Voriconazole

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 ) 1.1 Invasive Aspergillosis VFEND is indicated in adults and pediatric patients (2 years of age and older) for the treatment of invasive aspergillosis (IA). In clinical trials, the majority of isolates recovered were Aspergillus fumigatus . …

• Dosage
• In Adults 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 hours 5 mL every 12 hours o Adult patients weighing less than 40 kg: oral maintenance dose 100 mg or 150 mg every 12 hours o Hepatic Impairment : Use half the maintenance dose in adult patients with mild to moderate hepatic impairment (Child-Pugh Class A and B) o Renal Impairment : Avoid intravenous administration in adult patients with moderate to severe renal impairment (creatinine clearance

For Injection : Lyophilized powder containing 200 mg of voriconazole and 3,200 mg of sulfobutyl ether beta-cyclodextrin sodium (SBECD); after reconstitution 10 mg/mL of voriconazole and 160 mg/mL of SBECD ( 3 ) Powder for Solution for Injection VFEND I.V. …

• The safety and effectiveness of VFEND have been established
• In pediatric patients 2 years of age and older based on evidence from adequate and well-controlled studies in adult and pediatric patients and additional pediatric pharmacokinetic and safety data
• A total of 105
• Pediatric patients aged 2 to less than 12 [N=26] and aged 12 to less than 18 [N=79] from two, non-comparative Phase 3 pediatric studies and eight adult therapeutic trials provided safety information for VFEND use in the pediatric population [see Adverse Reactions , Clinical Pharmacology , and Clinical Studies …

In multiple dose therapeutic trials of voriconazole, 9.2% of patients were ≥65 years of age and 1.8% of patients were ≥75 years of age. In a study in healthy subjects, the systemic exposure (AUC) and peak plasma concentrations (C max ) were increased in elderly males compared to young males. …

• Advise the patient to read the FDA-approved patient labeling (Patient Information)
• Visual Disturbances Patients should be instructed that visual disturbances such as blurring and sensitivity to light may occur with the use of VFEND
• Photosensitivity • Advise patients of the risk of photosensitivity (with or without concomitant methotrexate), accelerated photoaging, and skin cancer. • Advise patients that VFEND can cause serious photosensitivity and to immediately contact their healthcare provider for new or worsening skin rash. • Advise patients to avoid exposure to direct sun light and to use measures such as protective clothing and sunscreen with high sun protection factor (SPF). …

• VFEND is contraindicated in patients with known hypersensitivity to voriconazole or its excipients [see Warnings and Precautions and Adverse Reactions ]
• There is no information regarding cross-sensitivity between VFEND and other azole antifungal agents
• Refer to the prescribing information for other azole antifungal agents. …

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) ] . …

• Hepatic Toxicity : Serious hepatic reactions reported. Evaluate liver function tests at start of and during VFEND therapy ( 5.1 ) • Arrhythmias and QT Prolongation : Correct potassium, magnesium, and calcium prior to use; caution patients with proarrhythmic conditions ( 5.2 ) • Infusion Related Reactions (including anaphylaxis) : Stop the infusion ( 5.3 ) • Visual Disturbances (including optic neuritis and papilledema): Monitor visual function if treatment continues beyond 28 days ( 5.4 ) • Severe Cutaneous Adverse Reactions : Discontinue for exfoliative cutaneous reactions ( 5.5 ) • Photosensitivity : Avoid sunlight due to risk of photosensitivity ( 5.6 ) • Adrenal Dysfunction : Carefully …

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) ] • Adult Patients : The most common adverse reactions (incidence ≥2%) were visual disturbances, fever, nausea, rash, vomiting, chills, headache, liver function test abnormal, tachycardia, hal …

8.1 Pregnancy Risk Summary Voriconazole can cause fetal harm when administered to a pregnant woman. There are no available data on the use of VFEND in pregnant women. In animal reproduction studies, oral voriconazole was associated with fetal malformations in rats and fetal toxicity in rabbits. …

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.

16.2 Storage VFEND I.V. for Injection unreconstituted vials should be stored at 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. VFEND is a single dose unpreserved sterile lyophile. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.