|Systematic (IUPAC) name|
|Metabolism||Hepatic (CYP2D6- and 3A4-mediated)|
|Biological half-life||8 hours, active metabolite desloratadine 27 hours|
|Excretion||40% as conjugated metabolites into urine
Similar amount into the feces
|Molar mass||382.88 g/mol|
|(what is this?)|
Loratadine is a second-generation peripheral histamine H1-receptors blocker 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.
Loratadine was discovered in 1981 and came to market in 1993. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system. It is available as a generic drug and is marketed for its nonsedating properties. There is a version combined with pseudoephedrine, a decongestant; known as pseudoephedrine/loratadine.
Loratadine is indicated for the symptomatic relief of allergy such as hay fever (allergic rhinitis), urticaria (hives), chronic idiopathic urticaria, 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. Loratadine could be also used to treat mild to moderate pain from headaches.
The drug is available in many different forms, such as: tablets, oral suspension, and syrup, and in combination with pseudoephedrine. 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.
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 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.
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.
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).
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.
Mechanism of action
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, which is largely responsible for the antihistaminergic effects, binds to plasma proteins by 73–76%.
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. 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.
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.
Loratadine was approved by the FDA in 1993. The drug continued to be available only by prescription in the U.S. until it went off patent in 2002. It was then subsequently approved for over-the-counter sales. Once it became an unpatented over-the-counter drug, the price dropped significantly.
Loratadine is available under many brand names and dosage forms worldwide.
In 1998, in an an unprecedented action, the American insurance company Anthem 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. In the US, Schering-Plough made loratadine available OTC in 2002. Loratadine is currently available in many countries OTC.
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