Evidence shows that it can improvequality of life and prevent hospitalization in those with COPD.[5] However, it does not appear to affect the risk of death or the frequency steroids are needed.[5] It is unclear if it differs from the similar medicationtiotropium or other commonly used medications from the class of LAMAs.[5]
The substance is generally well tolerated. Common side effects (in more than 1% of patients) aresinusitis,nasopharyngitis, headache, cough,diarrhoea and nausea. The latter is less common under the drug than underplacebo. Skin reactions such asrash, as well as side effects that are typical of muscarinic antagonists (fast heart rate,palpitations, andurinary retention), occur in less than 1% of patients.[7][8]
A small increase ofcardiovascular risk cannot be excluded from available data. Patients with relevant cardiovascular diseases were excluded from studies.[9]
No systematic interaction studies have been performed. It is expected that adverse effects of aclidinium increase if it is combined with other muscarinic antagonists. In clinical practice, no interactions with other COPD medications such asglucocorticoids,β2-adrenergic agonists andtheophylline have been described. As aclidinium does not relevantly interact withcytochrome P450 liver enzymes orP-glycoprotein, and is quicklymetabolized as soon as it reaches the bloodstream, it is considered to have a very low potential for interactions.[7][9]
Aclidinium is a long-acting,reversible antagonist atmuscarinic receptors, with similar affinity to all five subtypes, but with adissociation half-life from subtypeM3 of 29.2 hours, or six times longer than that fromM2. For comparison, M3 dissociation half-lives of the related drugsipratropium andtiotropium are 0.47 hours and 62.2 hours, respectively.[9]
Its action at subtype M3 at thesmooth muscle of thebronchioles is responsible for its desired effect: it reduces contraction of these muscles and improves the airflow.[7][8] M2 affinity is the main reason for adverse effects at the heart.[9]
About 30% of inhaled aclidinium are deposited in the lung.[9] Its action there lasts for more than 24 hours.[8] From the lung, it is absorbed into the bloodstream, reaching highestblood plasma concentrations after five minutes in healthy persons and after 10 to 15 minutes in COPD patients. The substance is quicklyhydrolysed to thecarboxylic acid and the alcohol, so that less than 5% of the inhaled dose are found unchanged in the plasma. Hydrolysis is both non-enzymatic and enzymatic, the latter mainly bybutyrylcholinesterase.[7][9]
The acid metabolite has a plasma protein binding of 87%, and the alcohol of 15%. Thesemetabolites are found to 65% in the urine and to 33% in the faeces. Elimination half-life is two to three hours. Unchanged aclidinium accounts for only 0.1% of the excreted dose.[7]
It is marketed under the brand nameTudorza Pressair in the US,Eklira Genuair in the UK, andTudorza Genuair in Canada; licensed to Menarini under the brand nameBretaris Genuair for majority of EU member states.[10]
^Gavaldà A, Miralpeix M, Ramos I, et al. (2009). "Characterization of aclidinium bromide, a novel inhaled muscarinic antagonist, with long duration of action and a favorable pharmacological profile".J Pharmacol Exp Ther.331 (2):740–51.doi:10.1124/jpet.109.151639.PMID19710368.S2CID10533142.
^World Health Organization (2021).World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization.hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
^abcdeHaberfeld H, ed. (2015).Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
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