The recommended dosing regimen for pediatric patients 2 to less than 12 years of age and 12 to 14 years of age with body weight less than 50 kg is shown in Table 2. For pediatric patients 12 to 14 years of age with a body weight greater than or equal to 50 kg and those 15 years of age and above regardless of body weight, administer the adult dosing regimen of VFEND [see Dosage and Administration (2.3)].
|Loading Dose||Maintenance Dose|
|Intravenous infusion||Intravenous infusion||Oral|
|Invasive Aspergillosis †||9 mg/kg every 12 hours for the first 24 hours||8 mg/kg every 12 hours after the first 24 hours||9 mg/kg every 12 hours(maximum dose of 350 mg every 12 hours)|
|Candidemia in nonneutropenics and other deep tissue Candida infections ‡|
|Scedosporiosis and Fusariosis|
|Esophageal Candidiasis ‡||Not Evaluated||4 mg/kg every 12 hours||9 mg/kg every 12 hours(maximum dose of 350 mg every 12 hours)|
Initiate therapy with an intravenous infusion regimen. Consider an oral regimen only after there is a significant clinical improvement. Note that an 8 mg/kg intravenous dose will provide voriconazole exposure approximately 2-fold higher than a 9 mg/kg oral dose.
The oral dose recommendation for children is based on studies in which VFEND was administered as the powder for oral suspension formulation. Bioequivalence between the VFEND powder for oral suspension and VFEND tablets has not been investigated in a pediatric population.
Oral bioavailability may be limited in pediatric patients 2 to 12 years with malabsorption and very low body weight for age. In that case, intravenous VFEND administration is recommended.
Method for Adjusting the Dosing Regimen in Pediatric Patients
Pediatric Patients 2 to less than 12 years of age and 12 to 14 years of age with body weight less than 50 kg
If patient response is inadequate and the patient is able to tolerate the initial intravenous maintenance dose, the maintenance dose may be increased by 1 mg/kg steps. If patient response is inadequate and the patient is able to tolerate the oral maintenance dose, the dose may be increased by 1 mg/kg steps or 50 mg steps to a maximum of 350 mg every 12 hours. If patients are unable to tolerate the initial intravenous maintenance dose, reduce the dose by 1 mg/kg steps. If patients are unable to tolerate the oral maintenance dose, reduce the dose by 1 mg/kg or 50 mg steps.
Pediatric patients 12 to 14 years of age weighing greater than or equal to 50 kg and 15 years of age and older regardless of body weight:
Use the optimal method for titrating dosage recommended for adults [see Dosage and Administration (2.3)].
The maintenance dose of VFEND should be reduced in adult patients with mild to moderate hepatic impairment, Child-Pugh Class A and B. There are no PK data to allow for dosage adjustment recommendations in patients with severe hepatic impairment (Child-Pugh Class C).
Duration of therapy should be based on the severity of the patient’s underlying disease, recovery from immunosuppression, and clinical response.
Adult patients with baseline liver function tests (ALT, AST) of up to 5 times the upper limit of normal (ULN) were included in the clinical program. Dose adjustments are not necessary for adult patients with this degree of abnormal liver function, but continued monitoring of liver function tests for further elevations is recommended [see Warnings and Precautions (5.1)].
It is recommended that the recommended VFEND loading dose regimens be used, but that the maintenance dose be halved in adult patients with mild to moderate hepatic cirrhosis (Child-Pugh Class A and B) [see Clinical Pharmacology (12.3)].
VFEND has not been studied in adult patients with severe hepatic cirrhosis (Child-Pugh Class C) or in patients with chronic hepatitis B or chronic hepatitis C disease. VFEND has been associated with elevations in liver function tests and with clinical signs of liver damage, such as jaundice. VFEND should only be used in patients with severe hepatic impairment if the benefit outweighs the potential risk. Patients with hepatic impairment must be carefully monitored for drug toxicity.
Dosage adjustment of VFEND in pediatric patients with hepatic impairment has not been established [see Use in Specific Populations (8.4)].
The pharmacokinetics of orally administered VFEND are not significantly affected by renal impairment. Therefore, no adjustment is necessary for oral dosing in patients with mild to severe renal impairment [see Clinical Pharmacology (12.3)].
In patients with moderate or severe renal impairment (creatinine clearance <50 mL/min) who are receiving an intravenous infusion of VFEND, accumulation of the intravenous vehicle, SBECD, occurs. Oral voriconazole should be administered to these patients, unless an assessment of the benefit/risk to the patient justifies the use of intravenous VFEND. Serum creatinine levels should be closely monitored in these patients, and, if increases occur, consideration should be given to changing to oral VFEND therapy [see Warnings and Precautions (5.7)].
Voriconazole and the intravenous vehicle, SBECD, are dialyzable. A 4-hour hemodialysis session does not remove a sufficient amount of voriconazole to warrant dose adjustment [see Clinical Pharmacology (12.3)].
Dosage adjustment of VFEND in pediatric patients with renal impairment has not been established [see Use in Specific Populations (8.4)].
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