Editing CYP3A4 (section)

== Ligands == <!--St. John's wort has link here-->
Following are lists of selected [[enzyme substrate|substrates]], [[enzyme induction and inhibition|inducers]] and [[enzyme induction and inhibition|inhibitors]] of CYP3A4. Where classes of agents are listed, there may be exceptions within the class.

=== Substrates ===
The substrates of CYP3A4 are:
* some [[immunosuppressant]]s:
** [[ciclosporin]] (cyclosporin),<ref name=Flockhart/><ref name=FASS>[[FASS (drug formulary)]]: [http://www.fass.se/LIF/produktfakta/fakta_lakare_artikel.jsp?articleID=18352 Swedish environmental classification of pharmaceuticals] {{Webarchive|url=https://web.archive.org/web/20020611044953/http://www.fass.se/LIF/produktfakta/fakta_lakare_artikel.jsp?articleID=18352 |date=11 June 2002 }} Facts for prescribers (Fakta för förskrivare). Retrieved July 2011</ref>
** [[tacrolimus]],<ref name=Flockhart/><ref name=FASS/>
** [[sirolimus]],<ref name=Flockhart/><ref name=FASS/>
** [[upadacitinib]];<ref name="Rinvoq-2020">"[https://www.ema.europa.eu/en/documents/assessment-report/rinvoq-epar-public-assessment-report_en.pdf Rinvoq: EPAR – Public assessment report] {{Webarchive|url=https://web.archive.org/web/20200721125405/https://www.ema.europa.eu/en/documents/assessment-report/rinvoq-epar-public-assessment-report_en.pdf |date=21 July 2020 }}" (PDF). [[European Medicines Agency]]. 5 March 2020. Archived (PDF) from the original on 21 July 2020. Retrieved 21 July 2020.</ref><ref name="Austria-Codex-DE">''Austria-Codex'' (in German). Vienna: Österreichischer Apothekerverlag. 2020. Rinvoq 15 mg Retardtabletten.</ref>
* many [[chemotherapeutic]]s:
** [[docetaxel]],<ref name=Flockhart/><ref name=FASS/>
** [[tamoxifen]],<ref name=Flockhart/><ref name=FASS/>
** [[paclitaxel]],<ref name=Flockhart/><ref name=FASS/>
** [[cyclophosphamide]],<ref name=FASS/>
** [[doxorubicin]],<ref name=FASS/>
** [[erlotinib]],<ref>{{cite web |title=Erlotinib |url=https://www.drugs.com/ppa/erlotinib.html |quote=Metabolized primarily by CYP3A4 and, to a lesser degree, by CYP1A2 and the extrahepatic isoform CYP1A1 |access-date=10 April 2018 |archive-date=24 December 2019 |archive-url=https://web.archive.org/web/20191224052924/https://www.drugs.com/ppa/erlotinib.html |url-status=live }}</ref>
** [[etoposide]],<ref name=FASS/>
** [[ifosfamide]],<ref name=FASS/>
** [[teniposide]],<ref name=FASS/>
** [[vinblastine]],<ref name=FASS/>
** [[vincristine]],<ref name=Flockhart/>
** [[vindesine]],<ref name=FASS/>
** [[imatinib]],<ref name=Flockhart/>
** [[irinotecan]],<ref name=Flockhart/>
** [[sorafenib]],<ref name=Flockhart/>
** [[sunitinib]],<ref name=Flockhart/>
** [[vemurafenib]],<ref name=Flockhart/>
** [[temsirolimus]],<ref name=Flockhart/>
** [[anastrozole]],
** [[gefitinib]];
* [[azole antifungal]]s:
** [[ketoconazole]]<ref name=FASS/>
** [[itraconazole]]<ref name=FASS/>
* [[macrolide antibiotics|macrolide]]s (except [[azithromycin]]):<ref name="Flockhart" />
** [[clarithromycin]],<ref name="Flockhart" /><ref name="FASS" />
** [[erythromycin]],<ref name="Flockhart" />
** [[telithromycin]];<ref name="Flockhart" />
* [[dapsone]]<ref name=Flockhart/> (in [[leprosy]]),
* [[tricyclic antidepressants]]:
** [[amitriptyline]],<ref name=FASS/>
** [[clomipramine]],<ref name=FASS/>
** [[imipramine]],<ref name=FASS/>
** [[cyclobenzaprine]];<ref>{{cite web|url=http://www.drugbank.ca/drugs/DB00924|title=Cyclobenzaprine|publisher=DrugBank|access-date=10 April 2018|archive-date=27 October 2018|archive-url=https://web.archive.org/web/20181027220500/https://www.drugbank.ca/drugs/DB00924|url-status=live}}</ref>
* [[Selective serotonin reuptake inhibitor|SSRI antidepressants]] :
** [[citalopram]]<ref name=FASS/>
** [[norfluoxetine]]<ref name=FASS/>
** [[sertraline]]<ref name=FASS/>
* some other antidepressants:
** [[mirtazapine]]<ref name=FASS/> ([[noradrenergic and specific serotonergic antidepressant|NaSSA]]),
** [[nefazodone]]<ref name=FASS/> ([[Atypical antidepressant|atypical]]),
** [[reboxetine]]<ref name=FASS/> ([[Norepinephrine reuptake inhibitor|NRI]]),
** [[venlafaxine]]<ref name=FASS/> ([[serotonin-norepinephrine reuptake inhibitor|SNRI]]),
** [[trazodone]]<ref name=Flockhart/> ([[serotonin antagonist and reuptake inhibitor|SARI]]),
** [[vilazodone]]<ref name=FASS/> ([[Serotonin modulator and stimulator|serotonin modulator]]),
* [[buspirone]]<ref name=Flockhart/><ref name=FASS/> ([[anxiolytic]]),
* [[antipsychotics]]:
** [[haloperidol]],<ref name=Flockhart/><ref name=FASS/>
** [[aripiprazole]],<ref name=Flockhart/>
** [[risperidone]],<ref name=Flockhart/>
** [[ziprasidone]],<ref name=Flockhart/>
** [[pimozide]],<ref name=FASS/>
** [[quetiapine]],<ref name=Flockhart/>
** [[lurasidone]];<ref>{{cite book |vauthors=Azhar Y, Shaban K |chapter=Lurasidone |date=2022 |chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK541057/ |title=StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31082101 |access-date=14 October 2022 |archive-date=18 May 2023 |archive-url=https://web.archive.org/web/20230518045845/https://www.ncbi.nlm.nih.gov/books/NBK541057/ |url-status=live }}</ref>
* [[opioids]] (mainly analgesics):
** [[alfentanil]],<ref name=Flockhart/><ref name=FASS/>
** [[buprenorphine]]<ref name="pmid19773542">{{cite journal | vauthors = Moody DE, Fang WB, Lin SN, Weyant DM, Strom SC, Omiecinski CJ | title = Effect of rifampin and nelfinavir on the metabolism of methadone and buprenorphine in primary cultures of human hepatocytes | journal = Drug Metabolism and Disposition | volume = 37 | issue = 12 | pages = 2323–9 | date = December 2009 | pmid = 19773542 | pmc = 2784702 | doi = 10.1124/dmd.109.028605 }}</ref> ([[analgesic]], [[Opioid use disorder#Management|addiction maintenance treatment]]),
** [[codeine]]<ref name=Flockhart/> ([[analgesic]], [[antitussive]], [[antidiarrheal]]),
** [[fentanyl]],<ref name=Flockhart/>
** [[hydrocodone]]<ref>{{cite journal|journal=British Journal of Clinical Pharmacology|title=CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes|vauthors=Hutchinson MR, Menelaou A, Foster DJ, Coller JK, Somogyi AA |pmid=14998425|volume=57|issue=3|date=Mar 2004|pages=287–97|doi=10.1046/j.1365-2125.2003.02002.x|pmc=1884456}}</ref> (partial involvement, not the bioactivation factor),
** [[methadone]]<ref name=Flockhart/> ([[analgesic]], [[Opioid use disorder#Management|addiction maintenance treatment]]),
** [[levacetylmethadol]],<ref name=Flockhart/>
** [[tramadol]] ([[analgesic]], [[Disease#Refractory disease|refractory]] [[restless legs syndrome#Medications 2|RLS treatment]]);
* [[benzodiazepines]]:
