Loratadine

Loratadine
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
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
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
ECHA InfoCard 100.120.122
Chemical and physical data
Formula C22H23ClN2O2
Molar mass 382.88 g/mol
3D model (JSmol)
 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

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

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

The drug is available in many different forms, including 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

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

As a "non-sedating" 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 problems.[8][11]

Interactions

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.

Pharmacology

Mechanism of action

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

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.[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

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.

Society and culture

Over the counter regulation

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.[22] In the US, Schering-Plough made loratadine available OTC in 2002.[22] As of 2015 loratadine was available in many countries OTC.[23]

Brands

As of 2017 loratadine was available under many brand names and dosage forms worldwide, including several combination drug formulations with pseudoephedrine, paracetamol, betamethasone, ambroxol, salbutamol, phenylephrine, and dexamethasone.[24]

Listing of brands

As of 2017 brands included: Actalor, Actidin, Aerotina, Alaspan, Alavert, Albatrina, Alerdina, Alerfast, Alergan, Alergiano, Alergiatadina, Alergin Ariston, Alergipan, Alergit, Alergitrat L, Aleric Lora, Alermuc, Alernitis, Alerpriv, Alertadin, Alertine, Aleze, Algac, Algecare, Algistop, Alledryl, Aller-Tab, Allerfre, Allerget, Allergex Non Drowsy, Allergyx, Allerhis, Allernon, Allerta, Allertyn, Allohex, Allor, Allorat, Alloris, Alor, Analor, Anhissen, Anti-Sneeze, Antial, Antil, Antimin, Ao Hui Feng, Ao Mi Xin, Ao Shu, Ardin, Atinac, Avotyne, Axcel Loratadine, Bai Wei Le, Bang Nuo, Bedix, Belodin, Benadryl, Besumin, Bi Sai Ning, Bi Yan Tong, Biliranin, Biloina, Biolorat, Bollinol, Boots Hayfever Relief, Boots Hooikoortstabletten, Boots Once-a-Day Allergy Relief, Carin, Carinose, Chang Ke, Civeran, Clara, Claratyne, Clarid, Clarihis, Clarihist, Clarilerg, Clarinese, Claritin, Claritine, Clarityne, Clarityne SP, Clarotadine, Clatatin, Clatine, Clear-Atadine, Clear-Atadine Children's, Clistin, Contral, Cronitin, Da Sheng Rui Li, Dao Min Qi, Dayhist, Debimin, Desa, Devedryl, Dexitis, Dimegan, Dimens, Dimetapp Children's ND Non-Drowsy Allergy, Doliallérgie Loratadine, Efectine, Eladin, Elo, Emilora, Encilor, Eradex, Erolin, Ezede, Fei Ge Man, Finska, Flonidan, Flonidan Control, Florgan, Folerin, Frenaler, Fristamin, Fu Lai Xi, Fucole Minlife, Genadine, Glodin, Gradine, Halodin, Helporigin, Hisplex, Histaclar, Histafax, Histalor, Horestyl, Hua Chang, Hysticlar, Igir, Immunix, Imunex, Inclarin, Inversyn, Jin Su Rui, Jing Wei, Ke Mi, Klarihist, Klinset, Klodin, Kui Yin, Lallergy, Larotin, Latoren, Laura, LD, Lei Ning, Lesidas, Liberec, Lisaler, Logadine, Logista, Lohist, Lolergi, Lolergy, Lomidine, Lomilan, Loptame, Lora, Lora-Lich, Lora-Mepha Allergie, Loracare, Loracil, Loraclear, Loradad, Loraderm, Loradin, Loradine, Lorado Pollen, Loradon, Lorafix, Lorahexal, Lorahist, Lorakids, Loralab-D, Loralerg, Loralivio, Loramax, Loramin, Loramine, Loran, Lorange, Loranil, Lorano, Loranox, Lorantis, LoraPaed, Lorastad, Lorastamin, Lorastine, Lorastyne, Lorat, Loratab, Loratadim, Loratadin, Loratadina, Loratadine, Loratadinum, Loratadyna, Loratan, Loratin, Loraton, Loratrim, Loratyne, Lorchimin, Lordamin, Lordinex, Loremex, Loremix, Lorfast, Lorid, Loridin, Lorihis, Lorimox, Lorin, Lorine, Loristal, Lorita, Loritex, Loritin, Lorly, Lormeg, Lorsedin, Lortadine, Losta, Lostop, Lotadin, Lotadine, Lotarin, Lotin, Megalorat, Mildin, Min Li Ke, Minlife, Mintapp, Mosedin, Mudantil L, Nasaler, Neoday, Niltro, Non-Drowsy Allergy Relief, Nosedin, Noseling, Novacloxab, NT-Alergi, Nufalora, Nularef, Numark Allergy, Omega, Oradin, Oradine, Oramine, Orin, Orinil, Pollentyme, Pressing, Pretin, Primorix, Profadine, Pulmosan Aller, Pylor, Rahistin, Ralinet, Ramitin, Refenax, Restamine, Rhinigine, Rihest, Rinalor, Rinconad, Rinityn, Rinolan, Riprazo, Rityne, Roletra, Rotadin, Rui Fu, Run Lai, Rupton, Sensibit, She Tai, Shi Nuo Min, Shi Tai Shu, Shu Rui, Shun Ta Xin, Silora, Sinaler, Sohotin, Soneryl, Sunadine, Symphoral, Tabcin, Tai Ming Ke, Ticevis, Tidilor, Tinnic, Tirlor, Toral, Triaminic, Tricel, Tuulix, Urtilar, Utel, Vagran, Winatin, Xanidine, Xepalodin, Xian Ning, Xin Da Yue, Xing Yuan Jia, XSM, Xue Fei, Yi Fei, Yi Shu Chang, Yibang, Zhengshu, Zhi Min, Zifar, Zoratadine, and Zylohist.[24]

