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Cetirizine: Difference between revisions - Wikipedia

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Cetirizine: Difference between revisions

Jump to navigation Jump to search Browse history interactively Revision as of 21:02, 10 November 2011 (edit) Beetstra (talk | contribs) (Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank').) ← Previous edit Latest revision as of 22:46, 15 September 2019 (edit) (undo) Monkbot (talk | contribs) m (Task 16: replaced (2×) / removed (0×) deprecated |dead-url= and |deadurl= with |url-status=;) Tags: AWB PHP7 (329 intermediate revisions by more than 100 users not shown) Line 1: Line 1: + {{short description|Antihistamine}} + {{Use dmy dates|date=September 2017}} {{Drugbox {{Drugbox + | Watchedfields = changed − | verifiedrevid = 443512033 + <!--[[airbag]]--> + | verifiedrevid = 460026203 | IUPAC_name = (±)-[2-[4-[(4-chlorophenyl)phenylmethyl]-1- piperazinyl]ethoxy]acetic acid | IUPAC_name = (±)-[2-[4-[(4-chlorophenyl)phenylmethyl]-1- piperazinyl]ethoxy]acetic acid | image = Cetirizine structure.svg | image = Cetirizine structure.svg − | imagename = Cetirizine + | width = 250px − | drug_name = Cetirizine + | image2 = Cetirizine-ball-and-stick.png + | width2 = 250px − <!--Clinical data--> + <!-- Clinical data --> − | tradename = Zyrtec + | pronounce = {{IPAc-en|s|ɛ|ˈ|t|ɪr|ᵻ|z|iː|n}} + | tradename = Zyrtec, Incidal, others | Drugs.com = {{drugs.com|monograph|cetirizine-hydrochloride}} | Drugs.com = {{drugs.com|monograph|cetirizine-hydrochloride}} | MedlinePlus = a698026 | MedlinePlus = a698026 − | licence_EU = + | licence_EU = | licence_US = Cetirizine | licence_US = Cetirizine | pregnancy_US = B | pregnancy_US = B + | pregnancy_AU = B2 | legal_UK = GSL | legal_UK = GSL | legal_US = OTC | legal_US = OTC + | legal_AU = Unscheduled − | legal_status = OTC in Canada + | legal_CA = OTC − | routes_of_administration = Oral + |legal_status=OTC − + | routes_of_administration = [[Oral administration|By mouth]] − <!--Pharmacokinetic data--> + <!-- Pharmacokinetic data --> − | bioavailability = well absorbed + | bioavailability = Well-absorbed (>70%)<ref name="pmid18781943">{{cite journal | vauthors = Chen C | title = Physicochemical, pharmacological and pharmacokinetic properties of the zwitterionic antihistamines cetirizine and levocetirizine | journal = Curr. Med. Chem. | volume = 15 | issue = 21 | pages = 2173–91 | year = 2008 | pmid = 18781943 | doi = 10.2174/092986708785747625| url = }}</ref> − | protein_bound = ~93% + | protein_bound = 88–96%<ref name="pmid18781943" /> − | metabolism = Excreted mainly unchanged + | metabolism = Minimal (non-[[cytochrome P450]]-mediated)<ref name="pmid14680442" /><ref name="pmid10384858" /> − | elimination_half-life = 8.3 Hours + | onset = 20–42 minutes<ref name="pmid10384858" /> − | excretion = Urine (mainly), hepatic or excrement (Small amounts) + | elimination_half-life = Mean: 8.3 hours<ref name="pmid14680442" /><ref name="pmid10384858" /><br />Range: 6.5–10 hours<ref name="pmid12517581">{{cite journal | vauthors = Simons FE | title = Comparative pharmacology of H1 antihistamines: clinical relevance | journal = Am. J. Med. | volume = 113 Suppl 9A | issue = 9| pages = 38S–46S | year = 2002 | pmid = 12517581 | doi = 10.1016/s0002-9343(02)01436-5| url = }}</ref> − + | duration_of_action = ≥24 hours<ref name="pmid12517581" /> − <!--Identifiers--> + | excretion = [[Urine]]: 70–85%<ref name="pmid14680442" /><br />[[Feces]]: 10–13%<ref name="pmid14680442" /> − | CASNo_Ref = {{cascite|correct|CAS}} + <!-- Identifiers --> + | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 83881-51-0 | CAS_number = 83881-51-0 | ATC_prefix = R06 | ATC_prefix = R06 Line 43: Line 52: | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1000 | ChEMBL = 1000 + <!-- Chemical data --> − + | C=21 | H=25 | Cl=1 | N=2 | O=3 − <!--Chemical data--> + | molecular_weight = 388.89 g/mol − | C=21 | H=25 | Cl=1 | N=2 | O=3 + | SMILES = Clc1ccc(cc1)C(c2ccccc2)N3CCN(CC3)CCOCC(=O)O − | molecular_weight = 388.89 − | smiles = Clc1ccc(cc1)C(c2ccccc2)N3CCN(CC3)CCOCC(=O)O − | InChI = 1/C21H25ClN2O3/c22-19-8-6-18(7-9-19)21(17-4-2-1-3-5-17)24-12-10-23(11-13-24)14-15-27-16-20(25)26/h1-9,21H,10-16H2,(H,25,26) − | InChIKey = ZKLPARSLTMPFCP-UHFFFAOYAC | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C21H25ClN2O3/c22-19-8-6-18(7-9-19)21(17-4-2-1-3-5-17)24-12-10-23(11-13-24)14-15-27-16-20(25)26/h1-9,21H,10-16H2,(H,25,26) | StdInChI = 1S/C21H25ClN2O3/c22-19-8-6-18(7-9-19)21(17-4-2-1-3-5-17)24-12-10-23(11-13-24)14-15-27-16-20(25)26/h1-9,21H,10-16H2,(H,25,26) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = ZKLPARSLTMPFCP-UHFFFAOYSA-N | StdInChIKey = ZKLPARSLTMPFCP-UHFFFAOYSA-N + | synonyms = − | synonyms = Alatrol, Alzene, Cetirizina, Cetirin, Cetzine, Cetirizin, Cezin, Humex, Letizen, Razene, Reactine, Zyrtec, Zirtec, Zodac, Zirtek, Zynor, Zyrlek, Zyllergy }} }} + <!