** [[alprazolam]],<ref name=Flockhart/><ref name=FASS/>
** [[midazolam]],<ref name=Flockhart/><ref name=FASS/>
** [[triazolam]],<ref name=Flockhart/><ref name=FASS/>
** [[diazepam]],<ref name=Flockhart/> (bioactivation to [[desmethyldiazepam]])
** [[clonazepam]];<ref>{{cite journal | vauthors = Tanaka E | title = Clinically significant pharmacokinetic drug interactions with benzodiazepines | journal = Journal of Clinical Pharmacy and Therapeutics | volume = 24 | issue = 5 | pages = 347–355 | date = October 1999 | pmid = 10583697 | doi = 10.1046/j.1365-2710.1999.00247.x | s2cid = 22229823 | doi-access = free }}</ref>
* some [[hypnotic]]s:
** [[zopiclone]],<ref name=FASS/>
** [[zaleplon]],<ref name=Flockhart/>
** [[zolpidem]],<ref name=Flockhart/>
* [[donepezil]]<ref name=FASS/> ([[acetylcholinesterase inhibitor]]),
* [[statin]]s (except [[pravastatin]]<ref name="Flockhart" /> and [[rosuvastatin]]<ref name="Flockhart" />):
** [[atorvastatin]],<ref name="Flockhart" /><ref name="FASS" />
** [[lovastatin]],<ref name="Flockhart" /><ref name="FASS" />
** [[simvastatin]],<ref name="FASS" />
** [[cerivastatin]];<ref name="Flockhart" />
* [[calcium channel blockers]]:
** [[diltiazem]]<ref name=Flockhart/><ref name=FASS/> ([[sensitive substrate]]<ref name="Sutton_1997">{{cite journal | vauthors = Sutton D, Butler AM, Nadin L, Murray M | title = Role of CYP3A4 in human hepatic diltiazem N-demethylation: inhibition of CYP3A4 activity by oxidized diltiazem metabolites | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 282 | issue = 1 | pages = 294–300 | date = July 1997 | pmid = 9223567 }}</ref>),
** [[felodipine]]<ref name=Flockhart/><ref name=FASS/> (sensitive substrate<ref name="U S Food and Drug Administration Home Page 2009">{{cite web | title=Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers | website=U S Food and Drug Administration Home Page | date=25 June 2009 | url=https://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm#table2-2 | access-date=1 February 2019 | archive-date=23 April 2019 | archive-url=https://web.archive.org/web/20190423033345/https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#table2-2 | url-status=dead }}</ref><ref name="Lown Bailey Fontana Janardan pp. 2545–2553">{{cite journal | vauthors = Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, Brown MB, Guo W, Watkins PB | title = Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression | journal = The Journal of Clinical Investigation | volume = 99 | issue = 10 | pages = 2545–53 | date = May 1997 | pmid = 9153299 | pmc = 508096 | doi = 10.1172/jci119439 | publisher = American Society for Clinical Investigation }}</ref><ref name="Bailey Bend Arnold Tran 1996 pp. 25–33">{{cite journal | vauthors = Bailey DG, Bend JR, Arnold JM, Tran LT, Spence JD | title = Erythromycin-felodipine interaction: magnitude, mechanism, and comparison with grapefruit juice | journal = Clinical Pharmacology and Therapeutics | volume = 60 | issue = 1 | pages = 25–33 | date = July 1996 | pmid = 8689808 | doi = 10.1016/s0009-9236(96)90163-0 | publisher = Springer Nature | s2cid = 1246705 }}</ref><ref name="Guengerich Brian Iwasaki Sari 1991 pp. 1838–44">{{cite journal | vauthors = Guengerich FP, Brian WR, Iwasaki M, Sari MA, Bäärnhielm C, Berntsson P | title = Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P-450 IIIA4 | journal = Journal of Medicinal Chemistry | volume = 34 | issue = 6 | pages = 1838–44 | date = June 1991 | pmid = 2061924 | doi=10.1021/jm00110a012}}</ref>),
** [[nifedipine]]<ref name=Flockhart/><ref name=FASS/> (sensitive substrate<ref name="Katoh Nakajima Yamazaki Yokoi 2001 pp. 505–13">{{cite journal | vauthors = Katoh M, Nakajima M, Yamazaki H, Yokoi T | title = Inhibitory effects of CYP3A4 substrates and their metabolites on P-glycoprotein-mediated transport | journal = European Journal of Pharmaceutical Sciences | volume = 12 | issue = 4 | pages = 505–13 | date = February 2001 | pmid = 11231118 | doi=10.1016/s0928-0987(00)00215-3}}</ref><ref name="Foti Rock Wienkers Wahlstrom 2010 pp. 981–987">{{cite journal | vauthors = Foti RS, Rock DA, Wienkers LC, Wahlstrom JL | s2cid = 6823063 | title = Selection of alternative CYP3A4 probe substrates for clinical drug interaction studies using in vitro data and in vivo simulation | journal = Drug Metabolism and Disposition | volume = 38 | issue = 6 | pages = 981–7 | date = June 2010 | pmid = 20203109 | doi = 10.1124/dmd.110.032094 | publisher = American Society for Pharmacology & Experimental Therapeutics (ASPET) }}</ref><ref>{{cite journal | vauthors = Odou P, Ferrari N, Barthélémy C, Brique S, Lhermitte M, Vincent A, Libersa C, Robert H | title = Grapefruit juice-nifedipine interaction: possible involvement of several mechanisms | journal = Journal of Clinical Pharmacy and Therapeutics | volume = 30 | issue = 2 | pages = 153–8 | date = April 2005 | pmid = 15811168 | doi = 10.1111/j.1365-2710.2004.00618.x | s2cid = 30463290 | doi-access = free }}</ref><ref name="DailyMed Nifedipine extended release 2012">{{cite web | title=NIFEDIPINE EXTENDED RELEASE- nifedipine tablet, extended release | website=DailyMed | date=29 November 2012 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4617417a-08df-4417-a944-dfc30de183db | access-date=1 February 2019 | quote=Drug Interactions: Nifedipine is mainly eliminated by metabolism and is a substrate of CYP3A. Inhibitors and inducers of CYP3A can impact the exposure to nifedipine and, consequently, its desirable and undesirable effects. In vitro and in vivo data indicate that nifedipine can inhibit the metabolism of drugs that are substrates of CYP3A, thereby increasing the exposure to other drugs. Nifedipine is a vasodilator, and coadministration of other drugs affecting blood pressure may result in pharmacodynamic interactions. | archive-date=31 January 2022 | archive-url=https://web.archive.org/web/20220131061535/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4617417a-08df-4417-a944-dfc30de183db | url-status=live }}</ref>),
** [[verapamil]]<ref name=Flockhart/><ref name=FASS/> (sensitive substrate<ref name="Zhang Guo Lin Benet 1998 pp. 360–6">{{cite journal | vauthors = Zhang Y, Guo X, Lin ET, Benet LZ | title = Overlapping substrate specificities of cytochrome P450 3A and P-glycoprotein for a novel cysteine protease inhibitor | journal = Drug Metabolism and Disposition | volume = 26 | issue = 4 | pages = 360–6 | date = April 1998 | pmid = 9531525 }}</ref><ref name="Stringer Mallet Clarke Lindenfeld 1992 pp. 35–8">{{cite journal | vauthors = Stringer KA, Mallet J, Clarke M, Lindenfeld JA | title = The effect of three different oral doses of verapamil on the disposition of theophylline | journal = European