxis Trial. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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