Loratadine

Structural formula
General
Non-proprietary name	Loratadine
other names	4- (8-chloro-5,6-dihydro-11 H -benzo [5,6] cyclohepta [1,2-b] pyridin-11-ylidene) piperidine-1-carboxylic acid ethyl ester ( IUPAC ); Loratadinum ( Latin );
Molecular formula	C 22 H 23 ClN 2 O 2
Brief description	white to almost white, polymorphic , crystalline powder
External identifiers / databases
EC number	616-734-5
ECHA InfoCard	100.120.122
PubChem	3957
DrugBank	DB00455
Wikidata	Q424049
Drug information
ATC code	R06 AX13
Drug class	Systemic antihistamines
Mechanism of action	Antagonist at histamine H 1 receptors
properties
Molar mass	382.88 g · mol -1
Physical state	firmly
Melting point	134-136 ° C
solubility	practically insoluble in water (0.011 mg l −1 at 25 ° C); Easily soluble in acetone and methanol ;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances	no GHS pictograms
	no GHS pictograms
H and P phrases	H: no H-phrases
	P: no P-phrases
Toxicological data	> 5 g kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Loratadine is a drug from the group of antihistamines that is used to relieve the symptoms of allergies and atopic eczema (neurodermatitis). It was introduced in Germany in 1989 and has no longer required a prescription since 1994. In Austria it is available in doses of up to 10 mg per day for adolescents over 12 years of age and adults without a prescription. In Germany, finished medicinal products containing loratadine are available as tablets or effervescent tablets , while juice is also available in the USA and Great Britain. It has been on the WHO Essential Medicines List since 2013 .

Mechanism of action

Loratadine is a H ₁ - antihistamine of the second generation. It blocks the special binding sites for histamine on the histamine H ₁ receptors . Histamine thus no longer finds enough free binding sites to exert its effects (e.g. reddening of the skin, itching , drop in blood pressure and bronchospasm ). As a representative of the 2nd generation of H ₁ antihistamines, loratadine is largely free of side effects on the central nervous system , such as B. Sedation . The cause is the return of the substance through permeable glycoproteins at the blood-brain barrier . The esterification of the acid group also enables good absorption. Loratadine is rapidly broken down in the body to desloratadine , which, however, has a three to four times higher affinity for the H ₁ receptor . Loratadine can therefore be formally regarded as a prodrug of desloratadine. Both substances also act as FIASMA (functional inhibitor of acid sphingomyelinase ). The plasma half-life is around eight hours, that of the metabolites around 12 to 24 hours.

Side effects

In addition to non-specific side effects such as headache , tiredness and gastrointestinal disorders , dry mouth and, in individual cases, hair loss , liver dysfunction and allergic reactions occur. Cardiac arrhythmias have also been observed occasionally . In rare cases, tinnitus can also occur.

Interactions

Loratadine is broken down by the enzyme CYP3A4 . If you take drugs that inhibit the CYP3A4 enzyme or have similar side effects, for example ketoconazole, erythromycin, macrolide antibiotics , HIV protease inhibitors, propafenone and grapefruit juice , the side effects mentioned, especially cardiac arrhythmias, can be increased.

Patent dispute

After the patent period for the manufacture of loratadine had expired, a major legal battle arose: Schering-Plow sued Geneva Pharmaceuticals for the manufacture of loratadine generics based on the argument that Schering-Plow had a valid patent on the artificial manufacture of the loratadine metabolite descarboethoxyloratadine ( Desloratadine ). Since the intake of loratadine also leads to the formation of descarboethoxyloratadine in humans, the manufacture of loratadine infringes this patent. The US Federal Court of Appeals ruled in favor of Geneva, raising major concerns among pharmaceutical companies about the protection options for their products. In fact, the therapeutic advantage of desloratadine compared to loratadine is correspondingly marginal, so that when the patent protection for loratadine ceased to exist and desloratadine was launched on the market, criticism was raised of evergreening of the drug.

Trade names

Monopreparations

Allernon (A), Claritine (CH), Clarityn (A) and various generics (D, A, CH)

Combination preparations

with pseudoephedrine : clarinase (A)

Individual evidence

↑ ^a ^b European Pharmacopoeia Commission (Ed.): EUROPEAN PHARMACOPOE 6TH EDITION . tape 6.0-6.2 , 2008.
↑ ^a ^b Entry on loratadine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
↑ ^a ^b Loratadine data sheet from Sigma-Aldrich , accessed on May 29, 2011 ( PDF ).

