Loratadine

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Loratadine
Loratadine.svg
Loratadine - 3d, portrait orientation.png
Clinical data
Trade names Claritin, Claratyne, Clarityn, others
AHFS/Drugs.com Monograph
MedlinePlus a697038
License data
Pregnancy
category
Routes of
administration 		By mouth
Drug class Second-generation antihistamine
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability almost 100%
Protein binding 97–99%
Metabolism Liver (CYP2D6- and 3A4-mediated)
Elimination half-life 8 hours, active metabolite desloratadine 27 hours
Excretion 40% as conjugated metabolites into urine
Similar amount into the feces
Identifiers
  • Ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.120.122 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H23ClN2O2
Molar mass 382.89 g·mol−1
3D model (JSmol)
  • O=C(OCC)N4CC/C(=C2/c1ccc(Cl)cc1CCc3cccnc23)CC4
  • InChI=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 Yes check.svgY
  • Key:JCCNYMKQOSZNPW-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Loratadine, sold under the brand name Claritin among others, is a medication used to treat allergies. [5] This includes allergic rhinitis (hay fever) and hives. [5] It is also available in drug combinations such as loratadine/pseudoephedrine, in which it is combined with pseudoephedrine, a nasal decongestant. [5] It is taken orally. [5]

Contents

Common side effects include sleepiness, dry mouth, and headache. [5] Serious side effects are rare and include allergic reactions, seizures, and liver problems. [6] Use during pregnancy appears to be safe but has not been well studied. [7] It is not recommended in children less than two years old. [6] It is in the second-generation antihistamine family of medication. [5]

Loratadine was patented in 1980 and came to market in 1988. [8] It is on the World Health Organization's List of Essential Medicines. [9] Loratadine is available as a generic medication. [5] [10] In the United States, it is available over the counter. [5] In 2021, it was the 67th most commonly prescribed medication in the United States, with more than 9 million prescriptions. [11] [12]

Medical uses

Loratadine is indicated for the symptomatic relief of allergies such as hay fever (allergic rhinitis), urticaria (hives), chronic idiopathic urticaria, [13] and other skin allergies. [14] For allergic rhinitis, loratadine is indicated for both nasal and eye symptoms including sneezing, runny nose, and itchy or burning eyes. [15]

Similarly to cetirizine, loratadine attenuates the itching associated with Kimura's disease. [16]

Combination drugs

Loratadine/pseudoephedrine is a fixed dose combination of the drug with pseudoephedrine, a nasal decongestant. [17]

Dosage forms

An example of a loratadine 10-mg tablet (Rx) 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. [14] Also available are quick-dissolving tablets. [14]

Contraindications

Loratadine is usually compatible with breastfeeding (classified category L-2 - probably compatible, by the American Academy of Pediatrics). [18] 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. [19]

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. [20]

Other side effects include headache and antimuscarinic effects, such as urinary retention, dry mouth, blurred vision, and gastrointestinal problems. [14] [21]

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. [22]

Antihistamines should be discontinued 48 hours prior to skin allergy tests, since these drugs may prevent or diminish otherwise-positive reactions to dermal activity indicators. [14]

Pharmacology

Pharmacodynamics

Loratadine is a tricyclic antihistamine, which acts as a selective inverse agonist of peripheral histamine H1 receptors. [21] [23] The potency of second generation histamine antagonists is (from strongest to weakest) desloratadine (Ki 0.4 nM) > levocetirizine (Ki 3 nM) > cetirizine (Ki 6 nM) > fexofenadine (Ki 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 concentration of free drug at the receptor must also be considered. [24] [23] Loratadine also shows anti-inflammatory properties independent of H1 receptors. [25] [26] 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. [27] [28]

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. [29] [30] 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%. [14]

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. [31] 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. [14]

In structure, it is closely related to tricyclic antidepressants, such as imipramine, and is distantly related to the atypical antipsychotic quetiapine. [32]

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. [33] 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. [34] [35]

Loratadine was approved by the FDA in 1993. [33] The drug continued to be available only by prescription in the U.S. until it went off patent in 2002. [36] 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 ]

