VISUAL DISTURBANCES: The effect of VFEND on visual function is not known if treatment
continues beyond 28 days. If treatment continues beyond 28 days, visual
function including visual acuity, visual field and color perception should be monitored
(see PRECAUTIONS – Information for Patients and ADVERSE REACTIONS – Visual Disturbances).
HEPATIC TOXICITY: In clinical trials, there have been uncommon cases of serious hepatic
reactions during treatment with VFEND (including clinical hepatitis, cholestasis
and fulminant hepatic failure, including fatalities). Instances of hepatic
reactions were noted to occur primarily in patients with serious underlying medical
conditions (predominantly hematological malignancy). Hepatic reactions, including
hepatitis and jaundice, have occurred among patients with no other identifiable
risk factors. Liver dysfunction has usually been reversible on discontinuation of
therapy (see PRECAUTIONS – Laboratory Tests and ADVERSE REACTIONS – Clinical Laboratory
Values).
Monitoring of hepatic function: Liver function tests should be evaluated
at the start of and during the course of VFEND therapy. Patients who develop abnormal
liver function tests during VFEND therapy should be monitored for the development
of more severe hepatic injury. Patient management should include laboratory evaluation
of hepatic function (particularly liver function tests and bilirubin). Discontinuation
of VFEND must be considered if clinical signs and symptoms consistent with liver
disease develop that may be attributable to VFEND (see PRECAUTIONS – Laboratory
Tests, DOSAGE AND ADMINISTRATION – Dosage Adjustment, ADVERSE REACTIONS - Clinical
Laboratory Tests).
Pregnancy Category D: Voriconazole can cause fetal harm when administered
to a pregnant woman.
Voriconazole was teratogenic in rats (cleft palates, hydronephrosis/hydroureter)
from 10 mg/kg (0.3 times the recommended maintenance dose (RMD) on a mg/m2
basis) and embryotoxic in rabbits at 100 mg/kg (6 times the RMD). Other effects
in rats included reduced ossification of sacral and caudal vertebrae, skull, pubic
and hyoid bone, supernumerary ribs, anomalies of the sternebrae and dilatation of
the ureter/renal pelvis. Plasma estradiol in pregnant rats was reduced at all dose
levels. Voriconazole treatment in rats produced increased gestational length and
dystocia, which were associated with increased perinatal pup mortality at the 10
mg/kg dose. The effects seen in rabbits were an increased embryomortality, reduced
fetal weight and increased incidences of skeletal variations, cervical ribs and
extrasternebral ossification sites.
If this drug is used during pregnancy, or if the patient becomes pregnant while
taking this drug, the patient should be apprised of the potential hazard to the
fetus.
Galactose intolerance: VFEND tablets contain lactose and should not be given
to patients with rare hereditary problems of galactose intolerance, Lapp lactase
deficiency or glucose-galactose malabsorption.