Journal of Clinical Pharmacology | volume = 43 | issue = 1 | pages = 35–8 | year = 1992 | pmid = 1505606 | doi=10.1007/bf02280751| s2cid = 8942097 }}</ref><ref name="Nielsen-Kudsk Buhl Johannessen 1990 pp. 101–3">{{cite journal | vauthors = Nielsen-Kudsk JE, Buhl JS, Johannessen AC | title = Verapamil-induced inhibition of theophylline elimination in healthy humans | journal = Pharmacology & Toxicology | volume = 66 | issue = 2 | pages = 101–3 | date = February 1990 | pmid = 2315261 | doi=10.1111/j.1600-0773.1990.tb00713.x}}</ref><ref name="Gin Stringer Welage Wilton 1989 pp. 728–32">{{cite journal | vauthors = Gin AS, Stringer KA, Welage LS, Wilton JH, Matthews GE | title = The effect of verapamil on the pharmacokinetic disposition of theophylline in cigarette smokers | journal = Journal of Clinical Pharmacology | volume = 29 | issue = 8 | pages = 728–32 | date = August 1989 | pmid = 2778093 | doi=10.1002/j.1552-4604.1989.tb03407.x| s2cid = 20446675 }}</ref><ref name="Sirmans Pieper Lalonde Smith 1988 pp. 29–34">{{cite journal | vauthors = Sirmans SM, Pieper JA, Lalonde RL, Smith DG, Self TH | title = Effect of calcium channel blockers on theophylline disposition | journal = Clinical Pharmacology and Therapeutics | volume = 44 | issue = 1 | pages = 29–34 | date = July 1988 | pmid = 3391002 | doi=10.1038/clpt.1988.108| s2cid = 39570845 }}</ref><ref name="Robson Miners Birkett 1988 pp. 397–400">{{cite journal | vauthors = Robson RA, Miners JO, Birkett DJ | title = Selective inhibitory effects of nifedipine and verapamil on oxidative metabolism: effects on theophylline | journal = British Journal of Clinical Pharmacology | volume = 25 | issue = 3 | pages = 397–400 | date = March 1988 | pmid = 3358901 | pmc = 1386365 | doi=10.1111/j.1365-2125.1988.tb03319.x}}</ref><ref name="Abernethy Egan Dickinson Carrum 1988 pp. 994–9">{{cite journal | vauthors = Abernethy DR, Egan JM, Dickinson TH, Carrum G | title = Substrate-selective inhibition by verapamil and diltiazem: differential disposition of antipyrine and theophylline in humans | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 244 | issue = 3 | pages = 994–9 | date = March 1988 | pmid = 3252045 }}</ref>),
** [[amlodipine]]<ref name=Flockhart/> (sensitive substrate<ref name="Katoh_2000">{{cite journal | vauthors = Katoh M, Nakajima M, Yamazaki H, Yokoi T | title = Inhibitory potencies of 1,4-dihydropyridine calcium antagonists to P-glycoprotein-mediated transport: comparison with the effects on CYP3A4 | journal = Pharmaceutical Research | volume = 17 | issue = 10 | pages = 1189–97 | date = October 2000 | pmid = 11145223 | doi = 10.1023/a:1007568811691 | s2cid = 24304693 }}</ref>),
** [[lercanidipine]],<ref name=Flockhart/>
** [[nitrendipine]],<ref name=Flockhart/>
** [[nisoldipine]],<ref name=Flockhart/>
* [[amiodarone]]<ref name=FASS/> ([[class III antiarrhythmic]]),
* [[dronedarone]]<ref name=FASS/> ([[class III antiarrhythmic]]),
* [[quinidine]]<ref name=Flockhart/> ([[class I antiarrhythmic agent|class I antiarrhythmic]]),
* [[PDE5 inhibitor]]s:
** [[sildenafil]],<ref name=Flockhart/><ref name=FASS/>
** [[tadalafil]],<ref>{{cite web | title = Active ingredient: Tadalafil - Brands, Medical Use, Clinical Data | url = http://www.druglib.com/activeingredient/tadalafil/ | publisher = Druglib.com | access-date = 13 March 2022 | archive-date = 28 November 2022 | archive-url = https://web.archive.org/web/20221128145825/http://www.druglib.com/activeingredient/tadalafil/ | url-status = live }}</ref>
* [[kinin]]s<ref name=FASS/> ([[vasodilator]]s, [[smooth muscle]] contractors),
* [[steroid]]s:
** [[sex hormones]] (agonists and antagonists):
*** [[finasteride]]<ref name=Flockhart/><ref name=FASS/> ([[antiandrogen]]),
*** [[estradiol]]<ref name=Flockhart/> ([[estrogen]]),
*** [[progesterone]],<ref name=Flockhart/>
*** [[ethinylestradiol]]<ref name=FASS/> ([[hormonal contraceptive]]),
*** [[testosterone]]<ref name=Flockhart/> ([[androgen]]),
*** [[toremifene]]<ref name=FASS/> ([[selective estrogen receptor modulator|SERM]]),
*** [[bicalutamide]];<ref name=AZ>{{cite journal | vauthors = Cockshott ID | title = Bicalutamide: clinical pharmacokinetics and metabolism | journal = Clinical Pharmacokinetics | volume = 43 | issue = 13 | pages = 855–78 | year = 2004 | pmid = 15509184 | doi = 10.2165/00003088-200443130-00003 | s2cid = 29912565 }}</ref>
** [[glucocorticoid]]s:
*** [[budesonide]],<ref name=FASS/>
*** [[hydrocortisone]] ([[cortisol]]),<ref name=Flockhart/><ref name="pmid34633961">{{cite journal | vauthors = Aquinos BM, García Arabehety J, Canteros TM, de Miguel V, Scibona P, Fainstein-Day P | title = [Adrenal crisis associated with modafinil use] | language = es | journal = Medicina | volume = 81 | issue = 5 | pages = 846–849 | year = 2021 | pmid = 34633961 }}</ref>
*** [[dexamethasone]],<ref name=Flockhart/>
*** [[fluticasone]];<ref>{{cite journal | vauthors = Ledger T, Tong W, Rimmer J | title = Iatrogenic Cushing's syndrome with inhaled fluticasone | journal = Australian Prescriber | volume = 42 | issue = 4 | pages = 139–140 | date = August 2019 | pmid = 31427846 | pmc = 6698236 | doi = 10.18773/austprescr.2019.040 }}</ref>
* some [[H1-receptor antagonist|H<sub>1</sub>-receptor antagonists]] (H<sub>1</sub> [[antihistamine]]s):
** [[ketotifen]],<ref name="El-Kommos-2015">{{cite journal | doi=10.1016/j.ancr.2014.11.003 | title=Analysis for commonly prescribed non-sedating antihistamines | date=2015 | journal=Analytical Chemistry Research | volume=3 | pages=1–12 | vauthors = El-Kommos ME, El-Gizawy SM, Atia NN, Hosny NM | doi-access=free }}</ref><ref name="pmid17357376">{{cite journal |vauthors=Jáuregui I, Mullol J, Bartra J, del Cuvillo A, Dávila I, Montoro J, Sastre J, Valero AL |title=H1 antihistamines: psychomotor performance and driving |journal=J Investig Allergol Clin Immunol |volume=16 |issue= Suppl 1|pages=37–44 |date=2006 |pmid=17357376}}</ref><ref name="pmid35538735">{{cite journal |vauthors=Li L, Liu R, Peng C, Chen X, Li J |title=Pharmacogenomics for the efficacy and side effects of antihistamines |journal=Exp Dermatol |volume=31 |issue=7 |pages=993–1004 |date=July 2022 |pmid=35538735 |doi=10.1111/exd.14602}}</ref><ref name="pmid11764306">{{cite journal |vauthors=Merk HF |title=Standard treatment: the role of antihistamines |journal=J Investig Dermatol Symp Proc |volume=6 |issue=2 |pages=153–6 |date=November 2001 |pmid=11764306 |doi=10.1046/j.0022-202x.2001.00032.x|doi-access=free | title-link=doi }}</ref>
** [[terfenadine]],<ref name="Flockhart" /><ref name="FASS" />
** [[astemizole]],<ref name="Flockhart" /><ref name="pmid11259984">{{cite journal | vauthors = Matsumoto S, Yamazoe Y | title = Involvement of multiple human cytochromes P450 in the liver microsomal metabolism of astemizole and a comparison with terfenadine | journal = British Journal of Clinical Pharmacology | volume = 51 | issue = 2 | pages = 133–42 | date = February 2001 | pmid = 11259984 | pmc = 2014443 | doi = 10.1111/j.1365-2125.2001.01292.x }}</ref>
** [[chlorphenamine]];<ref name="Flockhart" />
* [[protease inhibitors]]:
