Aclidinium bromide

Structural formula
General
Non-proprietary name	Aclidinium bromide
other names	(3 R ) -3 - [(Hydroxy) di (thiophen-2-yl) acetyloxy] -1- (3-phenoxypropyl) -1λ5-azabicyclo [2.2.2] octan-1-ylium bromide
Molecular formula	C 26 H 30 BrNO 4 S 2
External identifiers / databases
EC number	825-171-6
ECHA InfoCard	100.260.213
PubChem	11519741
ChemSpider	9694529
Wikidata	Q27888207
Drug information
ATC code	R03 BB05
properties
Molar mass	564.55 g · mol -1
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 331-361
	P: ?
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Aclidinium bromide is a drug in the group of anticholinergics and is used to widen the narrowed airways in adults with chronic obstructive pulmonary disease (COPD). It is used by inhalation using a powder inhaler .

Mechanism of action

Aclidinium bromide acts as an antagonist in particular on the muscarinic receptor M ₃ , to which it has a longer binding duration compared to the four other muscarinic receptors (M ₁ , M ₂ , M ₄ and M ₅ ). M ₃ receptors regulate the contraction of the smooth muscles of the airways. The M ₃ -receptor blockade with aclidinium bromide results in a long-lasting inhibition of the acetylcholine-mediated bronchial constriction .

Only a very small part, namely less than 5% of the inhaled dose, enters the systemic bloodstream unchanged. This low bioavailability is due to rapid and extensive systemic and presystemic hydrolysis of the active ingredient.

field of use

Aclidinium bromide has been approved as an inhalation powder in the EU since July 2012 under the names Bretaris Genuair and Eklira Genuair ( Almirall , SA) for symptomatic, long-term bronchodilator therapy in adults with chronic obstructive pulmonary disease (COPD).

Early benefit assessment

In Germany, since 2011, newly approved drugs with new active ingredients must be subjected to an " early benefit assessment " by the Federal Joint Committee (G-BA) in accordance with Section 35a SGB V if the pharmaceutical manufacturer wants to achieve a higher sales price than just the fixed amount . Only if there is an additional benefit can the pharmaceutical manufacturer negotiate a price with the umbrella association of statutory health insurance companies. The dossier evaluations, on the basis of which the G-BA makes its decisions, are created by the Institute for Quality and Efficiency in Health Care (IQWiG) .

The first G-BA decision of March 21, 2013 was repealed by a further benefit assessment procedure. In 2016, aclidimium bromide was compared with the long-acting beta-2 sympathomimetic formoterol for adults with COPD of a moderate severity ; The manufacturer did not provide any study data for those affected with further severity levels. According to the G-BA decision, an additional benefit has not been proven for patients with severity grade II, for patients with severity grade IV and under two exacerbations per year, as well as for more severe grades with at least two exacerbations per year. In contrast, there is an indication of a considerable added benefit for patients with severity III and less than two exacerbations per year.

In a further evaluation procedure, aclidinium bromide in combination with formoterol was compared with formoterol alone or, in the case of COPD exceeding moderate severity and at least two exacerbations per year, with formoterol and an inhaled corticosteroid. According to the G-BA decision, there is an indication of a minor added benefit for patients with COPD and who have had two exacerbations per year in severity grade II and an indication of considerable added benefit in severity grade III. An added benefit has not been proven for patients with less than two exacerbations per year and severity grade IV or for those with at least two exacerbations and severity grade III or IV.

Side effects and restrictions on use

The most common side effects, seen in up to 1 in 10 people, are headache, inflammation of the sinuses ( sinusitis ), rhinopharyngitis , cough and diarrhea. Very careful use is advisable in patients with previous specific diseases of the cardiovascular system (previous myocardial infarction , unstable angina pectoris , arrhythmia, hospitalization due to heart failure of stages NYHA III and IV), as well as in patients with symptomatic prostate enlargement , with obstruction of urine flow Bladder neck or narrow-angle glaucoma .

In in vitro studies, aclidinium bromide and its metabolites did not inhibit or stimulate CYP450 enzymes or esterases ; neither are they substrates or inhibitors of P-glycoprotein , so that application restrictions through such interactions are not to be expected.

Chemical-physical information

Aclidinium bromide has a chiral center, the pharmacologically active form is the ( R ) - enantiomer . Aclidinium bromide is a crystalline powder and very slightly soluble in water or ethanol .

preparations

Monopreparations: Eklira Genuair ( AstraZeneca ), Bretaris Genuair ( Berlin-Chemie )
Combination preparations made from aclidinium and formoterol: Duaklir (AstraZeneca), Brimica (Berlin-Chemie)

Web links

New drugs 2012: Aclidinium bromide, Eklira® Genuair® (Allmiral). In: Pharmaceutical newspaper online.

Information (public assessment report, information for healthcare professionals , package insert) on Bretaris Genuair. on the website of the European Medicines Agency .

Individual evidence

↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of Aclidinium bromide in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), which was accessed on November 16, 2019, is reproduced from a self-classification by the distributor .
↑ Benefit assessment procedure for the active ingredient aclidinium bromide - decision repealed. g-ba.de; accessed on March 23, 2020.
↑ A15-45 aclidinium bromide - benefit assessment according to § 35a SGB V. iqwig.de; accessed on March 23, 2020
↑ Benefit assessment procedure for the active ingredient aclidinium bromide (renewed benefit assessment § 14: COPD). iqwig.de; accessed on March 23, 2020.
↑ A15-06 Aclidinium / Formoterol - Benefit assessment according to Section 35a SGB V (dossier assessment). iqwig.de; accessed on March 23, 2020.
↑ Benefit assessment procedure for the active ingredient aclidinium bromide / formoterol (COPD). iqwig.de; accessed on March 23, 2020.

[1] Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of Aclidinium bromide in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), which was accessed on November 16, 2019, is reproduced from a self-classification by the distributor .

[2] Benefit assessment procedure for the active ingredient aclidinium bromide - decision repealed. g-ba.de; accessed on March 23, 2020.

[3] A15-45 aclidinium bromide - benefit assessment according to § 35a SGB V. iqwig.de; accessed on March 23, 2020

[4] Benefit assessment procedure for the active ingredient aclidinium bromide (renewed benefit assessment § 14: COPD). iqwig.de; accessed on March 23, 2020.

[5] A15-06 Aclidinium / Formoterol - Benefit assessment according to Section 35a SGB V (dossier assessment). iqwig.de; accessed on March 23, 2020.

[6] Benefit assessment procedure for the active ingredient aclidinium bromide / formoterol (COPD). iqwig.de; accessed on March 23, 2020.