Table 7.
Antifungal triazoles active against moulds: practical tips for use.
| Property Required /Variable Present | Select Itraconazole | Select Voriconazole | |
|---|---|---|---|
| Broad spectrum/potency | + | + | |
Good bioavailability , rapid time to steady state | + | ||
| Higher central nervous system drug exposure | + | ||
| Tolerability of oral formulation | + | ||
| Once a day dosing | + | ||
| Safety profile† | ? | ? | |
| Patient receiving warfarin* | + | ||
| Patient receiving benzodiazepines* | + | ||
| Patient of Japanese/Chinese descent§ | + | ||
| Triazoles and gut dysfunction: Always use itraconazole and voriconazole IV in the presence of significant gut dysfunction (mucositis, nausea and vomiting, gut graft versus host disease, severe diarrhea, ileus, other) | |||
| IV triazoles and renal failure: Cyclodextrins (carrier of IV itraconazole and voriconazole) are excreted unchanged via kidneys with a potential for accumulation in patients with renal dysfunction. Avoid IV formulation for patients on renal dialysis and those with creatinine clearance (CrCl) < 50 mL/min (voriconazole) or <30 mL/min (itraconazole). Use oral therapy instead. | |||
| PO Triazole and bioavailability: Always take with a Coke. For itraconazole capsule: take with meals; for itraconazole solution: take away from meals. | |||
| † Voriconazole precautions: Instruct patients taking voriconazole to avoid driving at night or exposing himself or herself to strong and direct sunlight. | |||
| * Drug Interactions: Voriconazole has higher likelihood of drug-drug interaction with cyclosporine, tacrolimus, warfarin, or rifampin compared to a higher likelihood of an itraconazole drug-drug interaction with benzodiazepines* | |||
| §Voriconazole and CYP 2C19: Voriconazole is metabolized by CYP isoenzymes including CYP2C19, which exhibits genetic polymorphism. An individual’s ability to metabolize a CYP2C19 substrate is genetically determined as homozygous extensive metabolizer (EM), heterozygous EM and poor metabolizer. Significantly higher voriconazole drug exposure occurs in heterozygous EM and homozygous poor metabolizers (below). | |||
| CYP 2C19 Genotype | Caucasian/Negroid | Japanese/Chinese | Voriconazole Concentration |
| Homozygous Extensive | ~75% | ~35% | 1 X |
| Heterozygous Extensive | ~23% | ~45% | ~ 2 X |
| Homozygous Poor | ~2% | ~20% | ~ 4 X |
| Property Required /Variable Present | Select Itraconazole | Select Voriconazole | |
|---|---|---|---|
| Broad spectrum/potency | + | + | |
| Good bioavailability, rapid time to steady state | + | ||
| Higher central nervous system drug exposure | + | ||
| Tolerability of oral formulation | + | ||
| Once a day dosing | + | ||
| Safety profile† | ? | ? | |
| Patient receiving warfarin* | + | ||
| Patient receiving benzodiazepines* | + | ||
| Patient of Japanese/Chinese descent§ | + | ||
| Triazoles and gut dysfunction: Always use itraconazole and voriconazole IV in the presence of significant gut dysfunction (mucositis, nausea and vomiting, gut graft versus host disease, severe diarrhea, ileus, other) | |||
| IV triazoles and renal failure: Cyclodextrins (carrier of IV itraconazole and voriconazole) are excreted unchanged via kidneys with a potential for accumulation in patients with renal dysfunction. Avoid IV formulation for patients on renal dialysis and those with creatinine clearance (CrCl) < 50 mL/min (voriconazole) or <30 mL/min (itraconazole). Use oral therapy instead. | |||
| PO Triazole and bioavailability: Always take with a Coke. For itraconazole capsule: take with meals; for itraconazole solution: take away from meals. | |||
| † Voriconazole precautions: Instruct patients taking voriconazole to avoid driving at night or exposing himself or herself to strong and direct sunlight. | |||
| * Drug Interactions: Voriconazole has higher likelihood of drug-drug interaction with cyclosporine, tacrolimus, warfarin, or rifampin compared to a higher likelihood of an itraconazole drug-drug interaction with benzodiazepines* | |||
| §Voriconazole and CYP 2C19: Voriconazole is metabolized by CYP isoenzymes including CYP2C19, which exhibits genetic polymorphism. An individual’s ability to metabolize a CYP2C19 substrate is genetically determined as homozygous extensive metabolizer (EM), heterozygous EM and poor metabolizer. Significantly higher voriconazole drug exposure occurs in heterozygous EM and homozygous poor metabolizers (below). | |||
| CYP 2C19 Genotype | Caucasian/Negroid | Japanese/Chinese | Voriconazole Concentration |
| Homozygous Extensive | ~75% | ~35% | 1 X |
| Heterozygous Extensive | ~23% | ~45% | ~ 2 X |
| Homozygous Poor | ~2% | ~20% | ~ 4 X |