Update on the optimal use of voriconazole for invasive fungal infections

Figures & data

Figure 1 Targets of systemic antifungal agents.

Reproduced with permission from reference ⁶.

Table 1 Voriconazole spectrum of activity

Organism	Activity
Aspergillus species	+
Candida species^a	+
Cryptococcus neoformans	+
Coccidioides species	+
Blastomyces	+
Histoplasma species	+
Fusarium species	+
Scedospermium apiospermum	+
Scedosporium prolificans	±
Sporothrix schenckii	−
Zygomycetes	−

Notes: Plus (+) signs indicate activity against the listed organism. Minus (−) signs indicate a lack of activity against the listed organism. Plus–minus signs (±) indicate variable activity against the listed organism.

a Cross-resistance with fluconazole common. Modified from reference ⁶.

Table 2 Adverse effects of voriconazole

Organ system	Adverse effect
Special senses	Altered light perception Photophobia, blurred vision (<30%)
Cardiovascular system	QTc prolongation
Gastrointestinal disorders	Nausea, vomiting (<5%) Abdominal pain (<10%)
Endocrine system	Adrenal insufficiency (rare)
Liver and biliary system	Increased transaminases (<15%) Hepatitis (rare)
Central nervous system	Hallucinations, confusion (10%) Headache
Skin and appendages	Pruritis, rash (<10%) Photosensitivity (<2%)
Immunologic	Anaphylaxis reported
Maximum tolerated dose in clinical trials	800 mg/day (10 mg/kg/day)

Modified from reference ⁹⁰.

Table 3 Voriconazole interactions with CYP450 enzymes

Drug mechanism	Activity
Inhibitor
2C19	+++
2C9	++
3A4	++
Substrate
2C19	+++
2C9	+
3A4	+

Note: Interactions from minimal (+) to extensive (+++).

Modified from reference ⁶.

Table 4 Summary of voriconazole-mediated drug–drug interactions

Type of interaction, drug	Recommendation
Decreases voriconazole levels
Carbamazepine	Contraindicated
Long-acting barbiturates	Contraindicated
Rifampin	Contraindicated
Ritonavir	Avoid unless benefit outweighs risk
Levels increased by voriconazole
Astemizole	Contraindicated
Cisapride	Contraindicated
Cyclosporine	Reduce cyclosporine dosage by half and monitor cyclosporine levels
Ergot alkaloids	Contraindicated
Omeprazole	Reduce dosage by half
Quinidine	Contraindicated
Sirolimus	Contraindicated Reduce sirolimus dose by 90% and monitor sirolimus levels
Tacrolimus	Reduce tacrolimus dosage by two-thirds and monitor tacrolimus levels
Terfenadine	Contraindicated
Warfarin	Monitor prothrombin time and international normalized ratio
Decreases voriconazole levels and increases other drug levels
Rifabutin	Contraindicated
Phenytoin	Double voriconazole dosage and monitor for increased phenytoin levels
Efavirenz	Double voriconazole dosage and reduce efavirenz dose by half
Levels likely increased by voriconazole: sulfonylureas, statins, vinca alkaloids, calcium channel blockers, benzodiazepines	Monitor effect of drug and consider decreasing dosage when voriconazole is started

Modified from reference ²⁷.

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