-- Definition and medical uses --> + '''Cetirizine''', sold under the brand name '''Zyrtec''' among others, is a [[second generation antihistamine]] used to treat [[allergic rhinitis]] (hay fever), [[dermatitis]], and [[urticaria]].<ref name=BNF76/> It is taken by mouth.<ref name=AHFS2019/> Effects generally begin within an hour and last for about a day.<ref name=AHFS2019/> The degree of benefit is similar to other antihistamines such as [[diphenhydramine]].<ref name=AHFS2019/> + <!-- Side effects and mechanism --> − '''Cetirizine''' ({{IPAc-en|icon|s|ɛ|ˈ|t|ɪr|ɨ|z|iː|n}}), a second-generation [[antihistamine]], is a major [[metabolite]] of [[hydroxyzine]], and a [[racemic]] [[histamine H1 receptor|selective H<sub>1</sub> receptor]] [[inverse agonist]] used in the treatment of [[allergies]], [[hay fever]], [[angioedema]], and [[urticaria]]. + Common side effects include sleepiness, dry mouth, headache, and abdominal pain.<ref name=AHFS2019/> The degree of sleepiness that occurs is generally less than with [[first generation antihistamine]]s.<ref name=BNF76/> Serious side effects may include aggression and [[angioedema]].<ref name=BNF76/> Use in [[pregnancy]] appears safe, but use during [[breastfeeding]] is not recommended.<ref name=Preg2019>{{cite web |title=Cetirizine Pregnancy and Breastfeeding Warnings|url=https://www.drugs.com/pregnancy/cetirizine.html |website=Drugs.com |accessdate=3 March 2019 |language=en}}</ref> The medication works by blocking [[histamine]] [[H1 receptor|H<sub>1</sub> receptors]], mostly outside the [[brain]].<ref name=AHFS2019>{{cite web |title=Cetirizine Hydrochloride Monograph for Professionals |url=https://www.drugs.com/monograph/cetirizine-hydrochloride.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |accessdate=3 March 2019 |language=en}}</ref> + <!-- Society and culture --> − ==Availability== + It was patented in 1981 and came into medical use in 1987.<ref name=Fis2006>{{cite book |last1=Fischer |first1=Jnos |last2=Ganellin |first2=C. Robin |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=549 |url=https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA549 |language=en}}</ref> It is available as a [[generic medication]].<ref name=BNF76>{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=279|edition=76}}</ref> A month's supply in the United Kingdom costs the [[NHS]] about £0.70 as of 2019.<ref name=BNF76/> In the United States the wholesale cost of this amount is about US$2.50.<ref name=NADAC2019>{{cite web |title=NADAC as of 2019-02-27 |url=https://data.medicaid.gov/Drug-Pricing-and-Payment/NADAC-as-of-2019-02-27/s7c9-pfa6 |website=Centers for Medicare and Medicaid Services |accessdate=3 March 2019 |language=en}}</ref> In 2016 it was the 74th most prescribed medication in the United States, with more than 10 million prescriptions.<ref>{{cite web |title=The Top 300 of 2019 |url=https://clincalc.com/DrugStats/Top300Drugs.aspx |website=clincalc.com |accessdate=22 December 2018}}</ref> − [[File:Cetirizine10.JPG|thumb|left|120px]] + {{TOC limit}} − Formerly prescription-only in the USA and Canada, cetirizine is now available [[Over-the-counter drug|over-the-counter]] in both countries as '''Zyrtec''' and '''Reactine''' respectively. Zyrtec was the highest-grossing new non-food product of 2008 in the US, generating sales of $315.9 million.<ref>{{cite news |first= Stuart|last= Elliott|coauthors= |title=A Strategy When Times Are Tough: "It's New!" |url= http://www.nytimes.com/2009/03/25/business/media/25adco.html |work= |page= |newspaper= [[The New York Times]]|date=24 March 2009 |accessdate=26 March 2009 |quote= }}</ref> It is also available as a [[generic drug]]. In Australia, Zyrtec is available over-the-counter in pharmacies and in the UK cetirizine can be sold in limited quantities off-the-shelf in any outlet and is often available in supermarkets. As of 2009, Germany made many generic drugs containing cetirizine available in pharmacies without prescription.<ref>{{cite web | title=Cetirizin | url=http://de.wikipedia.org/wiki/Cetirizin }}</ref> Norway, Sweden<ref>{{cite web | title=Cetirizin | url=http://receptfria.se/sandoz_camp/front/front/visa_underkategori?h_kategori_id=5&u_kategori_id=12 }}</ref> and Finland also recognize Cetirizine as an [[Over-the-counter drug|over-the-counter]] medicine. In India it is sold over-the-counter as brand-name 'Cetzine', even though it remains classified as a [[Schedule H]] (prescription) drug<ref>[http://www.drugscontrol.org/Schedule_H.pdf Drugs and Cosmetics (2nd amendment) rules, 2006]. item 104 in schedule H.