Voriconazole (2 brand names, 5 dosage forms, 4 routes)
Available dosage forms: SOLUTION, FOR SUSPENSION, INJECTABLE, POWDER, TABLET.
Routes of administration: INTRAVENOUS, ORAL, INJECTION, Iv (Infusion).
Brand Names
- VFEND
- VORICONAZOLE
Contraindications
Voriconazole is contraindicated in patients with known hypersensitivity to voriconazole or its excipients [see Warnings and Precautions (5.5) and Adverse Reactions (6.1, 6.2)]. There is no information regarding cross-sensitivity between voriconazole and other azole antifungal agents. Refer to the prescribing information for other azole antifungal agents. • Concomitant use of voriconazole with the interacting drugs described and listed below in this section are a guide and not considered a comprehensive list of all possible drugs that may be contraindicated with voriconazole. 1. Concomitant use of voriconazole is contraindicated with drugs that are highly dependent on CYP3A4 for metabolism, and for which elevated plasma concentrations are associated with serious and/or life-threatening reactions [see Drug Interactions (7)]: • Eplerenone • Ergot alkaloids (e.g., ergotamine, dihydroergotamine)• Finerenone• Ivabradine• Lurasidone• Naloxegol• Pimozide• Quinidine• Rifabutin [see Clinical Pharmacology (12.3)] • Sirolimus [see Clinical Pharmacology (12.3)] • Tolvaptan• Venetoclax: Coadministration 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 [see Drug Interactions (7)].• Voclosporin 2. Concomitant use of voriconazole is contraindicated with drugs and herbal products that induce CYP2C19, CYP2C9, and/or CYP3A4 and for which significantly reduced voriconazole plasma concentrations may be associated with loss of efficacy [see Drug Interactions (7)]: • Carbamazepine• EfavirenzConcomitant use with efavirenz dosages of 400 mg every 24 hours or higher is contraindicated [see Clinical Pharmacology (12.3)].• Long-acting barbiturates• Rifabutin• Rifampin• Ritonavir Concomitant use with high-dose ritonavir (400 mg every 12 hours) is contraindicated. Concomitant use with low-dose ritonavir (100 mg every 12 hours) should
Adverse Reactions
The following serious adverse reactions are described elsewhere in the labeling: Hepatic Toxicity [see Warnings and Precautions (5.1)] Arrhythmias and QT Prolongation [see Warnings and Precautions (5.2)] Infusion Related Reactions [see Warnings and Precautions (5.3)] Visual Disturbances [see Warnings and Precautions (5.4)] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5)] Photosensitivity [see Warnings and Precautions (5.6)] Renal Toxicity [see Warnings and Precautions (5.7)]
Drug 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. Table 10 and Table 11 provide listings of clinically significant drug interactions, including contraindicated drugs [see Contraindications (4)]. Drugs listed in Table 10 and Table 11 are a guide and not considered a comprehensive list of all possible drugs and herbal products that are contraindicated or may interact with voriconazole. Table 10: Effect of Other Drugs on Voriconazole Pharmacokinetics [see Clinical Pharmacology (12.3)] * 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 Drug/Drug Class (Mechanism of Interaction by the Drug) Voriconazole Plasma Exposure (C max and AUC τ after 200 mg every 12 hours) Prevention or Management Recommendations Rifampin* and Rifabutin* (CYP450 Induction) Significantly Reduced Contraindicated Efavirenz (400 mg every 24 hours)** (CYP450 Induction) Efavirenz (300 mg every 24 hours)** (CYP450 Induction) Significantly Reduced Slight Decrease in AUCτ Contraindicated When voriconazole is concomitantly administered 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. High-dose Ritonavir (400 mg every 12 hours)** (CYP450 Induction) Low-dose Ritonavir (100 mg every 12 hours)** (CYP450 Induction) Si
Mechanism of Action
Voriconazole is an antifungal drug [see Microbiology (12.4)].
Overdosage
In clinical trials, there were three cases of accidental overdose. All occurred in pediatric patients who received up to five times the recommended intravenous dose of voriconazole. A single adverse reaction of photophobia of 10 minutes duration was reported. There is no known antidote to voriconazole. Voriconazole is hemodialyzed with clearance of 121 mL/min. The intravenous vehicle, SBECD, is hemodialyzed with clearance of 55 mL/min. In an overdose, hemodialysis may assist in the removal of voriconazole and SBECD from the body.