aclidinium (Rx)

1-10%

Headache (6.6%)

Nasopharyngitis (5.5%)

Cough (3%)

Diarrhea (2.7%)

Sinusitis (1.7%)

Rhinitis (1.6%)

Toothache (1.1%)

Fall (1.1%)

Vomiting (1.1%)

Postmarketing reports

Anaphylaxis

Angioedema (including swelling of lips and tongue or throat)

Urticaria

Rash

Bronchospasm

Itching

Nausea

Dysphonia

Blurred vision

Urinary retention

Tachycardia

Stomatitis

Contraindications

Hypersensitivity to drug or formulation components or severe hypersensitivity to milk proteins

Cautions

Not for acute episodes of bronchospasm (ie, not for rescue therapy)

May cause paradoxical bronchospasm; if this occurs, discontinue and consider other treatments

Worsening of narrow-angle glaucoma may occur; use with caution in patients with narrow-angle glaucoma; instruct patients to consult a physician immediately if it occurs

Worsening of urinary retention may occur (eg, prostatic hyperplasia, bladder-neck obstruction); use with caution in patients with prostatic hyperplasia or bladder-neck obstruction; instruct patients to consult a physician immediately if it occurs

Immediate hypersensitivity reactions, including angioedema, bronchospasm, or anaphylaxis, may occur after administration; if hypersensitivity occurs, discontinue immediately and consider alternate treatment

Coadministration with other anticholinergics may increase risk for adverse effects

Pregnancy

There are no adequate and well-controlled studies of aclidinium in pregnant women to assess drug-associated risks

Animal studies

• No adverse developmental effects were seen with inhalation administration of aclidinium bromide to pregnant rats and rabbits during organogenesis at 15 or 20 times, respectively, the maximum recommended human daily inhaled dose (MRHDID)

Lactation

There are no available data on the breastfed child or on milk production or presence in human milk

Aclidinium bromide is present in rat milk; when a drug is present in animal milk, it is likely that the drug will be present in human milk

Animal studies

• Aclidinium bromide reduced pup weights when pregnant rats continued inhalation administration through lactation at 5 times the MRHDID

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Long-acting muscarinic antagonist (LAMA), often referred to as an anticholinergic; selective muscarinic antagonist with affinity for the M3 (subscript) receptor in the airways; produces bronchodilation by inhibiting acetylcholine’s effect on muscarinic receptors in the airway smooth muscle

Absorption

~55% of administered dose is swallowed, but negligible oral absorption is observed; fraction of inhaled dose that reaches systemic circulation is low (<5%)

Peak Plasma Time: 10-15 minutes (in COPD)

Peak Plasma Concentration: 80 pg/mL (in COPD)

Distribution

Whole lung deposition: 30% of the metered dose

Vd: 300 L (IV administration)

Metabolism

Aclidinium bromide is rapidly hydrolyzed in plasma into its alcohol (LAS34823) and acid (LAS34850) metabolites by both enzymatic and non-enzymatic cleavage; neither of these metabolites are active

Elimination

Half-life: 5-8 hr following repeat BID administration

Renal clearance: Low

Total clearance: 170 L/hr (IV administration)

Excretion: Urine 0.1% (as aclidinium bromide), 65% (as metabolites); feces 33% (as metabolites)