</ref> + + == Medical uses == + + === Allergies === + Cetirizine's primary indication is for [[hay fever]] and other allergies. Because the symptoms of itching and redness in these conditions are caused by histamine acting on the H<sub>1</sub> receptor, blocking those receptors temporarily relieves those symptoms. + + Cetirizine is also commonly prescribed to treat acute and (in particular cases) chronic [[urticaria]], more efficiently than any other second-generation antihistamine{{Citation needed|date=November 2016}}. + + === Available forms === + Cetirizine is available over-the-counter in the US in the form of 5 and 10&nbsp;mg [[tablet (pharmacy)|tablets]]. A 20 mg strength is available by prescription only.<ref name="pmid14680442" /> + In the UK up to 30 tablets of 10mg are on the general sales list (of pharmaceuticals) and can be purchased without a prescription and without pharmacist supervision. + + == Adverse effects == + Commonly reported side effects of cetirizine include [[headache]] (16%), [[dry mouth]] (5.7%), [[drowsiness]] (5–20%), and [[fatigue (medical)|fatigue]] (5.6%), while more serious but rare side effects include [[cardiac failure]], [[tachycardia]], and [[edema]].<ref>{{cite web|title=Zyrtec Side Effects|url=https://www.drugs.com/sfx/zyrtec-side-effects.html|website=drugs.com|publisher=Drugs.com|accessdate=21 August 2015}}</ref> + + Discontinuing cetirizine after prolonged use (typically, use beyond six months) may result in generalized [[itching]].<ref>{{cite journal|title=Unbearable Pruritus After Withdrawal of (Levo)cetirizine|journal=Drug Safety - Case Reports|volume=3|issue=1|pages=16|pmc=5124431|year=2016|last1=Ekhart|first1=C.|last2=Van Der Horst|first2=P.|last3=Van Hunsel|first3=F.|pmid=27889900|doi=10.1007/s40800-016-0041-9}}</ref><ref>{{cite web|title=Cetirizine (Zyrtec) Withdrawal & Unbearable Itching|url=https://www.peoplespharmacy.com/2013/05/06/cetirizine-zyrtec-withdrawal-unbearable-itching/|website=People's Pharmacy|accessdate=9 September 2017}}</ref><ref>{{cite web|title=addicted to zyrtec?|url=http://www.medhelp.org/posts/Allergy/addicted-to-zyrtec/show/600862|website=MedHelp|accessdate=9 September 2017}}</ref> == Pharmacology == == Pharmacology == + [[File:Cetirizine structure racemic.svg|thumb|200px|right|L-Stereoisomer, [[levocetirizine]] (top) and D-stereoisomer of cetirizine.]] − Cetirizine crosses the [[blood-brain barrier]] only slightly, reducing the sedative side-effect common with older antihistamines. <ref name="blood-brain">{{cite journal| doi = 10.1124/dmd.105.007211| title = Brain distribution of cetirizine enantiomers: comparison of three different tissue-to-plasma partition coefficients: K(p), K(p,u), and K(p,uu)| last = Gupta| first = A| coauthors = Chatelain P, Massingham R, Jonsson EN, Hammarlund-Udenaes M| journal = Drug Metab. Dispos.| volume = 34| issue = 2| pages = 318–23| year = 2006| month = February| pmid = 16303872| url = dmd.aspetjournals.org/content/34/2/318.long}}</ref> It has also been shown to inhibit [[eosinophil]] [[chemotaxis]] and [[LTB4]] release. At a dosage of 20&nbsp;mg, Boone ''et al.'' found that it inhibited the expression of [[VCAM-1]] in patients with [[atopic dermatitis]].<ref>{{cite journal| author = Boone M, Lespagnard L, Renard N, Song M, Rihoux JP| title = Adhesion molecule profiles in atopic dermatitis vs. allergic contact dermatitis: pharmacological modulation by cetirizine| journal = J Eur Acad Dermatol Venereol| volume = 14| issue = 4| pages = 263–6| year = 2000| month = July|doi = 10.1046/j.1468-3083.2000.00017.x − |url=http://www3.interscience.wiley.com/journal/119045164/abstract?CRETRY=1&SRETRY=0| accessdate = 2009-11-19| pmid = 11204513}}</ref> + === Pharmacodynamics === − The [[levorotary]] [[enantiomer]] of cetirizine, known as [[levocetirizine]], is the more active form. + Cetirizine acts as a highly [[binding selectivity|selective]] [[receptor antagonist|antagonist]] of the [[histamine]] [[H1 receptor|H<sub>1</sub> receptor]].<ref name="pmid14680442">{{cite journal | vauthors = Portnoy JM, Dinakar C | title = Review of cetirizine hydrochloride for the treatment of allergic disorders | journal = Expert Opin Pharmacother | volume = 5 | issue = 1 | pages = 125–35 | year = 2004 | pmid = 14680442 | doi = 10.1517/14656566.5.1.125 | url = }}</ref> The K<sub>i</sub> values for the H<sub>1</sub> receptor are approximately 6&nbsp;nM for cetirizine, 3&nbsp;nM for [[levocetirizine]], and 100&nbsp;nM for [[dextrocetirizine]], indicating that the [[levorotatory]] [[enantiomer]] is the main active form.<ref name="pmid14680442" /> Cetirizine has 600-fold or greater [[binding selectivity|selectivity]] for the H<sub>1</sub> receptor over a wide variety of other sites, including [[muscarinic acetylcholine receptor|muscarinic acetylcholine]], [[serotonin receptor|serotonin]], [[dopamine receptor|dopamine]], and [[α-adrenergic receptor]]s, among many others.<ref name="pmid14680442" /> The drug shows 20,000-fold or greater selectivity for the H<sub>1</sub> receptor over the five muscarinic acetylcholine receptors, and hence does not exhibit [[anticholinergic]] effects.