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Loratadine
Systematic (IUPAC) name
Ethyl 4-(8-chloro-5,6-dihydro-11H-
benzo[5,6]cyclohepta[1,2-b]pyridin-
11-ylidine)-1-piperidinecarboxylate
Identifiers
CAS number 79794-75-5
ATC code R06AX13
PubChem 3957
DrugBank APRD00384
ChemSpider 3820
Chemical data
Formula C22H23ClN2O2 
Mol. mass 382.88 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability N/A due to extensive first-pass metabolism
Metabolism Hepatic (CYP2D6- and 3A4-mediated)
Half life 8 hours (metabolites 12–24 hours)
Excretion 40% as conjugated metabolites into urine
Similar amount into the feces
Therapeutic considerations
Pregnancy cat. B1(AU) B(US)
Legal status GSL (UK) OTC (US) OTC(Canada)
Routes oral
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Loratadine is an antihistamine drug used to treat allergies, and marketed for its non-sedating properties. It is marketed by Schering-Plough and Shionogi in Japan under several trade names such as Claritin, Claritin-D, Claritine, Clarityn, Clarityne or Fristamin depending on the market; by Cadila as Lorfast; by Lek as Lomilan or Flonidan; by Sandoz as Symphoral; by Ranbaxy as Roletra; by Pliva as Rinolan; by Teva as AllergyX; by Wyeth as Alavert; and by Pharma International as Tidilor[1]. It is also available as a generic. 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 potential side-effects of insomnia, nervousness, and anxiety.

It is considered a second generation agent.[2]

Contents

Regulation and clinical trials

Schering-Plough developed Loratadine as part of a quest for a 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, Seldane (terfenadine), and therefore put Loratadine on a lower priority as a "me too" drug.[3] Trials also raised questions about whether there was any dose at which Loratadine was simultaneously nonsedating and highly effective. Reviewing a randomized, double-blind trial, Dr. Sherwin D. Straus of the FDA argued at one point that "10 milligrams is not very different than placebo clinically," and that the reason for making the dose so low was that at higher, more effective doses, it became sedating.[3] Schering counters that "The innovation of Claritin and the basis for its success are not only that it works, but also that it was the first antihistamine to provide effective relief of allergy symptoms without sedation and with an impeccable safety profile."[3]

Loratadine was eventually approved by the FDA, and in 2001, its last year on patent, it accounted for 28% of Schering's total sales. Although an FDA advisory panel ruled that Loratadine was safe enough to be sold over the counter, Schering opposed 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 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 Clarinex (Desloratadine), which is a metabolized form 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."[5] However, as of 2009, 10 mg loratadine tablets can be purchased relatively inexpensively, as generic manufacturers offer 120 day supplies for less than $25[6].

In the U.S. and UK, loratadine is the only drug of its class available over the counter (though it is no longer the only second generation antihistamine available in this manner). 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. However, packets of up to and including 32 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 as Sensibit without the Pseudophedrine additive

Drug profile

Forms

Loratadine 10 mg (Rx)

Loratadine 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.

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.

Mechanism of action

Loratadine is a tricyclic antihistamine, which selectively antagonizes peripheral histamine H1-receptors. Histamine is responsible for many features of allergic reactions.

Loratadine has a long-lasting effect.

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.[7][8] Loratadine is almost totally bound to plasma proteins. Its metabolite, desloratadine (descarboethoxyloratadine), is also active, but binds to plasma proteins only moderately.

Loratadine's peak effect occurs in 1–2 hours, and its biological half-life is on average 8 hours with its metabolite's half-life being 28 hours. 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.

Side-effects

Non-sedating antihistamine

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.

Most common side-effects

Drowsiness, headache, psychomotor impairment, and antimuscarinic effects such as urinary retention, dry mouth, blurred vision, and gastrointestinal disturbances are the most common side effects.

Other rarer side-effects

Hypotension, extrapyramidal effects, dizziness, confusion, depression, sleep disturbances, lower back pain, tremor, convulsions, palpitation, arrhythmias, hypersensitivity reactions (including bronchospasm, angioedema, and anaphylaxis, rashes, and photosensitivity reactions), blood disorders, liver dysfunction, erectile dysfunction, and angle-closure glaucoma are less common side effects.

Cautions and contraindications

Loratadine should be used with caution in hepatic disease and dose reduction may be necessary in renal impairment. Caution may be required in epilepsy.aggression Children and the elderly are more susceptible to side-effects (see Side-effects section above). Loratadine is a category L-2 (classified by the American Academy of Pediatrics as a drug "Usually Compatible With Breast-feeding"[9]) and category B in pregnancy[10].

References

  1. ^ "Tidilor". Pharma International. http://www.pic-jo.com/pop_up/tidilor.asp. Retrieved 17 December 2008. 
  2. ^ Kay GG, Harris AG (July 1999). "Loratadine: a non-sedating 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. PMID 10444229. http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0954-7894&date=1999&volume=29&issue=&spage=147. 
  3. ^ a b c The Claritin Effect; Prescription for Profit - New York Times
  4. ^ Patents and Prescription Drugs
  5. ^ See S (2003). "Desloratadine for allergic rhinitis". Am Fam Physician 68 (10): 2015–6. PMID 14655812. http://www.aafp.org/afp/20031115/steps.html. 
  6. ^ http://www.drugstore.com/products/prod.asp?pid=150910&catid=12203
  7. ^ 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. pp. 805. ISBN 0-683-30737-1.  Retrieved on 1 December 2009 through Google Book Search.
  8. ^ 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. 
  9. ^ Committee on Drugs, (1 September 2001). "Transfer of drugs and other chemicals into human milk". Pediatrics 108 (3): 776–89. PMID 11533352. http://aappolicy.aappublications.org/cgi/content/full/pediatrics;108/3/776. 
  10. ^ STEPS - November 15, 2003 - American Family Physician

External links








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