** [[indinavir]],<ref name=Flockhart/><ref name=FASS/>
** [[ritonavir]],<ref name=Flockhart/><ref name=FASS/>
** [[saquinavir]],<ref name=Flockhart/><ref name=FASS/>
** [[nelfinavir]];<ref name=Flockhart/><ref name=FASS/>
* non-nucleoside [[reverse-transcriptase inhibitors]] ([[antiretroviral drugs]]):
** [[nevirapine]]<ref name=FASS/><ref name="Marzinke-2016">{{cite book |vauthors=Marzinke MA |title=Chapter 6 - Therapeutic Drug Monitoring of Antiretrovirals |chapter=Therapeutic Drug Monitoring of Antiretrovirals |date=2016-01-01 |series=Clinical Challenges in Therapeutic Drug Monitoring |pages=135–163 |veditors=Clarke W, Dasgupta A |chapter-url=https://www.sciencedirect.com/science/article/pii/B9780128020258000064 |access-date=2024-02-06 |place=San Diego |publisher=Elsevier |doi=10.1016/B978-0-12-802025-8.00006-4 |isbn=978-0-12-802025-8 |archive-date=2 May 2024 |archive-url=https://web.archive.org/web/20240502101129/https://www.sciencedirect.com/science/article/abs/pii/B9780128020258000064 |url-status=live }}</ref>
** [[delavirdine]],<ref name="Marzinke-2016"/>
** [[efavirenz]],<ref name="Marzinke-2016"/>
** [[etravirine]],<ref name="Marzinke-2016"/>
** [[rilpivirine]];<ref name="Marzinke-2016"/>
* [[albendazole]]<ref>Enzyme [http://www.genome.jp/dbget-bin/www_bget?enzyme+1.14.13.32 1.14.13.32] {{Webarchive|url=https://web.archive.org/web/20170327070920/http://www.genome.jp/dbget-bin/www_bget?enzyme+1.14.13.32 |date=27 March 2017 }} at [[KEGG]]</ref><ref>{{cite web | title=Showing Protein Cytochrome P450 3A4 (HMDBP01018) | series=Human Metabolome Database | access-date=5 August 2017 | url=http://www.hmdb.ca/proteins/HMDBP01018 | archive-date=2 May 2024 | archive-url=https://web.archive.org/web/20240502101115/https://hmdb.ca/proteins/HMDBP01018 | url-status=live }}</ref> ([[antihelminthic]])
* [[cisapride]],<ref name=Flockhart/><ref name=FASS/> ([[5-HT4 receptor]] [[agonist]])
* [[aprepitant]],<ref name=Flockhart/> ([[antiemetic]])
* [[caffeine]],<ref name=Flockhart/> ([[stimulant]])
* [[cocaine]],<ref name=Flockhart/> ([[stimulant]])
* [[cilostazol]],<ref name=Flockhart/> ([[phosphodiesterase inhibitor]])
* [[dextromethorphan]],<ref name=Flockhart/> ([[antitussive]])
* [[domperidone]],<ref name=Flockhart/> ([[antidopaminergic]])
* [[eplerenone]],<ref name=Flockhart/> ([[aldosterone antagonist]])
* [[lidocaine]],<ref name=Flockhart/> ([[local anesthetic]], [[antiarrhythmic]])
* [[ondansetron]],<ref name=Flockhart/>  ([[5-HT3 antagonist]])
* [[propranolol]],<ref name=Flockhart/> ([[beta blocker]])
* [[salmeterol]],<ref name=Flockhart/> ([[beta agonist]])
* [[warfarin]],<ref name="pmid12724615">{{cite journal | vauthors = Daly AK, King BP | title = Pharmacogenetics of oral anticoagulants | journal = Pharmacogenetics | volume = 13 | issue = 5 | pages = 247–52 | date = May 2003 | pmid = 12724615 | doi =  10.1097/00008571-200305000-00002}}</ref> ([[anticoagulant]])
* [[clopidogrel]] becoming [[bioactivated]]<ref name="pmid12515739">{{cite journal | vauthors = Lau WC, Waskell LA, Watkins PB, Neer CJ, Horowitz K, Hopp AS, Tait AR, Carville DG, Guyer KE, Bates ER | title = Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction | journal = Circulation | volume = 107 | issue = 1 | pages = 32–7 | date = January 2003 | pmid = 12515739 | doi = 10.1161/01.CIR.0000047060.60595.CC | doi-access = free }}</ref> ([[antiplatelet agent|antiplatelet]]),
* [[2-oxo-clopidogrel]],<ref name="Alkattan A 2021"/>
* [[omeprazole]],<ref name=FASS/> ([[proton pump inhibitor]])
* [[nateglinide]],<ref name=Flockhart/> ([[antidiabetic]])
* [[methoxetamine]],<ref name="pmid23774830">{{cite journal | vauthors = Meyer MR, Bach M, Welter J, Bovens M, Turcant A, Maurer HH | s2cid = 27966043 | title = Ketamine-derived designer drug methoxetamine: metabolism including isoenzyme kinetics and toxicological detectability using GC-MS and LC-(HR-)MSn | journal = Analytical and Bioanalytical Chemistry | volume = 405 | issue = 19 | pages = 6307–21 | date = July 2013 | pmid = 23774830 | doi = 10.1007/s00216-013-7051-6 }}</ref>
* [[montelukast]] ([[leukotriene receptor antagonist]]),
* [[vilaprisan]] ([[selective progesterone receptor modulator]]),
* certain [[angiotensin II receptor blocker]]s:
** [[losartan]] ([[sensitive substrates]])<ref name="LOSARTAN 2018">{{cite web | title=LOSARTAN- losartan potassium tablet, film coated | website=DailyMed | date=26 December 2018 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a98a821c-7b81-4f9b-9801-1a16d71871ce | access-date=6 February 2019 | archive-date=7 February 2019 | archive-url=https://web.archive.org/web/20190207015904/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a98a821c-7b81-4f9b-9801-1a16d71871ce | url-status=live }}</ref><ref name="pmid10877007">{{cite journal |vauthors=Taavitsainen P, Kiukaanniemi K, Pelkonen O |title=In vitro inhibition screening of human hepatic P450 enzymes by five angiotensin-II receptor antagonists |journal=Eur J Clin Pharmacol |volume=56 |issue=2 |pages=135–40 |date=May 2000 |pmid=10877007 |doi=10.1007/s002280050731 |s2cid=26865251 |url=}}</ref>
** [[irbesartan]].<ref name="pmid10877007"/>

=== Inhibitors ===
Inhibitors of CYP3A4 are classified by [[potency (pharmacology)|potency]]:
* a '''Strong inhibitor''' causes at least a 5-fold increase in the plasma [[area under the curve (pharmacokinetics)|AUC values]], or more than 80% decrease in [[clearance (medicine)|clearance]].<ref name=Flockhart/>
* a '''Moderate inhibitor''' causes at least a 2-fold increase in the plasma AUC values, or 50–80% decrease in clearance.<ref name=Flockhart/>
* a '''Weak inhibitor''' causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20–50% decrease in clearance.<ref name=Flockhart>{{cite web |vauthors=Flockhart DA |title=Drug Interactions: Cytochrome P<sub>450</sub> Drug Interaction Table |publisher=[[Indiana University School of Medicine]] |year=2007 |url=http://medicine.iupui.edu/flockhart/table.htm |access-date=25 December 2008 |archive-date=10 October 2007 |archive-url=https://web.archive.org/web/20071010053126/http://medicine.iupui.edu/flockhart/table.htm |url-status=live }} Retrieved on 25 December 2008.</ref>

The inhibitors of CYP3A4 are the following substances.