<ref name="pmid23867423">{{cite journal | vauthors = Zhang L, Cheng L, Hong J | title = The clinical use of cetirizine in the treatment of allergic rhinitis | journal = Pharmacology | volume = 92 | issue = 1–2 | pages = 14–25 | year = 2013 | pmid = 23867423 | doi = 10.1159/000351843 | url = }}</ref><ref name="pmid15627436">{{cite journal | vauthors = Orzechowski RF, Currie DS, Valancius CA | title = Comparative anticholinergic activities of 10 histamine H1 receptor antagonists in two functional models | journal = Eur. J. Pharmacol. | volume = 506 | issue = 3 | pages = 257–64 | year = 2005 | pmid = 15627436 | doi = 10.1016/j.ejphar.2004.11.006 | url = }}</ref> It shows negligible inhibition of the [[hERG]] channel ({{abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}} > 30&nbsp;µM)<ref name="pmid9658196">{{cite journal | vauthors = Taglialatela M, Pannaccione A, Castaldo P, Giorgio G, Zhou Z, January CT, Genovese A, Marone G, Annunziato L | title = Molecular basis for the lack of HERG K+ channel block-related cardiotoxicity by the H1 receptor blocker cetirizine compared with other second-generation antihistamines | journal = Mol. Pharmacol. | volume = 54 | issue = 1 | pages = 113–21 | year = 1998 | pmid = 9658196 | doi = 10.1124/mol.54.1.113| url = }}</ref> and no [[cardiotoxicity]] has been observed with cetirizine at doses of up to 60&nbsp;mg/day, six times the normal recommended dose<ref name="pmid14680442" /> and the highest dose of cetirizine that has been studied in healthy subjects.<ref name="pmid17891537">{{cite journal | vauthors = Hulhoven R, Rosillon D, Letiexhe M, Meeus MA, Daoust A, Stockis A | title = Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study | journal = Eur. J. Clin. Pharmacol. | volume = 63 | issue = 11 | pages = 1011–7 | year = 2007 | pmid = 17891537 | doi = 10.1007/s00228-007-0366-5 | url = | quote = The equivalent dose of 60 mg cetirizine is also the highest dose ever administered in healthy subjects [13].}}</ref> + Cetirizine crosses the [[blood–brain barrier]] only slightly, and for this reason, it produces minimal sedation compared to many other antihistamines.<ref name="blood-brain">{{cite journal| doi = 10.1124/dmd.105.007211| title = Brain distribution of cetirizine enantiomers: comparison of three different tissue-to-plasma partition coefficients: K(p), K(p,u), and K(p,uu)| last = Gupta| first = A|author2=Chatelain P|author3=Massingham R|author4=Jonsson EN|author5=Hammarlund-Udenaes M| journal = Drug Metab. Dispos.| volume = 34| issue = 2| pages = 318–23|date=February 2006| pmid = 16303872}}</ref> A [[positron emission tomography]] (PET) study found that brain occupancy of the H<sub>1</sub> receptor was 12.6% for 10&nbsp;mg cetirizine, 25.2% for 20&nbsp;mg cetirizine, and 67.6% for 30&nbsp;mg hydroxyzine.<ref name="pmid19697300">{{cite journal | vauthors = Tashiro M, Kato M, Miyake M, Watanuki S, Funaki Y, Ishikawa Y, Iwata R, Yanai K | title = Dose dependency of brain histamine H(1) receptor occupancy following oral administration of cetirizine hydrochloride measured using PET with [11C]doxepin | journal = Hum Psychopharmacol | volume = 24 | issue = 7 | pages = 540–8 | year = 2009 | pmid = 19697300 | doi = 10.1002/hup.1051 | url = }}</ref> (A 10&nbsp;mg dose of cetirizine equals about a 30&nbsp;mg dose of hydroxyzine in terms of peripheral antihistamine effect.)<ref name="pmid28289538">{{cite journal |vauthors=van den Elzen MT, van Os-Medendorp H, van den Brink I, van den Hurk K, Kouznetsova OI, Lokin AS, Laheij-de Boer AM, Röckmann H, Bruijnzeel-Koomen CA, Knulst AC | title = Effectiveness and safety of antihistamines up to fourfold or higher in treatment of chronic spontaneous urticaria | journal = Clin Transl Allergy | volume = 7 | issue = | pages = 4 | year = 2017 | pmid = 28289538 | pmc = 5309999 | doi = 10.1186/s13601-017-0141-3 | url = | quote = [...] 30 mg of hydroxyzine equals about 10 mg cetirizine [11] [...]}}</ref> PET studies with antihistamines have found that brain H<sub>1</sub> receptor occupancy of more than 50% is associated with a high prevalence of somnolence and cognitive decline, whereas brain H<sub>1</sub> receptor occupancy of less than 20% is considered to be non-sedative.<ref name="pmid16890992">{{cite journal | vauthors = Yanai K, Tashiro M | title = The physiological and pathophysiological roles of neuronal histamine: an insight from human positron emission tomography studies | journal = Pharmacol. Ther. | volume = 113 | issue = 1 | pages = 1–15 | year = 2007 | pmid = 16890992 | doi = 10.1016/j.pharmthera.2006.06.008 | url = }}</ref> In accordance, H<sub>1</sub> receptor occupancy correlated well with subjective sleepiness for 30&nbsp;mg hydroxyzine but there was no correlation for 10 or 20&nbsp;mg cetirizine.