Infectious Diseases II
Voriconazole
Spectrum of activity
Candida spp. β Has coverage similar to fluconazole with the addition of activity against C.
krusei
ii.
Aspergillus, Fusarium, Scedosporium: Resistance against voriconazole has occurred with
these pathogens.
Dose
Drug of choice for invasive aspergillosis
ii.
6 mg/kg every 12 hours x 2 doses as the loading dose, followed by 4 mg/kg every 12 hours
iii.
Intravenous and oral formulations are available.
iv.
Intravenously formulated in sulfobutyl-ether-Ξ²-cyclodextrin, which accumulates in renal
dysfunction, although the clinical significance of this is unknown
Extensively metabolized by the liver, with 50% dose reductions recommended for patients
with moderate to severe cirrhosis
vi.
Genetic variations in CYP metabolism and high propensity for drug interactions lead to wide
interpatient variability in concentrations.
vii.
Therapeutic drug monitoring may be necessary. Please see the Pharmacokinetics/
Pharmacodynamics chapter for a discussion on voriconazole therapeutic drug monitoring.
Adverse reactions
Increase in liver function tests
ii.
Visual hallucinations
iii.
Rash
iv.
Nausea
CYP 3A4 and 2C9 inhibitor:
| (a) | Contraindicated with the use of rifampin, rifabutin, sirolimus, barbiturates, carbamazepine, |
|---|
and quinidine
| (b) | Significant dose reductions for cyclosporine and tacrolimus when coadministered with |
|---|
voriconazole
vi.
QTc prolongation
Posaconazole
Spectrum of activity: Wide spectrum of activity, which includes Candida (similar to voriconazole),
Aspergillus, Zygomycetes, and Fusarium
Dose
Oral suspension (immediate release): 200 mg every 6 hours. Oral suspension has extremely
erratic absorption that is enhanced by coadministration with a high-fat meal and acidic food. In
critically ill patients in whom coadministration with fatty meals is not possible and avoidance
of acid-suppressive stress ulcer prophylaxis cannot be avoided, would recommend considering
an alternative therapy or administration method (e.g., oral tablets or intravenous)
ii.
Oral tablets (delayed release): 300 mg every 12 hours x 2 doses, followed by 300 mg once
daily. Oral tablet is in an extended-release formulation, which cannot be crushed. Oral tablet
absorption not as dependent on gastric pH and meal lipid content.
iii.
Intravenous: 300 mg every 12 hours x 2 doses, followed by 300 mg once daily (intravenously
formulated in sulfobutyl-ether-Ξ²-cyclodextrin, which accumulates in renal dysfunction,
although the clinical significance of this is unknown)
iv.
Therapeutic drug monitoring may be necessary. Please see the Pharmacokinetics/
Pharmacodynamics chapter for further discussion.
Mainly used for fungal prophylaxis in immunocompromised patients and treatment when
patient is not responding to other therapies