Editing Loratadine

{{Short description|Antihistamine medication}}
{{Use dmy dates|date=October 2021}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields     = changed
| verifiedrevid      = 408580634
| image              = Loratadine.svg
| image_class        = skin-invert-image
| width              =
| alt                =
| image2             = Loratadine - 3d, portrait orientation.png
| image_class2       = bg-transparent
| width2             =
| alt2               =
| caption            =

<!-- Clinical data -->
| pronounce          =
| tradename          = Claritin, Claratyne, Clarityn, others
| Drugs.com          = {{drugs.com|monograph|loratadine}}
| MedlinePlus        = a697038
| DailyMedID         = Loratadine
| pregnancy_AU       = B1
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy"/>
| pregnancy_category =
| routes_of_administration = [[By mouth]]
| class              = [[Second-generation antihistamine]]
| ATC_prefix         = R06
| ATC_suffix         = AX13
| ATC_supplemental   =

<!-- Legal status -->
| legal_AU           = OTC
| legal_AU_comment   =
| legal_BR           = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->
| legal_BR_comment   =
| legal_CA           = OTC
| legal_CA_comment   = <ref>{{cite web | title=Claritin Allergy Product information | website=Health Canada | date=25 April 2012 | url=https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=10533 | access-date=7 June 2022}}</ref>
| legal_DE           = <!-- Anlage I, II, III or Unscheduled-->
| legal_DE_comment   =
| legal_NZ           = <!-- Class A, B, C -->
| legal_NZ_comment   =
| legal_UK           = GSL
| legal_UK_comment   = /&nbsp;Pharmacy<ref>{{cite web | title=Clarityn Allergy 10mg Tablets (P & GSL) - Patient Information Leaflet (PIL) | website=(emc) | date=30 August 2019 | url=https://www.medicines.org.uk/emc/product/8999/ | access-date=10 April 2020 | archive-date=10 April 2020 | archive-url=https://web.archive.org/web/20200410211508/https://www.medicines.org.uk/emc/product/8999/ | url-status=dead }}</ref>
| legal_US           = OTC
| legal_US_comment   = /&nbsp;Rx-only
| 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    = almost 100%
| protein_bound      = 97–99%
| metabolism         = [[Liver]] ([[CYP2D6]]- and [[CYP3A4|3A4]]-mediated)
| metabolites        =
| onset              =
| elimination_half-life = 8 hours, active metabolite [[desloratadine]] 27 hours
| duration_of_action =
| excretion          = 40% as conjugated metabolites into urine<br />Similar amount into the feces

<!-- Identifiers -->
| CAS_number_Ref     = {{cascite|correct|??}}
| CAS_number         = 79794-75-5
| CAS_supplemental   =
| PubChem            = 3957
| IUPHAR_ligand      = 7216
| DrugBank_Ref       = {{drugbankcite|changed|drugbank}}
| DrugBank           = DB00455
| ChemSpiderID_Ref   = {{chemspidercite|correct|chemspider}}
| ChemSpiderID       = 3820
| UNII_Ref           = {{fdacite|correct|FDA}}
| UNII               = 7AJO3BO7QN
| KEGG_Ref           = {{keggcite|correct|kegg}}
| KEGG               = D00364
| ChEBI_Ref          = {{ebicite|correct|EBI}}
| ChEBI              = 6538
| ChEMBL_Ref         = {{ebicite|correct|EBI}}
| ChEMBL             = 998
| NIAID_ChemDB       =
| PDB_ligand         =
| synonyms           =

<!-- Chemical and physical data -->
| IUPAC_name         = Ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylate
| C                  = 22
| H                  = 23
| Cl                 = 1
| N                  = 2
| O                  = 2
| SMILES             = O=C(OCC)N4CC/C(=C2/c1ccc(Cl)cc1CCc3cccnc23)CC4
| StdInChI_Ref       = {{stdinchicite|correct|chemspider}}
| StdInChI           = 1S/C22H23ClN2O2/c1-2-27-22(26)25-12-9-15(10-13-25)20-19-8-7-18(23)14-17(19)6-5-16-4-3-11-24-21(16)20/h3-4,7-8,11,14H,2,5-6,9-10,12-13H2,1H3
| StdInChI_comment   =
| StdInChIKey_Ref    = {{stdinchicite|correct|chemspider}}
| StdInChIKey        = JCCNYMKQOSZNPW-UHFFFAOYSA-N
| density            =
| density_notes      =
| melting_point      =
| melting_high       =
| melting_notes      =
| boiling_point      =
| boiling_notes      =
| solubility         =
| sol_units          =
| specific_rotation  =
}}