====Strong inhibitors====
* [[boceprevir]],<ref name="FDA_drug_development">{{cite journal|title=Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers|journal=FDA|date=6 May 2023|url=https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers|publisher=US Food and Drug Administration|access-date=21 June 2020|archive-date=4 November 2020|archive-url=https://web.archive.org/web/20201104173036/https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers|url-status=dead}}</ref>
* [[Pharmacologic protease inhibitor|protease inhibitors]]:
** [[ritonavir]],<ref name="Flockhart" /><ref name="FASS" /><ref name="lange6th" />
** [[indinavir]],<ref name="Flockhart" />
** [[nelfinavir]],<ref name="Flockhart" />
** [[saquinavir]];<ref name="Flockhart" />
* some [[Macrolide|macrolide antibiotic]]s:<ref name="lange6th" />
** [[clarithromycin]],<ref name="FDA_drug_development" /><ref name="pmid34467456">{{cite journal |vauthors=Kapetas AJ, Abuhelwa AY, Sorich MJ, McKinnon RA, Rodrigues AD, Rowland A, Hopkins AM |title=Evidence-Based Guidelines for Drug Interaction Studies: Model-Informed Time Course of Intestinal and Hepatic CYP3A4 Inhibition by Clarithromycin |journal=AAPS J |volume=23 |issue=5 |pages=104 |date=August 2021 |pmid=34467456 |doi=10.1208/s12248-021-00632-7 |s2cid=237373341 |url=}}</ref><ref name="pmid12152002">{{cite journal |vauthors=Ushiama H, Echizen H, Nachi S, Ohnishi A |title=Dose-dependent inhibition of CYP3A activity by clarithromycin during Helicobacter pylori eradication therapy assessed by changes in plasma lansoprazole levels and partial cortisol clearance to 6beta-hydroxycortisol |journal=Clin Pharmacol Ther |volume=72 |issue=1 |pages=33–43 |date=July 2002 |pmid=12152002 |doi=10.1067/mcp.2002.125559 |url=|doi-access=free }}</ref><ref name="Flockhart" /><ref name="FASS" /><ref name="pmid37874128">{{cite journal |vauthors=Herdegen T, Cascorbi I |title=Drug Interactions of Tetrahydrocannabinol and Cannabidiol in Cannabinoid Drugs: Recommendations for Clinical Practice |journal=Dtsch Ärztebl Int |volume= 120|issue=49 |pages= 833–840|date=December 2023 |pmid=37874128 |doi=10.3238/arztebl.m2023.0223 |pmc=10824494 |s2cid=264438050 |url=}}</ref><ref name="pmid31628882" />
** [[erythromycin]]<ref name="pmid31628882">{{cite journal |vauthors=Hougaard Christensen MM, Bruun Haastrup M, Øhlenschlaeger T, Esbech P, Arnspang Pedersen S, Bach Dunvald AC, Bjerregaard Stage T, Pilsgaard Henriksen D, Thestrup Pedersen AJ |title=Interaction potential between clarithromycin and individual statins-A systematic review |journal=Basic Clin Pharmacol Toxicol |volume=126 |issue=4 |pages=307–317 |date=April 2020 |pmid=31628882 |doi=10.1111/bcpt.13343 |quote=Erythromycin 500 mg three-four times daily for 6-7 days markedly increased lovastatin exposure (≈6-fold increase in AUC) |url=https://findresearcher.sdu.dk/ws/files/158846448/Interaction_Potential_between_Clarithromycin_and_Individual_Statins_a_Systematic_Review.pdf |access-date=2 February 2024 |archive-date=2 February 2024 |archive-url=https://web.archive.org/web/20240202140200/https://findresearcher.sdu.dk/ws/files/158846448/Interaction_Potential_between_Clarithromycin_and_Individual_Statins_a_Systematic_Review.pdf |url-status=live }}</ref> (although FDA lists it as a moderate inhibitor, and inhibitor of P-glycoprotein, defined as those increasing the AUC of digoxin to ≥1.25-fold);<ref name="FDA_drug_development"/>
** [[telithromycin]]
* [[ceritinib]]
* [[mibefradil]] (used for the treatment of [[hypertension]] and chronic [[angina pectoris]])
* [[nefazodone]] ([[antidepressant]])
* [[ribociclib]]
* [[tucatinib]]
* [[chloramphenicol]] ([[antibiotic]])<ref>{{cite journal | vauthors = Park JY, Kim KA, Kim SL | title = Chloramphenicol is a potent inhibitor of cytochrome P450 isoforms CYP2C19 and CYP3A4 in human liver microsomes | journal = Antimicrobial Agents and Chemotherapy | volume = 47 | issue = 11 | pages = 3464–9 | date = November 2003 | pmid = 14576103 | pmc = 253795 | doi = 10.1128/AAC.47.11.3464-3469.2003 }}</ref>
* some [[azole antifungal]]s:
** [[ketoconazole]],<ref name="Flockhart" /><ref name="FASS" />
** [[itraconazole]],<ref name="FDA_drug_development" /><ref name="Flockhart" /><ref name="FASS" />
** [[posaconazole]],<ref name="FDA-labeling">{{cite web|url=https://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm|title=Drug Interactions & Labeling - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers|author=Center for Drug Evaluation and Research|website=www.fda.gov|access-date=6 August 2018|archive-date=23 April 2019|archive-url=https://web.archive.org/web/20190423033345/https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm|url-status=dead}}</ref>
** [[voriconazole]];<ref name="FDA-labeling" />
* [[cobicistat]],<ref name="FDA-labeling" />
* green tea extract,<ref name="pmid33198812" /><ref name="pmid15499196" /><ref name="pmid19353999" />
* grape seed extract,<ref name="pmid33198812">{{cite journal | vauthors = Darweesh RS, El-Elimat T, Zayed A, Khamis TN, Babaresh WM, Arafat T, Al Sharie AH | title = The effect of grape seed and green tea extracts on the pharmacokinetics of imatinib and its main metabolite, N-desmethyl imatinib, in rats | journal = BMC Pharmacology & Toxicology | volume = 21 | issue = 1 | pages = 77 | date = November 2020 | pmid = 33198812 | pmc = 7670682 | doi = 10.1186/s40360-020-00456-9 | doi-access = free }}</ref><ref name="pmid15499196">{{cite journal | vauthors = Nishikawa M, Ariyoshi N, Kotani A, Ishii I, Nakamura H, Nakasa H, Ida M, Nakamura H, Kimura N, Kimura M, Hasegawa A, Kusu F, Ohmori S, Nakazawa K, Kitada M | display-authors = 6 | title = Effects of continuous ingestion of green tea or grape seed extracts on the pharmacokinetics of midazolam | journal = Drug Metabolism and Pharmacokinetics | volume = 19 | issue = 4 | pages = 280–289 | date = August 2004 | pmid = 15499196 | doi = 10.2133/dmpk.19.280 }}</ref><ref name="pmid19353999">{{cite journal | vauthors = Wanwimolruk S, Wong K, Wanwimolruk P | title = Variable inhibitory effect of different brands of commercial herbal supplements on human cytochrome P-450 CYP3A4 | journal = Drug Metabolism and Drug Interactions | volume = 24 | issue = 1 | pages = 17–35 | date = 2009 | pmid = 19353999 | doi = 10.1515/dmdi.2009.24.1.17 | url = http://pubmed.ncbi.nlm.nih.gov/19353999/ | access-date = 14 October 2023 | url-status = live | s2cid = 27192663 | archive-url = https://web.archive.org/web/20231021225447/https://pubmed.ncbi.nlm.nih.gov/19353999/ | archive-date = 21 October 2023 }}</ref>
