Important drug interaction with triazoles: effect of azoles on other agents.
| . | . | Pharmacokinetics of Azoles Affecting other Drugs . | ||
|---|---|---|---|---|
| Effect of Azoles on other agents . | Azole Used . | Effect of Azole on Drug Exposure . | Adjust Dose of or Discontinue Concomitant Drug . | Monitoring . |
| Abbreviations: AUC, area under the curve | ||||
| Antineoplastic | ||||
| Busulfan | Itraconazole | 25% ↑ | Avoid azole | Monitor for toxicity |
| Voriconazole | ↑ | |||
| Vinca alkaloids | Itraconazole | ↑ | ||
| Voriconazole | ↑ | |||
| Docetaxel | Itraconazole | ↑ | ||
| Voriconazole | ↑ | |||
| Cyclophosphamide | Itraconazole | ↑ | ||
| Immunosuppressives | ||||
| Methylprednisolone | Itraconazole | 2–3 x ↑ | Change to dexamethasone | |
| Voriconazole | ↑? | |||
| Cyclosporine | Itraconazole | 50% ↑ | Decrease cyclosporine dose by 50% and/or according to levels and clinical toxicity | Monitor immunosuppressant level daily |
| Voriconazole | 2 x ↑ | |||
| Fluconazole | 50% ↑ | |||
| Tacrolimus | Itraconazole | 5 x ↑ | Decrease tacrolimus dose by 50 % and/or according to levels and clinical toxicity | |
| Voriconazole | 3 x ↑ | |||
| Fluconazole | ↑ | |||
| Sirolimus | Ketoconazole | 11 x ↑AUC | Azoles contraindicated | |
| Itraconazole | ↑↑↑ | |||
| Voriconazole | ↑↑↑ | |||
| Fluconazole | ↑↑ | Decrease sirolimus dose | Decrease sirolimus level | |
| Digoxin | Itraconazole | 68% ↑ | Decrease digoxin dose according to digoxin level | Monitor digoxin level daily, EKG |
| Fluconazole | ↑ | |||
| Warfarin | Itraconazole | ↑ | Decrease warfarin dose according to INR | Monitor INR |
| Voriconazole | ↑ | |||
| Fluconazole | 70% ↑ | |||
| Benzodiazepines | ||||
| Midazolam | Itraconazole | 2 x ↑ | Avoid agent, decrease dose by 50%, or use oxazepam instead | Monitor for central nervous system toxicity (drowsiness, sleepiness) |
| Voriconazole | ↑? | |||
| Fluconazole | 2 x ↑ | |||
| Triazolam | Itraconazole | 2 x ↑ | ||
| Voriconazole | ↑? | |||
| Fluconazole | 2 x ↑ | |||
| Diazepam | Itraconazole | 35% ↑ | ||
| Voriconazole | ↑? | |||
| Zolpidem | Voriconazole | ↑? | ||
| Proton pump inhibitors | Voriconazole | ↑ | Reduce proton pump inhibitor dose by 50% | |
| Fluconazole | ↑ | |||
| Phenytoin | Itraconazole | ↑↑ AUC | Avoid triazole | Monitor phenytoin level |
| Voriconazole | ↑ 80 | |||
| Fluconazole | ↑↑ AUC | |||
| Rifampin | Itraconazole | ↑ AUC | Monitor for rifampin toxicity | |
| Voriconazole | ↑ AUC | Avoid voriconazole | ||
| Fluconazole | ↑ AUC | |||
| Rifabutin | Voriconazole | ↑↑↑AUC | Avoid voriconazole, fluconazole | |
| Fluconazole | ↑↑ | |||
| Oxybutynin | Itraconazole | 2 x ↑AUC | Avoid itraconazole | |
| Sulfonylurea | Voriconazole | ↑ | Adjust dose according to blood sugar | Monitor glucose concentration |
| Fluconazole | ↑ | |||
| HMG-CoA Reductase Inhibitors | ||||
| Lovastatin/Simvastatin | Itraconazole | 10–20 x ↑ | Avoid using simvastatin, lovastatin, atorvastatin. May use pravastatin or fluvastatin | Monitor for rhabdomyolysis |
| Voriconazole | ↑↑ | |||
| Fluconazole | ↑↑ | |||
| Atorvastatin | Itraconazole | 3 x ↑ | ||
| Voriconazole | ↑↑ | |||
| Fluconazole | ↑↑ | |||
| Ergot Alkaloids | Voriconazole | ↑ | Avoid concomitant use | |
| Buspirone | Itraconazole | 19 x ↑ | Avoid itraconazole, voriconazole | |
