CYP3A4/3A5 Inhibitors

    CYP3A4 and CYP3A5 inhibtors include, but are not limited to, aprepitant, clarithromycin, ciprofloxacin, grapefruit juice, ritonavir, verapamil, and several azole antifungals (e.g., fluconazole, itraconazole, ketoconazole, voriconazole). See glossary page for more information.

    Summary

    CYP3A4/3A5 inhibitors are compounds that reduce the activity of the CYP3A4 and CYP3A5 enzymes, which can reduce drug metabolism, potentially impacting the effects of drug therapy.

    CYP3A4 is the most abundant cytochrome P450 (CYP) enzyme in the body, and is found primarily in the liver and intestine. It is responsible for the metabolism of any medications that are CYP3A4 substrates, which includes around 50% of drugs.[1] CYP3A4/3A5 inhibitors can reduce the body’s metabolism of these medications. CYP3A4 and CYP3A5 are structurally very similar, but CYP3A5 is generally considered to be less metabolically active and is usually present in lower amounts, particularly in people of European descent.[2]

    The table below outlines some of the most common or clinically relevant CYP3A4/3A5 inhibitors.[2][3][4] Importantly, this list is not exhaustive.

    CYP3A4/5 Inhibitors
    Aprepitant
    Ciprofloxacin
    Clarithromycin
    Diltiazem
    Erythromycin
    Fluconazole
    Grapefruit juice
    Imatinib
    Indinavir
    Itraconazole
    Ketoconazole
    Ritonavir
    Verapamil
    Voriconazole

    References

    1. ^Lee SJ, Goldstein JAComparison of CYP3A4 and CYP3A5: the effects of cytochrome b5 and NADPH-cytochrome P450 reductase on testosterone hydroxylation activities.Drug Metab Pharmacokinet.(2012)
    2. ^Song Y, Li C, Liu G, Liu R, Chen Y, Li W, Cao Z, Zhao B, Lu C, Liu YDrug-Metabolizing Cytochrome P450 Enzymes Have Multifarious Influences on Treatment Outcomes.Clin Pharmacokinet.(2021-May)
    3. ^Zanger UM, Schwab MCytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation.Pharmacol Ther.(2013-Apr)
    4. ^Hakkola J, Hukkanen J, Turpeinen M, Pelkonen OInhibition and induction of CYP enzymes in humans: an update.Arch Toxicol.(2020-Nov)