<!-- Definition and medical uses -->
'''Loratadine''', sold under the brand name '''Claritin''' among others, is a medication used to treat [[allergies]].<ref name=AHFS2016/> This includes [[allergic rhinitis]] (hay fever) and [[hives]].<ref name=AHFS2016/> It is also available in drug combinations such as [[loratadine/pseudoephedrine]], in which it is combined with [[pseudoephedrine]], a [[nasal decongestant]].<ref name=AHFS2016/> It is taken orally.<ref name=AHFS2016>{{cite web|title=Loratadine|url=https://www.drugs.com/monograph/loratadine.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221001703/https://www.drugs.com/monograph/loratadine.html|archive-date=21 December 2016}}</ref>

<!-- Side effects and mechanism -->
Common side effects include sleepiness, dry mouth, and headache.<ref name=AHFS2016/> Serious side effects are rare and include [[allergic reactions]], [[seizures]], and [[liver problems]].<ref name=ERC2015/> Use during [[pregnancy]] appears to be safe but has not been well studied.<ref name="Drugs.com pregnancy">{{cite web|title=Loratadine Use During Pregnancy |url=https://www.drugs.com/pregnancy/loratadine.html|website=www.drugs.com|access-date=13 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221001209/https://www.drugs.com/pregnancy/loratadine.html|archive-date=21 December 2016}}</ref> It is not recommended in children less than two years old.<ref name=ERC2015>{{cite web|title=Clarityn Allergy 10mg Tablets (P) - Summary of Product Characteristics (SmPC) - (eMC)|url=https://www.medicines.org.uk/emc/medicine/29550|date=7 October 2015|website=www.medicines.org.uk|access-date=13 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220173725/https://www.medicines.org.uk/emc/medicine/29550|archive-date=20 December 2016}}</ref> It is in the [[second-generation antihistamine]] family of medications.<ref name=AHFS2016/>

<!-- History, society and culture -->
Loratadine was patented in 1980 and came to market in 1988.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=549 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA549 }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> Loratadine is available as a [[generic medication]].<ref name=AHFS2016/><ref>{{cite web | title=Competitive Generic Therapy Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=3 March 2023 | url=https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | archive-url=https://web.archive.org/web/20200220015057/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | url-status=dead | archive-date=20 February 2020 | access-date=6 March 2023}}</ref> In the United States, it is available [[over the counter]].<ref name=AHFS2016/> In 2022, it was the 72nd most commonly prescribed medication in the United States, with more than 9{{nbsp}}million prescriptions.<ref name="Top 300 of 2022">{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Loratadine Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Loratadine | access-date = 30 August 2024 }}</ref> In 2022, the combination with [[pseudoephedrine]] was the 289th most commonly prescribed medication in the United States, with more than 500,000 prescriptions.<ref name="Top 300 of 2022" /><ref>{{cite web | title = Loratadine; Pseudoephedrine Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/LoratadinePseudoephedrine | access-date = 30 August 2024 }}</ref>

== Medical uses ==
Loratadine is [[indicated]] for the [[symptomatic]] relief of [[allergies]] such as hay fever (allergic rhinitis), [[urticaria]] (hives), [[chronic idiopathic urticaria]],<ref>{{cite journal | vauthors = Pons-Guiraud A, Nekam K, Lahovsky J, Costa A, Piacentini A | title = Emedastine difumarate versus loratadine in chronic idiopathic urticaria: a randomized, double-blind, controlled European multicentre clinical trial | journal = European Journal of Dermatology | volume = 16 | issue = 6 | pages = 649–54 | year = 2006 | pmid = 17229605 }}</ref> and other skin allergies.<ref name="Austria-Codex">{{cite book|title=Austria-Codex| veditors = Jasek W |publisher=Österreichischer Apothekerverlag|location=Vienna|year=2007|edition=2007/2008|volume=1|pages=1768–71|isbn= 978-3-85200-181-4|language=de}}</ref> For allergic rhinitis, loratadine is indicated for both nasal and eye symptoms including sneezing, runny nose, and itchy or burning eyes.<ref>{{cite web | title=Claritin- loratadine tablet | website=DailyMed | date=10 February 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=660ac9df-f1b1-4c89-94dd-9fae0a013f3c | access-date=10 April 2020}}</ref>

