Aclidinium

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Aclidinium
Aclidinium bromide.svg
Names
Trade namesBretaris Genuair, Eklira Genuair, Tudorza Pressair
Other namesAclidinium bromide
  • [(8R)-1-(3-Phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-8-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate bromide
Clinical data
Routes of
use
Inhalation
Duration of action>24 hrs
External links
AHFS/Drugs.comMonograph
Legal
License data
Legal status
Pharmacokinetics
Bioavailability<5% (in system)
30% (in lung)
MetabolismEster hydrolysis
Elimination half-life2–3 hrs
Excretion65% urine, 33% faeces
Chemical and physical data
FormulaC26H30BrNO4S2
Molar mass564.55 g·mol−1
3D model (JSmol)
  • [Br-].O=C(O[C@@H]3C2CC[N+](CCCOc1ccccc1)(CC2)C3)C(O)(c4sccc4)c5sccc5
  • InChI=1S/C26H30NO4S2.BrH/c28-25(26(29,23-9-4-17-32-23)24-10-5-18-33-24)31-22-19-27(14-11-20(22)12-15-27)13-6-16-30-21-7-2-1-3-8-21;/h1-5,7-10,17-18,20,22,29H,6,11-16,19H2;1H/q+1;/p-1/t20?,22-,27?;/m0./s1 ☒N
  • Key:XLAKJQPTOJHYDR-QTQXQZBYSA-M ☒N
 ☒NcheckY (what is this?)  (verify)

Aclidinium is a medication used for maintenance treatment of chronic obstructive pulmonary disease (COPD).[1] It may improve quality of life and prevent hospitalization; but does not affect the risk of death or the need for steroids.[2] It is unclear if it differs from tiotropium or other medications in the LAMA class.[2] It is used by a dry powder inhaler.[1]

Common side effects include headache, cough, and inflammation of the nose and throat.[1] Other side effects may include diarrhea, bronchospasm, and urinary retention.[3][1] It is a long-acting muscarinic antagonist (LAMA).[1]

Aclidinium was approved for medical use in the United States in 2012.[1] In the United Kingdom a month costs the NHS about 33 pounds.[3] In the United States this amount costs about 560 USD as of 2021.[4] It is also available together with formoterol.[3]

Medical uses

It is used for the long term treatment of COPD.[1]

Dosage

It is inhaled twice a day at a dose of 375 to 400 ug.[3][1]

Side effects

The substance is generally well tolerated. Common side effects (in more than 1% of patients) are sinusitis, nasopharyngitis, headache, cough, diarrhoea and nausea. The latter is less common under the drug than under placebo. Skin reactions such as rash, as well as side effects that are typical of muscarinic antagonists (fast heart rate, palpitations, and urinary retention), occur in less than 1% of patients.[5][6]

A small increase of cardiovascular risk cannot be excluded from available data. Patients with relevant cardiovascular diseases were excluded from studies.[7]

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 glucocorticoids, β2-adrenergic agonists and theophylline have been described. As aclidinium does not relevantly interact with cytochrome P450 liver enzymes or P-glycoprotein, and is quickly metabolized as soon as it reaches the bloodstream, it is considered to have a very low potential for interactions.[5][7]

Pharmacology

Mechanism of action

Aclidinium is a long-acting, reversible antagonist at muscarinic receptors, with similar affinity to all five subtypes, but with a dissociation 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 and tiotropium are 0.47 hours and 62.2 hours, respectively.[7]

Its action at subtype M3 at the smooth muscle of the bronchioles is responsible for its desired effect: it reduces contraction of these muscles and improves the airflow.[5][6] M2 affinity is the main reason for adverse effects at the heart.[7]

Pharmacokinetics

About 30% of inhaled aclidinium are deposited in the lung.[7] Its action there lasts for more than 24 hours.[6] From the lung, it is absorbed into the bloodstream, reaching highest blood plasma concentrations after five minutes in healthy persons and after 10 to 15 minutes in COPD patients. The substance is quickly hydrolysed 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.[5][7]

The acid metabolite has a plasma protein binding of 87%, and the alcohol of 15%. These metabolites 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.[5]

Chemistry

Aclidinium is a quaternary ammonium cation with an asymmetric carbon 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.

Society and culture

Cost

In the U.S. the price of Aclidinium bromide is $50 (USD) for a one month supply[8]

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.[9]

An inhalable combination with formoterol is marketed as Brimica Genuair[10] and Duaklir Genuair[11] in the European Union.

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "Aclidinium Monograph for Professionals". Drugs.com. Retrieved 15 July 2021.
  2. 2.0 2.1 Ni, H; Soe, Z; Moe, S (2014). "Aclidinium bromide for stable chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews (9): CD010509. doi:10.1002/14651858.CD010509.pub2. PMID 25234126.
  3. 3.0 3.1 3.2 3.3 BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 260. ISBN 978-0-85711-369-6.CS1 maint: date format (link)
  4. "Aclidinium Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 15 July 2021.
  5. 5.0 5.1 5.2 5.3 5.4 Haberfeld, H, ed. (2015). Austria-Codex (in Deutsch). Vienna: Österreichischer Apothekerverlag.
  6. 6.0 6.1 6.2 FDA Professional Drug Information on Tudorza Pressair.
  7. 7.0 7.1 7.2 7.3 7.4 7.5 Dinnendahl, V; Fricke, U, eds. (2014). Arzneistoff-Profile (in Deutsch). 1 (27 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
  8. "Tudorza (Pressair Aclidinium) - $50 Per Month - Cost Comparison & Coupons". Prescription Hope. Retrieved 24 March 2021.
  9. "Almirall and Menarini sign a licence agreement and commercial alliance for Aclidinium in the majority of European member states and a number of non-EU countries" (Press release). Menarini. Retrieved 2012-03-26.
  10. "Brimica Genuair: Uses, Side Effects, Benefits/Risks". Drugs.com. 19 November 2014. Retrieved 26 July 2020.
  11. "Duaklir Genuair: Uses, Side Effects, Benefits/Risks". Drugs.com. 19 November 2014. Retrieved 26 July 2020.

External links

Identifiers: