Dosing and uses of Vfend (voriconazole)
Adult dosage forms and strengths
oral suspension
- 200mg/5mL
injection, powder for reconstitution
- 200mg
tablets
- 50mg
- 200mg
Invasive Aspergillosis
In clinical trials, the majority of isolates recovered were Aspergillus fumigatus
6 mg/kg IV q12hr for first 24 hours, then 4 mg/kg IV q12hr or 200 mg PO q12hr
Median duration of treatment: IV 10 days (range 2-90 days); PO 76 days (range 2-232 days)
Candidemia
Indicated for candidemia in non-neutropenic patients with other deep tissue Candida infections (eg, Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis)
6 mg/kg IV q12hr for first 24 hours, then 3- 4 mg/kg IV q12hr or 200 mg PO q12hr
Esophageal Candidiasis
Candida albicans, Candida glabrata, Candida krusei
200 mg PO q12hr
Serious Fungal Infections
Caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii) and Fusarium spp. including Fusarium solani, in patients intolerant of or refractory to other therapy
6 mg/kg IV q12hr for first 24 hours, then 4 mg/kg IV q12hr or 200 mg PO q12hr
Dosage modification
Adults weighing <40 mg: Decrease PO maintenance dose by 50%
Renal impairment (CrCl <50 mL/min): Use oral form only for maintenance; avoid IV administration because of accumulation of IV vehicle (SBECD)
Hepatic impairment
- Mild-moderate (Child-Pugh A or B): Administer standard loading dose, but decrease maintenance dose by 50%
- Severe (Child-Pugh C): No data available
- Hepatitis B or C: No data available
Inadequate response
- Increase PO maintenance dose from 200 mg q12hr to 300 mg q12hr
- <40 kg: Increase PO maintenance dose from 100 mg q12hr to 150 mg q12hr
Administration
Infuse IV over 1-2 hr, not to exceed 3 mg/kg/hr
Take oral form 1 hr before or after meaL
Pediatric dosage forms and strengths
oral suspension
- 200mg/5mL
injection, powder for reconstitution
- 200mg
tablets
- 50mg
- 200mg
Invasive Aspergillosis
In clinical trials, the majority of isolates recovered were Aspergillus fumigatus
<12 years: Safety and efficacy not established
≥12 years: 6 mg/kg IV q12hr for first 24 hours, then 4 mg/kg IV q12hr or 200 mg PO q12hr
Median duration of treatment: IV 10 days (range 2-90 days); PO 76 days (range 2-232 days)
Candidemia
Indicated for candidemia in non-neutropenic patients with other deep tissue Candida infections (eg, Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis)
<12 years: Safety and efficacy not established
≥12 years: 6 mg/kg IV q12hr for first 24 hours, then 3- 4 mg/kg IV q12hr or 200 mg PO q12hr
Esophageal Candidiasis
Candida albicans, Candida glabrata, Candida krusei
<12 years: Safety and efficacy not established
≥12 years: 200 mg PO q12hr
Serious Fungal Infections
Caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii) and Fusarium spp. including Fusarium solani, in patients intolerant of or refractory to other therapy
<12 years: Safety and efficacy not established
≥12 years: 6 mg/kg IV q12hr for first 24 hours, then 4 mg/kg IV q12hr or 200 mg PO q12hr
Susceptible Fungal Infections (Off-label, Aged 2-12 yr)
9 mg/kg/dose IV/PO q12hr; not to exceed 350 mg/dose
Vfend (voriconazole) adverse (side) effects
>10%
Visual changes (photophobia, color changes, increased or decreased visual acuity, or blurred vision occur in 21%)
1-10%
Tachycardia
Hypertension
Hypotension
Vasodilation
Peripheral edema
Fever
Chills
Headache
Hallucinations
Dizziness
Rash
Pruritus
Photosensitizing skin reactions
Hypokalemia
Hypomagnesemia
Nausea
Vomiting
Abdominal pain
Diarrhea
Xerostomia
Thrombocytopenia
Alkaline phosphatase increased
Serum transaminases increased, ALT/AST increased
Cholestatic jaundice
ARF
Postmarketing Reports
Visual disturbances including optic neuritis and papilledema
Fluorosis and periostitis
Warnings
Contraindications
Hypersensitivity
