umeclidinium bromide (Rx)

1-10%

Nasopharyngitis (8%)

Upper respiratory tract infection (5%)

Cough (3%)

Arthralgia (2%

Toothache (1%)

Pharyngitis (1%)

Viral upper respiratory tract infection (1%)

Tachycardia (1%)

<1%

Atrial fibrillation

Postmarketing Reports

Hypersensitivity reactions, including anaphylaxis, angioedema, pruritus, rash, and urticaria

Eye disorders: Eye pain, glaucoma, vision blurred

Renal and urinary disorders: Dysuria, urinary retention

Contraindications

Severe hypersensitivity to milk proteins

Demonstrated hypersensitivity to umeclidinium or any of the excipients

Cautions

Anaphylactic reactions reported in patients with severe milk protein allergy after inhalation of other powder products containing lactose (see Contraindications)

Hypersensitivity reactions such as anaphylaxis, angioedema, pruritus, rash, and urticaria may occur; discontinue if reactions occur

Do not initiate in patients during rapidly deteriorating or potentially life-threatening episodes of COPD; not be used for the relief of acute symptoms (ie, as rescue inhaler) from acute episodes of bronchospasm

Paradoxical bronchospasm reported; discontinue and treat immediately with an inhaled, prompt-acting bronchodilator (eg, albuterol)

Worsening of narrow-angle glaucoma may occur

Worsening of urinary retention may occur; caution in patients with prostatic hyperplasia or bladder-neck obstruction

Pregnancy

There are insufficient data on use in pregnant women to inform a drug-associated risk

Animal data

• Administered via inhalation or subcutaneously to pregnant rats and rabbits was not associated with adverse effect on embryofetal development at exposures approximately 50 and 200 times, respectively, the human exposure at maximum recommended human daily inhaled dose (MRHDID)

Lactation

There is no information available on presence of drug in human milk, effects on breastfed child, or on milk production; the drug was detected in plasma of offspring of lactating rats treated with umeclidinium suggesting its presence in maternal milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from umeclidinium or from underlying maternal condition

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; blocks action of acetylcholine at muscarinic receptors (M1 to M5) in the bronchial airways (M3) by preventing increase in intracellular calcium concentration, leading to relaxation of airway smooth muscle, improved lung function, and decreased mucus secretion; dissociates slowly from M3 muscarinic receptors extending its duration of action

Absorption

Plasma levels not predictive of therapeutic effect

Peak plasma time: 5-15 minutes

Distribution

Following IV administration

Protein bound: 89% (umeclidinium)

Vd: 86 L (umeclidinium)

Metabolism

Primarily metabolized by CYP2D6 and is a substrate for the P-gp transporter

Primary metabolic routes for umeclidinium are oxidative (hydroxylation, O-dealkylation) followed by conjugation (eg, glucuronidation), resulting in a range of metabolites with either reduced pharmacological activity or for which the pharmacological activity has not been established

Systemic exposure to the metabolites is low

Elimination

Half-life: 11 hr

Umeclidinium (IV): 58% feces; 22% urine

Umeclidinium (PO): 92% feces; <1% urine