Xylometazoline: Difference between revisions

{{Short description|Nasal decongestant}}

{{Use dmy dates|date=December 2019}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Infobox drug

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 459852622

| image = Xylometazoline.svg

| width = 150

| alt =

| pronounce = {{IPAc-en|ˌ|z|aɪ|l|oʊ|ˌ|m|ɛ|t|ə|ˈ|z|oʊ|l|iː|n}}<br />{{respell|ZY|lo|MET|ə|ZOH|leen}}

| tradename = Otrivin, Otrivine, others

| Drugs.com = {{drugs.com|monograph|oxymetazoline-hydrochloride}}

| MedlinePlus = a608026

| DailyMedID = Xylometazoline

| dependency_liability = Moderate<ref>{{cite journal|title=Fulga, Ana, Andrei Zenovia, Doriana Cristea Ene, Constantin Stan, Dorel Firescu, and Iuliu Fulga. 2021. "Addiction to Nasal Decongestants Based on Α-Adrenoceptor Agonists Case Series and Literature Review: Array". EuroEconomica 40 (2). |journal=Euroeconomica |date=18 November 2021 |volume=40 |issue=2 |url=https://dj.univ-danubius.ro/index.php/EE/article/view/1455 | vauthors = Fulga A, Zenovia A, Ene DC, Stan C, Firescu D, Fulga I }}</ref>

| routes_of_administration = [[Insufflation (medicine)|intranasal]] (spray or drops)

| class = α1 and α2 [[Adrenergic receptor agonist]],<br>[[Decongestant]]

| ATC_prefix = R01

| ATC_suffix = AA07

| ATC_supplemental = {{ATC|S01|GA03}}

<!-- Legal status -->

| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C5, D1, D2, E, F1, F2, F3, F4 -->

| legal_BR_comment =

| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_CA_comment =

| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

| legal_UK_comment =

| legal_US = OTC

| legal_US_comment =

| legal_EU =

| legal_EU_comment =

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->

| bioavailability =

| metabolism =

| elimination_half-life = 2–3 hours {{Cn|date=October 2024}}

| excretion = Urinary

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 526-36-3

| PubChem = 5709

| IUPHAR_ligand = 517

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB06694

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 5507

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = WPY40FTH8K

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D08684

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 312448

| IUPAC_name = 2-[(4-''tert''-butyl-2,6-dimethylphenyl)methyl]-<br />4,5-dihydro-1''H''-imidazole

| C = 16

| H = 24

| N = 2

| smiles = N\1=C(\NCC/1)Cc2c(cc(cc2C)C(C)(C)C)C

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C16H24N2/c1-11-8-13(16(3,4)5)9-12(2)14(11)10-15-17-6-7-18-15/h8-9H,6-7,10H2,1-5H3,(H,17,18)

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = HUCJFAOMUPXHDK-UHFFFAOYSA-N

<!-- Definition and medical uses -->

'''Xylometazoline''', also spelled '''xylomethazoline''', is a [[medication]] used to reduce symptoms of [[nasal congestion]], [[allergic rhinitis]], and [[sinusitis]].<ref name=UK2016>{{cite web|title=Otrivine Adult Measured Dose Sinusitis Spray - Summary of Product Characteristics (SPC) - (eMC)|url=https://www.medicines.org.uk/emc/medicine/21058|website=www.medicines.org.uk|access-date=28 December 2016|date=13 April 2016|url-status=live|archive-url=https://web.archive.org/web/20161229031912/https://www.medicines.org.uk/emc/medicine/21058|archive-date=29 December 2016}}</ref> It is used directly in the [[human nose|nose]] as a spray or drops.<ref name=BNF69/>