| Voriconazole | ↑? | |||
| . | . | Pharmacokinetics of Azoles Affecting other Drugs . | ||
|---|---|---|---|---|
| Effect of Azoles on other agents . | Azole Used . | Effect of Azole on Drug Exposure . | Adjust Dose of or Discontinue Concomitant Drug . | Monitoring . |
| Abbreviations: AUC, area under the curve | ||||
| Antineoplastic | ||||
| Busulfan | Itraconazole | 25% ↑ | Avoid azole | Monitor for toxicity |
| Voriconazole | ↑ | |||
| Vinca alkaloids | Itraconazole | ↑ | ||
| Voriconazole | ↑ | |||
| Docetaxel | Itraconazole | ↑ | ||
| Voriconazole | ↑ | |||
| Cyclophosphamide | Itraconazole | ↑ | ||
| Immunosuppressives | ||||
| Methylprednisolone | Itraconazole | 2–3 x ↑ | Change to dexamethasone | |
| Voriconazole | ↑? | |||
| Cyclosporine | Itraconazole | 50% ↑ | Decrease cyclosporine dose by 50% and/or according to levels and clinical toxicity | Monitor immunosuppressant level daily |
| Voriconazole | 2 x ↑ | |||
| Fluconazole | 50% ↑ | |||
| Tacrolimus | Itraconazole | 5 x ↑ | Decrease tacrolimus dose by 50 % and/or according to levels and clinical toxicity | |
| Voriconazole | 3 x ↑ | |||
| Fluconazole | ↑ | |||
| Sirolimus | Ketoconazole | 11 x ↑AUC | Azoles contraindicated | |
| Itraconazole | ↑↑↑ | |||
| Voriconazole | ↑↑↑ | |||
| Fluconazole | ↑↑ | Decrease sirolimus dose | Decrease sirolimus level | |
| Digoxin | Itraconazole | 68% ↑ | Decrease digoxin dose according to digoxin level | Monitor digoxin level daily, EKG |
| Fluconazole | ↑ | |||
| Warfarin | Itraconazole | ↑ | Decrease warfarin dose according to INR | Monitor INR |
| Voriconazole | ↑ | |||
| Fluconazole | 70% ↑ | |||
| Benzodiazepines | ||||
| Midazolam | Itraconazole | 2 x ↑ | Avoid agent, decrease dose by 50%, or use oxazepam instead | Monitor for central nervous system toxicity (drowsiness, sleepiness) |
| Voriconazole | ↑? | |||
| Fluconazole | 2 x ↑ | |||
| Triazolam | Itraconazole | 2 x ↑ | ||
| Voriconazole | ↑? | |||
| Fluconazole | 2 x ↑ | |||
| Diazepam | Itraconazole | 35% ↑ | ||
| Voriconazole | ↑? | |||
| Zolpidem | Voriconazole | ↑? | ||
| Proton pump inhibitors | Voriconazole | ↑ | Reduce proton pump inhibitor dose by 50% | |
| Fluconazole | ↑ | |||
| Phenytoin | Itraconazole | ↑↑ AUC | Avoid triazole | Monitor phenytoin level |
| Voriconazole | ↑ 80 | |||
| Fluconazole | ↑↑ AUC | |||
| Rifampin | Itraconazole | ↑ AUC | Monitor for rifampin toxicity | |
| Voriconazole | ↑ AUC | Avoid voriconazole | ||
| Fluconazole | ↑ AUC | |||
| Rifabutin | Voriconazole | ↑↑↑AUC | Avoid voriconazole, fluconazole | |
| Fluconazole | ↑↑ | |||
| Oxybutynin | Itraconazole | 2 x ↑AUC | Avoid itraconazole | |
| Sulfonylurea | Voriconazole | ↑ | Adjust dose according to blood sugar | Monitor glucose concentration |
| Fluconazole | ↑ | |||
| HMG-CoA Reductase Inhibitors | ||||
| Lovastatin/Simvastatin | Itraconazole | 10–20 x ↑ | Avoid using simvastatin, lovastatin, atorvastatin. May use pravastatin or fluvastatin | Monitor for rhabdomyolysis |
| Voriconazole | ↑↑ | |||
| Fluconazole | ↑↑ | |||
| Atorvastatin | Itraconazole | 3 x ↑ | ||
| Voriconazole | ↑↑ | |||
| Fluconazole | ↑↑ | |||
| Ergot Alkaloids | Voriconazole | ↑ | Avoid concomitant use | |
| Buspirone | Itraconazole | 19 x ↑ | Avoid itraconazole, voriconazole | |
| Voriconazole | ↑? | |||