Which drugs are contraindicated with fezolinetant?

Published

Fezolinetant is contraindicated in individuals using CYP1A2 inhibitors concomitantly

  • Several electronic resources include tables of cytochrome P450 (CYP) substrates, inhibitors, and inducers (e.g., FDA, UpToDate® Lexidrug™, Indiana University).1–3
    • It is important to be aware that drug-drug interactions may differ from one drug database to another, and from the fezolinetant approved product label information.

  • Fezolinetant is a substrate of CYP1A2.4
  • Concomitant use of fezolinetant with drugs that are weak, moderate, or strong CYP1A2 inhibitors increases the maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) of fezolinetant.4
    • Fezolinetant Cmax increased by 80% and AUC increased by 840% following concomitant use with fluvoxamine (strong CYP1A2 inhibitor)
    • Fezolinetant Cmax increased by 40% and AUC increased by 360% following concomitant use with mexiletine (moderate CYP1A2 inhibitor) 400 mg every 8 hours
    • Fezolinetant Cmax increased by 30% and AUC increased by 100% following concomitant use with cimetidine (weak CYP1A2 inhibitor) 300 mg every 6 hours
  • Based on in vitro and in vivo data, fezolinetant is not expected to affect the pharmacokinetics of drugs that are substrates of CYP isoenzymes or drug transporters.5
  • Fezolinetant and its metabolite ES259564 are not inhibitors of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Fezolinetant and ES259564 are not inducers of CYP1A2, CYP2B6, and CYP3A4.4

  1. Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. FDA. Available at: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers. Accessed 3JUN2024.

  2. Lexidrug Online. Inhibitors and Inducers of Cytochrome P450 Enzymes (Lexi-Drugs). Available at: https://online.lexi.com/lco/action/home. Accessed 19APR2024.

  3. Drug Interactions Flockhart TableTM. Indiana University. Available at: https://drug-interactions.medicine.iu.edu/MainTable.aspx. Accessed 19APR2024.

  4. VEOZAH [package insert]. Northbrook, IL, USA: Astellas Pharma, Inc. Available at: https://www.astellas.com/us/system/files/veozah_uspi.pdf.

  5. Data on file.

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