* [[dillapiole]] (compound present in [[dill]] plants),<ref>{{cite journal | vauthors = Francis Carballo-Arce A, Raina V, Liu S, Liu R, Jackiewicz V, Carranza D, Arnason JT, Durst T | display-authors = 6 | title = Potent CYP3A4 Inhibitors Derived from Dillapiol and Sesamol | journal = ACS Omega | volume = 4 | issue = 6 | pages = 10915–10920 | date = June 2019 | pmid = 31460189 | pmc = 6648837 | doi = 10.1021/acsomega.9b00897 }}</ref><ref>{{cite journal | vauthors = Briguglio M, Hrelia S, Malaguti M, Serpe L, Canaparo R, Dell'Osso B, Galentino R, De Michele S, Dina CZ, Porta M, Banfi G | display-authors = 6 | title = Food Bioactive Compounds and Their Interference in Drug Pharmacokinetic/Pharmacodynamic Profiles | journal = Pharmaceutics | volume = 10 | issue = 4 | page = 277 | date = December 2018 | pmid = 30558213 | pmc = 6321138 | doi = 10.3390/pharmaceutics10040277 | doi-access = free }}</ref>
* [[apigenin]] (compound present in plants such as [[celery]], [[parsley]], and [[chamomile]])<ref>{{cite journal | vauthors = Kondža M, Bojić M, Tomić I, Maleš Ž, Rezić V, Ćavar I | title = Characterization of the CYP3A4 Enzyme Inhibition Potential of Selected Flavonoids | journal = Molecules | volume = 26 | issue = 10 | page = 3018 | date = May 2021 | pmid = 34069400 | pmc = 8158701 | doi = 10.3390/molecules26103018 | doi-access = free }}</ref>
* ''[[Artemisia annua]]''<ref>{{cite journal | vauthors = Kondža M, Mandić M, Ivančić I, Vladimir-Knežević S, Brizić I | title = ''Artemisia annua'' L. Extracts Irreversibly Inhibit the Activity of CYP2B6 and CYP3A4 Enzymes | journal = Biomedicines | volume = 11 | issue = 1 | pages = 232 | date = January 2023 | pmid = 36672740 | pmc = 9855681 | doi = 10.3390/biomedicines11010232 | doi-access = free }}</ref>

====Moderate inhibitors====
* [[amiodarone]] ([[class III antiarrhythmic]]),<ref name="FDA-labeling" />
* [[aprepitant]],<ref name="FDA_drug_development" /> ([[antiemetic]])
* [[ciprofloxacin]],<ref name="FDA_drug_development" />
* [[conivaptan]],<ref name="FDA_drug_development" />
* [[crizotinib]],<ref name="FDA_drug_development" />
* [[rutin]] ''(in vitro)''<ref name="PMID27749250">{{cite journal | vauthors = Karakurt S | title = Modulatory effects of rutin on the expression of cytochrome P450s and antioxidant enzymes in human hepatoma cells | journal = Acta Pharmaceutica | volume = 66 | issue = 4 | pages = 491–502 | date = December 2016 | pmid = 27749250 | doi = 10.1515/acph-2016-0046 | s2cid = 20274417 | doi-access = free | url = https://hrcak.srce.hr/file/243341 | access-date = 2 February 2024 | archive-date = 18 June 2022 | archive-url = https://web.archive.org/web/20220618102746/https://hrcak.srce.hr/file/243341 | url-status = live }}</ref><ref name="PMID28539725">{{cite journal | vauthors = Ashour ML, Youssef FS, Gad HA, Wink M | title = Inhibition of Cytochrome P450 (CYP3A4) Activity by Extracts from 57 Plants Used in Traditional Chinese Medicine (TCM) | journal = Pharmacognosy Magazine | volume = 13 | issue = 50 | pages = 300–308 | year = 2017 | pmid = 28539725 | pmc = 5421430 | doi = 10.4103/0973-1296.204561 | doi-access = free }}</ref> (dietary [[flavonoid]]),
* [[tofisopam]],<ref name="FDA_drug_development" />
* some [[calcium channel blocker]]s:
** [[verapamil]],<ref name="FDA_drug_development" /><ref name="Flockhart" /><ref name="FDA-labeling" />
** [[diltiazem]];<ref name="Flockhart" />
* some [[azole antifungal]]s:<ref name="lange6th" />
** [[fluconazole]],<ref name="Flockhart" />
** [[miconazole]];<ref>Product Information: ORAVIG(R) buccal tablets, miconazole buccal tablets. Praelia Pharmaceuticals, Inc (per FDA), Cary, NC, 2013.</ref>
* [[bergamottin]]<ref name="pmid34570813">{{cite journal |vauthors=Vetrichelvan O, Gorjala P, Goodman O, Mitra R |title=Bergamottin a CYP3A inhibitor found in grapefruit juice inhibits prostate cancer cell growth by downregulating androgen receptor signaling and promoting G0/G1 cell cycle block and apoptosis |journal=PLOS ONE |volume=16 |issue=9 |pages=e0257984 |date=2021 |pmid=34570813 |pmc=8476002 |doi=10.1371/journal.pone.0257984 |bibcode=2021PLoSO..1657984V |url=|doi-access=free }}</ref><ref name="Flockhart" /> (constituent of [[grapefruit]] juice),
* [[Ciclosporin|cyclosporine]],<ref name="FDA-labeling" />
* [[Dronedarone|donedarone]],<ref name="FDA-labeling" />
* [[fluvoxamine]],<ref name="FDA-labeling" />
* [[imatinib]],<ref name="FDA-labeling" />
* [[Valerian (herb)|valerian]].<ref>{{cite web|url=http://www.rxlist.com/valerian-page3/supplements.htm#Interactions|title=Valerian: Health Benefits, Side Effects, Uses, Dose & Precautions|access-date=10 April 2018|archive-date=16 January 2018|archive-url=https://web.archive.org/web/20180116055514/https://www.rxlist.com/valerian-page3/supplements.htm#Interactions|url-status=dead}}</ref>

====Weak inhibitors====
* [[berberine]]<ref name="pmid34269665">{{cite journal |vauthors=Feng PF, Zhu LX, Jie J, Yang PX, Chen X |title=The Intracellular Mechanism of Berberine-Induced Inhibition of CYP3A4 Activity |journal=Curr Pharm Des |volume=27 |issue=40 |pages=4179–4185 |date=2021 |pmid=34269665 |doi=10.2174/1381612827666210715155809 |s2cid=235960940 |url=}}</ref><ref name="pmid37541764">{{cite journal |vauthors=Nguyen JT, Tian DD, Tanna RS, Arian CM, Calamia JC, Rettie AE, Thummel KE, Paine MF |title=An Integrative Approach to Elucidate Mechanisms Underlying the Pharmacokinetic Goldenseal-Midazolam Interaction: Application of In Vitro Assays and Physiologically Based Pharmacokinetic Models to Understand Clinical Observations |journal=J Pharmacol Exp Ther |volume=387 |issue=3 |pages=252–264 |date=December 2023 |pmid=37541764 |pmc=10658920 |doi=10.1124/jpet.123.001681 |url=}}</ref><ref name="pmid22855269">{{cite journal | vauthors = Hermann R, von Richter O | title = Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions | journal = Planta Medica | volume = 78 | issue = 13 | pages = 1458–77 | date = September 2012 | pmid = 22855269 | doi = 10.1055/s-0032-1315117 | url = | doi-access = free }}</ref><ref name="pmid30086269">{{cite journal | vauthors = Feng P, Zhao L, Guo F, Zhang B, Fang L, Zhan G, Xu X, Fang Q, Liang Z, Li B | title = The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins | journal = Chemico-Biological Interactions | volume = 293 | issue = | pages = 115–123 | date = September 2018 | pmid = 30086269 | doi = 10.1016/j.cbi.2018.07.022 | bibcode = 2018CBI...293..115F | s2cid = 206489481 }}</ref> (an [[alkaloid]] found in plants such as [[berberis]] or [[goldenseal]]),
