Loratadine

Loratadine

File:Loratadine.svg
Systematic (IUPAC) name
Ethyl 4-(8-chloro-5,6-dihydro-11H- benzo[5,6]ohepta[1,2-b]pyridin- 11-ylidine)-1-piperidinecarboxylate
Clinical data
Pregnancy category	AU: B1 US: B (No risk in non-human studies)
Routes of administration	oral
Legal status
Legal status	UK: General sales list (GSL, OTC) US: OTC OTC(Canada)
Pharmacokinetic data
Bioavailability	almost 100%
Protein binding	97–99%
Metabolism	Hepatic (CYP2D6- and 3A4-mediated)
Biological half-life	8 hours, active metabolite desloratadine 28 hours
Excretion	40% as conjugated metabolites into urine Similar amount into the feces
Identifiers
CAS Number	79794-75-5
ATC code	R06AX13 (WHO)
PubChem	CID 3957
DrugBank	APRD00384
ChemSpider	3820
Chemical data
Formula	C22H23ClN2O2
Molar mass	382.88 g/mol[[]]
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Loratadine is a second-generation antihistamine drug closely structurally related to tricyclic antidepressants such as imipramine, and distantly related to the atypical antipsychotic quetiapine, used to treat allergies. It is marketed by Schering-Plough under several trade names such as Claritin, and by Shionogi in Japan. Loratadine is available as a generic drug and is marketed for its non-sedating properties. In a version named Claritin-D or Clarinase, the substance is combined with pseudoephedrine, a decongestant; this makes it useful for colds as well as allergies, but adds potential side-effects of insomnia, nervousness, and anxiety.

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 non-sedating antihistamine, terfenadine (trade name Seldane), and, therefore, put loratadine on a lower priority as a "me too" drug.

Loratadine was eventually approved by the FDA in 1993. It accounted for 28% of Schering's total sales. The drug continued to be available only by prescription in the U.S. until it went off patent in 2002. It was then immediately approved for over-the-counter sales. Once it became an unpatented over-the-counter drug, the price dropped precipitously, and insurance companies no longer paid for it. In response, Schering launched an expensive advertising campaign to convince users to switch to desloratadine (descarboethoxyloratadine, trade name Clarinex), which is the active metabolite of loratadine. A 2003 study comparing the two drugs found that "There is no clinical advantage to switching a patient from loratadine to desloratadine. However, it may be an option for patients whose medical insurance no longer covers loratadine if the co-pay is less than the cost of the over-the-counter product." However, as of 2009, 10 mg loratadine tablets can be purchased relatively inexpensively, as generic manufacturers offer 120-day supplies for less than $25.

Indications

Loratadine is indicated for the symptomatic relief of allergy such as hay fever (allergic rhinitis), urticaria (hives), and other skin allergies. For allergic rhinitis (hay fever), loratadine is effective for both nasal and eye symptoms: sneezing, runny nose, itchy or burning eyes.

Forms

File:Loratadine10mg.png

Loratadine 10 mg (Rx)

The drug is available as tablets, oral suspension, and syrup, and also in combination with pseudoephedrine. Also available are quick-dissolving tablets, which are marketed as being faster to get into one's circulatory system but which require special handling to avoid degrading in the package.

Cautions and contraindications

Patients with severe hepatic disorders may need to start with a lower dose. No-dose adaptation is necessary for elderly or renally impaired patients.

Loratadine is usually compatible with breast-feeding (classified category L-2 by the American Academy of Pediatrics). In the U.S., it is classified as category B in pregnancy, meaning that animal reproduction studies have failed to demonstrate a risk to the fetus, and there are no adequate and well-controlled studies in pregnant women.

Adverse effects

As a 'non-sedating' antihistamine, loratadine causes less sedation and psychomotor retardation than the older antihistamines because it penetrates the blood brain barrier only to a slight 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); excess alcohol should be avoided, although an interaction between alcohol and loratadine has not been shown.

Other possible side-effects include headache and antimuscarinic effects such as urinary retention, dry mouth, blurred vision, and gastrointestinal disturbances.

Mechanism of action

Loratadine is a tricyclic antihistamine, which acts as a selective inverse agonists of peripheral histamine H₁-receptors. 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. Loratadine is almost totally (97–99%) bound to plasma proteins. Its metabolite desloratadine is largely responsible for the antihistaminergic effects. It binds to plasma proteins by 73–76%.

Loratadine's peak effect occurs in 1–2 hours, and its biological half-life is on average 8 hours (range 3–20 hours) with desloratadine's half-life being 28 hours (range 9–92 hours), accounting for its long-lasting effect. 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.

Interactions

Substances that act as inhibitors of the CYP3A4 enzyme such as ketoconazole, erythromycin, cimetidine and furanocoumarin derivates (found in grapefruit) lead to increased plasma levels of loratadine. This had no clinically significant effects in controlled trials.

Legal status

In the U.S. and UK, loratadine is available over the counter, as are some other second-generation antihistamines like cetirizine. In the UK, larger quantities are "P-Line" and can be sold only in the presence of a pharmacist. However, packets of up to and including 14 tablets are available "off the shelf" (GSL). Desloratadine is an over-the-counter drug in Canada, but is a prescription drug in the United States. It is also sold over the counter in pharmacies in Mexico.

External links

• Loratadine—MedlinePlus Drug Information, U.S. National Library of Medicine, National Institutes of Health
• Claritin (loratadine) drug description—RxList (Internet Drug Index)
• Claritin—patient information leaflet
• DrugBank: Loratadine—Wishart DS et al., DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 2006 1;34
• U.S. National Library of Medicine: Drug Information Portal - Loratadine

ar:كلاريناز zh:氯雷他定