<ref name="pmid19697300" /> As such, brain penetration and brain H<sub>1</sub> receptor occupancy by cetirizine are dose-dependent, and in accordance, while cetirizine at doses of 5 to 10&nbsp;mg have been reported to be non-sedating or mildly sedating, a higher dose of 20&nbsp;mg has been found to induce significant [[drowsiness]] in other studies.<ref name="pmid19697300" /> − [[File:Cetirizine structure racemic.svg|thumb|180px|left|L-Stereosimer, [[levocetirizine]] (top) and D-stereoisomer of cetirizine]]{{clear-left}} + Cetirizine has been shown to inhibit [[eosinophil]] [[chemotaxis]] and [[LTB4]] release.<ref name="pmid11204513">{{cite journal| vauthors = Boone M, Lespagnard L, Renard N, Song M, Rihoux JP| title = Adhesion molecule profiles in atopic dermatitis vs. allergic contact dermatitis: pharmacological modulation by cetirizine| journal = J Eur Acad Dermatol Venereol| volume = 14| issue = 4| pages = 263–6|date=July 2000|doi = 10.1046/j.1468-3083.2000.00017.x | url=http://www3.interscience.wiley.com/journal/119045164/abstract?CRETRY=1&SRETRY=0| archive-url=https://archive.today/20130105090552/http://www3.interscience.wiley.com/journal/119045164/abstract?CRETRY=1&SRETRY=0| url-status=dead| archive-date=2013-01-05| accessdate = 19 November 2009| pmid = 11204513}}</ref> At a dosage of 20&nbsp;mg, Boone ''et al.'' found that it inhibited the expression of [[VCAM-1]] in patients with [[atopic dermatitis]].<ref name="pmid11204513" /> − == Administration method and metabolism == + === Pharmacokinetics === − Chewable, non-chewable, and syrup forms of cetirizine are similarly absorbed rapidly and effectively, with absorbed food minutely affecting the absorption rate which yields a peak serum level one hour after administration;<ref name="drugref_cetirizine">{{cite book| author = Anderson, Philip; Knoben, James E.; Troutman, William G.| title = Handbook of clinical drug data| publisher = McGraw-Hill| location = New York| year = 2002| page = 807| isbn = 0-07-136362-9 − | accessdate = 2009-11-19}}</ref> in a study of healthy volunteers prescribed 10&nbsp;mg tablets, once daily for 10 days, a mean peak serum level of 311&nbsp;ng/mL was observed.<ref name="pfizer_ceti_p3">{{cite web| url = http://www.pfizer.com/files/products/uspi_zyrtec.pdf| title = Zyrtec prescribing information| date = May 2006 | accessdate = 2009-11-19}}</ref> The metabolic effects of cetirizine are long acting, remaining in the system for a maximum of 21 hours before being excreted; the average elimination half-life is 8 hours. About 70% of the drug is removed through urination, of which half is observed as unchanged cetirizine compound. Another 10% is excreted.<ref name="drugref_cetirizine"/><ref name="pfizer_ceti_p3"/> + ==== Absorption ==== − Like many other antihistamine medications, cetirizine is commonly prescribed in combination with [[pseudoephedrine hydrochloride]], a [[decongestant]]. These combinations are marketed using the same brand name as the cetirizine with a "-D" suffix ('''Zyrtec-D''', '''Virlix-D''', etc.) + Cetirizine is rapidly and extensively [[absorption (pharmacokinetics)|absorbed]] upon [[oral administration]] in tablet or syrup form.<ref name="pmid14680442" /> The [[oral administration|oral]] [[bioavailability]] of cetirizine is at least 70% and of levocetirizine is at least 85%.<ref name="pmid18781943" /> The [[Tmax (pharmacology)|T<sub>max</sub>]] of cetirizine is approximately 1.0&nbsp;hour regardless of formulation.<ref name="pmid10384858" /> The [[pharmacokinetics]] of cetirizine have been found to increase linearly with dose across a range of 5 to 60&nbsp;mg.<ref name="pmid14680442" /> Its [[Cmax (pharmacology)|C<sub>max</sub>]] following a single dose has been found to be 257&nbsp;ng/mL for 10&nbsp;mg and 580&nbsp;ng/mL for 20&nbsp;mg.<ref name="pmid10384858">{{cite journal | vauthors = Simons FE, Simons KJ | title = Clinical pharmacology of new histamine H1 receptor antagonists | journal = Clin Pharmacokinet | volume = 36 | issue = 5 | pages = 329–52 | year = 1999 | pmid = 10384858 | doi = 10.2165/00003088-199936050-00003| url = }}</ref> Food has no effect on the [[bioavailability]] of cetirizine but has been found to delay the T<sub>max</sub> by 1.7&nbsp;hours (i.e., to approximately 2.7&nbsp;hours) and to decrease the C<sub>max</sub> by 23%.<ref name="pmid14680442" /><ref name="pmid10384858" /><ref name="pmid28622592">{{cite journal | vauthors = Paśko P, Rodacki T, Domagała-Rodacka R, Palimonka K, Marcinkowska M, Owczarek D | title = Second generation H1 – antihistamines interaction with food and alcohol-A systematic review | journal = Biomed. Pharmacother. | volume = 93 | issue = | pages = 27–39 | year = 2017 | pmid = 28622592 | doi = 10.1016/j.biopha.2017.06.008 | url = }}</ref> Similar findings were reported for levocetirizine, which had its T<sub>max</sub> delayed by 1.25&nbsp;hours and its C<sub>max</sub> decreased by about 36% when administered with a high-fat meal.