Similarly to [[cetirizine]], loratadine attenuates the itching associated with [[Kimura's disease]].<ref>{{cite journal | vauthors = Ueda T, Arai S, Amoh Y, Katsuoka K | title = Kimura's disease treated with suplatast tosilate and loratadine | journal = European Journal of Dermatology | volume = 21 | issue = 6 | pages = 1020–1 | year = 2011 | pmid = 21914581 | doi = 10.1684/ejd.2011.1539 }}</ref>

=== Combination drugs ===
[[Loratadine/pseudoephedrine]] is a [[fixed dose combination]] of the drug with [[pseudoephedrine]], a nasal decongestant.<ref>{{cite book|title=Austria-Codex| veditors = Jasek W |publisher=Österreichischer Apothekerverlag|location=Vienna|year=2007|edition=2007/2008|volume=1|pages=1731–34|isbn=9783852001814|language=de}}</ref>

=== Dosage forms ===
[[File:Loratadine10mg.png|thumb|An example of a loratadine 10-mg tablet (Rx)]]

The medication is available in many different forms, including tablets, oral suspension, and syrups.<ref name="Austria-Codex" /> Also available are quick-dissolving tablets.<ref name="Austria-Codex" />

== Contraindications ==
Loratadine is usually compatible with [[breastfeeding]] (classified [[Breastfeeding and medications#L2 Probably Compatible|category L-2]] - probably compatible, by the [[American Academy of Pediatrics]]).<ref>{{cite journal | author = Committee on Drugs | title = Transfer of drugs and other chemicals into human milk | journal = Pediatrics | volume = 108 | issue = 3 | pages = 776–89 | date = September 2001 | pmid = 11533352 | doi = 10.1542/peds.108.3.776 | doi-access = free }}</ref> In the U.S., it is classified as category B in [[pregnancy]], meaning animal reproduction studies have failed to demonstrate a risk to the fetus, but no adequate and well-controlled studies in pregnant women have been conducted.<ref>{{cite journal | vauthors = See S | title = Desloratadine for allergic rhinitis | journal = American Family Physician | volume = 68 | issue = 10 | pages = 2015–6 | date = November 2003 | pmid = 14655812 | url = http://www.aafp.org/afp/20031115/steps.html | url-status = live | archive-url = https://web.archive.org/web/20050724082052/http://www.aafp.org/afp/20031115/steps.html | archive-date = 24 July 2005 }}</ref>

== Adverse effects ==
As a "non-sedating" antihistamine, loratadine causes less (but still significant, in some cases) [[sedation]] and [[psychomotor retardation]] than the older antihistamines, because it penetrates the [[blood brain barrier|blood/brain barrier]] less.<ref>{{cite web | url = http://allergies.emedtv.com/claritin/claritin-and-alcohol.html | title = Claritin and Alcohol | vauthors = Monson K | publisher = emedtv.com | url-status = dead | archive-url = https://web.archive.org/web/20120424203016/http://allergies.emedtv.com/claritin/claritin-and-alcohol.html | archive-date = 24 April 2012 | access-date = 7 May 2012 }}</ref> Headache is also a possible side effect.<ref name="Austria-Codex" /><ref name="Mutschler">{{cite book| vauthors = Mutschler E, Geisslinger G, Kroemer HK  |title=Arzneimittelwirkungen|publisher=Wissenschaftliche Verlagsgesellschaft|location=Stuttgart|year=2001|edition=8|pages=456–461|isbn=978-3-8047-1763-3|language=de}}</ref>

Unlike earlier-generation antihistamines, loratadine is considered largely free of [[antimuscarinic]] effects ([[urinary retention]], dry mouth, blurred vision).<ref>{{cite book|doi=10.1016/bs.podrm.2021.10.002 |title=Loratadine |date=2022 | vauthors = AlMasoud N, Bakheit AH, Alshammari MF, Abdel-Aziz HA, AlRabiah H |series=Profiles of Drug Substances, Excipients, and Related Methodology |volume=47 |pages=55–90 |pmid=35396016 |isbn=978-0-323-85482-5 }}</ref><ref>{{cite book|doi=10.1016/B978-0-444-53717-1.00314-0 |chapter=Antihistamines |title=Meyler's Side Effects of Drugs |date=2016 |pages=606–618 |isbn=978-0-444-53716-4 }}</ref>