<!-- Side effects and mechanism -->

Side effects include trouble sleeping, irritation of the nose, nausea, nosebleed (3%), period pain (10%) and headache (3%).<ref name=sideeff>{{cite journal | vauthors = Eccles R, Martensson K, Chen SC | title = Effects of intranasal xylometazoline, alone or in combination with ipratropium, in patients with common cold | journal = Current Medical Research and Opinion | volume = 26 | issue = 4 | pages = 889–899 | date = April 2010 | pmid = 20151787 | doi = 10.1185/03007991003648015 | s2cid = 34728458 }}</ref><ref name=UK2016/><ref name=BNF69/> Long term use (> 10 days) is not recommended due to a [[rhinitis medicamentosa]] when stopped.<ref name=sideeff/><ref name=Gra1997/> Use is not recommended during [[pregnancy]].<ref name=UK2016/> Xylometazoline is in the [[decongestant]] and [[alpha-adrenergic agonist]] families of medication.<ref name=Gra1997>{{cite journal | vauthors = Graf P | title = Rhinitis medicamentosa: aspects of pathophysiology and treatment | journal = Allergy | volume = 52 | issue = 40 Suppl | pages = 28–34 | date = 1997 | pmid = 9353558 | doi = 10.1111/j.1398-9995.1997.tb04881.x | s2cid = 72326981 }}</ref><ref name=MTM2016>{{cite web|title=Xylometazoline nasal medical facts from Drugs.com|url=https://www.drugs.com/mtm/xylometazoline-nasal.html|website=www.drugs.com|access-date=28 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161229032454/https://www.drugs.com/mtm/xylometazoline-nasal.html|archive-date=29 December 2016}}</ref>

One study classified it with selectivity ratios in alpha 2 adrenergic receptors of 151 for a2A vs a2B, 4.5 a2A vs a2C, and 33.9 a2B vs a2C.  Making it a highly selective a2A agonist.<ref>{{cite journal | vauthors = Proudman RG, Akinaga J, Baker JG | title = The signaling and selectivity of α-adrenoceptor agonists for the human α2A, α2B and α2C-adrenoceptors and comparison with human α1 and β-adrenoceptors | journal = Pharmacology Research & Perspectives | volume = 10 | issue = 5 | pages = e01003 | date = October 2022 | pmid = 36101495 | pmc = 9471048 | doi = 10.1002/prp2.1003 }}</ref>

<!-- Society and culture -->

Xylometazoline was patented in 1956 and came into medical use in 1959.<ref name=Fis2006>{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=978-3-527-60749-5|page=552|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA552|language=en|url-status=live|archive-url=https://web.archive.org/web/20161229100737/https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA552|archive-date=2016-12-29}}</ref><ref>{{cite patent|country=US|number=2868802A|title=2-(γ-TERT-BUTYL-O,O'-DIMETHYL-PHENYL-METHYL)-IMIDAZOLINE AND SALTS|status=patent|pubdate=|fdate=1957-06-11|pridate=1956-07-10|gdate=1959-01-13|invent1=Hüni|inventor1-first=Albrecht|assign1=Ciba Pharmaceutical Products Inc., Summit, N. J.}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> Xylometazoline is available as a [[generic medication]].<ref name=BNF69>{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=978-0-85711-156-2|page=786|edition=69}}</ref>

Xylometazoline works by stimulating [[adrenergic receptors]] on the [[lamina propria]] of [[blood vessel]]s in the nose. The decongestant effect is due to [[Vasoconstriction|constriction]] of large veins in the nose which swell up during the inflammation of any infection or allergy of the nose. The smaller arteries are also constricted and this causes the colour of the nasal [[epithelium]] to be visibly paler after dosage.

Xylometazoline is an [[imidazole]] derivative which is designed to mimic the molecular shape of [[adrenaline]]. It binds to [[Alpha-1 adrenergic receptor|α₁]] and [[Alpha-2 adrenergic receptor|α₂]] adrenergic receptors<ref>{{cite journal | vauthors = Haenisch B, Walstab J, Herberhold S, Bootz F, Tschaikin M, Ramseger R, Bönisch H | title = Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline | journal = Fundamental & Clinical Pharmacology | volume = 24 | issue = 6 | pages = 729–739 | date = December 2010 | pmid = 20030735 | doi = 10.1111/j.1472-8206.2009.00805.x | s2cid = 25064699 }}</ref> in the nasal mucosa. Due to its [[sympathomimetic]] effects, it should not be used by people with high [[blood pressure]], or other [[heart]] problems.

