Voriconazole (Vfend)

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]