Voriconazole

Voriconazole, sold under the brand name Vfend among others, is an antifungal medication used to treat a number of fungal infections.[2] This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by Scedosporium or Fusarium.[2] It can be taken by mouth or used by injection into a vein.[2]

Voriconazole
Clinical data
Pronunciation/vɒrɪˈkɒnəzoʊl/ vorr-i-KON-ə-zohl
Trade namesVfend, others
AHFS/Drugs.comMonograph
MedlinePlusa605022
License data
Pregnancy
category
  • AU: B3
Routes of
administration		Intravenous, by mouth (tablet, suspension)
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only
  • EU: Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability96% (oral)
Protein binding58%
MetabolismLiver: CYP2C19 (significant involvement), also CYP2C9, CYP3A4
MetabolitesVoriconazole N-oxide (major; minimal antifungal activity)
Elimination half-lifeDose-dependent
ExcretionUrine (80–83%)[1]
Identifiers
  • (2R,3S)-2-(2,4-Difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.157.870
Chemical and physical data
FormulaC16H14F3N5O
Molar mass349.317 g·mol−1
3D model (JSmol)
  • Fc1cncnc1[C@@H]([C@@](O)(c2ccc(F)cc2F)Cn3ncnc3)C
  • InChI=1S/C16H14F3N5O/c1-10(15-14(19)5-20-7-22-15)16(25,6-24-9-21-8-23-24)12-3-2-11(17)4-13(12)18/h2-5,7-10,25H,6H2,1H3/t10-,16+/m0/s1 checkY
  • Key:BCEHBSKCWLPMDN-MGPLVRAMSA-N checkY
  (verify)

Common side effects include vision problems, nausea, abdominal pain, rash, headache, and seeing or hearing things that are not present.[2] Use during pregnancy may result in harm to the baby.[2] It is in the triazole family of medications.[2] It works by affecting fungal metabolism and fungal cell membranes.[2]

Voriconazole was patented in 1990 and approved for medical use in the United States in 2002.[3][4] It is on the World Health Organization's List of Essential Medicines.[5]

Medical uses

Voriconazole is used to treat invasive aspergillosis and candidiasis and fungal infections caused by Scedosporium and Fusarium species, which may occur in immunocompromised patients, including people undergoing allogeneic bone marrow transplant (BMT), who have hematologic cancers or who undergo organ transplants.[6][7][8][9]

It is also used to prevent fungal infection in people as they undergo BMT.[8][6]

It is also the recommended treatment for the CNS fungal infections transmitted by epidural injection of contaminated steroids.[10]

It can be taken by mouth or given in a doctor's office or clinic by intravenous infusion.[6]

Contraindications

It is toxic to the fetus; pregnant women should not take it and women taking it should not become pregnant.[1]

People who have hereditary intolerance for galactose, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this drug. It should be used with caution in people with arrhythmias or long QT.[1]

No dose adjustment is necessary for renal impairment or advanced age, but children seem to clear voriconazole faster than adults and drug levels may need monitoring.[11]

Side effects

The labels carry several warnings of the risk of injection site reactions, hypersensitivity reactions; kidney, liver, and pancreas damage; trouble with vision; and adverse effects in skin including damage due to phototoxicity, squamous cell skin cancer, and Stevens–Johnson syndrome; in long-term use there is a warning of the risk of bone fluorosis and periostitis especially in elderly patients.[12][1][13][6]

Additionally, very common adverse effects, occurring in more than 10% of people, include peripheral edema, headaches, trouble breathing, diarrhea, vomiting, abdominal pain, nausea, rashes, and fever.[6]

Common adverse effects, occurring in between 1 and 10% of people, include sinus infections, low numbers of white and red blood cells (agranulocytosis, pancytopenia, thrombocytopenia, leukopenia, and anemia), low blood sugar, reduced amount of potassium and sodium, depression, hallucinations, anxiety, insomnia, agitation, confusion, convulsions, fainting, tremor, weakness, tingling, sleepiness, dizziness, bleeding retina, irregular heart beats, slow or fast heart beats, low blood pressure, inflamed veins, acute respiratory distress syndrome, pulmonary edema, inflamed lips, swollen face, stomach upset, constipation, gingivitis, jaundice, hair loss, flaky skin, itchiness, red skin, back pain, chest pain, and chills.[6]