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. [37] In the United States, Schering-Plough made loratadine available over the counter in 2002. [37] By 2015, loratadine was available over the counter in many countries. [38]

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. [39]

Marketing

The marketing of the Claritin brand is important in the history of direct-to-consumer advertising of drugs. [40] [41]

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 regulation 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. [40]

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]." [40] [41] The first ads made people aware of the brand and increased prescriptions, which led Schering-Plough and others to aggressively pursue the advertising strategy. [41]

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. [42]

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. [40] 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. [40] [43]

Schering-Plough invested US$322 million in Claritin direct-to-consumer advertising in 1998 and 1999, far more than any other brand. [33] Spending on direct-to-consumer advertising by the pharmaceutical industry rose from US$360 million in 1995 to US$1.3 billion in 1998, and by 2006, was US$5 billion. [40]

Related Research Articles

H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines; other agents may have antihistaminergic action but are not true antihistamines.

<span class="mw-page-title-main">Allergic rhinitis</span> Nasal inflammation due to allergens in the air

Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, itchy, and watery eyes, and swelling around the eyes. The fluid from the nose is usually clear. Symptom onset is often within minutes following allergen exposure, and can affect sleep and the ability to work or study. Some people may develop symptoms only during specific times of the year, often as a result of pollen exposure. Many people with allergic rhinitis also have asthma, allergic conjunctivitis, or atopic dermatitis.

<span class="mw-page-title-main">Brompheniramine</span> Chemical compound

Brompheniramine, sold under the brand name Dimetapp among others, is a first-generation antihistamine drug of the propylamine (alkylamine) class. It is indicated for the treatment of the symptoms of the common cold and allergic rhinitis, such as runny nose, itchy eyes, watery eyes, and sneezing. Like the other first-generation drugs of its class, it is considered a sedating antihistamine.

<span class="mw-page-title-main">Desloratadine</span> Allergy medication

Desloratadine (trade names Clarinex and Aerius) is a tricyclic H1 inverse agonist that is used to treat allergies. It is an active metabolite of loratadine.

<span class="mw-page-title-main">Cetirizine</span> Antihistamine medication

Cetirizine is a second-generation antihistamine used to treat allergic rhinitis, dermatitis, and urticaria (hives). It is taken by mouth. Effects generally begin within thirty minutes and last for about a day. The degree of benefit is similar to other antihistamines such as diphenhydramine, which is a first-generation antihistamine.

<span class="mw-page-title-main">Fexofenadine</span> Antihistamine medication

Fexofenadine, sold under the brand name Allegra among others, is an antihistamine pharmaceutical drug used in the treatment of allergy symptoms, such as hay fever and urticaria.

<span class="mw-page-title-main">Phenylephrine</span> Decongestant medication

Phenylephrine is a medication used as a decongestant for uncomplicated nasal congestion, used to dilate the pupil, used to increase blood pressure, and used to relieve hemorrhoids. It can be taken by mouth, as a nasal spray, given by injection into a vein or muscle, or applied to the skin.

<span class="mw-page-title-main">Montelukast</span> Medication used in asthma or COPD

Montelukast, sold under the brand name Singulair among others, is a medication used in the maintenance treatment of asthma. It is generally less preferred for this use than inhaled corticosteroids. It is not useful for acute asthma attacks. Other uses include allergic rhinitis and hives of long duration. For allergic rhinitis it is a second-line treatment.

<span class="mw-page-title-main">Olopatadine</span> Chemical compound

Olopatadine, sold under the brand name Patanol among others, is an antihistamine medication used to decrease the symptoms of allergic conjunctivitis and allergic rhinitis. It is used as eye drops or as a nasal spray. The eye drops generally result in an improvement within half an hour.

<span class="mw-page-title-main">Levocetirizine</span> Antihistamine drug

Levocetirizine, sold under the brand name Xyzal, among others, is a second-generation antihistamine used for the treatment of allergic rhinitis and long-term hives of unclear cause. It is less sedating than older antihistamines. It is taken by mouth.

