Voriconazole

Voriconazole
Clinical data
Pronunciation /vɒrɪˈkɒnəzoʊl/ vorr-i-KON-ə-zohl
Trade names Vfend, others
Synonyms (αR,βS)-α-(2,4-Difluorophenyl)-5-fluoro-β-methyl-α-(1H-1,2,4-triazol-1-ylmethyl)-4-pyrimidineethanol[1]
AHFS/Drugs.com Monograph
MedlinePlus a605022
License data
Pregnancy
category
  • D
Routes of
administration		 IV, by mouth (tablets, by mouth suspension)
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 96% (oral administration)
Protein binding 58%
Metabolism Liver: CYP2C19 (significant involvement), also CYP2C9, CYP3A4
Metabolites Voriconazole N-oxide (major; minimal antifungal activity)
Elimination half-life Dose-dependent
Excretion Urine (80–83%)[2]
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
Formula C16H14F3N5O
Molar mass 349.311 g/mol
3D model (JSmol)
  (verify)

Voriconazole, sold under the brand name Vfend among others, is an antifungal medication used to treat a number of fungal infections.[3] This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by Scedosporium or Fusarium.[3] It can be taken by mouth or used by injection into a vein.[3]

Common side effects include vision problems, nausea, abdominal pain, rash, headache, and seeing or hearing things that are not present.[3] Use during pregnancy may result in harm to the baby.[3] It is in the triazole family of medications.[3] It works by affecting the cell membrane or affecting fungal metabolism.[3]

Voriconazole was approved for medical use in the United States in 2002.[4] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[5] Generic versions have been approved.[6] The wholesale cost in the United States, as of 2017, is about 14.86 USD per day.[7]

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.[8][9][10][11]

It is also used to prevent fungal infection in people as they undergo BMT.[10][8]

It is also the recommended treatment for the CNS fungal infections transmitted by epidural injection of contaminated steroids.[12]

It can be taken by mouth or given in a doctor's office or clinic by intravenous infusion.[8]

Contraindications

It is toxic to the fetus; pregnant women should not take it and women taking it should not become pregnant.[2]

People who have hereditary intolerance for galactose, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this drug. It should be used in caution in people with arrhythmias or long QT.[2]

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.[13]

Adverse 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.[2][8]

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.[8]

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.[8]

Interactions

Being metabolized by hepatic cytochrome P450, voriconazole interacts with many drugs.[2][8] 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 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.[2]

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

As of July 2017 the drug was 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. ↑ "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names (Rec. INN): List 36" (PDF). WHO Drug Information. World Health Organization. 10 (3): 162. 1996. Retrieved 6 November 2016.
  2. 1 2 3 4 5 6 "US voriconazole label" (PDF). FDA. June 2017. Retrieved 30 July 2017. For label updates see FDA index page for NDA 021630
  3. 1 2 3 4 5 6 7 "Voriconazole". The American Society of Health-System Pharmacists. Retrieved 8 December 2017.
  4. ↑ Kendig, Edwin L.; Wilmott, Robert W.; Chernick, Victor (2012). Kendig and Chernick's Disorders of the Respiratory Tract in Children. Elsevier Health Sciences. p. 539. ISBN 1437719848.
  5. ↑ "WHO Model List of Essential Medicines (20th List)" (PDF). World Health Organization. March 2017. Retrieved 29 June 2017.
  6. ↑ "Generic Vfend Availability". Drugs.com. Retrieved 10 December 2017.
  7. ↑ "NADAC as of 2017-12-06". Centers for Medicare and Medicaid Services. Retrieved 10 December 2017.
  8. 1 2 3 4 5 6 7 "Vfend tablet and powder". UK Electronic Medicines Compendium. January 2017. Retrieved 30 July 2017.
  9. ↑ Patterson, TF; Thompson GR, 3rd; Denning, DW; Fishman, JA; Hadley, S; Herbrecht, R; Kontoyiannis, DP; Marr, KA; Morrison, VA; Nguyen, MH; Segal, BH; Steinbach, WJ; Stevens, DA; Walsh, TJ; Wingard, JR; Young, JA; Bennett, JE (15 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.
  10. 1 2 Omrani, AS; Almaghrabi, RS (13 June 2017). "Complications of hematopoietic stem transplantation: Fungal infections". Hematology/oncology and stem cell therapy. 10: 239–244. doi:10.1016/j.hemonc.2017.05.013. PMID 28636889.
  11. ↑ Herbrecht, R; Denning, DW; Patterson, TF; Bennett, JE; Greene, RE; Oestmann, JW; Kern, WV; Marr, KA; Ribaud, P; Lortholary, O; Sylvester, R; Rubin, RH; Wingard, JR; Stark, P; Durand, C; Caillot, D; Thiel, E; Chandrasekar, PH; Hodges, MR; Schlamm, HT; Troke, PF; de Pauw, B (8 August 2002). "Voriconazole versus Amphotericin B for Primary Therapy of Invasive Aspergillosis". The New England Journal of Medicine. 347 (6): 408–15. doi:10.1056/NEJMoa020191. PMID 12167683. Retrieved 6 November 2016.
  12. ↑ "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.
  13. ↑ Smith, J; Safdar, N; Knasinski, V; Simmons, W; Bhavnani, SM; Ambrose, PG; Andes, D (April 2006). "Voriconazole Therapeutic Drug Monitoring" (PDF). Antimicrobial Agents and Chemotherapy. 50 (4): 1570–2. doi:10.1128/AAC.50.4.1570-1572.2006. PMC 1426935. PMID 16569888. Retrieved 6 November 2016.
  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.
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