Therapeutic Classification: antifungals
Pharmacologic Classification: azoles
Absorption: 96% absorbed following oral administration; IV administration results in complete bioavailability.
Distribution: Widely distributed to tissues.
Metabolism/Excretion: Primarily metabolized by liver via the CYP2C19, CYP2C9, and CYP3A4 isoenzymes; <2% excreted unchanged in urine. The CYP2C19 isoenzyme exhibits genetic polymorphism; 1520% of Asian patients and 35% of Caucasian and Black patients may be poor metabolizers and may have significantly ↑ voriconazole concentrations and an ↑ risk of adverse effects.
Half-Life: Dose-dependent (adults: 69 hr); ↑ in hepatic impairment.
Invasive Aspergillosis, Scedosporiosis, or Fusariosis
- IV PO (Adults ≥40 kg): Loading dose (IV): 6 mg/kg IV every 12 hr for 2 doses, followed by maintenance dose (IV) of 4 mg/kg IV every 12 hr (use 5 mg/kg IV every 12 hr if concurrently using with phenytoin). Continue IV therapy for ≥7 days, then switch to oral maintenance dose once patient has clinically improved and can tolerate oral medications. Maintenance dose (PO): 200 mg PO every 12 hr (use 400 mg PO every 12 hr if concurrently using with phenytoin or efavirenz); if response inadequate, may ↑ to 300 mg every 12 hr. Total duration of therapy: ≥612 wk.
- IV PO (Adults <40 kg): Loading dose (IV): 6 mg/kg IV every 12 hr for 2 doses, followed by maintenance dose (IV) of 4 mg/kg IV every 12 hr (use 5 mg/kg IV every 12 hr if concurrently using with phenytoin). Continue IV therapy for ≥7 days, then switch to oral maintenance dose once patient has clinically improved and can tolerate oral medications. Maintenance dose (PO): 100 mg PO every 12 hr (use 200 mg PO every 12 hr if concurrently using with phenytoin; use 400 mg PO every 12 hr if concurrently using with efavirenz); if response inadequate, may ↑ to 150 mg every 12 hr. Total duration of therapy: ≥612 wk.
- IV PO (Children ≥15 yr): Loading dose (IV): 6 mg/kg IV every 12 hr for 2 doses, followed by maintenance dose (IV) of 4 mg/kg IV every 12 hr. Continue IV therapy for ≥7 days, then switch to oral maintenance dose once patient has clinically improved and can tolerate oral medications. Maintenance dose (PO): 200 mg every 12 hr; if response inadequate, may ↑ to 300 mg every 12 hr. Total duration of therapy: ≥612 wk.
- IV PO (Children 1214 yr and ≥50 kg): Loading dose (IV): 6 mg/kg IV every 12 hr for 2 doses, followed by maintenance dose (IV) of 4 mg/kg IV every 12 hr. Continue IV therapy for ≥7 days, then switch to oral maintenance dose once patient has clinically improved and can tolerate oral medications. Maintenance dose (PO): 200 mg every 12 hr; if response inadequate, may ↑ to 300 mg every 12 hr. Total duration of therapy: ≥612 wk.
- IV PO (Children 1214 yr and <50 kg): Loading dose (IV): 9 mg/kg IV every 12 hr for 2 doses, followed by maintenance dose (IV) of 8 mg/kg IV every 12 hr; if response inadequate, may ↑ maintenance dose by 1 mg/kg. Continue IV therapy for ≥7 days, then switch to oral maintenance dose once patient has clinically improved and can tolerate oral medications. Maintenance dose (PO): 9 mg/kg every 12 hr (not to exceed 350 mg every 12 hr); if response inadequate, may ↑ by 1 mg/kg or 50 mg (not to exceed 350 mg every 12 hr). Total duration of therapy: ≥612 wk.
- IV PO (Children 211 yr): Loading dose (IV): 9 mg/kg IV every 12 hr for 2 doses, followed by maintenance dose (IV) of 8 mg/kg IV every 12 hr; if response inadequate, may ↑ maintenance dose by 1 mg/kg. Continue IV therapy for ≥7 days, then switch to oral maintenance dose once patient has clinically improved and can tolerate oral medications. Maintenance dose (PO): 9 mg/kg every 12 hr (not to exceed 350 mg every 12 hr); if response inadequate, may ↑ by 1 mg/kg or 50 mg (not to exceed 350 mg every 12 hr). Total duration of therapy: ≥612 wk.
Hepatic Impairment
- IV PO (Adults ): Mild or moderate hepatic impairment: Use standard IV loading dose, ↓ maintenance doses (IV or PO) by 50%; Severe hepatic impairment: Not recommended.
Candidemia in Non-Neutropenic Patients or Other Deep Tissue Candida Infections
- IV PO (Adults ≥40 kg): Loading dose (IV): 6 mg/kg IV every 12 hr for 2 doses, followed by maintenance dose (IV) of 34 mg/kg IV every 12 hr (use 5 mg/kg IV every 12 hr if concurrently using with phenytoin). Switch to oral dosing once patient has clinically improved and can tolerate oral medications. Maintenance dose (PO): 200 mg PO every 12 hr (use 400 mg PO every 12 hr if concurrently using with phenytoin or efavirenz); if response inadequate, may ↑ to 300 mg every 12 hr. Total duration of therapy: ≥14 days following resolution of symptoms or following last positive culture, whichever is longer.