== Interactions ==
Substances that act as inhibitors of the [[CYP3A4]] enzyme such as [[ketoconazole]], [[erythromycin]], [[cimetidine]], and [[furanocoumarin]] derivatives (found in grapefruit) lead to increased plasma levels of loratadine — that is, more of the drug was present in the bloodstream than typical for a dose. This had clinically significant effects in controlled trials of 10&nbsp;mg loratadine treatment. <ref name="BJCP: Evaluation of the pharmacokinetics and electrocardiographic pharmacodynamics of loratadine with concomitant administration of ketoconazole or cimetidine">{{cite journal | vauthors = Kosoglou T, Salfi M, Lim JM, Batra VK, Cayen MN, Affrime MB | title = Evaluation of the pharmacokinetics and electrocardiographic pharmacodynamics of loratadine with concomitant administration of ketoconazole or cimetidine | journal = British Journal of Clinical Pharmacology | volume = 50 | issue = 6 | pages = 581–9 | date = December 2000 | pmid = 11136297 | pmc = 2015013 | doi = 10.1046/j.1365-2125.2000.00290.x }}</ref>

Antihistamines should be discontinued 48 hours before [[skin allergy test]]s, since these drugs may prevent or diminish otherwise positive reactions to dermal activity indicators.<ref name="Austria-Codex" />

== Pharmacology ==
=== Pharmacodynamics ===
Loratadine is a [[tricyclic antihistamine]], which acts as a selective [[inverse agonist]] of peripheral [[histamine]] [[histamine H1 receptor|H<sub>1</sub> receptors]].<ref name="Mutschler" /><ref name=Devillier2008rev>{{cite journal | vauthors = Devillier P, Roche N, Faisy C | title = Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine, and levocetirizine: a comparative review | journal = Clinical Pharmacokinetics | volume = 47 | issue = 4 | pages = 217–30 | year = 2008 | pmid = 18336052 | doi = 10.2165/00003088-200847040-00001 | s2cid = 9189476 }}</ref> The potency of second generation histamine antagonists is (from strongest to weakest) [[desloratadine]] ([[Dissociation constant|K<sub>i</sub>]] 0.4&nbsp;nM) > [[levocetirizine]] (K<sub>i</sub> 3&nbsp;nM) > [[cetirizine]] (K<sub>i</sub> 6&nbsp;nM) > [[fexofenadine]] (K<sub>i</sub> 10&nbsp;nM) > terfenadine > loratadine.  However, the onset of action varies significantly and clinical efficacy is not always directly related to only the H<sub>1</sub> receptor potency, as the concentration of free drug at the receptor must also be considered.<ref>{{cite journal | vauthors = Church MK, Church DS | title = Pharmacology of antihistamines | journal = Indian Journal of Dermatology | volume = 58 | issue = 3 | pages = 219–24 | date = May 2013 | pmid = 23723474 | pmc = 3667286 | doi = 10.4103/0019-5154.110832 | doi-access = free }}</ref><ref name=Devillier2008rev/> Loratadine also shows anti-inflammatory properties independent of H<sub>1</sub> receptors.<ref name="pmid15631542">{{cite journal | vauthors = Bielory L, Lien KW, Bigelsen S | title = Efficacy and tolerability of newer antihistamines in the treatment of allergic conjunctivitis | journal = Drugs | volume = 65 | issue = 2 | pages = 215–28 | date = 2005 | pmid = 15631542 | doi = 10.2165/00003495-200565020-00004 | s2cid = 46791611 | url = }}</ref><ref name="pmid23268457">{{cite journal | vauthors = Canonica GW, Blaiss M | title = Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence | journal = The World Allergy Organization Journal | volume = 4 | issue = 2 | pages = 47–53 | date = February 2011 | pmid = 23268457 | pmc = 3500039 | doi = 10.1097/WOX.0b013e3182093e19 | url = }}</ref> The effect is exhibited through suppression of the [[NF-κB]] pathway, and by regulating the release of cytokines and chemokines, thereby regulating the recruitment of inflammatory cells.<ref name="pmid32251678">{{cite journal | vauthors = Hunto ST, Kim HG, Baek KS, Jeong D, Kim E, Kim JH, Cho JY | title = Loratadine, an antihistamine drug, exhibits anti-inflammatory activity through suppression of the NF-kB pathway | journal = Biochemical Pharmacology | volume = 177 | issue = | pages = 113949 | date = July 2020 | pmid = 32251678 | doi = 10.1016/j.bcp.2020.113949| s2cid = 215408324 }}</ref><ref name="pmid15245363">{{cite journal | vauthors = Fumagalli F, Baiardini I, Pasquali M, Compalati E, Guerra L, Massacane P, Canonica GW | title = Antihistamines: do they work? Further well-controlled trials involving larger samples are needed | journal = Allergy | volume = 59 | issue = Suppl 78 | pages = 74–7 | date = August 2004 | pmid = 15245363 | doi = 10.1111/j.1398-9995.2004.00573.x| s2cid = 39936983 }}</ref>

