Aclidinium bromide
JFDA label: Eklira Genuair 322 mcg Inhalation Powder
Mechanism of Action
Antagonist of Muscarinic acetylcholine receptor M3 — Muscarinic acetylcholine receptor M3 antagonist
| Target | Action | Gene / class |
|---|---|---|
| Muscarinic acetylcholine receptor M3 efficacy | ANTAGONIST | CHRM3 |
Indications
Approved
- Chronic obstructive pulmonary disease
Contraindications
Source: Lexicomp
- Hypersensitivity to aclidinium or any component of the formulation Absolute
- severe hypersensitivity to milk proteins Absolute
Adverse Reactions
Nervous system disorders (2)
Common falling · Headache
Gastrointestinal disorders (3)
Common Diarrhea · toothache · vomiting
Respiratory, thoracic and mediastinal disorders (4)
Common cough · Nasopharyngitis · rhinitis · sinusitis
Dosing
Source: Lexicomp
Warnings & Precautions
Source: Lexicomp
Bronchospasm
Rarely, paradoxical bronchospasm may occur with use of inhaled bronchodilating agents; discontinue use and consider other therapy if bronchospasm occurs.
Hypersensitivity reactions
Immediate hypersensitivity reactions (eg, anaphylaxis, urticaria, angioedema, rash, bronchospasm, itching) may occur; discontinue immediately if signs/symptoms of a hypersensitivity reaction occur. Use with caution in patients with a history of hypersensitivity to atropine; aclidinium has a similar structure to atropine. Disease-related concerns:
Cardiovascular disease
Use with caution; patients with unstable cardiac disease were excluded from clinical trials. Cardiac effects (eg, cardiac failure, 1st degree AV block, cardiopulmonary arrest) were observed at an incidence of • Glaucoma: Use with caution in patients with narrow angle glaucoma; may worsen symptoms. Monitor for signs/symptoms (eg, eye pain/discomfort, blurred vision, visual halos or colored images associated with red eyes from conjunctival congestion and corneal edema).
Myasthenia gravis
Use with caution in patients with myasthenia gravis; may worsen symptoms.
Prostatic hyperplasia/bladder neck obstruction
Use with caution in patients with prostatic hyperplasia and/or bladder neck obstruction (eg, dysuria, difficulty in passing urine); may worsen symptoms. Dosage form specific issues:
Lactose
Powder for oral inhalation contains lactose; use is contraindicated in patients with severe milk protein allergy. Other warnings/precautions:
Appropriate use
Not indicated for the initial (rescue) treatment of acute episodes of bronchospasm.
Pregnancy & Lactation
Pregnancy
Adverse events have been observed in animal reproduction studies.
Lactation
Excretion of aclidinium in human milk is probable. The manufacturer recommends caution should be exercised when administering aclidinium to nursing women.
Monitoring
| Clinical pearl | FEV1, peak flow (or other pulmonary function studies) |
|---|
Chemistry & Properties
| Formula | C26H30BrNO4S2 |
|---|---|
| Molecular weight | 564.57 g/mol |
| IUPAC name | [(3R)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate bromide |
| CAS | 320345-99-1 |
| PubChem CID | 11519741 |
| InChIKey | XLAKJQPTOJHYDR-QTQXQZBYSA-M |
| logP | 4.67 |
| Polar surface area | 55.76 Ų |
| H-bond acceptors / donors | 6 / 1 |
| Drug-likeness (QED) | 0.27 |
| Lipinski violations | 0 |
SMILES
O=C(O[C@H]1C[N+]2(CCCOc3ccccc3)CCC1CC2)C(O)(c1cccs1)c1cccs1.[Br-]Biology & Pharmacokinetics
Pharmacokinetics predicted
| Bioavailability | 70.0% |
|---|---|
| Half-life | 0.951 h |
| Volume of distribution | 5.225 L/kg |
| Protein binding | 93.2% |
| BBB penetrant | No |
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP1A2 | Inhibitor | — |
| CYP2B6 | Inhibitor | — |
| CYP2C19 | Substrate | — |
| CYP2C8 | Inhibitor | — |
| CYP2C9 | Inhibitor | — |
| CYP2C9 | Substrate | — |
| CYP2D6 | Substrate | — |
| CYP3A4 | Substrate | — |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)
Drug–drug interactions (100+, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| Acetylcholine | moderate | |
| Acrivastine | moderate | |
| Alimemazine | moderate | |
| Amitriptyline | moderate | |
| Amoxapine | moderate | |
| Aripiprazole | moderate | |
| Atropine | moderate | |
| Azatadine | moderate | |
| Belladonna | moderate | |
| Benzatropine | moderate | |
| Bethanechol | moderate | |
| Biperiden | moderate | |
| Brompheniramine | moderate | |
| Carbamoylcholine (ophthalmic) | moderate | |
| Carbinoxamine | moderate | |
| Cevimeline | moderate | |
| Chlorcyclizine | moderate | |
| Chlorpheniramine | moderate | |
| Chlorpromazine | moderate | |
| Clemastine | moderate | |
| Clidinium | moderate | |
| Clomipramine | moderate | |
| Clozapine | moderate | |
| Cyclizine | moderate | |
| Cyclobenzaprine | moderate | |
| Cyproheptadine | moderate | |
| Darifenacin | moderate | |
| Demecarium (ophthalmic) | moderate | |
| Desipramine | moderate | |
| Dexbrompheniramine | moderate | |
| Dicyclomine | moderate | |
| Dimenhydrinate | moderate | |
| Diphenhydramine | moderate | |
| Disopyramide | moderate | |
| Doxepin | moderate | |
| Doxepin (topical) | moderate | |
| Doxylamine | moderate | |
| Echothiophate (ophthalmic) | moderate | |
| Eluxadoline | moderate | |
| Fesoterodine | moderate |
Showing 40 of 100+.
Registered Products (1)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Eklira Genuair 322 mcg Inhalation Powder | Powder 322 mcg | 60 Unit Doses | Shawi & Rushedat Drug Store | 32.500 |