Itraconazole

Itraconazole
Clinical data
Trade namesSporanox, Sporaz, Orungal, others
Other namesITZ
AHFS/Drugs.comMonograph
MedlinePlusa692049
License data
Pregnancy
category
Routes of
administration		By mouth, solution), vaginal suppository, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability~55%, maximal if taken with full meal
Protein binding99.8%
MetabolismExtensive in liver (CYP3A4)
MetabolitesHydroxy-itraconazole, keto-itraconazole,
N-desalkyl-itraconazole[4]
Elimination half-life21 hours
ExcretionKidney (35%), faeces (54%)[5]
Identifiers
  • (±)-1-[(RS)-sec-butyl]-4-[p-[4-[p-[[(2R,4S)-rel-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-Δ2-1,2,4-triazolin-5-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.123.596 Edit this at Wikidata
Chemical and physical data
FormulaC35H38Cl2N8O4
Molar mass705.64 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
Melting point165[6] °C (329 °F)
Solubility in water7.8 ± 0.4 × 10−6 mol/L (pH 1.6)[6] mg/mL (20 °C)
  • O=C1N(/N=C\N1c2ccc(cc2)N7CCN(c6ccc(OC[C@@H]3O[C@](OC3)(c4ccc(Cl)cc4Cl)Cn5ncnc5)cc6)CC7)C(C)CC
  • InChI=1S/C35H38Cl2N8O4/c1-3-25(2)45-34(46)44(24-40-45)29-7-5-27(6-8-29)41-14-16-42(17-15-41)28-9-11-30(12-10-28)47-19-31-20-48-35(49-31,21-43-23-38-22-39-43)32-13-4-26(36)18-33(32)37/h4-13,18,22-25,31H,3,14-17,19-21H2,1-2H3/t25?,31-,35-/m0/s1 checkY
  • Key:VHVPQPYKVGDNFY-ZPGVKDDISA-N checkY
  (verify)

Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections.[7] This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis.[7] It may be given by mouth or intravenously.[7]

Common side effects include nausea, diarrhea, abdominal pain, rash, and headache.[7] Severe side effects may include liver problems, heart failure, Stevens–Johnson syndrome and allergic reactions including anaphylaxis.[7] It is unclear if use during pregnancy or breastfeeding is safe.[1] It is in the triazole family of medications.[7] It stops fungal growth by affecting the cell membrane or affecting their metabolism.[7]

Itraconazole was patented in 1978 and approved for medical use in the United States in 1992.[7][8] It is on the World Health Organization's List of Essential Medicines.[9]

Recent research works suggest itraconazole (ITZ) could also be used in the treatment of cancer by inhibiting the hedgehog pathway[10] in a similar way to sonidegib.

  1. ^ a b "Itraconazole Use During Pregnancy". Drugs.com. 20 March 2019. Retrieved 15 May 2020.
  2. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  3. ^ "Sporanox 10 mg/mL Oral Solution - Summary of Product Characteristics (SmPC)". (emc). 1 February 2018. Retrieved 15 May 2020.
  4. ^ Isoherranen N, Kunze KL, Allen KE, Nelson WL, Thummel KE (October 2004). "Role of itraconazole metabolites in CYP3A4 inhibition". Drug Metabolism and Disposition. 32 (10): 1121–1131. doi:10.1124/dmd.104.000315. PMID 15242978. S2CID 6941636.
  5. ^ "Sporanox (itraconazole) Capsules. Full Prescribing Information" (PDF). Janssen Pharmaceuticals, Inc. Archived from the original (PDF) on 17 May 2018. Retrieved 28 August 2016.
  6. ^ a b Vasilev NA, Surov AO, Voronin AP, Drozd KV, Perlovich GL (April 2021). "Novel cocrystals of itraconazole: Insights from phase diagrams, formation thermodynamics and solubility". International Journal of Pharmaceutics. 599: 120441. doi:10.1016/j.ijpharm.2021.120441. PMID 33675927. S2CID 232135660.
  7. ^ a b c d e f g h "Itraconazole". The American Society of Health-System Pharmacists. Retrieved 8 December 2017.
  8. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 503. ISBN 9783527607495.
  9. ^ 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.
  10. ^ Li K, Fang D, Xiong Z, Luo R (2019). "Inhibition of the hedgehog pathway for the treatment of cancer using Itraconazole". OncoTargets and Therapy. 12: 6875–6886. doi:10.2147/OTT.S223119. PMC 6711563. PMID 31692536.