* [[buprenorphine]] ([[analgesic]]),<ref name="pmid12756210">{{cite journal | vauthors = Zhang W, Ramamoorthy Y, Tyndale RF, Sellers EM | s2cid = 16229370 | title = Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro | journal = Drug Metabolism and Disposition | volume = 31 | issue = 6 | pages = 768–72 | date = June 2003 | pmid = 12756210 | doi = 10.1124/dmd.31.6.768 }}</ref>
* [[cafestol]] (in unfiltered coffee)<ref>{{cite journal| title = Interaction of coffee diterpenes, cafestol and kahweol, with human P-glycoprotein | vauthors = Nabekura T, Yamaki T, Kitagawa S | date = 2009 | journal = AAPS Journal | publisher = The American Association of Pharmaceutical Scientists | url = http://www.aapsj.org/abstracts/AM_2009/AAPS2009-001235.PDF | archive-url = https://web.archive.org/web/20110721141830/http://www.aapsj.org/abstracts/AM_2009/AAPS2009-001235.PDF | archive-date= 21 July 2011 }}</ref>
* [[cilostazol]],<ref name="FDA-labeling" />
* [[cimetidine]],<ref name="FDA-labeling" />
* [[fosaprepitant]],<ref name="FDA-labeling" />
* [[lomitapide]],<ref name="FDA-labeling" />
* [[orphenadrine]],
* [[omeprazole]]<ref name="Flockhart" /> ([[proton pump inhibitor]]),
* [[quercetin]],<ref name="pmid34601070">{{cite journal |vauthors=Kheoane PS, Enslin GM, Tarirai C |title=Determination of effective concentrations of drug absorption enhancers using in vitro and ex vivo models |journal=Eur J Pharm Sci |volume=167 |issue= |pages=106028 |date=December 2021 |pmid=34601070 |doi=10.1016/j.ejps.2021.106028 |s2cid=238257296 }}</ref><ref name="Flockhart" />
* [[ranitidine]],<ref name="FDA-labeling" />
* [[ranolazine]],<ref name="FDA-labeling" />
* [[tacrolimus]],<ref name="FDA-labeling" />
* [[ticagrelor]],<ref name="FDA-labeling" />
* [[valproic acid]],<ref>{{cite journal | pmc= 2014611 | pmid=11736863 | volume=52 | issue=5 | title=In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9) | journal=Br J Clin Pharmacol | pages=547–53 | vauthors=Wen X, Wang JS, Kivistö KT, Neuvonen PJ, Backman JT | doi=10.1046/j.0306-5251.2001.01474.x| year=2001 }}</ref>
* [[amlodipine]],<ref name="Katoh_2000" />
* [[azithromycin]] ([[macrolide antibiotic]]).<ref name="pmid31628882" />

====Inhibitors of unspecified potency====
* [[bergaptol]] (a [[furocoumarin]] in [[citrus]]),<ref name="pmid38338457">{{cite journal |vauthors=Phucharoenrak P, Trachootham D |title=Bergaptol, a Major Furocoumarin in Citrus: Pharmacological Properties and Toxicity |journal=Molecules |volume=29 |issue=3 |date=February 2024 |page=713 |pmid=38338457 |pmc=10856120 |doi=10.3390/molecules29030713 |doi-access=free }}</ref>
* [[cannabidiol]],<ref name="pmid21356216">{{cite journal | vauthors = Yamaori S, Ebisawa J, Okushima Y, Yamamoto I, Watanabe K | title = Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety | journal = Life Sciences | volume = 88 | issue = 15–16 | pages = 730–6 | date = April 2011 | pmid = 21356216 | doi = 10.1016/j.lfs.2011.02.017 }}</ref>
* [[dithiocarbamate]]<ref name="Flockhart" /> (functional group),
* [[flavonoid]]s,<ref name="pmid38540257">{{cite journal |vauthors=Kondža M, Brizić I, Jokić S |title=Flavonoids as CYP3A4 Inhibitors In Vitro |journal=Biomedicines |volume=12 |issue=3 |date=March 2024 |page=644 |pmid=38540257 |pmc=10968035 |doi=10.3390/biomedicines12030644|doi-access=free }}</ref>
* [[mifepristone]]<ref name="Flockhart" /> ([[abortifacient]]),
* [[norfloxacin]]<ref name="Flockhart" /> ([[Quinolone antibiotic|fluoroquinolone]] antibiotic),
* some non-nucleoside [[reverse-transcriptase inhibitor]]s:<ref name="nnrti">Non-nucleoside reverse-transcriptase inhibitors have been shown to both induce and inhibit CYP3A4.</ref>
** [[delavirdine]];<ref name="Flockhart" />
* [[gestodene]]<ref name="Flockhart" /> ([[hormonal contraceptive]]),
* [[carambola|star fruit]],<ref name="Flockhart" /><ref>{{cite journal | vauthors = Hidaka M, Fujita K, Ogikubo T, Yamasaki K, Iwakiri T, Okumura M, Kodama H, Arimori K | s2cid = 17392051 | title = Potent inhibition by star fruit of human cytochrome P450 3A (CYP3A) activity | journal = Drug Metabolism and Disposition | volume = 32 | issue = 6 | pages = 581–3 | date = June 2004 | pmid = 15155547 | doi = 10.1124/dmd.32.6.581 }}</ref>
* [[milk thistle]],<ref>{{cite web|url=http://www.hcvadvocate.org/hepatitis/hepC/mthistle.html|archiveurl=https://web.archive.org/web/20100305175124/http://www.hcvadvocate.org/hepatitis/hepC/mthistle.html|url-status=dead|title=HCVadvocate.org|archivedate=5 March 2010}}</ref>
* [[Niacin (nutrient)|niacin]]<ref name="Gaudineau_2004">{{cite journal | vauthors = Gaudineau C, Auclair K | title = Inhibition of human P450 enzymes by nicotinic acid and nicotinamide | journal = Biochemical and Biophysical Research Communications | volume = 317 | issue = 3 | pages = 950–6 | date = May 2004 | pmid = 15081432 | doi = 10.1016/j.bbrc.2004.03.137 }}</ref> ([[nicotinic acid]]) and its form – [[niacinamide]] ([[nicotinamide]]), collectively called as Vitamin B<sub>3</sub>,
* [[ginkgo biloba]],<ref name="pmid19883715">{{cite journal | vauthors = Kimura Y, Ito H, Ohnishi R, Hatano T | title = Inhibitory effects of polyphenols on human cytochrome P450 3A4 and 2C9 activity | journal = Food and Chemical Toxicology | volume = 48 | issue = 1 | pages = 429–35 | date = January 2010 | pmid = 19883715 | doi = 10.1016/j.fct.2009.10.041 | quote = Ginko Biloba has been shown to contain the potent inhibitor amentoflavone }}</ref>
* [[sesamin]]<ref name="pmid22645625">{{cite journal | vauthors = Lim YP, Ma CY, Liu CL, Lin YH, Hu ML, Chen JJ, Hung DZ, Hsieh WT, Huang JD | title = Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation | journal = Evidence-Based Complementary and Alternative Medicine | volume = 2012 | pages = 242810 | year = 2012 | pmid = 22645625 | pmc = 3356939 | doi = 10.1155/2012/242810 | doi-access = free }}</ref> (a [[lignan]] constituent in [[sesame]] seeds and oil),
