Editing Erythromycin (section)

== Interactions ==
Erythromycin is metabolized by enzymes of the [[cytochrome P450]] system, in particular, by [[isozymes]] of the [[CYP3A]] superfamily.<ref name="pmid1732074">{{cite journal | vauthors = Hunt CM, Watkins PB, Saenger P, Stave GM, Barlascini N, Watlington CO, Wright JT, Guzelian PS | title = Heterogeneity of CYP3A isoforms metabolizing erythromycin and cortisol | journal = Clinical Pharmacology and Therapeutics | volume = 51 | issue = 1 | pages = 18–23 | date = January 1992 | pmid = 1732074 | doi = 10.1038/clpt.1992.3 | hdl = 2027.42/109905 | s2cid = 28056649 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/109905/1/cptclpt19923.pdf | hdl-access = free | access-date = 29 August 2019 | archive-date = 28 August 2021 | archive-url = https://web.archive.org/web/20210828075533/https://deepblue.lib.umich.edu/bitstream/handle/2027.42/109905/cptclpt19923.pdf;jsessionid=E4EB0A4C0D1D5A07533C041190B23FA0?sequence=1 | url-status = live }}</ref> The activity of the CYP3A enzymes can be induced or inhibited by certain drugs (e.g., dexamethasone), which can cause it to affect the [[metabolism]] of many different drugs, including erythromycin. If other CYP3A substrates — drugs that are broken down by CYP3A — such as [[simvastatin]] (Zocor), [[lovastatin]] (Mevacor), or [[atorvastatin]] (Lipitor) — are taken concomitantly with erythromycin, levels of the substrates increase, often causing adverse effects. A noted drug interaction involves erythromycin and simvastatin, resulting in increased simvastatin levels and the potential for [[rhabdomyolysis]]. Another group of CYP3A4 substrates are drugs used for [[migraine]] such as [[ergotamine]] and [[dihydroergotamine]]; their adverse effects may be more pronounced if erythromycin is associated.<ref name="BCFI">{{cite web | url = http://www.bcfi.be/GGR/MPG/MPG_KABA.cfm | title = Erythromycine | work = Belgisch Centrum voor Farmacotherapeutische Informatie | url-status = live | archive-url = https://web.archive.org/web/20151006100756/http://www.bcfi.be/GGR/MPG/MPG_KABA.cfm | archive-date = 6 October 2015 }}</ref>

Earlier case reports on sudden death prompted a study on a large cohort that confirmed a link between erythromycin, [[ventricular tachycardia]], and sudden cardiac death in patients also taking drugs that prolong the metabolism of erythromycin (like [[verapamil]] or [[diltiazem]]) by interfering with CYP3A4.<ref>{{cite journal | vauthors = Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM | title = Oral erythromycin and the risk of sudden death from cardiac causes | journal = The New England Journal of Medicine | volume = 351 | issue = 11 | pages = 1089–96 | date = September 2004 | pmid = 15356306 | doi = 10.1056/NEJMoa040582 | doi-access = free }}</ref> Hence, erythromycin should not be administered to people using these drugs, or drugs that also prolong the [[QT interval]]. Other examples include [[terfenadine]] (Seldane, Seldane-D),<ref>{{cite web |url=https://www.drugs.com/drug-interactions/erythromycin-with-terfenadine-1009-0-2164-0.html?professional=1 |title=Drug Interactions between erythromycin and terfenadine |access-date=21 December 2023 |website=Drugs.com}}</ref> [[astemizole]] (Hismanal),<ref>{{cite web |url=https://www.drugs.com/drug-interactions/astemizole-with-erythromycin-271-0-1009-0.html?professional=1 |title=Drug Interactions between astemizole and erythromycin |access-date=21 December 2023 |website=Drugs.com}}</ref> [[cisapride]]<ref>{{cite journal | vauthors = Michalets EL, Williams CR | title = Drug interactions with cisapride: clinical implications | journal = Clinical Pharmacokinetics | volume = 39 | issue = 1 | pages = 49–75 | date = July 2000 | pmid = 10926350 | doi = 10.2165/00003088-200039010-00004 | s2cid = 41704853 }}</ref> (Propulsid, withdrawn in many countries for prolonging the QT time) and [[pimozide]] (Orap).<ref>{{cite web |url=https://gpnotebook.com/pages/ear-nose-and-throat/erythromycin/interactions |title=Erythromycin Interactions |date=20 December 2020 |access-date=21 December 2023 |website=GPnotebook |archive-url=https://web.archive.org/web/20231221161502/https://gpnotebook.com/pages/ear-nose-and-throat/erythromycin/interactions |archive-date=21 December 2023 |url-status=live}}</ref> Interactions with [[theophylline]], which is used mostly in asthma, were also shown.<ref>{{cite web |url=https://www.drugs.com/drug-interactions/erythromycin-with-theophylline-1009-0-2177-0.html?professional=1 |title=Drug Interactions between erythromycin and theophylline |access-date=21 December 2023 |website=Drugs.com |archive-url=https://web.archive.org/web/20231221104101/https://www.drugs.com/drug-interactions/erythromycin-with-theophylline-1009-0-2177-0.html?professional=1 |archive-date=21 December 2023 |url-status=live}}</ref>