Extended usage of xylometazoline can result in decreased effectiveness or a buildup of tolerance against the drug.<ref>[http://www.harrisonspractice.com/practice/ub?cmd=ref&style.cp=421620&style.cpa=0 Gold Standard Clinical Pharmacology<!-- Bot generated title -->] {{webarchive|url=https://web.archive.org/web/20080525220506/http://www.harrisonspractice.com/practice/ub?cmd=ref&style.cp=421620&style.cpa=0 |date=2008-05-25 }}</ref> The number of receptors decreases, and when the administration of the drug is ceased, chronic congestion can occur; this is called [[rhinitis medicamentosa]], commonly referred to as rebound congestion. Moreover, long-term overdosing can cause degenerative changes in nasal [[mucous membrane]]s that pose another health problem.{{citation needed|date=December 2011}}

==Society and culture==

In 2021, a US FDA Drug Safety Communication stated that, while a US Consumer Product Safety Commission (CPSC) proposed rule regarding child-resistant packaging covered products containing xylometazoline, no such products were marketed in the United States at that time.<ref>{{Cite web|url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-serious-adverse-events-accidental-ingestion-children-over-counter-eye |title = FDA Drug Safety Communication: Serious adverse events from accidental ingestion by children of over-the-counter eye drops and nasal sprays |website = FDA|date = July 2021}}</ref>

===Brand names===

The most common name for over-the-counter products containing xylometazoline internationally is "Otrivin" (used in Australia,<ref>{{Cite web|url=https://www.healthdirect.gov.au/medicines/medicinal-product/aht,21627/xylometazoline|title=xylometazoline|website=Healthdirect Australia|access-date=2019-10-25}}</ref> Canada, Estonia, Finland, Greece, Hungary, India,<ref>{{Cite news|url=https://india-consumer.gsk.com/en-in/products/otrivin/|title=Otrivin {{!}} GSK Consumer Healthcare INDIA|access-date=2018-06-17}}</ref> Israel, Jordan, Netherlands, New Zealand, Norway, Poland, South Africa, Egypt, Sweden, Vietnam, Hong Kong), "Otrivine" (United Kingdom, Ireland, Turkey, Belgium), or "Otriven" (Germany). A product marketed as "Otrivin Oxy" contains [[oxymetazoline]] instead of xylometazoline.

Other product names used include Antazol (Square, in [[Bangladesh]]), Xylomet (Opsonin, [[Bangladesh]]), Cirovin, Klarigen (in Denmark), Nasolin (in Finland), Neo-Rinoleina, Novorin, Olynth, Otrinoz, Galazolin (Russia, Ukraine, Belarus), Nasomist-X, Otrix, Rhinoset, Zenfresh, Naphthyzinium, Xymelyn (in [[Latvia]]), Sinutab Nasal Spray, Snup akut, Sudafed, Xylo-COMOD, Xylolin (in the United Arab Emirates), Xylovit, Olynth (in Serbia, the Czech Republic, Lithuania and Slovakia), Meralys (in [[Croatia]]) Xynosine (in [[Pakistan]], [[Afghanistan]], [[Kyrgyzstan]] and [[Kazakhstan]]), Xymelin, Zymelin, Xylostar, Xylorin (in Poland), Nasobol, Xylo Mepha and others (Switzerland), Decozal (in Jordan), Nasic, Orinox (Romania), Narhimed (Italy), nasa Rhinathiol (Belgium), Zolinol, Nasorhinathiol, and Vibrocil (Portugal).

===Formulations===

The standard adult solution strength is 0.1%&nbsp;[[Mass concentration (chemistry)|w/v]] xylometazoline (or 1&nbsp;mg per 1&nbsp;mL solution).<ref>{{cite web |url=https://www.drugs.com/mtm/xylometazoline-nasal.html |title=Xylometazoline nasal Uses, Side Effects & Warnings |access-date=2015-02-22 |url-status=live |archive-url=https://web.archive.org/web/20150222102749/http://www.drugs.com/mtm/xylometazoline-nasal.html |archive-date=2015-02-22 }}</ref>

== References ==

{{Reflist}}

{{Adrenergic receptor modulators}}

{{Portal bar | Medicine}}

{{Authority control}}

[[Category:Alpha-1 adrenergic receptor agonists]]

[[Category:Alpha-2 adrenergic receptor agonists]]

[[Category:Tert-butyl compounds]]

[[Category:Topical decongestants]]

[[Category:Vasoconstrictors]]

[[Category:World Health Organization essential medicines]]

[[Category:Wikipedia medicine articles ready to translate]]