=== Pharmacokinetics ===
Loratadine is given orally, is well absorbed from the gastrointestinal tract, and has rapid [[first-pass metabolism|first-pass hepatic metabolism]]; it is metabolized by [[isoenzyme]]s of the [[cytochrome P450]] system, including [[CYP3A4]], [[CYP2D6]], and, to a lesser extent, several others.<ref name=Foye>{{cite book | vauthors = Nelson WL | veditors = Williams DH, Foye WO, Lemke TL |title=Foye's principles of medicinal chemistry |publisher=Lippincott Williams & Wilkins |location=Hagerstown, MD |year=2002 |chapter=Antihistamines and related antiallergic and antiulcer agents |pages=805 |isbn=978-0-683-30737-5}}</ref><ref>{{cite journal | vauthors = Ghosal A, Gupta S, Ramanathan R, Yuan Y, Lu X, Su AD, Alvarez N, Zbaida S, Chowdhury SK, Alton KB | title = Metabolism of loratadine and further characterization of its in vitro metabolites | journal = Drug Metabolism Letters | volume = 3 | issue = 3 | pages = 162–70 | date = August 2009 | pmid = 19702548 | doi = 10.2174/187231209789352067 }}</ref> Loratadine is almost totally (97–99%) bound to [[plasma proteins]]. Its metabolite [[desloratadine]], which is largely responsible for the antihistaminergic effects, binds to plasma proteins by 73–76%.<ref name="Austria-Codex" />

Loratadine's peak effect occurs after 1–2 hours, and its biological [[half life]] is on average eight hours (range 3 to 20 hours) with [[desloratadine]]'s half-life being 27 hours (range 9 to 92 hours), accounting for its long-lasting effect.<ref>{{cite journal | vauthors = Affrime M, Gupta S, Banfield C, Cohen A | title = A pharmacokinetic profile of desloratadine in healthy adults, including elderly | journal = Clinical Pharmacokinetics | volume = 41 | issue = Suppl 1 | pages = 13–9 | year = 2002 | pmid = 12169042 | doi = 10.2165/00003088-200241001-00003 | s2cid = 25555379 }}</ref> About 40% is excreted as [[Biotransformation#Phase II reaction|conjugated metabolites]] into the urine, and a similar amount is excreted into the feces. Traces of unmetabolised loratadine can be found in the urine.<ref name="Austria-Codex" />

In structure, it is closely related to [[tricyclic antidepressant]]s, such as [[imipramine]], and is distantly related to the atypical [[antipsychotic]] [[quetiapine]].<ref name="pmid10444229">{{cite journal | vauthors = Kay GG, Harris AG | title = Loratadine: a non-sedating antihistamine. Review of its effects on cognition, psychomotor performance, mood and sedation | journal = Clinical and Experimental Allergy | volume = 29 | issue = Suppl 3 | pages = 147–50 | date = July 1999 | pmid = 10444229 | doi = 10.1046/j.1365-2222.1999.0290s3147.x | s2cid = 26012715 }}</ref>

