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Loratadine (INN) is a second-generation^[1] selective inverse agonist of peripheral histamine H₁-receptors.^[2] used to treat allergies. In structure, it is closely related to tricyclic antidepressants, such as imipramine, and is distantly related to the atypical antipsychotic quetiapine.^[3]

Loratadine is marketed by Schering-Plough^{[needs update]} under several trade names (e.g., Claritin) and also by Shionogi in Japan. It is available as a generic drug and is marketed for its nonsedating properties. In a version named Claritin-D or Clarinase, it is combined with pseudoephedrine, a decongestant; this makes it useful for colds, as well as allergies but adds potential side effects of insomnia, anxiety, and nervousness.

History

Schering-Plough developed loratadine as part of a quest for a potential blockbuster drug: a nonsedating antihistamine. However, 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.^[4]

Loratadine was approved by the FDA in 1993.^[4] The drug continued to be available only by prescription in the U.S. until it went off patent in 2002.^{[citation needed]} It was then subsequently approved for over-the-counter sales. Once it became an unpatented over-the-counter drug, the price dropped significantly.

Schering also developed desloratadine (Clarinex), which is an active metabolite of loratadine.

Indications

Loratadine is indicated for the symptomatic relief of allergy such as hay fever (allergic rhinitis), urticaria (hives), chronic idiopathic urticaria,^[5] and other skin allergies.^[6] For allergic rhinitis (hay fever), loratadine is effective for both nasal and eye symptoms: sneezing, runny nose, itchy or burning eyes. Loratadine could be also used to treat mild to moderate pain from headaches.^{[citation needed]}

Similarly to cetirizine, loratadine attenuates the itching associated with Kimura's disease.^[7]

Forms

An example of a loratadine 10-mg tablet (Rx)

The drug is available in many different forms, such as: tablets, oral suspension, and syrup,^[6] and in combination with pseudoephedrine.^[8] Also available are quick-dissolving tablets, which are marketed as being faster to get into one's circulatory system, but require special handling to avoid degrading in the package.

Cautions and contraindications

Patients with severe hepatic (liver) disorders may need to start with a lower dose. No dose adaptation is necessary for elderly or renally (kidney) impaired patients.^[6]^[2]

Loratadine is usually compatible with breast-feeding (classified category L-2 by the American Academy of Pediatrics).^[9] 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, and no adequate and well-controlled studies in pregnant women have been conducted.^[10]

Adverse effects

As a "nonsedating" 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 to a smaller extent. Although drowsiness is rare at the common 10-mg dose, patients should, nevertheless, be advised that it can occur and may affect performance of skilled tasks (e.g., driving). Patients who do experience drowsiness while taking loratadine should avoid the use of alcohol, as it can cause excessive drowsiness. Otherwise, loratadine and alcohol are unlikely to cause problems. Nevertheless, it would be in the patient's best interest to take caution when combining alcohol and any medication.^[11]

Other possible side effects include headache and antimuscarinic effects such as urinary retention, dry mouth, blurred vision, and gastrointestinal disturbances.^[6]^[2]

Mechanism of action

Loratadine is a tricyclic antihistamine, which acts as a selective inverse agonist of peripheral histamine H₁-receptors.^[2] Histamine is responsible for many features of allergic reactions.

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.^[12]^[13] 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%.^[6]

Loratadine's peak effect occurs after one to two hours, and its biological half-life is on average 8 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.^[14] 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.^[6]

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. This had clinically significant effects in controlled trials of higher-than-usual doses of loratadine (20 mg).^{[citation needed]}

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

Availability

Loratadine is available under many brand names and dosage forms worldwide.^[15] In the US, in an unprecedented action, in 1998 the insurance company Wellpoint petitioned the FDA to allow loratadine and two other antihistamines to be made available over the counter (OTC) while it was still under patent; the FDA granted the request, which was not binding on manufacturers.^[16] In the US, Schering-Plough made loratadine available OTC in 2002.^[16] Loratadine is available in many countries OTC.^[17]

