| 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 cat. | B1(AU) B(US) |
| Legal status | GSL (UK) OTC (US) OTC(Canada) |
| Routes | oral |
| Pharmacokinetic data | |
| Bioavailability | almost 100% |
| Protein binding | 97–99% |
| Metabolism | Hepatic (CYP2D6- and 3A4-mediated) |
| 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 |
| PubChem | CID 3957 |
| DrugBank | DB00455 |
| ChemSpider | 3820 |
| UNII | 7AJO3BO7QN |
| KEGG | D00364 |
| ChEMBL | CHEMBL998 |
| Chemical data | |
| Formula | C22H23ClN2O2 |
| Mol. mass | 382.88 g/mol |
| SMILES | eMolecules & PubChem |
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Loratadine (INN) is a second-generation H1 histamine antagonist drug used to treat allergies. Structurally, it is closely related to tricyclic antidepressants, such as imipramine, and is distantly related to the atypical antipsychotic quetiapine.[1]
Loratadine is marketed by Schering-Plough 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 non-sedating 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.
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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.[2]
Loratadine was eventually approved by the FDA in 1993.[2] 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."[3] However, as of 2009, 10 mg loratadine tablets can be purchased relatively inexpensively, as generic manufacturers offer 120-day supplies for less than $25.
Loratadine is indicated for the symptomatic relief of allergy such as hay fever (allergic rhinitis), urticaria (hives), and other skin allergies.[4] 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.
The drug is available as tablets, oral suspension, and syrup,[4] and also in combination with pseudoephedrine.[5] 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.
Patients with severe hepatic (liver) disorders may need to start with a lower dose. No-dose adaptation is necessary for elderly or renally impaired patients.[4][6]
Loratadine is usually compatible with breast-feeding (classified category L-2 by the American Academy of Pediatrics).[7] 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.[8]
As a 'non-sedating' antihistamine, loratadine causes less but still significant sedation and psychomotor retardation than the older antihistamines because it penetrates the blood brain barrier only 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); there is no reason to avoid drinking alcohol while using loratadine, as no interaction between alcohol and loratadine can be demonstrated.
Other possible side-effects include headache and antimuscarinic effects such as urinary retention, dry mouth, blurred vision, and gastrointestinal disturbances.[4][6]
Lastly, in rare cases, loratadine has been shown to cause severe mood shifts with effects ranging from depression to rage.[9]
Loratadine is a tricyclic antihistamine, which acts as a selective inverse agonists of peripheral histamine H1-receptors.[6] Histamine is responsible for many features of allergic reactions.
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.[10][11] 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%.[4]
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.[4]
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 clinically significant effects in controlled trials of higher than usual doses of loratadine (20 mg).
Antihistamines should be discontinued approximately 48 hours prior to skin allergy tests since these drugs may prevent or diminish otherwise positive reactions to dermal activity indicators.
In Canada, Mexico, the U.S., Australia, the UK and many other countries 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).[12]
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