Posaconazole

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