Overview
11 DESCRIPTION VFEND (voriconazole), an azole antifungal agent is available as a lyophilized powder for solution for intravenous infusion. The structural formula is: Voriconazole is designated chemically as (2R,3S)-2-(2, 4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1 H -1,2,4-triazol-1-yl)-2-butanol with an empirical formula of C 16 H 14 F 3 N 5 O and a molecular weight of 349.3.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Voriconazole is an antifungal drug [see Microbiology (12.4) ]. 12.2 Pharmacodynamics Exposure-Response Relationship for Efficacy and Safety In 10 clinical trials (N=1121), the median values for the average and maximum voriconazole plasma concentrations in individual patients across these studies was 2.51 µg/mL (inter-quartile range 1.21 to 4.44 µg/mL) and 3.79 µg/mL (inter-quartile range 2.06 to 6.31 µg/mL), respectively. A pharmacokinetic-pharmacodynamic analysis of patient data from 6 of these 10 clinical trials (N=280) could not detect a positive association between mean, maximum or minimum plasma voriconazole concentration and efficacy.
Indications
- 1 INDICATIONS AND USAGE VFEND is an azole antifungal indicated for the treatment of adults and pediatric patients 2 years of age and older with: • Invasive aspergillosis ( 1.1 ) • Candidemia in non-neutropenics and other deep tissue Candida infections ( 1.2 ) • Esophageal candidiasis ( 1.3 ) • Serious fungal infections caused by Scedosporium apiospermum and Fusarium species including Fusarium solani , in patients intolerant of, or refractory to, other therapy ( 1.4 ) 1.
Common Doses
- 6 mg
- 4 mg
- 200 mg
- 5 mL
Dosage
2 DOSAGE AND ADMINISTRATION • Dosage in Adults ( 2.3 ) Infection Loading Dose Maintenance Dose Intravenous infusion Intravenous infusion Oral tablets Oral suspension Invasive Aspergillosis 6 mg/kg every 12 hours for the first 24 hours 4 mg/kg every 12 hours 200 mg every 12 hours 5 mL every 12 hours Candidemia in nonneutropenics and other deep tissue Candida infections 3–4 mg/kg every 12 hours 200 mg every 12 hours 5 mL every 12 hours Scedosporiosis and Fusariosis 4 mg/kg every 12 hours 200 mg every 12 hours 5 mL every 12 hours Esophageal Candidiasis Not Evaluated Not Evaluated 200 mg every 12...
Contraindications
- 4 CONTRAINDICATIONS • VFEND 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 VFEND and other azole antifungal agents. Refer to the prescribing information for other azole antifungal agents. • Concomittant use of VFEND 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 VFEND. 1.
Side Effects
- 6 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.
Interactions
- 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) ] .