<ref name="pmid28622592" /> [[Steady-state (pharmacokinetics)|Steady-state levels]] of cetirizine occur within 3&nbsp;days and there is no accumulation of the drug with chronic administration.<ref name="pmid10384858" /> Following once-daily administration of 10&nbsp;mg cetirizine for 10&nbsp;days, the mean C<sub>max</sub> was 311&nbsp;ng/mL.<ref name="pfizer_ceti_p3">{{cite web|url=http://www.pfizer.com/files/products/uspi_zyrtec.pdf |title=Zyrtec prescribing information |date=May 2006 |accessdate=19 November 2009 |url-status=dead |archiveurl=https://web.archive.org/web/20100104143424/http://www.pfizer.com/files/products/uspi_zyrtec.pdf |archivedate=4 January 2010 }}</ref> + ==== Distribution ==== − Formerly only available by a prescription, both Zyrtec and Zyrtec-D in November 2007 became available over-the-counter in the United States.<ref> + The mean [[plasma protein binding]] of cetirizine has been found to be 93 to 96% across a range of 25 to 1,000&nbsp;ng/mL independent of concentration.<ref name="pmid10384858" /> Plasma protein binding of 88 to 96% has also been reported across multiple studies.<ref name="pmid18781943" /> The drug is bound to [[human serum albumin|albumin]] with high [[affinity (pharmacology)|affinity]], while [[orosomucoid|α<sub>1</sub>-acid glycoprotein]] and [[lipoprotein]]s contribute much less to total plasma protein binding.<ref name="pmid18781943" /> The unbound or free fraction of levocetirizine has been reported to be 8%.<ref name="pmid18781943" /> The true [[volume of distribution]] of cetirizine is unknown but is estimated to be 0.3 to 0.45&nbsp;L/kg.<ref name="pmid14680442" /><ref name="pmid18781943" /> Cetirizine poorly and slowly crosses the [[blood–brain barrier]], which is due mainly to its chemical properties but also to a minor extent to its activity as a [[P-glycoprotein]] [[substrate (biochemistry)|substrate]].<ref name="pmid18781943" /> − {{cite journal| title = Over-the-Counter Zyrtec: a Money-Saver?| first = January W| last = Payne| journal = [[U.S. News & World Report]]| date = 2008-01-09|url = http://health.usnews.com/articles/health/2008/01/09/over-the-counter-zyrtec-is-about-to-arrive.html}}</ref> − == Indications == + ==== Metabolism ==== + Cetirizine does not undergo extensive [[metabolism]].<ref name="pmid14680442" /> It is notably not metabolized by the [[cytochrome P450]] system.<ref name="Mahmoudi2016">{{cite book|author=Massoud Mahmoudi|title=Allergy and Asthma: Practical Diagnosis and Management|url=https://books.google.com/books?id=spdPDAAAQBAJ&pg=PA574|date=2 June 2016|publisher=Springer|isbn=978-3-319-30835-7|pages=574–}}</ref> Because of this, it does not interact significantly with drugs that [[enzyme inhibitor|inhibit]] or [[enzyme inducer|induce]] cytochrome P450 enzymes such as [[theophylline]], [[erythromycin]], [[clarithromycin]], [[cimetidine]], or [[alcohol (drug)|alcohol]].<ref name="pmid14680442" /> While cetirizine does not undergo extensive metabolism or metabolism by the cytochrome P450 enzyme, it does undergo some metabolism by other means, the [[metabolic pathway]]s of which include [[oxidation]] and [[conjugation (biochemistry)|conjugation]].<ref name="pmid14680442" /><ref name="pmid10384858" /> Plasma radioactivity attributed to unchanged cetirizine is more than 90% at 2&nbsp;hours, 80% at 10&nbsp;hours, and 70% at 24&nbsp;hours, indicating limited and slow metabolism.<ref name="pmid10384858" /> The enzymes responsible for [[biotransformation|transformation]] of cetirizine have not been identified.<ref name="pmid14680442" /> − === Allergies === − Cetirizine's primary indication is for hay fever and other allergies. Because the symptoms of itching and redness in these conditions are caused by histamine acting on the H1 receptor, blocking those receptors temporarily relieves those symptoms. − === Rhinovirus infection === + ==== Elimination ==== + Cetirizine is [[elimination (pharmacology)|eliminated]] approximately 70 to 85% in the [[urine]] and 10 to 13% in the [[feces]].<ref name="pmid14680442" /> About 50 or 60% of cetirizine eliminated in the urine is unchanged.<ref name="pmid14680442" /><ref name="pmid10384858" /> It is eliminated in the urine via an [[active transport]] mechanism.<ref name="pmid10384858" /> The [[elimination half-life]] of cetirizine ranges from 6.5 to 10&nbsp;hours in healthy adults, with a mean across studies of approximately 8.3&nbsp;hours.<ref name="pmid14680442" /><ref name="pmid10384858" /> Its [[duration of action]] is at least 24&nbsp;hours.<ref name="pmid10384858" /> The elimination half-life of cetirizine is increased in the elderly (to 12&nbsp;hours), in [[hepatic impairment]] (to 14&nbsp;hours), and in [[renal impairment]] (to 20&nbsp;hours).