Indications

• Invasive Pulmonary Aspergillosis (see Invasive Pulmonary Aspergillosis, [[Invasive Pulmonary Aspergillosis]])
• Candidemia in Non-Neutropenic Patients (see Candida, [[Candida]])
  • Abdominal Infections
  • Bladder Wall Infections
  • Disseminated Skin Infections
  • Kidney Infections
  • Wound Infections
• Candida Esophagitis (see Candida, [[Candida]])
• Scedosporium Apiospermum (see Scedosporiosis, [[Scedosporiosis]]): asexual form of Pseudallescheria boydii) in patients refractory to, or intolerant of, other therapy
• Fusarium (see Fusarium, [[Fusarium]]): in patients refractory to, or intolerant of, other therapy

---

Pharmacology

• Triazole Antifungal: inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation
• Oral Bioavailabiltiy: 96%
• Half-Life: dose-dependent (non-linear kinetics)

Metabolism

• Hepatic Cytochrome P450 Metabolism: with 80% excreted in the urine
  • Children clear voriconazole faster than adults
• Hepatic Impairment: adminster standard loading dose, with 50% reduction in PO maintenance dose
• Renal Impairment: avoid use of voriconazole IV, due to accumulation of its intravenous solvent vehicle, sulphobutylether-beta-cyclodextrin sodium (SBECD, Captisol)
  • Data suggest that this solvent may not be cleared with hemodialysis
• Drug Interactions-Contraindication to Concomitant Use with Voriconazole
  • Astemizole
  • Cisapride
  • Ergot Alkaloids
  • Lovastatin
  • Sirolimus
  • Rifampin
  • Rifabutin
  • Ritonavir
• Drug Interactions-Cautious Use with Voriconazole
  • Amiodarone
  • Cyclosporine A (CSA)
  • *Tacrolimus
  • Omeprazole
  • Phenytoin (Dilantin)

---

Administration

• Invasive Aspergillosis/Scedosporiosis/Fusarium: 6 mg/kg IV q12hrs for first 24 hrs, then 4 mg/kg IV q12hr (or 200 mg PO q12hrs)
• Candidemia: 6 mg/kg IV q12hrs for first 24 hrs, then 3-4 mg/kg IV q12hr (or 200 mg PO q12hrs)
• Candida Esophagitis: 200 mg PO q12hrs

Dose Adjustment

• Hepatic
• Renal

---

Adverse Effects

Cardiovascular Adverse Effects

• Q-T Prolongation (see Torsade, [[Torsade]])

Gastrointestinal Adverse Effects

• Abdominal Pain (see Abdominal Pain, [[Abdominal Pain]])
• Diarrhea (see Diarrhea, [[Diarrhea]])
• Hepatotoxicity (see xxxx, [[xxxx]]): common to azole anti-fungals
• Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]])

Neurologic Adverse Effects

• Headache (see Headache, [[Headache]])
• Transient Visual Disturbances: typically occur 1 hr after administration (and may last 30 min)
  • Blurred Vision
  • Photophobia (see Photophobia, [[Photophobia]])

Other Adverse Effects

• Fever (see Fever, [[Fever]])
• Increased Risk of Squamous Cell Carcinoma of Skin (see xxxx, [[xxxx]])
• Peripheral Edema (see Peripheral Edema, [[Peripheral Edema]])
• Rash

---

References

• Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347(6):408-415 [MEDLINE]
• The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica. 2006;91(8):1068-1075 [MEDLINE]
• Accumulation of the solvent vehicle sulphobutylether beta cyclodextrin sodium in critically ill patients treated with intravenous voriconazole under renal replacement therapy. BMC Clin Pharmacol. 2006 Sep 18;6:6 [MEDLINE]
• Evaluation of intravenous voriconazole in patients with compromised renal function. BMC Infect Dis. 2013 Jan 16;13:14 [MEDLINE]