voriconazole (Vfend)
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Introduction
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
- rash 3%
- abnormal liver function tests 14%
- adverse ocular effects a blurry vision 11%
- optic neuritis
- papilledema
- ocular adverse effects have occurred mainly in severely ill patients
- hallucinations[2]
- less nephrotoxic than amphotericin B
- phototoxicity
- progression from phototoxic erythema to cutaneous pre-malignancies & skin cancers[6]
- cutaneous squamous cell carcinoma[5][6]
- cutaneous melanoma
- alopecia[7]
- > 1 month of therapy
- *hair loss stops & regrowth begins within 3 months of stopping the drug
- nail disease - nail loss[7]
Laboratory
Mechanism of action
- good in vitro activity against Aspergillus species
Management
- avoidance of sun exposure, protective clothing, & sunscreen
More general terms
Additional terms
References
- ↑ Journal Watch 22(7):55, 2002 Denning DW et al, Clin Invect Dis 34:563, 2002
- ↑ 2.0 2.1 2.2 Prescriber's Letter 9(7):40 2002
- ↑ 3.0 3.1 Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260704&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 4.0 4.1 4.2 Deprecated Reference
- ↑ 5.0 5.1 Medical Knowledge Self Assessment Program (MKSAP) 16 American College of Physicians, Philadelphia 2012
- ↑ 6.0 6.1 6.2 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24046296 <Internet> http://cid.oxfordjournals.org/content/57/12/e182
- ↑ 7.0 7.1 7.2 Malani AN et al. Alopecia and nail changes associated with voriconazole therapy. Clin Infect Dis 2014 Aug 1; 59:e61 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24855150 <Internet> http://cid.oxfordjournals.org/content/59/3/e61
- ↑ 8.0 8.1 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: https://www.ncbi.nlm.nih.gov/pubmed/29544767