Tablet contains lactose and is contraindicated in patients with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
Cisapride, astemizole, cisapride, pimozide, or quinidine: Voriconazole may increase plasma levels of these drugs and result in QT prolongation
Efavirenz (doses ≥400 mg/day): Efavirenz decreases voriconazole levels and voriconazole increases efavirenz levels
Ritonavir (high dose – 400 mg q12hr): Ritonavir decreases voriconazole levels
Ergot alkaloids: Voriconazole increases levels of ergot alkaloids (ergotamine, dihydroergotamine)
Rifabutin: Voriconazole increases rifabutin levels, and rifabutin decreases voriconazole levels
Sirolimus: Voriconazole increases sirolimus levels
St. John’s wort, rifampin, carbamazepine, barbiturates: Decreases voriconazole levels
Cautions
Hypersensitivity to other azoles
Do not give IV bolus
Review patient’s concomitant medications
Caution with renal impairment
Serious hepatic reactions reported; evaluate liver function tests at start of and during therapy
Avoid intense or prolonged exposure to direct sunlight; in patients with photosensitivity skin reactions, squamous cell carcinoma of the skin and melanoma have been reported during long-term therapy
No activity against Zygomycetes; some evidence suggests expanded use associated with increase incidence of zygomycosis
Visual disturbances, including optic neuritis and papilledema, reported; monitor visual function if treatment lasts >28 days
Not for administration to pregnant women unless benefits outweigh risks to fetus; inform patient of hazard
Not for use in patients with hereditary galactose, intolerance, Lapp lactase deficienty, or glucose-galactose malabsorption
Therapy associated with prolongation of the QT interval; caution in patients with proarrhythmic conditions, including congenital or acquired QT-prolongation, sinus bradycardia, existing symptomatic arrhythmias, or cardiomyopathy, especially if heart failure present; correct potassium, magnesium, and calcium before initiating therapy
Stop infusion if infusion related reactions occur
Discontinue for exfoliative cutaneous reactions or phototoxicity; avoid sunlight due to risk of photosensitivity
Fluorosis and priostitis reported with long-term treatment; discontinue if they occur
Monitor patients with risk factors for acute pancreatitis (eg, recent chemotherapy, hematopoietic stem cell transplantation) for pancreatitis symptoms during therapy
Pregnancy and lactation
Pregnancy category: d
Lactation: Not known if excreted in breast milk, a decision should be made whether to discontinue nursing or drug; weigh risk/benefit
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Vfend (voriconazole)
Mechanism of action
Triazole antifungal agent: Acts by inhibition of fungal cytochrome P-450 and sterol C-14 alpha-demethylation; decreases ergosterol synthesis and inhibits fungal cell membrane formation
Pharmacokinetics
Half-Life: Variable, dose-dependent due to non-linear kinetics
Peak Plasma Time: 1-2 hr
Vd: 4.6 L/Kg
Protein binding: 58%
Metabolism: Via hepatic CYP2C19, CYP2C9, CYP3A4
Bioavailability: 96%
Excretion: urine (80%)
Administration
IV Preparation
Reconstitute with 19 mL SWI to obtain an extractable volume of 20 mL of 10 mg/mL solution
Shake until fully dissolved
Reconstituted product can be further diluted for infusion in NS, LR, D5W, 1/2NS, 5% dextrose in LR, 5% dextrose in NS, 5% dextrose in 1/2NS, 5% dextrose in 20 mEq KCL
No preservatives-best to use immediately after reconstitution
IV Administration
Calculate amount of Vfend required, withdraw and discard at least an equal volume from infusion bag or bottle and add Vfend solution to the bag or bottle
Final infusion conc should be 5 mg/mL or less
IV infusion over 1-2 hr, NMT 3 mg/kg/hr
IV Incompatibilities
Any other drugs, parenteral nutrition, Na bicarB
Storage
Store vials at 15-30°C (59-86°F)
