CYP3A4 inhibition

CYP3A4 inhibition. Slows the enzyme that metabolises roughly half of all prescription drugs. A CYP3A4 substrate taken with a CYP3A4 inhibitor reaches higher blood levels than its dose implies.

CYP3A4 induction. Increases CYP3A4 expression, usually via the pregnane X receptor. The mirror hazard: the drug is destroyed faster and silently stops working. Transplant rejection, HIV breakthrough, contraceptive failure.

What acts on it

What is affected by it

What a clean result means here

A clean result means NO DOCUMENTED INTERACTION IN THIS DATASET. It does not mean safe, and it is not a clearance. Most substances are not in this dataset at all, and for many pairs that are, nobody has ever studied the combination.

In this dataset

  • Monoamine oxidase inhibition (prescription MAOIs, RIMAs, linezolid, methylene blue, harmala alkaloids)
  • Serotonergic drugs and the serotonin-toxicity mechanism
  • Dietary tyramine and L-dopa loads
  • The major cytochrome P450 pathways: CYP3A4, CYP2D6, CYP1A2, CYP2C9, CYP2C19 — inhibition and induction
  • P-glycoprotein inhibition and induction
  • 11β-HSD2 inhibition (the licorice mechanism) and the potassium consequences that follow it
  • QT prolongation as an additive pharmacodynamic axis
  • Culinary seasonings and common foods with documented pharmacological activity
  • A selected set of narrow-therapeutic-index drugs where those shifts matter most

Not in this dataset

  • Any substance not named in this dataset — which is most substances. There are tens of thousands of marketed drugs and this table holds fewer than a hundred entries.
  • Phase-2 conjugation (UGT, SULT, NAT2, COMT) except where a specific entry names it. The oilahuasca corpus turns heavily on phase 2 and this engine models it only in passing.
  • Pharmacogenomics. CYP2D6 and CYP2C19 are strongly polymorphic; a poor metaboliser and an ultra-rapid metaboliser can have opposite outcomes from the same pair, and this engine does not know your genotype.
  • Dose, timing, duration, formulation and route — all of which change whether a documented interaction is clinically real for you.
  • Renal and hepatic impairment, age, pregnancy, and body composition.
  • Additive sedation, respiratory depression, bleeding risk, hypoglycaemia and most other pharmacodynamic axes beyond the ones listed above.
  • Herb–herb interactions outside the named entries, and essentially the whole botanical world: most plants have no interaction literature at all.
  • Allergy, intolerance, and contamination or adulteration of unregulated products.
  • Anything published after the last-reviewed date below.

72 substances, 20 mechanisms, 64 citations. Last reviewed . Primary literature (every DOI resolved against the Crossref API) and FDA drug labelling. There is no free, openly-licensed, comprehensive drug-interaction dataset to draw on; NLM retired its Drug Interaction API on 2024-01-02 and DrugBank's interaction set is a commercial licence.

References

  1. Bailey DG, Dresser G, Arnold JMO (2013). Grapefruit–medication interactions: Forbidden fruit or avoidable consequences?. CMAJ (published online 2012-11-26). doi:10.1503/cmaj.120951
  2. Flockhart DA, Thacker D, McDonald C, Desta Z (2021). The Flockhart Cytochrome P450 Drug-Drug Interaction Table. Division of Clinical Pharmacology, Indiana University School of Medicine. https://drug-interactions.medicine.iu.edu
  3. Bailey DG, Spence JD, Munoz C, Arnold JMO (1991). Interaction of citrus juices with felodipine and nifedipine. The Lancet. doi:10.1016/0140-6736(91)90872-M
  4. Paine MF, Widmer WW, Hart HL, et al. (2006). A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction. The American Journal of Clinical Nutrition. doi:10.1093/ajcn/83.5.1097
  5. Lown KS, Bailey DG, Fontana RJ, et al. (1997). Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. Journal of Clinical Investigation. doi:10.1172/JCI119439
  6. Lundahl J, Regårdh CG, Edgar B, Johnsson G (1995). Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. European Journal of Clinical Pharmacology. doi:10.1007/BF00192360
  7. Greenblatt DJ, von Moltke LL, Harmatz JS, et al. (2003). Time course of recovery of cytochrome p450 3A function after single doses of grapefruit juice. Clinical Pharmacology & Therapeutics. doi:10.1016/S0009-9236(03)00118-8
  8. Edwards DJ, Bellevue FH 3rd, Woster PM (1996). Identification of 6',7'-dihydroxybergamottin, a cytochrome P450 inhibitor, in grapefruit juice. Drug Metabolism and Disposition. doi:10.1016/s0090-9556(25)08464-8
  9. Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF (2002). Piperine, a Major Constituent of Black Pepper, Inhibits Human P-glycoprotein and CYP3A4. The Journal of Pharmacology and Experimental Therapeutics. doi:10.1124/jpet.102.034728
  10. Volak LP, Ghirmai S, Cashman JR, Court MH (2008). Curcuminoids Inhibit Multiple Human Cytochromes P450, UDP-Glucuronosyltransferase, and Sulfotransferase Enzymes, whereas Piperine is a Relatively Selective CYP3A4 Inhibitor. Drug Metabolism and Disposition. doi:10.1124/dmd.108.020552
  11. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PSSR (1998). Influence of Piperine on the Pharmacokinetics of Curcumin in Animals and Human Volunteers. Planta Medica. doi:10.1055/s-2006-957450
  12. Bahramsoltani R, Rahimi R, Farzaei MH (2017). Pharmacokinetic interactions of curcuminoids with conventional drugs: A review. Journal of Ethnopharmacology. doi:10.1016/j.jep.2017.07.022
  13. Beyer J, Ehlers D, Maurer HH (2006). Abuse of Nutmeg (Myristica fragrans Houtt.): Studies on the Metabolism and the Toxicologic Detection of its Ingredients Elemicin, Myristicin, and Safrole in Rat and Human Urine Using Gas Chromatography/Mass Spectrometry. Therapeutic Drug Monitoring. doi:10.1097/00007691-200608000-00013
  14. Moore LB, Goodwin B, Jones SA, et al. (2000). St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. PNAS. doi:10.1073/pnas.130155097
  15. Ruschitzka F, Meier PJ, Turina M, Lüscher TF, Noll G (2000). Acute heart transplant rejection due to Saint John's wort. The Lancet. doi:10.1016/S0140-6736(99)05467-7
  16. Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J (2000). Indinavir concentrations and St John's wort. The Lancet. doi:10.1016/S0140-6736(99)05712-8
  17. Henderson L, Yue QY, Bergquist C, Gerden B, Arlett P (2002). St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. British Journal of Clinical Pharmacology. doi:10.1046/j.1365-2125.2002.01683.x
  18. Gurley BJ, Gardner SF, Hubbard MA, et al. (2005). In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clinical Pharmacology & Therapeutics. doi:10.1016/j.clpt.2005.01.009
  19. U.S. Food and Drug Administration (2023). Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. FDA. https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers
  20. Lilja JJ, Kivistö KT, Neuvonen PJ (1998). Grapefruit juice—simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clinical Pharmacology & Therapeutics. doi:10.1016/S0009-9236(98)90130-8
  21. Holbrook AM, Pereira JA, Labiris R, et al. (2005). Systematic Overview of Warfarin and Its Drug and Food Interactions. Archives of Internal Medicine. doi:10.1001/archinte.165.10.1095

Every DOI above was resolved against the Crossref API on 2026-09-09 and the returned title checked against the one printed here. Three DOIs in the first draft resolved to real but different papers and were corrected before publication.

Last reviewed . All interaction pages.