umeclidinium bromide/vilanterol inhaled (Anoro Ellipta)

Dosing and uses of Anoro Ellipta (umeclidinium bromide/vilanterol inhaled)

• Adult
• Pediatric

 

Adult dosage forms and strengths

umeclidinium/vilanteroL

powder for inhalation

• (62.5mcg/25mcg)/actuation

 

Chronic Obstructive Pulmonary Disease

Combination anticholinergic/long-acting beta2-adrenergic agonist (LABA) indicated for long-term maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema

62.5 mcg/25 mcg (1 actuation) inhaled PO qDay

 

Dosage modifications

Renal impairment (including severe [CrCl <30 mL/min]): No dosage adjustment required

Moderate hepatic impairment (Child-Pugh 7-9): No dosage adjustment required

Severe hepatic impairment: Unknown, not evaluated

Geriatric patients: No dosage adjustment require

 

Administration

Inhaler is not reusable

Store at room temperature between 68-77°F (20-25°C); excursions permitted from 59-86°F (15-30°C)

Store in a dry place away from direct heat or sunlight

Before the inhaler is used for the 1st time, the counter should show the number 30 (7 if a sample or institutional pack); this is the number of doses in the inhaler

See prescribing information for detailed description regarding how to administer

 

Pediatric dosage forms and strengths

Safety and efficacy not established

 

Anoro Ellipta (umeclidinium bromide/vilanterol inhaled) adverse (side) effects

1-10%

Pharyngitis (2%)

Diarrhea (2%)

Pain in extremity (2%)

Muscle spasms (1%)

Neck pain (1%)

Chest pain (1%)

Sinusitis (1%)

Lower respiratory tract infection (1%)

Constipation (1%)

 

<1%

Productive cough

Dry mouth

Dyspepsia

Abdominal pain

GERd

Vomiting

Musculoskeletal chest pain

Chest discomfort

Asthenia

Atrial fibrillation

Ventricular extrasystoles

Supraventricular extrasystoles

Myocardial infarction

Pruritus

Rash

Conjunctivitis

 

Postmarketing reports

Cardiac Disorders : Palpitations

Immune System Disorders: Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria

Nervous System Disorders: Dysgeusia, tremor

Psychiatric Disorders: Anxiety

 

Warnings

Black box warnings

Long-acting beta2-adrenergic agonists (LABAs), such as vilanterol, increase the risk for asthma-related death

A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths; this finding is considered a class effect of all LABA, including vilanteroL

Safety and efficacy not established in patients with asthma; NOT approved for treatment of asthma

 

Contraindications

Severe hypersensitivity to milk proteins

Demonstrated hypersensitivity to umeclidinium, vilanterol, 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)

Not indicated for relief of acute bronchospasm or for the treatment of asthma; data from a large placebo-controlled trial in subjects with asthma showed that LABAs may increase the risk of asthma-related death (see Black box warnings)

Do not initiate in patients during rapidly deteriorating or potentially life-threatening episodes of COPd

Beta2-agonists can produce clinically significant cardiovascular effects including increased pulse rate or increased systolic or diastolic blood pressure

Do not exceed recommended dose (ie, 1 actuation once daily) or coadminister with other medicines containing a LABA; may result in overdose

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

Beta2-agonists should be used with caution with convulsive disorders, thyrotoxicosis, narrow-angle glaucoma, conditions causing urinary retention, and in individuals who are unusually responsive to sympathomimetic amines

Potential for beta2-agonists to produce significant hypokalemia (possibly through intracellular shunting) and transient hyperglycemia (not observed in clinical trials)

Caution with coadministration with strong CYP3A4 inhibitors because increased cardiovascular adverse effects may occur

Use beta2-agonists with extreme caution in patients being treated with MAOIs, TCAs, or drugs known to prolong the QTc interval or within 2 weeks of discontinuation of such agents

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Unknown if distributed in human breast milk

 

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.

 

Pharmacology of Anoro Ellipta (umeclidinium bromide/vilanterol inhaled)

Mechanism of action

Umeclidinium bromide: 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 mucous secretion; dissociates slowly from M3 muscarinic receptors extending its duration of action

Vilanterol: Long-acting selective beta2-adrenergic agonist (LABA); stimulates intracellular adenyl cyclase resulting in increased cAMP levels causing bronchial smooth muscle relaxation; also inhibits release of mediators of immediate hypersensitivity from cells, especially from mast cells

 

Absorption

Plasma levels not predictive of therapeutic effect

Peak plasma time: 5-15 minutes (umeclidinium/vilanterol)

 

Distribution

Following IV administration of each component

Protein bound: 89% (umeclidinium); 94% (vilanterol)

Vd: 86 L (umeclidinium); 165 L (vilanterol)

 

Metabolism

Umeclidinium

• 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

VilanteroL

• Metabolized principally by CYP3A4 and is a substrate for the P-gp transporter
• Metabolized to a range of metabolites with significantly reduced beta1- and beta2-agonist activity

 

Elimination

Half-life: 11 hr (umeclidinium/vilanterol)

Excretion

• Umeclidinium (IV): 58% feces; 22% urine
• Umeclidinium (PO): 92% feces; <1% urine
• Vilanterol (PO): 30% feces; 70% urine