Sirolimus
(CYP3A4 Inhibition) |
Significantly Increased |
Contraindicated
|
Rifabutin
(CYP3A4 Inhibition) |
Significantly Increased |
Contraindicated
|
Efavirenz
(CYP3A4 Inhibition) |
Significantly Increased |
When voriconazole is coadministered with efavirenz, voriconazole oral maintenance dose should be increased to 400 mg q12h and efavirenz should be decreased to 300 mg q24h |
High-dose Ritonavir (400 mg q12h)(CYP3A4 Inhibition) |
No Significant Effect of Voriconazole on Ritonavir Cmax or AUCτ
|
Contraindicated because of significant reduction of voriconazole Cmax and AUCτ
|
|
|
|
Low-dose Ritonavir (100 mg q12h)
|
Slight Decrease in Ritonavir Cmax and AUCτ
|
Coadministration of voriconazole and low-dose ritonavir (100 mg q12h) should be avoided (due to the reduction in voriconazole Cmax and AUCτ) unless an assessment of the benefit/risk to the patient justifies the use of voriconazole |
Terfenadine, Astemizole, Cisapride, Pimozide, Quinidine (CYP3A4 Inhibition) |
Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased |
Contraindicated because of potential for QT prolongation and rare occurrence of torsade de pointes
|
Ergot Alkaloids (CYP450 Inhibition) |
Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased |
Contraindicated
|
Cyclosporine
(CYP3A4 Inhibition) |
AUCτ Significantly Increased; No Significant Effect on Cmax
|
When initiating therapy with VFEND in patients already receiving cyclosporine, reduce the cyclosporine dose to one-half of the starting dose and follow with frequent monitoring of cyclosporine blood levels. Increased cyclosporine levels have been associated with nephrotoxicity. When VFEND is discontinued, cyclosporine concentrations must be frequently monitored and the dose increased as necessary. |
Methadone
(CYP3A4 Inhibition) |
Increased |
Increased plasma concentrations of methadone have been associated with toxicity including QT prolongation. Frequent monitoring for adverse events and toxicity related to methadone is recommended during coadministration. Dose reduction of methadone may be needed |
Fentanyl (CYP3A4 Inhibition) |
Increased |
Reduction in the dose of fentanyl and other long-acting opiates metabolized by CYP3A4 should be considered when coadministered with VFEND. Extended and frequent monitoring for opiate-associated adverse events may be necessary [see Drug Interactions (7)
] |
Alfentanil (CYP3A4 Inhibition) |
Significantly Increased |
Reduction in the dose of alfentanil and other opiates metabolized by CYP3A4 (e.g., sufentanil) should be considered when coadministered with VFEND. A longer period for monitoring respiratory and other opiate-associated adverse events may be necessary [see Drug Interactions (7)
]. |
Oxycodone (CYP3A4 Inhibition) |
Significantly Increased |
Reduction in the dose of oxycodone and other long-acting opiates metabolized by CYP3A4 should be considered when coadministered with VFEND. Extended and frequent monitoring for opiate-associated adverse events may be necessary [see Drug Interactions (7)
]. |
NSAIDs
including. ibuprofen and diclofenac (CYP2C9 Inhibition) |
Increased |
Frequent monitoring for adverse events and toxicity related to NSAIDs. Dose reduction of NSAIDs may be needed [see Drug Interactions (7)
]. |
Tacrolimus
(CYP3A4 Inhibition) |
Significantly Increased |
When initiating therapy with VFEND in patients already receiving tacrolimus, reduce the tacrolimus dose to one-third of the starting dose and follow with frequent monitoring of tacrolimus blood levels. Increased tacrolimus levels have been associated with nephrotoxicity. When VFEND is discontinued, tacrolimus concentrations must be frequently monitored and the dose increased as necessary. |
Phenytoin
(CYP2C9 Inhibition) |
Significantly Increased |
Frequent monitoring of phenytoin plasma concentrations and frequent monitoring of adverse effects related to phenytoin. |
Oral Contraceptives containing ethinyl estradiol and norethindrone (CYP3A4 Inhibition)
|
Increased |
Monitoring for adverse events related to oral contraceptives is recommended during coadministration. |
Warfarin
(CYP2C9 Inhibition) |
Prothrombin Time Significantly Increased |
Monitor PT or other suitable anti-coagulation tests. Adjustment of warfarin dosage may be needed. |
Omeprazole
(CYP2C19/3A4 Inhibition) |
Significantly Increased |
When initiating therapy with VFEND in patients already receiving omeprazole doses of 40 mg or greater, reduce the omeprazole dose by one-half. The metabolism of other proton pump inhibitors that are CYP2C19 substrates may also be inhibited by voriconazole and may result in increased plasma concentrations of other proton pump inhibitors. |
Other HIV Protease Inhibitors (CYP3A4 Inhibition) |
In Vivo Studies Showed No Significant Effects on Indinavir Exposure |
No dosage adjustment for indinavir when coadministered with VFEND |
|
|
|
|
In Vitro Studies Demonstrated Potential for Voriconazole to Inhibit Metabolism (Increased Plasma Exposure) |
Frequent monitoring for adverse events and toxicity related to other HIV protease inhibitors |
Other NNRTIs
(CYP3A4 Inhibition) |
A Voriconazole-Efavirenz Drug Interaction Study Demonstrated the Potential for Voriconazole to Inhibit Metabolism of Other NNRTIs (Increased Plasma Exposure) |
Frequent monitoring for adverse events and toxicity related to NNRTI |
Benzodiazepines (CYP3A4 Inhibition) |
In Vitro Studies Demonstrated Potential for Voriconazole to Inhibit Metabolism (Increased Plasma Exposure) |
Frequent monitoring for adverse events and toxicity (i.e., prolonged sedation) related to benzodiazepines metabolized by CYP3A4 (e.g., midazolam, triazolam, alprazolam). Adjustment of benzodiazepine dosage may be needed. |
HMG-CoA Reductase Inhibitors (Statins) (CYP3A4 Inhibition) |
In Vitro Studies Demonstrated Potential for Voriconazole to Inhibit Metabolism (Increased Plasma Exposure) |
Frequent monitoring for adverse events and toxicity related to statins. Increased statin concentrations in plasma have been associated with rhabdomyolysis. Adjustment of the statin dosage may be needed. |
Dihydropyridine Calcium Channel Blockers (CYP3A4 Inhibition) |
In Vitro Studies Demonstrated Potential for Voriconazole to Inhibit Metabolism (Increased Plasma Exposure) |
Frequent monitoring for adverse events and toxicity related to calcium channel blockers. Adjustment of calcium channel blocker dosage may be needed. |
Sulfonylurea Oral Hypoglycemics (CYP2C9 Inhibition) |
Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased |
Frequent monitoring of blood glucose and for signs and symptoms of hypoglycemia. Adjustment of oral hypoglycemic drug dosage may be needed. |
Vinca Alkaloids (CYP3A4 Inhibition) |
Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased |
Frequent monitoring for adverse events and toxicity (i.e., neurotoxicity) related to vinca alkaloids. Adjustment of vinca alkaloid dosage may be needed. |