Loratadine

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Loratadine
Loratadine.svg
Loratadine - 3d, portrait orientation.png
Clinical data
Trade names Claritin, Claratyne, others
AHFS/Drugs.com Monograph
MedlinePlus a697038
Pregnancy
category
  • AU: B1
  • US: B (No risk in non-human studies)
Routes of
administration
by mouth
ATC code R06AX13 (WHO)
Legal status
Legal status
Pharmacokinetic data
Bioavailability almost 100%
Protein binding 97–99%
Metabolism liver (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
Identifiers
CAS Number 79794-75-5 YesY
PubChem (CID) 3957
IUPHAR/BPS 7216
DrugBank DB00455 N
ChemSpider 3820 YesY
UNII 7AJO3BO7QN YesY
KEGG D00364 YesY
ChEMBL CHEMBL998 YesY
ECHA InfoCard 100.120.122
Chemical and physical data
Formula C22H23ClN2O2
Molar mass 382.88 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

Loratadine, sold under the brand name Claritin among others, is a medication used to treat allergies. This includes allergic rhinitis (hay fever) and hives. It is also available in combination with pseudoephedrine, a decongestant, known as loratadine/pseudoephedrine. It is taken by mouth.[1]

Common side effects include sleepiness, dry mouth, and headache.[1] Serious side effects are rare and include allergic reactions, seizures, and liver problems.[2] Use during pregnancy appears to be safe but has not been well studied.[3] It is not recommended in children less than two years old.[2] It is in the second-generation antihistamine family of medication.[1]

Loratadine was discovered in 1981 and came to market in 1993.[4] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[5] Loratadine is available as a generic medication.[1] The wholesale cost in the developing world is about 0.01 to 0.08 USD per dose.[6] In the United States it is available over the counter.[1]

Medical uses[edit]

Loratadine is indicated for the symptomatic relief of allergy such as hay fever (allergic rhinitis), urticaria (hives), chronic idiopathic urticaria,[7] and other skin allergies.[8] For allergic rhinitis (hay fever), loratadine is effective for both nasal and eye symptoms: sneezing, runny nose, itchy or burning eyes.

Similarly to cetirizine, loratadine attenuates the itching associated with Kimura's disease.[9] It is marketed for its less sedating properties.

Forms[edit]

An example of a loratadine 10-mg tablet (Rx)

The drug is available in many different forms, such as: tablets, oral suspension, and syrup,[8] and in combination with pseudoephedrine.[10] 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.

Contraindications[edit]

Patients with severe hepatic (liver) disorders may need to start with a lower dose. No dose adaptation is necessary for elderly or renally (kidney) impaired patients.[8][11]

Loratadine is usually compatible with breast-feeding (classified category L-2 by the American Academy of Pediatrics).[12] 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 but no adequate and well-controlled studies in pregnant women have been conducted.[13]

Adverse effects[edit]

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.[14]

Other possible side effects include headache and antimuscarinic effects such as urinary retention, dry mouth, blurred vision, and gastrointestinal disturbances.[8][11]

Interactions[edit]

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).[citation needed]

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[edit]

Loratadine is a tricyclic antihistamine, which acts as a selective inverse agonist of peripheral histamine H1-receptors.[11][15] The inverse agonist potency of 2nd generation histamine antagonists is desloratadine > cetirizine > loratadine > fexofenadine.[15]

Pharmacokinetics[edit]

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.[16][17] 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%.[8]

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.[18] 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.[8]

In structure, it is closely related to tricyclic antidepressants, such as imipramine, and is distantly related to the atypical antipsychotic quetiapine.[19]

History[edit]

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.[20]

Loratadine was approved by the FDA in 1993.[20] The drug continued to be available only by prescription in the U.S. until it went off patent in 2002.[21] It was then subsequently approved for over-the-counter sales. Once it became an unpatented over-the-counter drug, the price dropped significantly.

Schering also developed desloratadine (Clarinex), which is an active metabolite of loratadine.

Availability[edit]

Loratadine is available under many brand names and dosage forms worldwide.[22]

Loratadine is marketed by Bayer (formerly Schering-Plough, later Merck & Co.) under several trade names (e.g., Claritin, and Claratyne) and also by Shionogi in Japan. It is manufactured by Pfizer[23] among others.

In 1998, in 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.[24] In the US, Schering-Plough made loratadine available OTC in 2002.[24] Loratadine is currently available in many countries OTC.[25] Brand names include Claritin, Claratyne, Lorel (in Pakistan),[26][27] others.