As of 2017, in a combination drug with pseudoephedrine, it was available under the brands: Airet, Alavert D-12, Aldisa SR, Alerfast D, Alergical LP, Alergin Plus Ariston, Alerpriv D, Alledryl-D, Allerpid, Aseptobron Descongestivo, Bai Wei Qing, Benadryl 24 D, Ciprocort D, Claridex, Claridon, Clarinase, Clarinase Repetab, Claritine Active, Claritin Allergy + Sinus, Clarityne, Clarityne D, Clarityne-D, Clear-Atadine, Coderin, Cronase, De-Cold, Decidex Plus, Decongess I, Defonase, Demazin NS, Dimegan-D, Effectine D, Ephedrol, Fedyclar, Finska-LP, Frenaler-D, Hui Fei Shun, Ke Shuai, Claritin-D, Larotin D, Lertamine, Lohist-Extra, Lora Plus, Loralerg D, Loranil-D, Loratin D, Loratin Plus, Lordinex D, Loremix D, Lorexin-D, Lorfast-D, Loridin-D, Lorinase, Minlife -P, Mosedin plus sr, Narine Repetabs, Nasaler Plus, Nularef-D, Oradin Plus, Pretin-D, Primorix-D, Rhinos SR, QiKe, Rinomex, Sinaler D, Sudamin, Sudolor, Tricel-D, Zhuang Qi, Zoman-D, and Zoratadine-P.[24]

As of 2017, in a combination drug with paracetamol it was available as Sensibit D and in combination with paracetamol and pseudoephedrine it was available as: Atshi, Clariflu, and Trimed Flu.[24]

As of 2017, in a combination drug with betamethasone it was available as Celestamincort, Celestamine NF, Celestamine NS, Celestamine* L, Ciprocort L, Claricort, Clarityne cort, Corticas L, Cortistamin-L, Histafax Compuesto, Histamino Corteroid L, Labsalerg-B, Lisaler Beta, and Sinaler B, and in combination with betamethadol with available as Nularef Cort.[24]

As of 2017, in a combination drug with ambroxol it was available as Aliviatos, Ambroclar, Antitusivo L Labsa, Bronar, Broncovital, Broquixol, Clarixol, Ideobron, Lorabrox, Lorfast-AM, Sensibit XP, and Toraxan, and in a combination drug with ambroxol and salbutamol as Sibilex.[24]

As of 2017, in a combination drug with phenylephrine it was available as Bramin-Flu, Clarityne D, Clarityne Plus, Clarityne-D, Histafax D, Brafelix, Loramine R, Loraped, Maxiclear Cold & Nasal, Maxiclear Hayfever & Sinus Relief, and Rinavent, and in combination with phenylephrine and paracetamol it was available as Sensibit D NF.[24]

As of 2017, in a combination drug with dexamethasone it was available as Alerfast Forte and Frenaler Forte.[24]

See also

References

  1. 1 2 3 4 5 "Loratadine". The American Society of Health-System Pharmacists. Retrieved 8 December 2016.
  2. 1 2 "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. 1 2 3 4 5 6 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. PMID 21914581. doi:10.1684/ejd.2011.1539 (inactive 2017-01-16).
  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. 1 2 3 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. 1 2 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. PMID 19702548. doi:10.2174/187231209789352067.
  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. PMID 12169042. doi:10.2165/00003088-200241001-00003.
  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. PMID 10444229. doi:10.1046/j.1365-2222.1999.0290s3147.x.
  20. 1 2 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. 1 2 Cohen JP et al. Switching prescription drugs to over the counter. BMJ. 2005 Jan 1;330(7481):39-41. PMID 15626806 PMC 539854
  23. ↑ Association of the European Self-Medication Industry Database. Loratadine OTC regulation Page accessed April 11, 2015
  24. 1 2 3 4 5 6 7 8 "Loratadine International Brands". Drugs.com. Retrieved 19 February 2017.
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