Posaconazole

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Background

  • Azole antifungal

Pharmacokinetics and Pharmacodynamics

  • Generally distributes well, with the notable exception of non-inflamed brain

Clinical Breakpoints

Species ECV (μg/mL) Breakpoints (μg/mL)
S I SDD R
Candida albicans 0.06 ≤0.06 ≥0.12
Candida dubliniensis
Candida glabrata 2
Candida guilliermondii 0.5
Candida kefyr 0.25
Candida krusei 0.5
Candida lusitaniae 0.12
Candida parapsilosis 0.25 ≤0.06 ≥0.12
Candida tropicalis 0.12 ≤0.06 ≥0.12
Cryptococcus neoformans
Cryptococcus gattii
Aspergillus flavus 0.5
Aspergillus fumigatus 0.25 ≤0.125 >0.25
Aspergillus nidulans 0.5
Aspergillus niger 0.5
Aspergillus terreus 0.25 ≤0.125 >0.25

Dosing

Therapeutic Drug Monitoring

  • Measure trough 7 days after starting or adjusting dose, or adjusting interacting medications, or concerns of poor adherence or absorption
  • For prophylaxis, target trough >0.7 mg/L, or random level 0.35 mg/L 48 h after starting therapy
  • For treatment, target trough >1 mg/L

Safety

Adverse Events

  • Liver toxicity
    • Generally transient and asymptomatic and self-limited
    • See also LiverTox