Azelastine

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Structural formula
Structural formula of azelastine
( R ) shape (left) and ( S ) shape (right)
General
Non-proprietary name Azelastine
other names
  • ( RS ) -4- (4-chlorobenzyl) -2- (1-methylazepan-4-yl) -2 H -phthalazin-1-one ( IUPAC )
  • 4 - [(4-chlorophenyl) methyl] -2- (hexahydro-1-methyl-1 H -azepin-4-yl) - (±) -1- (2 H ) -phthalazinone
Molecular formula
  • C 22 H 24 ClN 3 O (azelastine)
  • C 22 H 24 ClN 3 O HCl (azelastine hydrochloride)
Brief description

Oil, soluble in dichloromethane (azelastine)

External identifiers / databases
CAS number
EC number 611-699-2
ECHA InfoCard 100.133.278
PubChem 2267
DrugBank DB00972
Wikidata Q419820
Drug information
ATC code
Drug class

H 1 antihistamines

Mechanism of action

Antagonist at H 1 receptors

properties
Molar mass
Physical state

firmly

Melting point

225–229 ° C (azelastine hydrochloride)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 302
P: no P-phrases
Toxicological data

42.8 mg kg −1 ( LD 50 ,  mouse ,  ip )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Azelastine is a medicinal substance . It is a selective antihistamine of the second generation H1 blocker type . It is used for mild, moderate and severe seasonal and mild year-round allergic rhinitis (e.g. hay fever).

Azelastine is available as a nasal spray (0.1 percent and in the USA also as a 0.15 percent solution) and as eye drops (0.05 percent solution). In some countries, the nasal spray and eye drops are also available over the counter from pharmacies.

Azelastine is chiral . Azelastine is mostly used as a racemic [1: 1 mixture of the ( R ) form and the ( S ) form] hydrochloride . The hydrochloride is a colorless, almost odorless substance with a bitter taste.

Pharmacokinetics and metabolism

The systemic bioavailability of azelastine when administered into the nose is approximately 40%. Maximum concentrations in blood plasma are observed within 2 to 3 hours. The elimination half-life is 22 h, the constant distribution concentration is 14.5 l / kg and the rate of removal from blood plasma (plasma clearance) is 0.5 l / h / kg (based on data on intravenous and oral administration). Azelastine is oxidatively metabolized by the cytochrome P450 family to desmethylazelastine as the active metabolite and to two inactive carboxylic acid metabolites. About 75% of an oral dose is excreted in the faeces . The pharmacokinetic properties of orally administered azelastine are unaffected by age and gender and do not affect liver function.

effect

Azelastine works in three ways:

  1. anti histaminic
  2. mast cell stabilizing and
  3. anti-inflammatory

Azelastine works quickly: 15 minutes after using the nasal spray and 3 minutes after instilling the eye drops. The effect lasts up to 12 hours.

application areas

As a nasal spray, azelastine is used in adults and children from 6 years of age for the local treatment of symptoms of seasonal allergic rhinitis ( hay fever ) and perennial allergic rhinitis (year-round allergic rhinitis), which include a runny nose (rhinorrhea), frequent sneezing and itchy nose. In some countries, azelastine is also used to treat non- allergic rhinitis (vasomotor rhinitis) in adults and children aged 12 and over. Azelastine eye drops are used for the local treatment of seasonal and year-round allergic conjunctivitis ( conjunctivitis ).

In contrast to cromoglicic acid , which only has a preventive anti-allergic effect and is hardly absorbed by the body, azelastine can also be used acutely and sometimes has a systemic effect.

Security and tolerance

Azelastine nasal spray is safe to use and well tolerated by adults and children aged 6 and over who suffer from allergic rhinitis. The most commonly reported adverse effects are bitter taste, headache, burning nose and somnolence (tiredness and drowsiness). The prescribing recommendations in the USA warn against the simultaneous consumption of alcohol and / or other drugs that have a depressant effect on the central nervous system. A similarly low degree of somnolence as in the placebo group (approx. 2%) was observed in, among others, while higher values ​​were given for earlier studies. The problem with the bitter taste is alleviated in some preparations (Vividrin) by adding sweeteners .

Trade names

Azelastine is approved as a nasal spray in more than 60 countries and is marketed as a monopreparation under various brand names: Allergodil (D), Astelin (USA), Astepro (USA), Rhinolast (GB), Vividrin Akut (D), Afluon (ES). As a combination preparation with fluticasone : Dymista (D, USA, LT).

The eye drops are sold in more than 30 countries: Allergodil (D, A), Optilast (Great Britain), Optivar (USA), Afluon (ES), Vividrin Akut  (DE).

Web links

Individual evidence

  1. ^ A b c The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; P. 153, ISBN 978-0-911910-00-1 .
  2. ↑ Entry on azelastine. In: Römpp Online . Georg Thieme Verlag, accessed on November 10, 2014.
  3. ↑ a b Datasheet Azelastine hydrochloride from Sigma-Aldrich , accessed on March 21, 2011 ( PDF ).
  4. ↑ Entry on azelastine in the ChemIDplus database of the United States National Library of Medicine (NLM)
  5. ↑ a b F Horak, UP. Zieglmayer: Azelastine nasal spray for the treatment of allergic and non-allergic rhinitis. In: Expert Rev Clin Immunol , 2009, 5, pp. 659-669.
  6. ↑ Horak F et al .: Azelastine nasal spray and desloratadine tablets in pollen-induced seasonal allergic rhinitis: a pharmacodynamic study of onset of action and efficacy. In: Curr Med Res Opin , 2006, 22, pp. 151-157.
  7. ↑ Friedlaender MH et al .: Evaluation of the onset and duration of effect of azelastine eye drops (0.05%) versus placebo in patients with allergic conjunctivitis using an allergen challenge model. In: Opthalmology , 2000, 107, pp. 2152-2157.
  8. ↑ Greiff F et al .: Topical azelastine has a 12-hour duration of action as assessed by histamine challenge-induced exudation of alpha 2-macroglobulin into human nasal airways. In: Clin Exp Allergy , 1997, 27, pp. 438-444.
  9. ↑ a b Rhinolast® nasal spray Summary of Product Characteristics , Astelin® FDA prescribing information.
  10. ↑ Optilast® eye drops Summary of Product Characteristics , Optivar® eye drops FDA prescribing information .
  11. ↑ onmeda.de Chromoglicic acid description, accessed on June 6, 2018.
  12. ^ Ratner PH et al .: A double-blind, controlled trial to assess the safety and efficacy of azelastine nasal spray in seasonal allergic rhinitis. In: J Allergy Clin Immunol , 1994, 94, pp. 818-825.
  13. ↑ LaForce C et al .: Safety and efficacy of azelastine nasal spray (astelin NS) for seasonal allergic rhinitis. In: Ann Allergy Asthma Immunol , 1996, 76, pp. 181-188.
  14. ↑ Berger W et al .: Impact of azelastine nasal spray on symptoms and quality of life compared with cetirizine oral tablets in patients with seasonal allergic rhinitis. In: Ann Allergy Asthma Immunol , 2006, 97, pp. 375-381.
  15. ↑ Friedrich Horak: Effectiveness of twice daily azelastine nasal spray in patients with seasonal allergic rhinitis . In: Therapeutics and Clinical Risk Management Vol. 5 (2008) Issue 4 (October), pp. 1009-1022, PMC 2621402 (free full text).
  16. ↑ Package insert with ingredients of the drug Vividrin. (PDF)  ( Page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.@1@ 2Template: Dead Link / www.apobike.de