Loratadine

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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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is not recommended in children less than two years old.<ref name=ERC2015>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is in the second-generation antihistamine family of medications.<ref name=AHFS2016/>

Loratadine was patented in 1980 and came to market in 1988.<ref name=Fis2006>Template:Cite book</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">Template:Cite book</ref> Loratadine is available as a generic medication.<ref name=AHFS2016/><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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 9Template:Nbspmillion prescriptions.<ref name="Top 300 of 2022">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medical uses

Loratadine is indicated for the symptomatic relief of allergies such as hay fever (allergic rhinitis), urticaria (hives), chronic idiopathic urticaria,<ref>Template:Cite journal</ref> and other skin allergies.<ref name="Austria-Codex">Template:Cite book</ref> For allergic rhinitis, loratadine is indicated for both nasal and eye symptoms including sneezing, runny nose, and itchy or burning eyes.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Similarly to cetirizine, loratadine attenuates the itching associated with Kimura's disease.<ref>Template:Cite journal</ref>

Combination drugs

Loratadine/pseudoephedrine is a fixed dose combination of the drug with pseudoephedrine, a nasal decongestant.<ref>Template:Cite book</ref>

Dosage forms

File:Loratadine10mg.png

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 category L-2 - probably compatible, by the American Academy of Pediatrics).<ref>Template:Cite journal</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>Template:Cite journal</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 less.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Headache is also a possible side effect.<ref name="Austria-Codex" /><ref name="Mutschler">Template:Cite book</ref>

Unlike earlier-generation antihistamines, loratadine is considered largely free of antimuscarinic effects (urinary retention, dry mouth, blurred vision).<ref>Template:Cite book</ref><ref>Template:Cite book</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 mg loratadine treatment. <ref name="BJCP: Evaluation of the pharmacokinetics and electrocardiographic pharmacodynamics of loratadine with concomitant administration of ketoconazole or cimetidine">Template:Cite journal</ref>

Antihistamines should be discontinued 48 hours before skin allergy tests, 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 H₁ receptors.<ref name="Mutschler" /><ref name=Devillier2008rev>Template:Cite journal</ref> The potency of second generation histamine antagonists is (from strongest to weakest) desloratadine (K_i 0.4 nM) > levocetirizine (K_i 3 nM) > cetirizine (K_i 6 nM) > fexofenadine (K_i 10 nM) > terfenadine > loratadine. However, the onset of action varies significantly and clinical efficacy is not always directly related to only the H₁ receptor potency, as the concentration of free drug at the receptor must also be considered.<ref>Template:Cite journal</ref><ref name=Devillier2008rev/> Loratadine also shows anti-inflammatory properties independent of H₁ receptors.<ref name="pmid15631542">Template:Cite journal</ref><ref name="pmid23268457">Template:Cite journal</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">Template:Cite journal</ref><ref name="pmid15245363">Template:Cite journal</ref>

Pharmacokinetics

Loratadine is given orally, is well absorbed from the gastrointestinal tract, and has rapid first-pass hepatic metabolism; it is metabolized by isoenzymes of the cytochrome P450 system, including CYP3A4, CYP2D6, and, to a lesser extent, several others.<ref name=Foye>Template:Cite book</ref><ref>Template:Cite journal</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>Template:Cite journal</ref> About 40% is excreted as 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 antidepressants, such as imipramine, and is distantly related to the atypical antipsychotic quetiapine.<ref name="pmid10444229">Template:Cite journal</ref>

History

Schering-Plough developed loratadine as part of a quest for a potential blockbuster drug: a 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">Template:Cite news</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="jama96">Template:Cite journal</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It was then subsequently approved for over-the-counter sales. Once it became an unpatented over-the-counter drug, the price dropped significantly.Template:Citation needed

Schering also 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>Template:Cite journal</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. Loratadine OTC regulation Template:Webarchive 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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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. 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>Template:Cite news</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>Template:Cite news</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 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.<ref name=Batman>Template:Citation </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>Template:Cite news</ref>

Schering-Plough invested Template:US$Template:Nbspmillion in Claritin direct-to-consumer advertising in 1998 and 1999, far more than any other brand.<ref name="NYTimes" /> Spending on direct-to-consumer advertising by the pharmaceutical industry rose from Template:US$Template:Nbspmillion in 1995 to Template:US$Template:Nbspbillion in 1998, and by 2006, was Template:US$Template:Nbspbillion.<ref name=statmarketing/>