<ref name="pmid10384858" /> + == Chemistry == − [[Interleukin 6]] and [[interleukin 8]] have been shown to be elevated in acute respiratory distress syndrome.<ref name="pmid8406851">{{cite journal| last1=Chollet-Martin| first1=S| last2=Montravers| first2=P| last3=Gibert| first3=C| last4=Elbim| first4=C| last5=Desmonts| first5=JM| last6=Fagon| first6=JY| last7=Gougerot-Pocidalo| first7=MA| title=High levels of interleukin-8 in the blood and alveolar spaces of patients with pneumonia and adult respiratory distress syndrome.| journal=Infection and immunity| volume=61| issue=11| pages=4553–9| year=1993| pmid=8406851| pmc=281204}}</ref> Cetirizine contains <small>L</small>- and <small>D</small>-[[stereoisomer]]s. Chemically, [[levocetirizine]] is the active <small>L</small>-[[enantiomer]] of cetirizine. In a recent study of airway epithelial cells the following was observed: Levocetirizine inhibits the production of intercellular adhesion molecule [[ICAM-1]] and secretion of interleukin (IL)-6 and IL-8, which may have beneficial effects on the pathophysiologic changes related to human rhinovirus ([[rhinovirus|HRV]]) infection. Levocetirizine treatment inhibited the HRV-induced increase in ICAM-1 mRNA and protein levels, as well as the HRV-induced expression of IL-6 and IL-8 mRNA and protein levels. Viral titer, as measured by culture in MRC-5 cells, was reduced by levocetirizine. Levocetirizine treatment also reduced the increased nuclear factor-kappa B ([[NF-κB]]) expression seen with HRV infection. Levocetirizine inhibited the expression of Toll-like receptor 3 ([[TLR 3|TLR3]]) mRNA and protein levels. These findings indicate that, in HNEC and [[A549 cell|A549]] cells, levocetirizine inhibits HRV replication and HRV-induced upregulation of ICAM-1, IL-6, and IL-8, TLR3 expression and NF-κB activation. The results of this study suggest that levocetirizine may have a possible clinical application in the treatment of airway inflammation caused by HRV infection.<ref name="pmid19110001">{{cite journal| author = Jang YJ, Wang JH, Kim JS, Kwon HJ, Yeo NK, Lee BJ| title = Levocetirizine inhibits rhinovirus-induced ICAM-1 and cytokine expression and viral replication in airway epithelial cells + Cetirizine contains <small>L</small>- and <small>D</small>-[[stereoisomer]]s. Chemically, [[levocetirizine]] is the active <small>L</small>-[[enantiomer]] of cetirizine. The drug is a member of the [[diphenylmethylpiperazine]] group of antihistamines. [[Structural analog|Analogues]] include [[cyclizine]] and [[hydroxyzine]]. − | journal = Antiviral Res.| volume = 81| issue = 3| pages = 226–33| year = 2009| month = March| pmid = 19110001| doi = 10.1016/j.antiviral.2008.12.001| accessdate = 2009-11-19}}</ref> Airway inflammation caused from a [[cytokine storm]] secondary to acute respiratory distress syndrome could also theoretically benefit. − === Kimura's disease === + === Synthesis === + :[[File:Cetirizine synthesis.png|700px|thumb|center|Cetirizine synthesis:<ref>{{ cite patent | country = US | number = 4525358 | status = patent | title = 2-[4-(Diphenylmethyl)-1-piperazinyl]-acetic acids and their amides | gdate = 25 June 1985 | fdate = 17 May 1983 | pridate = YYYY-MM-DD | inventor = Baltes E, De Lannoy J, Rodriguez L | assign1 = UCB Pharmaceuticals, Inc. }}</ref>]] − Cetirizine is an effective agent in treating the symptoms of [[Kimura's disease]], which mostly occurs in young Asian men, affecting the lymph nodes and soft tissue of the head and neck in the form of tumor-like lesions. Cetirizine's properties of being effective both in the treatment of [[pruritus]] (itching) and as an anti-inflammatory agent make it suitable for the treatment of the pruritus associated with these lesions.<ref name="kimura">{{cite journal|author = Ben-Chetrit E, Amir G, Shalit M| title = Cetirizine: An effective agent in Kimura's disease| journal = Arthritis Rheum.| volume = 53| issue = 1|pages = 117–8| year = 2005| month = February|doi = 10.1002/art.20908| accessdate = 2009-11-19| pmid = 15696573}}</ref> In a 2005 study, the American College of Rheumatology conducted treatments initially using [[prednisone]], followed by steroid dosages and [[azathioprine]], [[omeprazole]], and [[calcium]] and [[vitamin D]] supplements over the course of two years.<ref name="kimura" /> The skin condition of the patient began to improve and the skin lesions lessened. However, there were symptoms of [[cushing syndrome|cushingoid]] and [[hirsutism]] observed before the patient was removed from the courses of steroids and placed on 10&nbsp;mg/day of cetirizine to prevent skin lesions;<ref name="kimura" /> an agent suitable for the treatment of pruritus associated with such lesions.<ref name="kimura" /> Asymptomatically, the patient's skin lesions disappeared after treatment with cetirizine, blood [[eosinophil]] counts became normal,<ref name="kimura" /> corticosteroid effects were resolved,<ref name="kimura" /> and a remission began within a period of two months.