See also[edit]

References[edit]

  1. ^ a b c d e "Loratadine". The American Society of Health-System Pharmacists. Retrieved 8 December 2016. 
  2. ^ a b "Clarityn Allergy 10mg Tablets (P) - Summary of Product Characteristics (SPC) - (eMC)". www.medicines.org.uk. 7 October 2015. Retrieved 13 December 2016. 
  3. ^ "Loratadine Use During Pregnancy | Drugs.com". www.drugs.com. Retrieved 13 December 2016. 
  4. ^ Corey, E.J. (2012). "Loratadine". Molecules and Medicine. John Wiley & Sons. ISBN 9781118361733. 
  5. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016. 
  6. ^ "Loratadine". International Drug Price Indicator Guide. Retrieved 8 December 2016. 
  7. ^ Pons-Guiraud, A; Nekam, K; Lahovsky, J; Costa, A; Piacentini, A (2006). "Emedastine difumarate versus loratadine in chronic idiopathic urticaria: A randomized, double-blind, controlled European multicentre clinical trial". European journal of dermatology : EJD. 16 (6): 649–54. PMID 17229605. 
  8. ^ a b c d e f Jasek, W, ed. (2007). Austria-Codex (in German). 1 (2007/2008 ed.). Vienna: Österreichischer Apothekerverlag. pp. 1768–71. ISBN 978-3-85200-181-4. 
  9. ^ Ueda, T; Arai, S; Amoh, Y; Katsuoka, K (2011). "Kimura's disease treated with suplatast tosilate and loratadine". European journal of dermatology : EJD. 21 (6): 1020–1. doi:10.1684/ejd.2011.1539 (inactive 2017-01-16). PMID 21914581. 
  10. ^ Jasek, W, ed. (2007). Austria-Codex (in German). 1 (2007/2008 ed.). Vienna: Österreichischer Apothekerverlag. pp. 1731–34. ISBN 978-3-85200-181-4. 
  11. ^ a b c Mutschler, Ernst; Gerd Geisslinger; Heyo K. Kroemer; Monika Schäfer-Korting (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 456–461. ISBN 3-8047-1763-2. 
  12. ^ Committee on Drugs (1 September 2001). "Transfer of drugs and other chemicals into human milk". Pediatrics. 108 (3): 776–89. PMID 11533352. 
  13. ^ See, Sharon (November 15, 2003). "Desloratadine for Allergic Rhinitis". American Family Physician. 
  14. ^ Kristi Monson, PharmD. "Claritin and Alcohol". emedtv.com. 
  15. ^ a b Devillier P, Roche N, Faisy C. Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review. Clin Pharmacokinet. 2008;47(4):217-30. PMID 18336052
  16. ^ 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. p. 805. ISBN 0-683-30737-1. 
  17. ^ 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. 
  18. ^ Affrime, M; Gupta, S; Banfield, C; Cohen, A (2002). "A pharmacokinetic profile of desloratadine in healthy adults, including elderly". Clinical pharmacokinetics. 41 Suppl 1: 13–9. doi:10.2165/00003088-200241001-00003. PMID 12169042. 
  19. ^ Kay GG, Harris AG (July 1999). "Loratadine: a nonsedating antihistamine. Review of its effects on cognition, psychomotor performance, mood and sedation". Clinical and Experimental Allergy. 29 Suppl 3: 147–50. doi:10.1046/j.1365-2222.1999.0290s3147.x. PMID 10444229. 
  20. ^ a b Hall, Stephen S. (2001-03-11). "The Claritin Effect; Prescription for Profit". The New York Times. Retrieved 2010-06-28. 
  21. ^ "Schering-Plough Loses Patent Lawsuit Over Claritin, Opening Door For Cheaper Generic Versions". PRNewswire. Leiner Health Products. 2003-08-05. Retrieved 2016-06-26. 
  22. ^ drugs.com Loratadine at drugs.com international listings Page accessed April 11, 2015]
  23. ^ "Pfizer Prescription Products". Pfizer Inc. Retrieved March 9, 2010. 
  24. ^ a b Cohen JP et al. Switching prescription drugs to over the counter. BMJ. 2005 Jan 1;330(7481):39-41. PMID 15626806 PMC 539854
  25. ^ Association of the European Self-Medication Industry Database. Loratadine OTC regulation Page accessed April 11, 2015
  26. ^ http://www.standpharm.com/index.php/component/content/category/11-demo-articles
  27. ^ https://sehat.com.pk/products/Lorel-Tab-10mg-1x10's.html

External links[edit]