Voriconazole

Background

• Azole antifungal
• Indications include Alternaria, Blastomyces dermatitidis, Coccidioides immitis, Exophiala, Exserohilum, Fungal endocarditis, Histoplasma capsulatum, Rasamsonia

Breakpoints

Species	ECV (μg/mL)	Breakpoints (μg/mL)				Breakpoints (mm)
		S	I	SDD	R	S	I	SDD	R
Candida albicans	0.3	≤0.12	0.25-0.5	—	≥1	≥17	15-16	—	≤14
Candida glabrata	0.25	—	—	—	—	—	—	—	—
Candida krusei	0.5	≤0.5	1	—	≥2	≥15	13-14	—	≤12
Candida parapsilosis	0.03	≤0.12	0.25-0.5	—	≥1	≥17	15-16	—	≤14
Candida tropicalis	0.12	≤0.12	0.25-0.5	—	≥1	≥17	15-16	—	≤14
Cryptococcus neoformans	0.25
Cryptococcus gattii	0.5
Aspergillus flavus	2
Aspergillus fumigatus	1
Aspergillus niger	2
Aspergillus terreus	2

Therapeutic Drug Monitoring

• Measure trough within 7 days of starting, and at regular intervals or following dose adjustment
• Target trough > 1 mg/L for prophylaxis and treatment

Trough (mcg/mL)	Recommendation
0.0 to 0.6	Increase dose by 100 mg and recheck trough on day 5 of new regimen
0.7 to 0.9	Increase dose by 50 mg and recheck trough on day 5 of new regimen
1.0 to 4.0	At target, no dose adjustment needed
4.1 to 5.5	Decrease dose by 50 mg and recheck trough on day 5 of new regimen
5.6 to 7.9	Hold dose. Follow daily trough levels, then restart when trough is ≤2.5 at a dose decreased by 100 mg. Recheck trough on day 5 of new regimen.
≥8.0	Hold dose. Follow daily trough levels, then restart when trough is ≤2.5 at a dose decreased by 50%. Recheck trough level on day 5 of new regimen.

Safety

• Elevated levels predict neurotoxicity, but not hepatotoxicity

Adverse Drug Reactions

• Visual
  • Floaters etc that may improve with time
  • Visual hallucinations
  • Colour vision loss
• Photosensitivity
• Hepatotoxicity
• QTc prolongation

Further Reading

• Voriconazole Dose Modification Guideline to Optimize Therapeutic Levels in Patients With Hematologic Malignancies. Open Forum Infect Dis. 2015;2(S1):810. doi: 10.1093/ofid/ofv133.527