* [[piperine]],<ref>{{cite journal | vauthors = Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF | s2cid = 7398172 | title = Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4 | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 302 | issue = 2 | pages = 645–50 | date = August 2002 | pmid = 12130727 | doi = 10.1124/jpet.102.034728 }}</ref>
* [[isoniazid]],<ref>{{cite journal | vauthors = Wen X, Wang JS, Neuvonen PJ, Backman JT | s2cid = 19299097 | title = Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes | journal = European Journal of Clinical Pharmacology | volume = 57 | issue = 11 | pages = 799–804 | date = January 2002 | pmid = 11868802 | doi = 10.1007/s00228-001-0396-3 }}</ref>
* [[serenoa]],<ref>{{cite journal | vauthors = Ekstein D, Schachter SC | title = Natural Products in Epilepsy-the Present Situation and Perspectives for the Future | journal = Pharmaceuticals | volume = 3 | issue = 5 | pages = 1426–1445 | date = May 2010 | pmid = 27713311 | pmc = 4033990 | doi = 10.3390/ph3051426 | doi-access = free }}</ref>
* [[phenelzine]].<ref>{{Cite journal |last=Gillman |first=Peter Kenneth |date=February 2011 |title=Advances pertaining to the pharmacology and interactions of irreversible nonselective monoamine oxidase inhibitors |url=https://pubmed.ncbi.nlm.nih.gov/21192146 |journal=Journal of Clinical Psychopharmacology |volume=31 |issue=1 |pages=66–74 |doi=10.1097/JCP.0b013e31820469ea |issn=1533-712X |pmid=21192146}}</ref>

=== Inducers ===
Strong and moderate CYP3A4 inducers are drugs that decrease the AUC of sensitive substrates of a given pathway where CYP3A4 is involved by ≥80 percent and ≥50 to <80 percent, respectively.<ref name="FDA_drug_development"/><ref name="pmid34526892"/> Weak inducers decrease the AUC by ≥20 to <50 percent.<ref name="pmid34526892">{{cite journal |vauthors=Molenaar-Kuijsten L, Van Balen DE, Beijnen JH, Steeghs N, Huitema AD |title=A Review of CYP3A Drug-Drug Interaction Studies: Practical Guidelines for Patients Using Targeted Oral Anticancer Drugs |journal=Front Pharmacol |volume=12 |issue= |pages=670862 |date=2021 |pmid=34526892 |pmc=8435708 |doi=10.3389/fphar.2021.670862|doi-access=free }}</ref>

The inducers of CYP3A4 are the following substances.

====Strong inducers====
* [[carbamazepine]],<ref name="FDA_drug_development"/><ref name=lange6th>{{cite book | vauthors = Flower R, Rang HP, Dale MM, Ritter JM |title=Rang & Dale's pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2007 |isbn=978-0-443-06911-6 }}{{page needed|date=November 2015}}</ref>
* [[antiandrogen]]s:
** [[enzalutamide]],<ref>{{cite web | title = Highlights of Prescribing Information: XTANDI (enzalutamide) capsules for oral use | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203415lbl.pdf | author = Astellas Pharma US, Inc. | publisher = U.S. Food and Drug Administration | date = August 2012 | access-date = 10 April 2018 | archive-date = 31 July 2018 | archive-url = https://web.archive.org/web/20180731002946/https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203415lbl.pdf | url-status = dead }}</ref>
** [[apalutamide]];
* [[primidone]]<ref>{{cite journal | vauthors = Schelleman H | title = AExposure to CYP3A4 inducing and CYP3A4 non-inducing antiepileptic agents and the risk of fractures | journal = Pharmacoepidemiol Drug Saf | volume = 20 | issue = 6 | pages = 619–625 | date = Feb 2015| doi =  10.1002/pds.2141 | pmid = 21538673 | pmc = 4340253 }}</ref>
* [[phenytoin]]<ref name="FDA_drug_development"/><ref>{{cite journal | vauthors = Johannessen SI, Landmark CJ | title = Antiepileptic drug interactions - principles and clinical implications | journal = Current Neuropharmacology | volume = 8 | issue = 3 | pages = 254–67 | date = September 2010 | pmid = 21358975 | pmc = 3001218 | doi = 10.2174/157015910792246254 }}</ref> ([[anticonvulsant]]),
* [[rifampin]].<ref name="FDA_drug_development"/>

====Weak inducers====
* [[upadacitinib]].<ref name="Rinvoq-2020" /><ref name="Austria-Codex-DE" />

====Inducers of unspecified potency====
* [[anticonvulsant]]s, [[mood stabilizers]]:
** [[oxcarbazepine]],<ref name=Flockhart/>
** [[topiramate]];<ref>{{cite journal | vauthors = Nallani SC, Glauser TA, Hariparsad N, Setchell K, Buckley DJ, Buckley AR, Desai PB | title = Dose-dependent induction of cytochrome P450 (CYP) 3A4 and activation of pregnane X receptor by topiramate | journal = Epilepsia | volume = 44 | issue = 12 | pages = 1521–8 | date = December 2003 | pmid = 14636322 | doi = 10.1111/j.0013-9580.2003.06203.x | s2cid = 6915760 }}</ref>
* [[barbiturates]]:<ref name=lange6th/>
** [[phenobarbital]],<ref name=Flockhart/><ref name=FASS/>
** [[butalbital]]:
* [[St. John's wort]],<ref name=Flockhart/><ref name=FASS/>
* some [[bactericidal]]s:
** [[rifampicin]],<ref name=Flockhart/><ref name=lange6th/>
** [[rifabutin]];<ref name=Flockhart/><ref name=FASS/>
* some non-nucleoside [[reverse-transcriptase inhibitor]]s:<ref name=nnrti/>
** [[efavirenz]],<ref name=Flockhart/>
** [[nevirapine]];<ref name=Flockhart/>
* [[troglitazone]] ([[hypoglycemic]]),
* [[glucocorticoids]]<ref name=Flockhart/> ([[blood glucose]] increase, [[immunosuppressive]]),
* [[modafinil]]<ref name="pmid34633961" /><ref name=Flockhart/> ([[stimulant]]),
* [[capsaicin]],<ref>{{cite journal | vauthors = Han EH, Kim HG, Choi JH, Jang YJ, Lee SS, Kwon KI, Kim E, Noh K, Jeong TC, Hwang YP, Chung YC, Kang W, Jeong HG | s2cid = 26584141 | title = Capsaicin induces CYP3A4 expression via pregnane X receptor and CCAAT/enhancer-binding protein β activation | journal = Molecular Nutrition & Food Research | volume = 56 | issue = 5 | pages = 797–809 | date = May 2012 | pmid = 22648626 | doi = 10.1002/mnfr.201100697 }}</ref>
* [[brigatinib]],<ref name=Flockhart/>
* [[clobazam]],<ref name=Flockhart/>
* [[dabrafenib]],<ref name=Flockhart/>
* [[elagolix]],<ref name=Flockhart/>
* [[eslicarbazepine]],<ref name=Flockhart/>
* [[letermovir]],<ref name=Flockhart/>
* [[lorlatinib]],<ref name=Flockhart/>
* [[oritavancin]],<ref name=Flockhart/>
* [[perampanel]],<ref name=Flockhart/>
* [[telotristat]].<ref name=Flockhart/>