Table 3.
Drug | Mechanism | Results/Drug plasma exposure | Recommendation |
---|---|---|---|
Astemizole, terfenadine, quinidine, dofetilide | Voriconazole inhibits CYP3A4 metabolism. | ↑ plasma concentrations of astemizole. | Contraindicated. An increased risk of cardiotoxicity (QT prolongation, torsade de pointes, cardiac arrest). |
Azithromycin | Azithromycin inhibits CYP450 metabolism of voriconazole (unclear). | ↑ voriconazole Cmax (8%) and AUC (1%). | No adjustment of voriconazole dose. |
Barbiturates | Barbiturates inhibit CYP450 metabolism of voriconazole. | Systemic exposure to voriconazole significantly reduced. | Contraindicated. |
Benzodiazepines | Voriconazole inhibits CYP3A4 metabolism. | ↑ plasma exposure. | Frequent monitoring for adverse events and toxicity (prolonged sedation). Dose adjustment of benzodiazepine may be necessary. |
Calcium channel blockers | Voriconazole inhibits CYP3A4 metabolism. | ↑ plasma concentrations of calcium channel blockers. | Frequent monitoring for adverse events and toxicity. Dose adjustment of calcium channel blockers. |
Carbamazepine | Carbamazepine inhibits CYP450 metabolism. | ↓ systemic exposure of voriconazole. | Contraindicated. |
Cyclosporine | Voriconazole inhibits CYP3A4 metabolism. | ↑ AUC cyclosporine ˜70% | ↓ cyclosporine dose by 50%.Monitor cyclosporine levels and signs of toxicity. |
↑ cyclosporine trough levels by 2.5. | |||
Digoxin | Voriconazole inhibits CYP3A4 metabolism. | ↑ digoxin Cmax (10%) and AUC (1%). | No dose adjustment recommended. |
Ergot alkaloids | Voriconazole inhibits CYP. | Likely to be increased (based on available data; not studied). | Contraindicated. |
Erythromycin | Erythromycin and voriconazole inhibit their CYP3A4 metabolism. | ↑ plasma concentrations of voriconazole (Cmax 8% and AUC 1%) and erythromycin. | No adjustment of voriconazole dose. Monitor patients for signs. |
HMG-CoA reductase inhibitors (statins) | Voriconazole inhibits CYP3A4 metabolism. | ↑ plasma exposure of HMG-CoA reductase inhibitors (in vitro studies). | Frequent monitoring for adverse events and toxicity related to statins. Increased statin concentrations in plasma have been associated with rhabdomyolysis. Adjustment of the statin dose may be necessary. |
Imatinib | Voriconazole inhibits CYP3A4 metabolism. | ↑ plasma exposure of imatinib. | Monitor for signs of imatinib dose-related adverse events (fluid retention/water gain, nausea and vomiting, neutropenia). |
Indinavir HIV protease inhibitors | Indinavir inhibits CYP450 metabolism of voriconazole. | ↑ voriconazole Cmax (2%) and AUC (7%). | No dose adjustment required for indinavir. Frequent monitoring for adverse events related to other HIV protease inhibitors. |
Voriconazole inhibits | ↑ voriconazole exposure. | ||
CYP3A4 metabolism of indinavir. | ↑ indinavir Cmax (9%) and AUC (11%). | ||
NNRTIs | Voriconazole inhibits CYP3A4 metabolism. | ↑ plasma exposure (in vitro studies). | Frequent monitoring for adverse events and toxicity related to NNRTIs. |
Omeprazole | Competitive inhibition of omeprazole and voriconazole metabolim by CYP2C19 and CYP3A4. | ↑ voriconazole Cmax (15%) and AUC (41%). | Reduce omeprazole dose by 50% when starting voriconazole. No change in voriconazole dose. |
↑ omeprazole Cmax (3.8-fold) and AUC (2.2-fold). | |||
↑ exposure to voriconazole and omeprazole. | |||
Phenytoin | Voriconazole inhibits CYP2C9 metabolism of phenytoin. | ↑ phenytoin Cmax (67%) and AUC (81%). | Monitor phenytoin levels and phenytoin-related adverse events. Adjust voriconazole dose to 5 mg/kg intravenously or to 400 mg orally, twice daily. |
Phenytoin induces CYP3A4 metabolism of voriconazole. | ↓ voriconazole Cmax (51%) and AUC (31%). | ||
Prednisolone | Competitive inhibition of CYP3A4. | - prednisolone Cmax (11%) and AUC (34%). Slight accumulation of voriconazole. | No dose adjustment required. |
Rifabutin | Rifabutin induces CYP450 metabolism of voriconazole. | ↓ voriconazole Cmax (66%) and AUC (79%) | Contraindicated. |
Voriconazole inhibits CYP3A4 metabolism of rifabutin. | ↓ rifabutin Cmax (69%) and AUC (78%). | If benefits of co-administration outweigh risks, adjust voriconazole dose to 5 mg/kg intravenously or to 400 mg orally, twice daily. | |
Rifampin | Rifampin induces CYP450 metabolism of voriconazole. | ↓ voriconazole Cmax (92%) and AUC (96%). | Contraindicated. |
Sirolimus | Voriconazole inhibits CYP3A4 metabolism. | ↑ plasma concentrations of sirolimus. | Contraindicated. |
Sulfonylureas (tolbutamida, glipizide, glyburide) | Voriconazole inhibits CYP3A4 metabolism. | ↑ plasma concentrations of sulfonylureas. | Frequent monitoring of blood glucose and appropriate adjustment of the sulfonylurea dose. |
Tacrolimus | Voriconazole inhibits CYP3A4 metabolism (dose dependent). | ↑ tacrolimus Cmax (2.2-fold) and AUC (3.2-fold). | Reduce tacrolimus dose by a third when starting voriconazole. |
Monitor plasma levels frequently. | |||
Vinca alkaloids (vincristine, vinblastine, vinorelbine) | Voriconazole inhibits CYP3A4 metabolism. | ↑ plasma concentrations of vinca alkaloids. | Dose adjustment of vinca alkaloids. |
Warfarin oral anticoagulants | Voriconazole inhibits CYP3A4 metabolism. | ↑ warfarin effect | Monitor prothrombin time. |
(↑ prothrombin time). | Adjust warfarin dose if necessary. Increased risk of bleeding. |
Abbreviations: NNRTIs, nonnucleoside reverse transcriptase inhibitor; AUC, area under the curve; Cmax, maximum concentration; CY, cytochrome.