== History ==
[[Schering-Plough]] developed loratadine as part of a quest for a potential [[blockbuster drug]]: a [[sedative|nonsedating]] antihistamine. By the time Schering submitted the drug to the [[U.S. Food and Drug Administration]] (FDA) for approval, the agency had already approved a competitor's nonsedating antihistamine, [[terfenadine]] (trade name Seldane), and, therefore, put loratadine on a lower priority.<ref name="NYTimes">{{cite news | url=https://www.nytimes.com/2001/03/11/magazine/the-claritin-effect-prescription-for-profit.html?pagewanted=all | work=[[The New York Times]] | title=The Claritin Effect; Prescription for Profit | vauthors = Hall SS | date=11 March 2001 | access-date=28 June 2010 | url-status=live | archive-url=https://web.archive.org/web/20150527160442/http://www.nytimes.com/2001/03/11/magazine/the-claritin-effect-prescription-for-profit.html?pagewanted=all | archive-date=27 May 2015 }}</ref>  However, terfenadine had to be removed from the U.S. market by the manufacturer in late 1997 after reports of serious ventricular arrhythmias among those taking the drug.<ref>{{cite web| title= FDA Approves Allegra-D, Manufacturer To Withdraw Seldane From Marketplace | publisher= [[Food and Drug Administration]] | url= https://www.fda.gov/bbs/topics/ANSWERS/ANS00843.html | archive-url= https://web.archive.org/web/20080223144824/https://www.fda.gov/bbs/topics/ANSWERS/ANS00843.html | archive-date= 23 February 2008 | access-date=11 November 2010}}</ref><ref name="jama96">{{cite journal | vauthors = Thompson D, Oster G | title = Use of terfenadine and contraindicated drugs | journal = JAMA | volume = 275 | issue = 17 | pages = 1339–41 | date = May 1996 | pmid = 8614120 | doi = 10.1001/jama.1996.03530410053033 | publisher = [[American Medical Association]] }}</ref>

Loratadine was approved by the FDA in 1993.<ref name="NYTimes" /> The drug continued to be available only by prescription in the U.S. until it went off patent in 2002.<ref>{{Cite web|url=http://www.prnewswire.com/news-releases/schering-plough-loses-patent-lawsuit-over-claritin-opening-door-for-cheaper-generic-versions-70880857.html|title=Schering-Plough Loses Patent Lawsuit Over Claritin, Opening Door For Cheaper Generic Versions|date=5 August 2003|website=[[PRNewswire]]|publisher=Leiner Health Products|access-date=26 June 2016|url-status=live|archive-url=https://web.archive.org/web/20160812201604/http://www.prnewswire.com/news-releases/schering-plough-loses-patent-lawsuit-over-claritin-opening-door-for-cheaper-generic-versions-70880857.html|archive-date=12 August 2016}}</ref> It was then subsequently approved for over-the-counter sales. Once it became an unpatented over-the-counter drug, the price dropped significantly.{{citation needed|date=April 2020}}

Schering also [[drug development|developed]] [[desloratadine]] (Clarinex/Aerius), which is an [[active metabolite]] of loratadine.

== Society and culture ==
===Over the counter===
In 1998, in an unprecedented action in the United States, an American insurance company, [[Anthem Inc.]], petitioned the federal Food and Drug Administration to allow loratadine and two other antihistamines to be made available [[over the counter]] (OTC) while they were still protected by patents; the administration granted the request, which was not binding on manufacturers.<ref name=Cohen>{{cite journal | vauthors = Cohen JP, Paquette C, Cairns CP | title = Switching prescription drugs to over the counter | journal = BMJ | volume = 330 | issue = 7481 | pages = 39–41 | date = January 2005 | pmid = 15626806 | pmc = 539854 | doi = 10.1136/bmj.330.7481.39 }}</ref> In the United States, [[Schering-Plough]] made loratadine available over the counter in 2002.<ref name=Cohen /> By 2015, loratadine was available over the counter in many countries.<ref>Association of the European Self-Medication Industry Database.  [http://www.aesgp.eu/facts-figures/otc-ingredients/?result=name&multiselect=all&country=28&country=29&country=4&country=1&country=18&country=31&country=32&country=33&country=19&country=20&country=6&country=42&country=7&country=9&country=3&country=10&country=21&country=11&country=12&country=34&country=22&country=36&country=37&country=23&country=38&country=24&country=14&country=39&country=25&country=26&country=35&country=15&country=16&country=27&country=13&country=17&country=40&country=41&otc=230  Loratadine OTC regulation] {{webarchive|url=https://web.archive.org/web/20151208062901/http://www.aesgp.eu/facts-figures/otc-ingredients/?result=name&multiselect=all&country=28&country=29&country=4&country=1&country=18&country=31&country=32&country=33&country=19&country=20&country=6&country=42&country=7&country=9&country=3&country=10&country=21&country=11&country=12&country=34&country=22&country=36&country=37&country=23&country=38&country=24&country=14&country=39&country=25&country=26&country=35&country=15&country=16&country=27&country=13&country=17&country=40&country=41&otc=230 |date=8 December 2015 }} Page accessed 11 April 2015</ref>