References

^ Holdcroft, C. (1993). "Terfenadine, astemizole and loratadine: Second generation antihistamines". The Nurse practitioner 18 (11): 13–14. doi:10.1097/00006205-199311000-00005. PMID 8278087. edit
^ ^a ^b ^c ^d Mutschler, Ernst; Gerd Geisslinger; Heyo K. Kroemer; Monika Schäfer-Korting (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 456–461. ISBN 3-8047-1763-2.
^ Kay GG, Harris AG (July 1999). "Loratadine: a nonsedating antihistamine. Review of its effects on cognition, psychomotor performance, mood and sedation". Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology. 29 Suppl 3: 147–50. doi:10.1046/j.1365-2222.1999.0290s3147.x. PMID 10444229.
^ ^a ^b Hall, Stephen S. (2001-03-11). "The Claritin Effect; Prescription for Profit". The New York Times. Retrieved 2010-06-28.
^ Pons-Guiraud, A; Nekam, K; Lahovsky, J; Costa, A; Piacentini, A (2006). "Emedastine difumarate versus loratadine in chronic idiopathic urticaria: A randomized, double-blind, controlled European multicentre clinical trial". European journal of dermatology : EJD 16 (6): 649–54. PMID 17229605. edit
^ ^a ^b ^c ^d ^e ^f Jasek, W, ed. (2007). Austria-Codex (in German) 1 (2007/2008 ed.). Vienna: Österreichischer Apothekerverlag. pp. 1768–71. ISBN 978-3-85200-181-4.
^ Ueda, T; Arai, S; Amoh, Y; Katsuoka, K (2011). "Kimura's disease treated with suplatast tosilate and loratadine". European journal of dermatology : EJD 21 (6): 1020–1. doi:10.1684/ejd.2011.1539. PMID 21914581. edit
^ Jasek, W, ed. (2007). Austria-Codex (in German) 1 (2007/2008 ed.). Vienna: Österreichischer Apothekerverlag. pp. 1731–34. ISBN 978-3-85200-181-4.
^ Committee on Drugs (1 September 2001). "Transfer of drugs and other chemicals into human milk". Pediatrics 108 (3): 776–89. PMID 11533352.
^ See, Sharon (November 15, 2003). "Desloratadine for Allergic Rhinitis". American Family Physician.
^ Kristi Monson, PharmD. "Claritin and Alcohol". emedtv.com.
^ Nelson, Wendel L. (2002). "Antihistamines and related antiallergic and antiulcer agents". In Williams, David H.; Foye, William O.; Lemke, Thomas L. Foye's principles of medicinal chemistry. Hagerstown, MD: Lippincott Williams & Wilkins. p. 805. ISBN 0-683-30737-1. Retrieved on 1 December 2009 through Google Book Search.
^ Ghosal A, Gupta S, Ramanathan R et al. (August 2009). "Metabolism of loratadine and further characterization of its in vitro metabolites". Drug Metab Lett 3 (3): 162–70. doi:10.2174/187231209789352067. PMID 19702548.
^ Affrime, M; Gupta, S; Banfield, C; Cohen, A (2002). "A pharmacokinetic profile of desloratadine in healthy adults, including elderly". Clinical pharmacokinetics. 41 Suppl 1: 13–9. PMID 12169042. edit
^ drugs.com Loratadine at drugs.com international listings Page accessed April 11, 2015]
^ ^a ^b Cohen JP et al. Switching prescription drugs to over the counter. BMJ. 2005 Jan 1;330(7481):39-41. PMID 15626806 PMC 539854
^ Association of the European Self-Medication Industry Database. Loratadine OTC regulation Page accessed April 11, 2015

External links

Loratadine—MedlinePlus Drug Information, U.S. National Library of Medicine, National Institutes of Health
Claritin (loratadine) drug description—RxList (Internet Drug Index)
U.S. National Library of Medicine: Drug Information Portal - Loratadine
Claritin.ph—Claritin Philippines Website

UpToDate Contents

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1. アレルギー性鼻炎の薬物療法 pharmacotherapy of allergic rhinitis
2. 妊娠中のアレルギー疾患の認識およびマネージメント recognition and management of allergic disease during pregnancy
3. 慢性蕁麻疹：標準的なマネージメントおよび患者教育 chronic urticaria standard management and patient education
4. 空中アレルゲン皮下免疫療法：促進スケジュール（クラスター法および急速法） subcutaneous aeroallergen immunotherapy accelerated schedules cluster and rush
5. アレルギー性鼻炎および結膜炎に対する補完代替療法 complementary and alternative therapies for allergic rhinitis and conjunctivitis

English Journal

Yiqi Wenyang Fang ameliorates allergic rhinitis through inhibiting inflammatory response and promoting the expression of Foxp3.

