Editing Hydrocodone (section)

== Interactions ==

Hydrocodone is [[metabolism|metabolized]] by the [[cytochrome P450]] [[enzyme]]s [[CYP2D6]] and [[CYP3A4]], and [[enzyme inhibitor|inhibitor]]s and [[enzyme inducer|inducer]]s of these enzymes can modify hydrocodone exposure.<ref name="pmid28579821">{{cite journal | vauthors = Feng XQ, Zhu LL, Zhou Q | title = Opioid analgesics-related pharmacokinetic drug interactions: from the perspectives of evidence based on randomized controlled trials and clinical risk management | journal = Journal of Pain Research | volume = 10 | issue = | pages = 1225–1239 | date = 2017 | pmid = 28579821 | pmc = 5449157 | doi = 10.2147/JPR.S138698 | doi-access = free }}</ref> One study found that combination of [[paroxetine]], a [[selective serotonin reuptake inhibitor]] (SSRI) and strong CYP2D6 inhibitor, with once-daily extended-release hydrocodone, did not modify exposure to hydrocodone or the incidence of adverse effects.<ref name="pmid28579821" /><ref name="pmid26350273">{{cite journal | vauthors = Kapil RP, Friedman K, Cipriano A, Michels G, Shet M, Mondal SA, Harris SC | title = Effects of paroxetine, a CYP2D6 inhibitor, on the pharmacokinetic properties of hydrocodone after coadministration with a single-entity, once-daily, extended-release hydrocodone tablet | journal = Clinical Therapeutics | volume = 37 | issue = 10 | pages = 2286–2296 | date = October 2015 | pmid = 26350273 | doi = 10.1016/j.clinthera.2015.08.007 | doi-access = free }}</ref> These findings suggest that hydrocodone can be coadministered with CYP2D6 inhibitors without dosage modification.<ref name="pmid28579821" /><ref name="pmid26350273" /> Conversely, combination of [[hydrocodone/acetaminophen]] with the [[antiviral]] regimen of [[ombitasvir]], [[paritaprevir]], [[ritonavir]], and [[dasabuvir]] for treatment of [[hepatitis C]] increased [[Cmax (pharmacology)|peak concentrations]] of hydrocodone by 27%, [[area-under-the-curve (pharmacokinetics)|total exposure]] by 90%, and [[elimination half-life]] from 5.1{{nbsp}}hours to 8.0{{nbsp}}hours.<ref name="pmid26895022">{{cite journal | vauthors = Polepally AR, King JR, Ding B, Shuster DL, Dumas EO, Khatri A, Chiu YL, Podsadecki TJ, Menon RM | display-authors = 6 | title = Drug-Drug Interactions Between the Anti-Hepatitis C Virus 3D Regimen of Ombitasvir, Paritaprevir/Ritonavir, and Dasabuvir and Eight Commonly Used Medications in Healthy Volunteers | journal = Clinical Pharmacokinetics | volume = 55 | issue = 8 | pages = 1003–1014 | date = August 2016 | pmid = 26895022 | pmc = 4933729 | doi = 10.1007/s40262-016-0373-8 }}</ref> Ritonavir is a strong CYP3A4 inhibitor as well as inducer of CYP3A and other enzymes, and the other antivirals are known to inhibit [[drug transporter]]s like [[organic anion transporting polypeptide]] (OATP) [[OATP1B1|1B1]] and [[OATP1B3|1B3]], [[P-glycoprotein]], and [[breast cancer resistance protein]] (BCRP).<ref name="pmid26895022" /> The changes in hydrocodone levels are consistent with CYP3A4 inhibition by ritonavir.<ref name="pmid26895022" /> Based on these findings, a 50% lower dose of hydrocodone and closer clinical monitoring was recommended when hydrocodone is used in combination with this antiviral regimen.<ref name="pmid26895022" />

People consuming [[alcohol (drug)|alcohol]], other opioids, [[anticholinergic]] [[antihistamine]]s, [[antipsychotic]]s, [[anxiolytic]]s, or other [[central nervous system]] (CNS) [[depressant]]s together with hydrocodone may exhibit an additive [[CNS depression]].<ref name="DailyMed-Reprexain">{{cite web |url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=7b71e4c3-86f2-464a-b0a9-4f98adfef9c5 |title=REPREXAIN (hydrocodone bitartrate, ibuprofen) tablet, film coated |website=dailymed.nlm.nih.gov |publisher=NIH |access-date=27 April 2013 |archive-date=6 July 2013 |archive-url=https://web.archive.org/web/20130706022619/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=7b71e4c3-86f2-464a-b0a9-4f98adfef9c5 |url-status=live }}</ref> Hydrocodone taken concomitantly with [[Serotonin|serotonergic]] medications like SSRI [[antidepressant]]s may increase the risk of [[serotonin syndrome]].<ref name="pmid15948273">{{cite journal | vauthors = Gnanadesigan N, Espinoza RT, Smith RL | title = The serotonin syndrome | journal = The New England Journal of Medicine | volume = 352 | issue = 23 | pages = 2454–6; author reply 2454–6 | date = June 2005 | pmid = 15948273 | doi = 10.1056/NEJM200506093522320 }}</ref>