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voriconazole (Vfend)

New drug. 2002 Indications: - aspergillosis*, - Fusarium solani [4] - alternative to amphotericin B for life-threatening fungal infections - empiric treatment of febrile neutropenia [4] * invasive aspergillosis: 14% cure, 55% improvement Contraindications: Caution: avoid driving at night (blurred vision) Dosage: - mean duration of treatment: 11.5 days (1-40 days) Pharmacokinetics: - metabolized to voriconazole N-oxide - similar to itraconazole in cyt P450 interactions [2] {cyt P450 3A4} Monitor: - liver function tests (serum ALT, serum AST, serum bilirubin) baseline & periodically [3] - if administration > 28 days, visual function should be monitored - therapeutic drug monitoring recommended when used to treat invasive aspergillosis [8] Adverse effects: 1) rash 3% 2) abnormal liver function tests 14% 3) adverse ocular effects a blurry vision 11% b) optic neuritis c) papilledema d) ocular adverse effects have occurred mainly in severely ill patients 4) hallucinations [2] 5) less nephrotoxic than amphotericin B 6) phototoxicity a) progression from phototoxic erythema to cutaneous pre-malignancies & skin cancers [6] b) cutaneous squamous cell carcinoma [5,6] c) cutaneous melanoma 7) alopecia [7] - > 1 month of therapy - *hair loss stops & regrowth begins within 3 months of stopping the drug 8) nail disease - nail loss [7] Laboratory: - voriconazole in CSF - voriconazole in dried blood spot - voriconazole in serum/plasma Mechanism of action: - good in vitro activity against Aspergillus species Management: - avoidance of sun exposure, protective clothing, & sunscreen

Interactions

drug interactions

Related

aspergillosis Aspergillus liver (function) tests (LFT, liver panel, hepatic function panel)

General

antifungal agent triazole; pyrrodiazole

Database Correlations

PUBCHEM cid=71616

References

  1. Journal Watch 22(7):55, 2002 Denning DW et al, Clin Invect Dis 34:563, 2002
  2. Prescriber's Letter 9(7):40 2002
  3. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  4. Deprecated Reference
  5. Medical Knowledge Self Assessment Program (MKSAP) 16 American College of Physicians, Philadelphia 2012
  6. Epaulard O et al. A multistep voriconazole-related phototoxic pathway may lead to skin carcinoma: Results from a French nationwide study. Clin Infect Dis 2013 Dec 15; 57:e182 PMID: 24046296 http://cid.oxfordjournals.org/content/57/12/e182
  7. Malani AN et al. Alopecia and nail changes associated with voriconazole therapy. Clin Infect Dis 2014 Aug 1; 59:e61 PMID: 24855150 http://cid.oxfordjournals.org/content/59/3/e61
  8. Ullmann AJ, Aguado JM, Arikan-Akdagli S et al Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018 Mar 12 PMID: 29544767