Erythromycin and [[doxycycline]] can have a synergistic effect when combined and kill bacteria (''E. coli)'' with a higher potency than the sum of the two drugs together. This synergistic relationship is only temporary. After approximately 72 hours, the relationship shifts to become antagonistic, whereby a 50/50 combination of the two drugs kills less bacteria than if the two drugs were administered separately.<ref>{{cite journal | vauthors = Pena-Miller R, Laehnemann D, Jansen G, Fuentes-Hernandez A, Rosenstiel P, Schulenburg H, Beardmore R | title = When the most potent combination of antibiotics selects for the greatest bacterial load: the smile-frown transition | journal = PLOS Biology | volume = 11 | issue = 4 | pages = e1001540 | date = 23 April 2013 | pmid = 23630452 | pmc = 3635860 | doi = 10.1371/journal.pbio.1001540 | doi-access = free }}</ref>

It may alter the effectiveness of [[combined oral contraceptive pill]]s because of its effect on the gut flora. A review found that when erythromycin was given with certain oral contraceptives, there was an increase in the maximum serum concentrations and [[Area under the curve (pharmacokinetics)|AUC]] of [[Estradiol-containing birth control pill|estradiol]] and [[dienogest]].<ref>{{cite journal | vauthors = Blode H, Zeun S, Parke S, Zimmermann T, Rohde B, Mellinger U, Kunz M | title = Evaluation of the effects of rifampicin, ketoconazole and erythromycin on the steady-state pharmacokinetics of the components of a novel oral contraceptive containing estradiol valerate and dienogest in healthy postmenopausal women | language = en | journal = Contraception | volume = 86 | issue = 4 | pages = 337–44 | date = October 2012 | pmid = 22445438 | doi = 10.1016/j.contraception.2012.01.010 | url = https://www.contraceptionjournal.org/article/S0010-7824(12)00041-8/abstract | access-date = 2 August 2019 | archive-date = 28 August 2021 | archive-url = https://web.archive.org/web/20210828075535/https://www.contraceptionjournal.org/article/S0010-7824%2812%2900041-8/fulltext | url-status = live }}</ref><ref>{{cite journal | vauthors = Simmons KB, Haddad LB, Nanda K, Curtis KM | title = Drug interactions between non-rifamycin antibiotics and hormonal contraception: a&nbsp;systematic review | language = en | journal = American Journal of Obstetrics and Gynecology | volume = 218 | issue = 1 | pages = 88–97.e14 | date = January 2018 | pmid = 28694152 | doi = 10.1016/j.ajog.2017.07.003 | s2cid = 36567820 | url = https://www.ajog.org/article/S0002-9378(17)30845-1/abstract | access-date = 2 August 2019 | archive-date = 28 August 2021 | archive-url = https://web.archive.org/web/20210828075543/https://www.ajog.org/article/S0002-9378%2817%2930845-1/fulltext | url-status = live }}</ref>

Erythromycin is an inhibitor of the cytochrome P450 system, which means it can have a rapid effect on levels of other drugs metabolised by this system, e.g., [[warfarin]].<ref>{{cite journal | vauthors = Westphal JF | title = Macrolide - induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin | journal = British Journal of Clinical Pharmacology | volume = 50 | issue = 4 | pages = 285–295 | date = October 2000 | pmid = 11012550 | pmc = 2015000 | doi = 10.1046/j.1365-2125.2000.00261.x }}</ref>