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Antifungal — Aspergillosis Prophylaxis / Salvage Pregnancy: Contraindicated — teratogenic; use liposomal amphotericin B for IFI treatment in pregnancy

Posaconazole

Brand names: Noxafil

Adult dose

Dose: Prophylaxis: 300 mg once daily (gastro-resistant tablet) or 200 mg three times daily (oral suspension with food). Salvage: 300 mg once daily (tablet)
Route: Oral (gastro-resistant tablet preferred — more consistent absorption)
Frequency: Once daily (tablet) or three times daily (suspension)
Max: 300 mg/day (tablet); 600 mg/day (suspension)
Extended-spectrum triazole antifungal for: (1) prophylaxis of invasive fungal infections in high-risk immunocompromised patients (neutropenia — AML induction, HSCT, GVHD); (2) salvage treatment for invasive aspergillosis refractory to or intolerant of voriconazole/itraconazole; (3) Mucormycosis.

Paediatric dose

Dose: Suspension: 5 mg/kg up to 200 mg three times daily mg/kg
Route: Oral suspension (take with full meal or nutritional supplement)
Frequency: Three times daily (suspension) or once daily (tablet — ≥13 years)
Max: 200 mg three times daily (suspension)
BNFc: licensed from 13 years for prophylaxis (tablet); suspension may be used from 2 years under specialist guidance — suspension absorption highly food-dependent

Dose adjustments

Renal

No dose adjustment required (tablet); IV vehicle — avoid IV if eGFR <50

Hepatic

No dose adjustment required in mild-moderate impairment; use with caution in severe impairment

Paediatric weight-based calculator

BNFc: licensed from 13 years for prophylaxis (tablet); suspension may be used from 2 years under specialist guidance — suspension absorption highly food-dependent

Clinical pearls

  • ESCMID/IDSA guidelines: posaconazole prophylaxis recommended in AML induction chemotherapy and GVHD patients — dramatically reduces IFI-related mortality (NEJM 2007 Cornely trial: 44% relative risk reduction in IFI)
  • Gastro-resistant tablet superior to suspension: 3-fold higher and more consistent AUC vs suspension; tablet is now preferred where available
  • Suspension absorption highly food-dependent: must be taken with full caloric meal or nutritional supplement (Ensure, Fortisip) — inadequate absorption in fasted/poorly eating patients is a major clinical problem
  • Broad spectrum: covers Aspergillus, Candida, Mucormycetes (Mucorales) — unlike voriconazole which has no activity against Mucor
  • TDM recommended: target trough ≥0.7 mg/L (prophylaxis); ≥1.0 mg/L (treatment) — check at day 5–7 especially with suspension
  • Mucormycosis: posaconazole is second-line after liposomal amphotericin B — often used for step-down or salvage in mucormycosis

Contraindications

  • Hypersensitivity to posaconazole or other azoles
  • Co-administration with ergot alkaloids, sirolimus, or QT-prolonging CYP3A4 substrates

Side effects

  • Nausea (suspension — better with tablet)
  • QT prolongation
  • Hepatotoxicity
  • Headache
  • Hypokalaemia
  • Peripheral oedema

Interactions

  • Ciclosporin, tacrolimus, sirolimus — significantly increase immunosuppressant levels (strong CYP3A4 inhibitor)
  • Rifampicin, phenytoin, carbamazepine — reduce posaconazole levels
  • Warfarin — increased INR
  • Statins — increased myopathy risk

Monitoring

  • Posaconazole trough levels (target >0.7 mg/L prophylaxis; >1.0 mg/L treatment)
  • LFTs
  • Electrolytes (K⁺, Mg²⁺)
  • ECG (QTc)
  • Drug interactions review

Reference: BNFc; BNF 90; BNFc; Cornely et al. NEJM 2007 (posaconazole prophylaxis AML); ESCMID/ECMM/ERS Aspergillosis Guidelines 2018; NICE; SPC Noxafil. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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