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Loratadine



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
Chemical data
Formula C22H23ClN2O2 
Mol. mass 382.88 g/mol
Pharmacokinetic data
Bioavailability N/A due to extensive first-pass metabolism
Metabolism hepatic
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)

Routes oral

Loratadine is a drug used to treat allergies, and marketed for its nonsedating properties. It is marketed by Schering-Plough under several trade names such as Claritin, Claritine, Clarityn or Clarityne depending on the market; by Lek as Lomilan ; by Sandoz as Symphoral; by Ranbaxy as Roletra; and by Wyeth as Alavert. 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 a potential side-effect of insomnia, nervousness and anxiety.

Additional recommended knowledge

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 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.[1] 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.[2] 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]

In the U.S. and UK, loratadine is the only drug of its class available over the counter. 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), whereas packets of up to and including 7 tablets are available "off the shelf" (GSL). (Desloratadine is an over the counter drug in Canada, but is a prescription drug in the U.S.)

Further information: desloratadine

Drug profile

 

Forms

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.

Dose

Treatment by mouth (oral)

  • Adult and CHILD over 6 years: 10 mg daily
  • CHILD 2-5 years: 5 mg daily

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 and does not normally cause drowsiness because it does not readily enter the central nervous system (see Side-effects section below).

Pharmacokinetics

Loratadine is given orally, is well absorbed from the gastrointestinal tract, and has rapid first-pass hepatic metabolism. 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 impairment than the older antihistamines because it penetrates the blood brain barrier only to a slight extent.

Although drowsiness is rare, nevertheless patients should 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, tremor, convulsions, palpitation, arrhythmias, hypersensitivity reactions (including bronchospasm, angioedema, and anaphylaxis, rashes, and photosensitivity reactions), blood disorders, liver 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. 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"[6]) and category B in pregnancy[7].

References

  1. ^ [1]
  2. ^ [2]
  3. ^ http://query.nytimes.com/gst/fullpage.html?res=9807E3DA1E3CF932A35757C0A9679C8B63&sec=&spon=&partner=permalink&exprod=permalink
  4. ^ http://www.therubins.com/legal/patext.htm
  5. ^ See S (2003). "Desloratadine for allergic rhinitis.". Am Fam Physician 68 (10): 2015-6. PMID 14655812.
  6. ^ (2001) "Transfer of drugs and other chemicals into human milk.". Pediatrics 108 (3): 776-89.
  7. ^ [3]

See also

 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Loratadine". A list of authors is available in Wikipedia.
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