Shi J1, Liu Y2, Yan S1, Yan D3.
International journal of immunopathology and pharmacology.Int J Immunopathol Pharmacol.2015 Dec 18. pii: 0394632015621769. [Epub ahead of print]
Allergic rhinitis (AR) is an inflammatory disease with a hypersensitivity response to environmental stimulus. The aim of this study was to evaluate the effect of Yiqi Wenyang Fang (YWF) on AR and investigate the underlying mechanism. A total of 48 female Sprague-Dawley rats were randomly divided int
PMID 26684623

Human UDP-glucuronosyltransferase (UGT) 2B10: Validation of cotinine as a selective probe substrate, inhibition by UGT enzyme selective inhibitors and antidepressant and antipsychotic drugs, and structural determinants of enzyme inhibition.

Pattanawongsa A1, Nair PC1, Rowland A1, Miners JO2.
Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2015 Dec 15. pii: dmd.115.068213. [Epub ahead of print]
Although there is evidence for an important role of UGT2B10 in the N-glucuronidation of drugs and other xenobiotics, the inhibitor selectivity of this enzyme is poorly understood. This study sought primarily to characterize the inhibition selectivity of UGT2B10 by UDP-glucuronosyltransferase (UGT) e
PMID 26669329

Prevalence of Desloratadine Slow-metabolizer Phenotype and Food-dependent Pharmacokinetics of Desloratadine in Healthy Chinese Volunteers.

Wang T1, Zhang K1, Li T2, He L3, Xie H1, Jiang X1, Wang L4.
Clinical drug investigation.Clin Drug Investig.2015 Dec;35(12):807-13. doi: 10.1007/s40261-015-0343-1.
BACKGROUND AND OBJECTIVES: Desloratadine, the major active metabolite of loratadine, is a non-sedating long-acting antihistamine that is widely used in the treatment of allergic rhinitis and chronic idiopathic urticaria. This study aimed to investigate the prevalence of desloratadine slow-metabolize
PMID 26446005

Japanese Journal

Detection of metabolic activation leading to drug-induced phospholipidosis in rat hepatocyte spheroids

The Journal of Toxicological Sciences 41(1), 155-164, 2016
NAID 130005119791

27頭の猫に発症したアレルギー性そう痒を管理するためのロラタジンの有効性に関するオープン臨床試験

獣医臨床皮膚科 21(1), 7-9, 2015
NAID 130005069976

治療他抗ヒスタミン薬で効果不十分な慢性蕁麻疹患者に対するロラタジンの臨床的有用性の検討

西日本皮膚科 74(3), 293-300, 2012-06
NAID 40019365976

Related Pictures

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★リンクテーブル★

リンク元	「ロラタジン」「dimetapp」「Claritin」

「ロラタジン」

Loratadine
Systematic (IUPAC) name
	Ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylate
Clinical data
Trade names	Claritin
AHFS/Drugs.com	monograph
MedlinePlus	a697038
Pregnancy; category	AU: B1; US: B (No risk in non-human studies);
Legal status	CA: OTC; UK: General sales list (GSL, OTC); US: OTC;
Routes of; administration	oral
Pharmacokinetic data
Bioavailability	almost 100%
Protein binding	97–99%
Metabolism	Hepatic (CYP2D6- and 3A4-mediated)
Half-life	8 hours, active metabolite desloratadine 27 hours
Excretion	40% as conjugated metabolites into urine; Similar amount into the feces
Identifiers
CAS Registry Number	79794-75-5
ATC code	R06AX13
PubChem	CID: 3957
IUPHAR ligand	7216
DrugBank	DB00455
ChemSpider	3820
UNII	7AJO3BO7QN
KEGG	D00364
ChEMBL	CHEMBL998
Chemical data
Formula	C22H23ClN2O2
Molecular mass	382.88 g/mol
	SMILES O=C(OCC)N4CC/C(=C2/c1ccc(Cl)cc1CCc3cccnc23)CC4;
	InChI 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 ; Key:JCCNYMKQOSZNPW-UHFFFAOYSA-N ;
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