Interactions

Being metabolized by hepatic cytochrome P450, voriconazole interacts with many drugs.[1][6] Voriconazole should not be used in conjunction with many drugs (including sirolimus, rifampicin, rifabutin, carbamazepine, quinidine and ergot alkaloids) and dose adjustments and/or monitoring should be done when coadministered with others (including fluconazole, warfarin, ciclosporin, tacrolimus, omeprazole, and phenytoin). Voriconazole may be safely administered with cimetidine, ranitidine, indinavir, macrolide antibiotics, mycophenolate, digoxin and prednisolone.[1]

Pharmacology

Pharmacokinetics

Voriconazole is well absorbed orally with a bioavailability of 96%, allowing patients to be switched between intravenous and oral administration.

History

Pfizer brought the drug to market as Vfend. A generic version of the tablet form of voriconazole was introduced in the US in 2011 after Pfizer and Mylan settled litigation under the Hatch-Waxman Act; a generic version of the injectable form was introduced in 2012. In Europe patent protection expired in 2011 and pediatric administrative exclusivity expired in Europe in 2016.[14]

Society and culture

Brand names

As of July 2017, the medication is marketed under the following names worldwide: Cantex, Pinup, Vedilozin, Vfend, Vodask, Volric, Voramol, Voriconazol, Voriconazole, Voriconazolum, Voricostad, Vorikonazol, Voritek, Voriz, Vornal, and Vosicaz.[15]

References
  1. "Vfend- voriconazole tablet, film coated Vfend- voriconazole injection, powder, lyophilized, for solution Vfend- voriconazole powder, for suspension". DailyMed. 16 September 2020. Retrieved 15 October 2020.
  2. "Voriconazole". The American Society of Health-System Pharmacists. Retrieved 8 December 2017.
  3. Kendig EL, Wilmott RW, Chernick V (2012). Kendig and Chernick's Disorders of the Respiratory Tract in Children. Elsevier Health Sciences. p. 539. ISBN 978-1437719840.
  4. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 503. ISBN 9783527607495.
  5. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  6. "Vfend tablet and powder". UK Electronic Medicines Compendium. January 2017. Retrieved 30 July 2017.
  7. Patterson TF, Thompson GR, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. (August 2016). "Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America". Clinical Infectious Diseases. 63 (4): e1–e60. doi:10.1093/cid/ciw326. PMC 4967602. PMID 27365388.
  8. Omrani AS, Almaghrabi RS (December 2017). "Complications of hematopoietic stem transplantation: Fungal infections". Hematology/Oncology and Stem Cell Therapy. 10 (4): 239–244. doi:10.1016/j.hemonc.2017.05.013. PMID 28636889.
  9. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. (August 2002). "Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis". The New England Journal of Medicine. 347 (6): 408–415. doi:10.1056/NEJMoa020191. hdl:2066/185528. PMID 12167683.
  10. "Interim Treatment Guidance for Central Nervous System and Parameningeal Infections Associated with Injection of Contaminated Steroid Products". Centers for Disease Control and Prevention. Retrieved 6 November 2016.
  11. Smith J, Safdar N, Knasinski V, Simmons W, Bhavnani SM, Ambrose PG, Andes D (April 2006). "Voriconazole therapeutic drug monitoring". Antimicrobial Agents and Chemotherapy. 50 (4): 1570–1572. doi:10.1128/AAC.50.4.1570-1572.2006. PMC 1426935. PMID 16569888.
  12. Stefan S, Altork N, Alzedaneen Y, Whitlatch H, Munir KM (2022-09-01). "Voriconazole-Induced Diffuse Periostitis". AACE Clinical Case Reports. 8 (5): 191–193. doi:10.1016/j.aace.2022.05.001. PMC 9508586. PMID 36189133.
  13. Guarascio AJ, Bhanot N, Min Z (September 2021). "Voriconazole-associated periostitis: Pathophysiology, risk factors, clinical manifestations, diagnosis, and management". World Journal of Transplantation. 11 (9): 356–371. doi:10.5500/wjt.v11.i9.356. PMC 8465512. PMID 34631468.
  14. "Vfend loses its paediatric protection" (PDF). IMS Health Generics Bulletin. 22 July 2016.
  15. "Voriconazole international brand names". Drugs.com. Retrieved 30 July 2017.

Further reading
  • "Voriconazole". Drug Information Portal. U.S. National Library of Medicine.
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