VFEND® Drug Interactions

Slight Decrease in AUCτ

When voriconazole is coadministered with efavirenz, voriconazole oral maintenance dose should be increased to 400 mg every 12 hours and efavirenz should be decreased to 300 mg every 24 hours.

Reduced

Coadministration of voriconazole and low-dose ritonavir (100 mg every 12 hours) should be avoided, unless an assessment of the benefit/risk to the patient justifies the use of voriconazole.

Not Studied In Vivo or In Vitro, but Likely to Result in Significant Reduction

Contraindicated

Not Studied In Vivo or In Vitro, but Likely to Result in Significant Reduction

Contraindicated

Significantly Reduced

Increase voriconazole maintenance dose from 4 mg/kg to 5 mg/kg IV every 12 hours or from 200 mg to 400 mg orally every 12 hours (100 mg to 200 mg orally every 12 hours in patients weighing less than 40 kg).

Reduced

If concomitant administration of voriconazole with letermovir cannot be avoided, monitor for reduced effectiveness of voriconazole.

Significantly Reduced

Contraindicated

Increased

Monitoring for adverse reactions and toxicity related to voriconazole is recommended when coadministered with oral contraceptives.

Significantly Increased

Avoid concomitant administration of voriconazole and fluconazole. Monitoring for adverse reactions and toxicity related to voriconazole is started within 24 hours after the last dose of fluconazole.

In Vitro Studies Demonstrated Potential for Inhibition of Voriconazole Metabolism (Increased Plasma Exposure)

Frequent monitoring for adverse reactions and toxicity related to voriconazole when coadministered with other HIV protease inhibitors.

Significantly Increased

Contraindicated

Slight Increase in AUCτ

When voriconazole is coadministered with efavirenz, voriconazole oral maintenance dose should be increased to 400 mg every 12 hours and efavirenz should be decreased to 300 mg every 24 hours.

Slight Decrease in Ritonavir Cmax and AUCτ

Coadministration of voriconazole and low-dose ritonavir (100 mg every 12 hours) 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.

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.

Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased

Contraindicated

Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased which may Increase the Risk of Adverse Reactions

Contraindicated

Although Not Studied Clinically, Voriconazole is Likely to Significantly Increase the Plasma Concentrations of Tolvaptan

Contraindicated

Not studied In Vivo or In Vitro, but Venetoclax Plasma Exposure Likely to be Significantly Increased

Coadministration of voriconazole is contraindicated at initiation and during the ramp-up phase in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Refer to the venetoclax labeling for safety monitoring and dose reduction in the steady daily dosing phase in CLL/SLL patients.
For patients with acute myeloid leukemia (AML), dose reduction and safety monitoring are recommended across all dosing phases when coadministering VFEND with venetoclax. Refer to the venetoclax prescribing information for dosing instructions.

Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased

Avoid concomitant use of VFEND with lemborexant.

Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased

Consider alternative therapies. If concomitant use cannot be avoided, monitor patients for increased risk of adverse reactions including QTc interval prolongation.

Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased

Avoid concomitant use of VFEND. If concomitant use cannot be avoided, dose reduction of the tyrosine kinase inhibitor is recommended. Refer to the prescribing information for the relevant product.

Not Studied In Vivo or In Vitro, but Voriconazole is Likely to Significantly Increase the Plasma Concentrations of Lurasidone

Contraindicated

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.

Increased

Increased plasma concentrations of methadone have been associated with toxicity including QT prolongation. Frequent monitoring for adverse reactions and toxicity related to methadone is recommended during coadministration. Dose reduction of methadone may be needed.

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 reactions may be necessary.

Significantly Increased

An increase in the incidence of delayed and persistent alfentanil-associated nausea and vomiting were observed when coadministered with VFEND. 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 reactions may be necessary.

Significantly Increased

Increased visual effects (heterophoria and miosis) of oxycodone were observed when coadministered with VFEND.
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 reactions may be necessary.

Increased

Frequent monitoring for adverse reactions and toxicity related to NSAIDs. Dose reduction of NSAIDs may be needed.

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.

Significantly Increased

Frequent monitoring of phenytoin plasma concentrations and frequent monitoring of adverse effects related to phenytoin.

Increased

Monitoring for adverse reactions related to oral contraceptives is recommended during coadministration.

In Vivo Studies Showed No Significant Effects of VFEND on Prednisolone Exposure
Not Studied In vitro or In vivo for Other Corticosteroids, but Drug Exposure Likely to be Increased

No dosage adjustment for prednisolone when coadministered with VFEND [see Clinical Pharmacology (12.3)].
Monitor for potential adrenal dysfunction when VFEND is administered with other corticosteroids [See Warnings and Precautions (5.8)].

If patients receiving coumarin preparations are treated simultaneously with voriconazole, the prothrombin time or other suitable anticoagulation tests should be monitored at close intervals and the dosage of anticoagulants adjusted accordingly.

Not Studied In Vivo or In Vitro for other Oral Coumarin Anticoagulants, but Drug Plasma Exposure Likely to be Increased

Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased which may Increase the Risk of Adverse Reactions

Dose reduction of ivacaftor is recommended. Refer to the prescribing information for ivacaftor

Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased which may Increase the Sedative Effect of Eszopiclone

Dose reduction of eszopiclone is recommended. Refer to the prescribing information for eszopiclone.

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.

In Vitro Studies Demonstrated Potential for Voriconazole to Inhibit Metabolism
(Increased Plasma Exposure)

Frequent monitoring for adverse reactions and toxicity related to other HIV protease inhibitors.

A Voriconazole-Efavirenz Drug Interaction Study Demonstrated the Potential for Voriconazole to Inhibit Metabolism of Other NNRTIs
(Increased Plasma Exposure)

Frequent monitoring for adverse reactions and toxicity related to NNRTI.

Although Not Studied, Voriconazole may Increase Tretinoin Concentrations and Increase the Risk of Adverse Reactions

Frequent monitoring for signs and symptoms of pseudotumor cerebri or hypercalcemia.

In Vitro Studies Demonstrated Potential for Voriconazole to Inhibit Metabolism
(Increased Plasma Exposure)

Refer to drug-specific labeling for details.

In Vitro Studies Demonstrated Potential for Voriconazole to Inhibit Metabolism
(Increased Plasma Exposure)

Frequent monitoring for adverse reactions and toxicity related to statins. Increased statin concentrations in plasma have been associated with rhabdomyolysis. Adjustment of the statin dosage may be needed.

In Vitro Studies Demonstrated Potential for Voriconazole to Inhibit Metabolism
(Increased Plasma Exposure)

Frequent monitoring for adverse reactions and toxicity related to calcium channel blockers. Adjustment of calcium channel blocker dosage may be needed.

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.

Not Studied In Vivo or In Vitro, but Drug Plasma Exposure Likely to be Increased

Frequent monitoring for adverse reactions and toxicity (i.e., neurotoxicity) related to vinca alkaloids. Reserve azole antifungals, including voriconazole, for patients receiving a vinca alkaloid who have no alternative antifungal treatment options.