Aclidinium bromide (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

) is a long-acting, inhaled

muscarinic antagonist A muscarinic receptor antagonist (MRA) is a type of anticholinergic agent that blocks the activity of the muscarinic acetylcholine receptor. The muscarinic receptor is a protein involved in the transmission of signals through certain parts of the ...

(LAMA) approved in the United States on July 24, 2012 as a maintenance treatment for

chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...

(COPD). Evidence shows that it can improve

quality of life Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...

and prevent hospitalization in those with COPD. However, it does not appear to affect the risk of death or the frequency steroids are needed. It is unclear if it differs from the similar medication

tiotropium Tiotropium bromide, sold under the brand name Spiriva among others, is a long-acting bronchodilator (LAMA: long acting muscarinic antagonist) used in the management of chronic obstructive pulmonary disease (COPD) and asthma. Specifically it is ...

or other commonly used medications from the class of LAMAs. Aclidinium is delivered via a multidose

dry powder inhaler A dry-powder inhaler (DPI) is a device that delivers medication to the lungs in the form of a dry powder. DPIs are commonly used to treat respiratory diseases such as asthma, bronchitis, emphysema and COPD although DPIs (such as Inhalable insulin ...

, the Genuair inhaler. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

Adverse effects

The substance is generally well tolerated. Common side effects (in more than 1% of patients) are

sinusitis Sinusitis, also known as rhinosinusitis, is inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include thick nasal mucus, a plugged nose, and facial pain. Other signs and symptoms may include fever, head ...

nasopharyngitis The common cold or the cold is a viral infectious disease of the upper respiratory tract that primarily affects the respiratory mucosa of the nose, throat, sinuses, and larynx. Signs and symptoms may appear fewer than two days after exposu ...

, headache, cough,

diarrhoea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

and nausea. The latter is less common under the drug than under

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...

. Skin reactions such as

rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, c ...

, as well as side effects that are typical of muscarinic antagonists (

fast heart rate Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...

, palpitations, and

urinary retention Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladd ...

), occur in less than 1% of patients. on Tudorza Pressair. A small increase of cardiovascular risk cannot be excluded from available data. Patients with relevant cardiovascular diseases were excluded from studies.

Interactions

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 as

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every verteb ...

s, β₂-adrenergic agonists and

theophylline Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...

have been described. As aclidinium does not relevantly interact with

cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...

liver enzymes or P-glycoprotein, and is quickly

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

as soon as it reaches the bloodstream, it is considered to have a very low potential for interactions.

Pharmacology

Mechanism of action

Aclidinium is a long-acting,

reversible antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of recep ...

muscarinic receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several r ...

s, with similar affinity to all five subtypes, but with a

dissociation Dissociation, in the wide sense of the word, is an act of disuniting or separating a complex object into parts. Dissociation may also refer to: * Dissociation (chemistry), general process in which molecules or ionic compounds (complexes, or salts ...

half-life from subtype M₃ of 29.2 hours, or six times longer than that from M₂. For comparison, M₃ dissociation half-lives of the related drugs

ipratropium Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic (SAMA: short acting muscarinic antagonist) medication which opens up the medium and large airways in the lungs. It is used to treat the symptoms ...

and

are 0.47 hours and 62.2 hours, respectively. Its action at subtype M₃ at the smooth muscle of the

bronchiole The bronchioles or bronchioli (pronounced ''bron-kee-oh-lee'') are the smaller branches of the bronchial airways in the lower respiratory tract. They include the terminal bronchioles, and finally the respiratory bronchioles that mark the start ...

s is responsible for its desired effect: it reduces contraction of these muscles and improves the airflow. M₂ affinity is the main reason for adverse effects at the heart.

Pharmacokinetics

About 30% of inhaled aclidinium are deposited in the lung. Its action there lasts for more than 24 hours. From the lung, it is absorbed into the bloodstream, reaching highest

blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intr ...

concentrations after five minutes in healthy persons and after 10 to 15 minutes in COPD patients. The substance is quickly

hydrolysed Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...

to the carboxylic 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 by

butyrylcholinesterase Butyrylcholinesterase ( HGNC symbol BCHE; EC 3.1.1.8), also known as BChE, BuChE, BuChase, pseudocholinesterase, or plasma (cholin)esterase, is a nonspecific cholinesterase enzyme that hydrolyses many different choline-based esters. In humans, it ...

. The acid metabolite has a plasma protein binding of 87%, and the alcohol of 15%. These

metabolites In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

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.

Chemistry

Aclidinium is a quaternary ammonium cation with an

asymmetric carbon An asymmetric carbon atom (chiral carbon) is a carbon atom that is attached to four different types of atoms or groups of atoms. Le Bel-van't Hoff rule states that the number of stereoisomers of an organic compound is 2n, where n represents the num ...

atom. It is used as the pure ''R''- enantiomer. The salt, aclidinium bromide, is a crystalline powder that is hardly soluble in water or

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...

Society and culture

Brand names

It is marketed under the brand name ''Tudorza Pressair'' in the US, ''Eklira Genuair'' in the UK, and ''Tudorza Genuair'' in Canada; licensed to Menarini under the brand name ''Bretaris Genuair'' for majority of EU member states. An inhalable combination with formoterol is marketed as ''Brimica Genuair'' and ''Duaklir Genuair'' in the European Union.

References

{{Muscarinic acetylcholine receptor modulators Muscarinic antagonists Bromides Quaternary ammonium compounds AbbVie brands AstraZeneca brands Quinuclidines Thiophenes Phenol ethers