- IV PO (Adults <40 kg): Loading dose (IV): 6 mg/kg IV every 12 hr for 2 doses, followed by maintenance dose (IV) of 34 mg/kg IV every 12 hr (use 5 mg/kg IV every 12 hr if concurrently using with phenytoin). Switch to oral dosing once patient has clinically improved and can tolerate oral medications. Maintenance dose (PO): 100 mg PO every 12 hr (use 200 mg PO every 12 hr if concurrently using with phenytoin; use 400 mg PO every 12 hr if using concurrently with efavirenz); if response inadequate, may ↑ to 150 mg every 12 hr. Total duration of therapy: ≥14 days following resolution of symptoms or following last positive culture, whichever is longer.
- IV PO (Children ≥15 yr): Loading dose (IV): 6 mg/kg IV every 12 hr for 2 doses, followed by maintenance dose (IV) of 34 mg/kg IV every 12 hr. Switch to oral dosing once patient has clinically improved and can tolerate oral medications. Maintenance dose (PO): 200 mg every 12 hr; if response inadequate, may ↑ to 300 mg every 12 hr. Total duration of therapy: ≥14 days following resolution of symptoms or following last positive culture, whichever is longer.
- IV PO (Children 1214 yr and ≥50 kg): Loading dose (IV): 6 mg/kg IV every 12 hr for 2 doses, followed by maintenance dose (IV) of 34 mg/kg IV every 12 hr. Switch to oral dosing once patient has clinically improved and can tolerate oral medications. Maintenance dose (PO): 200 mg every 12 hr; if response inadequate, may ↑ to 300 mg every 12 hr. Total duration of therapy: ≥14 days following resolution of symptoms or following last positive culture, whichever is longer.
- IV PO (Children 1214 yr and <50 kg): Loading dose (IV): 9 mg/kg IV every 12 hr for 2 doses, followed by maintenance dose (IV) of 8 mg/kg IV every 12 hr; if response inadequate, may ↑ maintenance dose by 1 mg/kg. Switch to oral dosing once patient has clinically improved and can tolerate oral medications. Maintenance dose (PO): 9 mg/kg every 12 hr (not to exceed 350 mg every 12 hr); if response inadequate, may ↑ by 1 mg/kg or 50 mg (not to exceed 350 mg every 12 hr). Total duration of therapy: ≥14 days following resolution of symptoms or following last positive culture, whichever is longer.
- IV PO (Children 211 yr): Loading dose (IV): 9 mg/kg IV every 12 hr for 2 doses, followed by maintenance dose (IV) of 8 mg/kg IV every 12 hr; if response inadequate, may ↑ maintenance dose by 1 mg/kg. Switch to oral dosing once patient has clinically improved and can tolerate oral medications. Maintenance dose (PO): 9 mg/kg every 12 hr (not to exceed 350 mg every 12 hr); if response inadequate, may ↑ by 1 mg/kg or 50 mg (not to exceed 350 mg every 12 hr). Total duration of therapy: ≥14 days following resolution of symptoms or following last positive culture, whichever is longer.
Hepatic Impairment
- IV PO (Adults ): Mild or moderate hepatic impairment: Use standard IV loading dose, ↓ maintenance doses (IV or PO) by 50%; Severe hepatic impairment: Not recommended.
Esophageal Candidiasis
- PO (Adults ≥40 kg): 200 mg every 12 hr (use 400 mg every 12 hr if concurrently using with phenytoin or efavirenz); if response inadequate, may ↑ to 300 mg every 12 hr. Duration of therapy: ≥14 days and for ≥7 days following resolution of symptoms.
- PO (Adults <40 kg): 100 mg every 12 hr (use 200 mg every 12 hr if concurrently using with phenytoin; use 400 mg every 12 hr if using concurrently with efavirenz); if response inadequate, may ↑ to 150 mg every 12 hr. Duration of therapy: ≥14 days and for ≥7 days following resolution of symptoms.
- PO (Children ≥15 yr): 200 mg every 12 hr; if response inadequate, may ↑ to 300 mg every 12 hr. Duration of therapy: ≥14 days and for ≥7 days following resolution of symptoms.
- PO (Children 1214 yr and ≥50 kg): 200 mg every 12 hr; if response inadequate, may ↑ to 300 mg every 12 hr. Duration of therapy: ≥14 days and for ≥7 days following resolution of symptoms.
- IV PO (Children 1214 yr and <50 kg): Initiate therapy with maintenance dose (IV) of 4 mg/kg IV every 12 hr; if response inadequate, may ↑ maintenance dose by 1 mg/kg. Switch to oral dosing once patient has clinically improved and can tolerate oral medications. Maintenance dose (PO): 9 mg/kg every 12 hr (not to exceed 350 mg every 12 hr); if response inadequate, may ↑ by 1 mg/kg or 50 mg (not to exceed 350 mg every 12 hr). Total duration of therapy: ≥14 days and for ≥7 days following resolution of symptoms.
- IV PO (Children 211 yr): Initiate therapy with maintenance dose (IV) of 4 mg/kg IV every 12 hr; if response inadequate, may ↑ maintenance dose by 1 mg/kg. Switch to oral dosing once patient has clinically improved and can tolerate oral medications. Maintenance dose (PO): 9 mg/kg every 12 hr (not to exceed 350 mg every 12 hr); if response inadequate, may ↑ by 1 mg/kg or 50 mg (not to exceed 350 mg every 12 hr). Total duration of therapy: ≥14 days and for ≥7 days following resolution of symptoms.
Hepatic Impairment
- IV PO (Adults ): Mild or moderate hepatic impairment: Use standard IV loading dose, ↓ maintenance doses (IV or PO) by 50%; Severe hepatic impairment: Not recommended.