<span class="mw-page-title-main">Terfenadine</span> Chemical compound

Terfenadine is an antihistamine formerly used for the treatment of allergic conditions. It was brought to market by Hoechst Marion Roussel and was marketed under various brand names, including Seldane in the United States, Triludan in the United Kingdom, and Teldane in Australia. It was superseded by fexofenadine in the 1990s due to the risk of a particular type of disruption of the electrical rhythms of the heart and has been withdrawn from markets worldwide.

<span class="mw-page-title-main">Azelastine</span> Chemical compound

Azelastine, sold under the brand name Optivar among others, is a H1 receptor-blocking medication primarily used as a nasal spray to treat allergic rhinitis (hay fever) and as eye drops for allergic conjunctivitis. Other uses may include asthma and skin rashes for which it is taken by mouth. Onset of effects is within minutes when used in the eyes and within an hour when used in the nose. Effects last for up to 12 hours.

<span class="mw-page-title-main">Acrivastine</span> Chemical compound

Acrivastine is a medication used for the treatment of allergies and hay fever. It is a second-generation H1-receptor antagonist antihistamine and works by blocking histamine H1 receptors.

<span class="mw-page-title-main">Azatadine</span> Chemical compound

Azatadine (Optimine) is a first-generation antihistamine and anticholinergic drug that was synthesized in 1963 by Schering-Plough, a former American pharmaceutical company.

<span class="mw-page-title-main">Ebastine</span> Antihistamine drug

Ebastine is a H1 antihistamine with low potential for causing drowsiness.

<span class="mw-page-title-main">Antihistamine</span> Drug that blocks histamine or histamine agonists

Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic drug that can be bought without a prescription and provides relief from nasal congestion, sneezing, or hives caused by pollen, dust mites, or animal allergy with few side effects. Antihistamines are usually for short-term treatment. Chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection. Consultation of a medical professional is recommended for those who intend to take antihistamines for longer-term use.

Pseudoephedrine/loratadine (trade names Claritin-D, Clarinase, Clarinase Repetabs, Lorinase, Rhinos SR, Allerclear-D) is an orally administered combination drug used for the treatment of allergic rhinitis and the common cold. This drug can be bought "over the counter" in some countries (United States, Hong Kong), but it is restricted to prescription in others (Czech Republic, Israel).

<span class="mw-page-title-main">Bilastine</span> Antihistamine medication

Bilastine is an antihistamine medication used to treat hives (urticaria), allergic rhinitis and itchy inflamed eyes (allergic conjunctivitis) caused by an allergy. It is a second-generation antihistamine and takes effect by selectively inhibiting the histamine H1 receptor, preventing these allergic reactions. Bilastine has an effectiveness similar to cetirizine, fexofenadine, and desloratadine.

Fexofenadine/pseudoephedrine, sold under the brand name Allegra-D among others, is a fixed-dose combination medication used for the treatment of nasal congestion and other symptoms of allergies and the common cold. It contains fexofenadine, as the hydrochloride, an antihistamine; and pseudoephedrine, as the hydrochloride, a nasal decongestant.

Cetirizine/pseudoephedrine (Zyrtec-D) is an antihistamine and decongestant formulation. It is a fixed-dose combination drug containing 5 mg cetirizine hydrochloride and 120 mg pseudoephedrine hydrochloride for symptoms related to seasonal allergic rhinitis. Cetirizine/pseudoephedrine gained approval from the U.S. Food and Drug Administration in 2001 as a prescription drug and became over-the-counter (OTC) in 2007.

References

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  2. ↑ "Claritin Allergy Product information". Health Canada. 25 April 2012. Retrieved 7 June 2022.
  3. ↑ "Clarityn Allergy 10mg Tablets (P & GSL) - Patient Information Leaflet (PIL)". (emc). 30 August 2019. Archived from the original on 10 April 2020. Retrieved 10 April 2020.
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  40. 1 2 3 4 5 6 "The untold story of TV's first prescription drug ad". STAT. 11 December 2015. Retrieved 26 October 2017.
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  43. ↑ "Ten Years Later: Direct to Consumer Drug Advertising" . Retrieved 26 October 2017.
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