↑ Entire legal regulation for prescription regulation . Federal legal information system. October 23, 2014. Retrieved October 23, 2014.

↑ https://www.ncbi.nlm.nih.gov/pubmed/?term=P-GLYCOPROTEIN+LIMITS+THE+BRAIN+PENETRATION+OF+NONSEDATING+BUT+NOT+SEDATING+H1-ANTAGONISTS

↑ Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P: Identification of novel functional inhibitors of acid sphingomyelinase . In: PLoS ONE . 6, No. 8, 2011, p. E23852. doi : 10.1371 / journal.pone.0023852 .

↑ ehealthme.com: Could Loratadine cause Tinnitus?

↑ Annette Immel-Sehr: When the defense runs amok . In: Pharmaceutical newspaper . No. 16 , 2007 ( online ).

↑ Cornelia Rufke, University of Leipzig: Page no longer available , search in web archives: case study of the interaction between azole-antimycotics and terfenadine (PDF; 243 kB)

↑ QT prolongations after taking the antihistamine loratadine. BfArM , August 1, 2002, accessed on September 12, 2017 .

↑ A. De La Rosa: A Hard Pill to Swallow - Does Schering v. Geneva Endanger Research and Development within the Pharmaceutical Industry? June 6, 2006, bepress Legal Series . Working Paper 1414.

^ Ulrich Schwabe, Dieter Paffrath: Drug Ordinance Report 2004: Current data, costs, trends and comments. Springer, 2004, ISBN 3-540-21359-7 .

↑ Antje-Christina Raasch: Strategy and success factors when the patent expiry of the antihistamine Lisino from essex pharma. In: The patent expiry of pharmaceuticals as a challenge in the management of the product life cycle. Springer, 2006, ISBN 978-3-8350-0632-4 , pp. 211-225.

[Ph._Eur._6-1] European Pharmacopoeia Commission (Ed.): EUROPEAN PHARMACOPOE 6TH EDITION . tape 6.0-6.2 , 2008.

[ChemIDplus-2] Entry on loratadine in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[Sigma-3] Loratadine data sheet from Sigma-Aldrich , accessed on May 29, 2011 ( PDF ).

[4] Entire legal regulation for prescription regulation . Federal legal information system. October 23, 2014. Retrieved October 23, 2014.

[5] ttps://www.ncbi.nlm.nih.gov/pubmed/?term=P-GLYCOPROTEIN+LIMITS+THE+BRAIN+PENETRATION+OF+NONSEDATING+BUT+NOT+SEDATING+H1-ANTAGONISTS

[pmid18504571-6] Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P: Identification of novel functional inhibitors of acid sphingomyelinase . In: PLoS ONE . 6, No. 8, 2011, p. E23852. doi : 10.1371 / journal.pone.0023852 .

[7] thme.com: Could Loratadine cause Tinnitus?

[8] Annette Immel-Sehr: When the defense runs amok . In: Pharmaceutical newspaper . No. 16 , 2007 ( online ).

[9] Cornelia Rufke, University of Leipzig: Page no longer available , search in web archives: case study of the interaction between azole-antimycotics and terfenadine (PDF; 243 kB)@1@ 2

[10] QT prolongations after taking the antihistamine loratadine. BfArM , August 1, 2002, accessed on September 12, 2017 .

[11] A. De La Rosa: A Hard Pill to Swallow - Does Schering v. Geneva Endanger Research and Development within the Pharmaceutical Industry? June 6, 2006, bepress Legal Series . Working Paper 1414.

[12] Ulrich Schwabe, Dieter Paffrath: Drug Ordinance Report 2004: Current data, costs, trends and comments. Springer, 2004, ISBN 3-540-21359-7 .

[13] Antje-Christina Raasch: Strategy and success factors when the patent expiry of the antihistamine Lisino from essex pharma. In: The patent expiry of pharmaceuticals as a challenge in the management of the product life cycle. Springer, 2006, ISBN 978-3-8350-0632-4 , pp. 211-225.