<ref name="kimura" /> It is also thought that the inhibition of eosinophils may be the key to treatment of Kimura's disease due to the role of eosinophils, rather than other cells with regards to the lesions of the skin.<ref name="kimura"/> + The 1-[(4-chlorophenylmethyl]-piperazine is alkylated with methyl (2-chloroethoxy)-acetate in the presence of sodium carbonate and xylene solvent to produce the Sn2 substitution product in 28% yield. Saponification of the acetate ester is done by refluxing with [[potassium hydroxide]] in absolute ethanol to afford a 56% yield of the potassium salt intermediate. This is then hydrolyzed with aqueous HCl and extracted to give an 81% yield of the carboxylic acid product. − ==Side Effects== − Dryness of the mouth, nose and throat, urinary retention, blurred vision and stomach ache are commonly reported side effects of this drug.<ref>{{cite book | title=British National Formulary (BNF) 61 | year=2011}}</ref> + == Society and culture == − ==Synthesis== + {{Multiple image − The following synthesis of this compound was reported in 1985:<ref>Baltes, E.; De Lannoy, J.; Rodriguez, L.; 1985, {{US Patent|4,525,358}}.</ref> + | direction = horizontal + | total_width = 425 + | caption_align = + | header = + | footer = + | image1 = Cetirizine10.JPG + | width1 = 320 + | height1 = 213 + | alt1 = + | caption1 = A package of 10&nbsp;mg cetirizine tablets. + | image2 = Zyrtec-D blister pack.png + | width2 = 296 + | height2 = 240 + | alt2 = + | caption2 = Zyrtec-D, a combination of cetirizine and pseudoephedrine. + }} + === Brand names === − :[[File:Cetirizine synthesis.png|500px]] + Cetirizine is marketed under the brand names Alatrol, Alerid, Alzene, Cetirin, Cetzine, Cezin, Cetgel, Histazine, Humex, Letizen, Okacet ([[Cipla]]), Reactine, Razene, Rigix, Sensahist (Oethmann, South Africa), Triz, Zetop, Zirtec, Zirtek, Zodac, Zyllergy, Zynor, Zyrlek, and Zyrtec ([[Johnson & Johnson]]), among others. − == References == + === Availability === + Formerly prescription-only in many countries, cetirizine is now available without prescription in most countries. In some countries it is available over-the-counter only in packages containing seven or ten 10&nbsp;mg doses. − {{reflist|2}} + Like many other antihistamine medications, cetirizine is commonly prescribed in combination with [[pseudoephedrine]], a [[decongestant]]. These combinations are often marketed using the same brand name as the cetirizine with a "-D" suffix (Zyrtec-D, Virlix-D, etc.) − === Books and journals === + {{Clear}} − # Anderson, P. O., Knoben, J. E., et al. (2002) ''Handbook of clinical drug data 10th ed.'' McGraw-Hill International + − # Pfizer Inc, et al. (2006) ''ZYRTEC (cetirizine hydrochloride) Tablets, Chewable Tablets and Syrup For Oral Use'' Pfizer Incorporated publications + == References == − # Chetrit, E. B., Amir, G., Shalit, M. (2005). ''Cetirizine: an effective agent in Kimura's Disease'' Arthritis & Rheumatism (Arthritis care & research) Vol 53, p117-118 + {{Reflist|2}} == External links == == External links == + * [http://druginfo.nlm.nih.gov/drugportal/dpdirect.jsp?name=Cetirizine U.S. National Library of Medicine: Drug Information Portal – Cetirizine] − *[http://www.pfizer.com/pfizer/download/uspi_zyrtec.pdf Zyrtec prescribing information] [[Pfizer]] − *[http://egeneralmedical.com/rxlist00000612.html List of brand names] − *[http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109025.htm US FDA approves Zyrtec-D for over the counter sales] − *[http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109033.htm US FDA approves Zyrtec for over the counter sales] − * [http://druginfo.nlm.nih.gov/drugportal/dpdirect.jsp?name=Cetirizine U.S. National Library of Medicine: Drug Information Portal - Cetirizine] {{Antihistamines}} {{Antihistamines}} + {{Histamine receptor modulators}} − {{Histaminergics}} + {{PAF receptor modulators}} − + [[Category:RTT]] + [[Category:Belgian inventions]] + [[Category:Carboxylic acids]] + [[Category:Ethers]] [[Category:H1 receptor antagonists]] [[Category:H1 receptor antagonists]] − [[Category:Piperazines]] − [[Category:Pfizer]] [[Category:Johnson & Johnson]] [[Category:Johnson & Johnson]] − [[Category:Ethers]] + [[Category:Peripherally selective drugs]] − [[Category:Organochlorides]] + [[Category:Pfizer products]] − [[Category:Carboxylic acids]] + [[Category:Chlorcyclizines]] − − [[da:Cetirizin]] − [[de:Cetirizin]] − [[fa:ستیریزین]] − [[fr:Cétirizine]] − [[it:Cetirizina]] − [[ka:პარლაზინი]] − [[hu:Cetirizin]] − [[nl:Cetirizine]] − [[ja:セチリジン]] − [[pl:Cetyryzyna]] − [[pt:Cetirizina]] − [[ru:Цетиризин]] − [[fi:Setiritsiini]] − [[th:เซทิไรซีน]] − [[tr:Setirizin]] − [[zh:盐酸西替利嗪]] Retrieved from "[en.wikipedia.org]"

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