Schering-Plough developed loratadine as part of the search for a potential blockbuster drug: a non-sedating antihistamine. When 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 placed loratadine in a lower priority. [31] However, the manufacturer had to withdraw terfenadine from the U.S. market in late 1997 following reports of severe ventricular arrhythmias taking the drug. [32] [33] Substances that act as inhibitors of the enzyme CYP3A4, such as ketoconazole, erythromycin, cimetidine and furanocoumarin derivatives (found in grapefruit), result in increased plasma levels of loratadine – that is, more of the drug was present in the bloodstream than usual. This had clinically significant effects in controlled trials with loratadine 10 mg treatment [20] The maximum effect of loratadine occurs after 1 to 2 hours and its biological half-life averages eight hours (range 3 to 20 hours), with the half-life of desloratadine being 27 hours (range 9 to 92 hours), This explains its long-term effects. [29] Approximately 40% is excreted in the urine as conjugated metabolites, and a similar amount is excreted in the faeces. Traces of unmetabolized loratadine can be found in the urine. [12] Loratadine undergoes extensive first-pass metabolism in the liver and is primarily metabolized by CYP3A4, CYP2D6, CYP1A1 and CYP2C19. [37] Do not use loratadine to treat hives that are bruised or swollen, unusual in colour, or unitchy. Call your doctor if you have this type of hives.
The bioavailability parameters of loratadine and the active metabolite are dose-related. Loratadine is absorbed quickly and well. Simultaneous intake of food may slightly delay the absorption of loratadine, but without affecting the clinical effect. The bioavailability parameters of loratadine and the active metabolite are dose-related. In the United States and the United Kingdom, loratadine is the only over-the-counter drug in its class. In the UK, larger quantities are only available over the counter (they are “P-Line” and can only be sold in the presence of a pharmacist), while packs of up to 7 “ready-to-use” tablets (GSLs) are available. (Desloratadine is an over-the-counter drug in Canada, but it is a prescription drug in the United States.) Concomitant use of Fool may slightly delay the absorption of loratadine without affecting the clinical effect. In healthy subjects, the plasma distribution half-life of loratadine and its active metabolite is approximately 1 and 2 hours, respectively. Loratadine is highly bound (97% to 99%) and its main active metabolite, desloratadine (DL), is moderately bound (73% to 76%) to plasma proteins. Alberto Stampa, Pelayo Camps, Gloria Rodriguez, Jordi Bosch, Maria del Carmen Onrubia, “Loratadine Production Process.” U.S.
Patent US6084100, issued July 4, 2000. In patients with chronic renal failure, AUC and peak plasma levels (Cmax) of loratadine and its active metabolites increased compared to AUCs and peak plasma levels (Cmax) in patients with normal renal function. The mean elimination half-lives of loratadine and its active metabolite did not differ significantly from those observed in normal subjects. Haemodialysis does not affect the pharmacokinetics of loratadine or its active metabolite in patients with chronic renal failure. In 1998, a U.S. insurance company, Anthem Inc., in an unprecedented effort in the United States, petitioned the Federal Food and Drug Administration to make loratadine and two other antihistamines available over-the-counter (OTC) while remaining protected by patents; The administration acceded to the request, which was not binding on manufacturers. [35] In the United States, Schering-Plough made loratadine available over-the-counter in 2002. [35] In 2015, loratadine was available over-the-counter in many countries. [36] As a “non-sedative” antihistamine, loratadine causes less (but in some cases significant) sedation and psychomotor delay than older antihistamines because it penetrates less into the blood-brain barrier. [19] Loratadine was eventually approved by the FDA and in 2001, its final year of patent, accounted for 28% of Schering`s total sales. Although an FDA advisory committee ruled that loratadine was safe enough to be sold over-the-counter, Schering rejected such a decision on the grounds that it would reduce the price that could be charged for the drug. [4] The drug continued to be available by prescription in the United States until it was patented in 2002.
It was then immediately approved for stationary sale. Once it became an unpatented over-the-counter drug, the price dropped and insurance companies stopped paying for it. In response, Schering launched an expensive advertising campaign to convince users to switch to Clarinex (desloratadine), a metabolized form of loratadine. A 2003 study comparing the two drugs found: “There is no clinical benefit to switching a patient from loratadine to desloratadine. However, it may be an option for patients whose health insurance no longer covers loratadine if the co-payment is less than the cost of the over-the-counter product. “[5] Stop taking loratadine and call your doctor if your hives do not improve during the first 3 days of your treatment or if your hives persist for more than 6 weeks. If you don`t know the cause of your hives, call your doctor. Histamine release is an important mediator in allergic rhinitis and hives.1278 As a result, loratadine exerts its effect by targeting histamine H1 receptors. In addition, one study shows that descarboethoxyloratadine is first glucuronidated by UGT2B10 and then hydroxylated to 3-hydroxydesloratadine by CYP2C8.15 Additional glucuronidation of 3-hydroxydesloratadine facilitates excretion.16 Patients with severe hepatic impairment should receive a lower starting dose, as they may have reduced clearance of loratadine. An initial dose of 10 mg every other day is recommended for adults and children weighing more than 30 kg, and for children weighing 30 kg or less, 5 ml (5 mg) every other day is recommended. Less than 1% of the active substance is excreted unchanged in the form of loratadine or DL.
Loratadine is used to temporarily relieve the symptoms of hay fever (allergy to pollen, dust or other substances in the air) and other allergies. These symptoms include sneezing, runny nose, and itchy eyes, nasal or throat. Loratadine is also used to treat itching and redness caused by hives. However, loratadine does not prevent hives or other allergic skin reactions. Loratadine belongs to a class of medications called antihistamines. It blocks the action of histamine, a substance in the body that causes allergic symptoms. Like other antihistamines of 2. Loratadine is selective for peripheral H1 receptors.9 Loratadine does not effectively penetrate the central nervous system and has a low affinity for CNS H1 receptors.9 These properties result in an absence of CNS depressant effects such as drowsiness, sedation, and impaired psychomotor function.9 Loratadine is an allergy treatment drug marketed for its non-sedative properties.
It is marketed by Schering-Plough depending on the market under different trade names such as Claritin, Claritine, Clarityn or Clarityne; by Lek as Lomilan; von Ranbaxy as Roletra; and by Wyeth as Alavert. It is also available as a generic drug. In a version marketed as Claritin-D or Clarinase, loratadine is combined with pseudoephedrine, a decongestant; This makes it somewhat useful for colds as well as allergies, but adds a possible side effect of insomnia, nervousness, and anxiety. The volume of distribution of loratadine is 120 L/kg.18 Over a 10-day period, 40% of loratadine is excreted in urine and 42% in faeces.17 Loratadine is excreted in breast milk, so the use of loratadine in breastfeeding women is not recommended.