===Brands===
In 2017, loratadine was available under many brand names and in many forms worldwide, including several [[combination drug]] formulations with [[pseudoephedrine]], [[paracetamol]], [[betamethasone]], [[ambroxol]], [[salbutamol]], [[phenylephrine]], and [[dexamethasone]].<ref name=brands>{{cite web|title=Loratadine International Brands|url=https://www.drugs.com/international/loratadine.html|publisher=Drugs.com|access-date=19 February 2017|url-status=live|archive-url=https://web.archive.org/web/20160304002803/http://www.drugs.com/international/loratadine.html|archive-date=4 March 2016}}</ref>

=== Marketing ===
The marketing of the Claritin brand is important in the history of [[direct-to-consumer advertising]] of drugs.<ref name=statmarketing/><ref name=mmm/>

The first television commercial for a prescription drug was broadcast in the United States in 1983, by [[Boots UK|Boots]]. It caused controversy. The federal Food and Drug Administration responded with strong regulations requiring disclosure of side effects and other information. These rules made pharmaceutical manufacturers balk at spending money on ads that had to highlight negative aspects.<ref name=statmarketing>{{Cite news|url=https://www.statnews.com/2015/12/11/untold-story-tvs-first-prescription-drug-ad/|title=The untold story of TV's first prescription drug ad|date=11 December 2015|work=STAT|access-date=26 October 2017}}</ref>

In the mid-1990s, the marketing team for Claritin at Schering-Plough found a way around these rules. They created [[brand awareness]] commercials that never actually said what the drug was for, but instead showed sunny images, and the [[voiceover]] said such things as "At last, a clear day is here" and "It's time for Claritin" and repeatedly told viewers "Ask your doctor [about Claritin]."<ref name=statmarketing/><ref name=mmm/>   The first ads made people aware of the brand and increased prescriptions, which led Schering-Plough and others to aggressively pursue the advertising strategy.<ref name=mmm>{{Cite news|url=http://www.mmm-online.com/features/dtc-the-first-10-years/article/24443/|title=DTC: The first 10 years|date=1 April 2007|work=MM&M|access-date=26 October 2017}}</ref>

In 1998, a 12-page one-shot comic based on the ''[[Batman: The Animated Series]]'' was given away to advertise Claritin. The book, written by [[Christopher Priest (comic book writer)|PRIEST]], penciled by [[Joe Staton]], and inked by [[Mike DeCarlo]], sees [[Tim Drake]] unable to perform his crime-fighting duties because hay fever and antihistamines make him drowsy. After being given a prescription for Claritin, he saved Batman from [[Poison Ivy (character)|Poison Ivy]].<ref name=Batman>{{Citation |title=Batman: Claritin Allergy Special |url=https://comicbookrealm.com/series/49106/417043/dc-comics-batman-claritin-allergy-special-one-shot-issue-1 |access-date=6 December 2020}} </ref>

This trend, along with advice from the Food and Drug Administration's attorneys that it could not win a [[First Amendment]] case on the issue, prompted the administration to issue new rules for television commercials in 1997.<ref name=statmarketing/> Instead of including the "brief summary" that took up a full page in magazine ads and would take too long to explain in a short television advertisement, drug makers were allowed to refer viewers to print ads, informative telephone lines, and websites, and to urge people to talk to their doctors if they wanted additional information.<ref name=statmarketing/><ref>{{Cite news|url=http://adage.com/article/news/ten-years-direct-consumer-drug-advertising/112215/|title=Ten Years Later: Direct to Consumer Drug Advertising|access-date=26 October 2017}}</ref>

Schering-Plough invested {{US$|322}}{{nbsp}}million in Claritin direct-to-consumer advertising in 1998 and 1999, far more than any other brand.<ref name="NYTimes" /> Spending on direct-to-consumer advertising by the pharmaceutical industry rose from {{US$|360}}{{nbsp}}million in 1995 to {{US$|1.3}}{{nbsp}}billion in 1998, and by 2006, was {{US$|5}}{{nbsp}}billion.<ref name=statmarketing/>

== References ==
{{Reflist}}

{{Antihistamines}}
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[[Category:Drugs developed by Schering-Plough]]
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