Absorption: Well absorbed following oral administration (96%); IV administration results in complete bioavailability.
Distribution: Extensive tissue distribution.
Protein Binding: 58%.
Metabolism/Excretion: Highly metabolized by the hepatic P450 enzymes (CYP2C19, CYP2C9, CYP3A4); <2% excreted unchanged in urine. Much individual variation in metabolism; metabolites are inactive. The CYP2C19 enzyme system 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 hrs); ↑ in hepatic impairment.
CV: changes in BP, peripheral edema, QT interval prolongation, tachycardia.
Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS, MELANOMA, SQUAMOUS CELL CARCINOMA, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS, photosensitivity, rash.
EENT: visual disturbances, eye hemorrhage.
Endo: ADRENAL INSUFFICIENCY.
F and E: hypokalemia, hypomagnesemia, hyperglycemia.
GI: HEPATOTOXICITY, abdominal pain, diarrhea, nausea, pancreatitis, vomiting.
MS: fluorosis, periostitis.
Neuro: dizziness, hallucinations, headache.
Misc: chills, fever, infusion reactions.

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): Child-Pugh Class A and B Use standard IV loading dose, ↓ maintenance doses (IV or PO) by 50%; Child-Pugh Class C 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): Child-Pugh Class A and B Use standard IV loading dose, ↓ maintenance doses (IV or PO) by 50%; Child-Pugh Class C 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): Child-Pugh Class A and B Use standard IV loading dose, ↓ maintenance doses (IV or PO) by 50%; Child-Pugh Class C Not recommended.
Therapeutic Classification: antifungals