Voriconazole

Side effects, and when to stop

The following serious adverse reactions are described elsewhere in the labeling: Hepatic Toxicity Arrhythmias and QT Prolongation

Who should not take it

• Voriconazole is contraindicated in patients with known hypersensitivity to voriconazole or its excipients. There is no information regarding crosssensitivity between voriconazole and other azole antifungal agents. Caution should be used when prescribing voriconazole to patients with hypersensitivity to other azoles.
• Coadministration of pimozide, quinidine or ivabradine with voriconazole is contraindicated because increased plasma concentrations of these drugs can lead to QT prolongation and rare occurrences of torsade de pointes.
• Coadministration of voriconazole with sirolimus is contraindicated because voriconazole significantly increases sirolimus concentrations.
• Coadministration of voriconazole with rifampin, carbamazepine, long-acting barbiturates or St John's Wort is contraindicated because these drugs are likely to decrease plasma voriconazole concentrations significantly.
• Coadministration of standard doses of voriconazole with efavirenz doses of 400 mg every 24 hours or higher is contraindicated, because efavirenz significantly decreases plasma voriconazole concentrations in healthy subjects at these doses. Voriconazole also significantly increases efavirenz plasma concentrations.
• Coadministration of voriconazole with high-dose ritonavir (400 mg every 12 hours) is contraindicated because ritonavir (400 mg every 12 hours) significantly decreases plasma voriconazole concentrations. 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.
• Coadministration of voriconazole with rifabutin is contraindicated since voriconazole significantly increases rifabutin plasma concentrations and rifabutin also significantly decreases voriconazole plasma concentrations.
• Coadministration of voriconazole with ergot alkaloids (ergotamine and dihydroergotamine) is contraindicated because voriconazole may increase the plasma concentration of ergot alkaloids, which may lead to ergotism.
• Coadministration of voriconazole with naloxegol is contraindicated because voriconazole may increase plasma concentrations of naloxegol which may precipitate opioid withdrawal symptoms.
• Coadministration of voriconazole with tolvaptan is contraindicated because voriconazole may increase tolvaptan plasma concentrations and increase risk of adverse reactions.
• Coadministration of voriconazole with venetoclax at initiation and during the ramp-up phase is contraindicated in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) due to the potential for increased risk of tumor lysis syndrome.
• Coadministration of voriconazole with lurasidone is contraindicated since it may result in significant increases in lurasidone exposure and the potential for serious adverse reactions.
• Coadministration of voriconazole with finerenone is contraindicated since it may result in significant increases in finerenone exposure and the potential for serious adverse reactions.

Other medicines and interactions

Voriconazole is metabolized by cytochrome P450 isoenzymes, CYP2C19, CYP2C9, and CYP3A4. Therefore, inhibitors or inducers of these isoenzymes may increase or decrease voriconazole plasma concentrations, respectively. Voriconazole is a strong inhibitor of CYP3A4, and also inhibits CYP2C19 and CYP2C9. Therefore, voriconazole may increase the plasma concentrations of substances metabolized by these CYP450 isoenzymes. Tables 10 and 11 provide the clinically significant interactions between voriconazole and other medical products.

Table 10: Effect of Other Drugs on Voriconazole Pharmacokinetics

* Results based on in vivo clinical studies generally following repeat oral dosing with 200 mg every 12 hours voriconazole to healthy subjects ** Results based on in vivo clinical study following repeat oral dosing with 400 mg every 12 hours for 1 day, then 200 mg every 12 hours for at least 2 days voriconazole to healthy subjects *** Non-Nucleoside Reverse Transcriptase Inhibitors Table 11: Effect of Voriconazole on Pharmacokinetics of Other Drugs

*Results based on in vivo clinical studies generally following repeat oral dosing with 200 mg BID voriconazole to healthy subjects

** Results based on in vivo clinical study following repeat oral dosing with 400 mg every 12 hours for 1 day, then 200 mg every 12 hours for at least 2 days voriconazole to healthy subjects *** Results based on in vivo clinical study following repeat oral dosing with 400 mg every 12 hours for 1 day, then 200 mg every 12 hours for 4 days voriconazole to subjects receiving a methadone maintenance dose (30 to 100 mg every 24 hours) **** Non-Steroidal Anti-Inflammatory Drug ***** Non-Nucleoside Reverse Transcriptase Inhibitors