(umeclidinium and vilanterol inhalation powder)
FOR ORAL INHALATION USE
The following is a brief summary only; see full prescribing information for complete product information.
WARNING: ASTHMA-RELATED DEATH
Long-acting beta2-adrenergic agonists (LABA) increase the risk of asthma-related death. Data from
a large placebo-controlled US trial that compared the safety of another LABA (salmeterol) with placebo
added to usual asthma therapy showed an increase in asthma-related deaths in subjects receiving
salmeterol. This finding with salmeterol is considered a class effect of all LABA, including vilanterol,
one of the active ingredients in ANORO ELLIPTA [see Warnings and Precautions ( 5. 1)].
The safety and efficacy of ANORO ELLIPTA in patients with asthma have not been established.
ANORO ELLIPTA is not indicated for the treatment of asthma.
1 INDICATIONS AND USAGE
ANORO ELLIPTA is a combination anticholinergic/long-acting beta2-adrenergic agonist (anticholinergic/LABA)
indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic
obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.
Important Limitations of Use: ANORO ELLIPTA is NOT indicated for the relief of acute bronchospasm or for the
treatment of asthma.
4 CON TRAINDICATIONS
The use of ANORO ELLIPTA is contraindicated in patients with severe hypersensitivity to milk proteins or who have
demonstrated hypersensitivity to umeclidinium, vilanterol, or any of the excipients [see Warnings and Precautions
( 5. 6), Description ( 11) of full Prescribing Information].
5 WARNINGS AND PRECAUTIONS
5. 1 Asthma-Related Death
• Data from a large placebo-controlled trial in subjects with asthma showed that LABA may increase the risk of
asthma-related death. Data are not available to determine whether the rate of death in patients with COPD is
increased by LABA.
• A 28-week, placebo-controlled, US trial comparing the safety of another LABA (salmeterol) with placebo, each
added to usual asthma therapy, showed an increase in asthma-related deaths in subjects receiving salmeterol
(13/13,176 in subjects treated with salmeterol vs. 3/13,179 in subjects treated with placebo; relative risk:
4.37 [95% CI: 1.25, 15.34]). The increased risk of asthma-related death is considered a class effect of LABA,
including vilanterol, one of the active ingredients in ANORO ELLIPTA.
• No trial adequate to determine whether the rate of asthma-related death is increased in subjects treated with
ANORO ELLIPTA has been conducted. The safety and efficacy of ANORO ELLIPTA in patients with asthma have
not been established. ANORO ELLIPTA is not indicated for the treatment of asthma.
5. 2 Deterioration of Disease and Acute Episodes
ANORO ELLIP TA should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes
of COPD. ANORO ELLIPTA has not been studied in subjects with acutely deteriorating COPD. The initiation of ANORO
ELLIP TA in this setting is not appropriate.
ANORO ELLIP TA should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute
episodes of bronchospasm. ANORO ELLIPTA has not been studied in the relief of acute symptoms and extra doses
should not be used for that purpose. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.
When beginning treatment with ANORO ELLIPTA, patients who have been taking oral or inhaled, short-acting
beta2-agonists on a regular basis (e.g., 4 times a day) should be instructed to discontinue the regular use of these
drugs and to use them only for symptomatic relief of acute respiratory symptoms. When prescribing ANORO ELLIP TA,
the healthcare provider should also prescribe an inhaled, short-acting beta2-agonist and instruct the patient on how
it should be used. Increasing inhaled, short-acting beta2-agonist use is a signal of deteriorating disease for which
prompt medical attention is indicated.
COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If ANORO
ELLIPTA no longer controls symptoms of bronchoconstriction; the patient’s inhaled, short-acting, beta2-agonist
becomes less effective; or the patient needs more short-acting beta2-agonist than usual, these may be markers of
deterioration of disease. In this setting a re-evaluation of the patient and the COPD treatment regimen should be
undertaken at once. Increasing the daily dose of ANORO ELLIPTA beyond the recommended dose is not appropriate
in this situation.
5. 3 Excessive Use of ANORO ELLIPTA and Use With Other Long-Acting Beta2-Agonists
ANORO ELLIP TA should not be used more often than recommended, at higher doses than recommended, or in
conjunction with other medicines containing LABA, as an overdose may result. Clinically significant cardiovascular
effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.
Patients using ANORO ELLIP TA should not use another medicine containing a LABA (e.g., salmeterol, formoterol
fumarate, arformoterol tartrate, indacaterol) for any reason.
5. 4 Drug Interactions With Strong Cytochrome P450 3A4 Inhibitors
Caution should be exercised when considering the coadministration of ANORO ELLIPTA with long-term ketoconazole
and other known strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, clarithromycin, conivaptan,
indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole)
because increased cardiovascular adverse effects may occur [see Drug Interactions ( 7. 1), Clinical Pharmacology
( 12. 3) of full Prescribing Information].
5. 5 Paradoxical Bronchospasm
As with other inhaled medicines, ANORO ELLIPTA can produce paradoxical bronchospasm, which may be life
threatening. If paradoxical bronchospasm occurs following dosing with ANORO ELLIPTA, it should be treated
immediately with an inhaled, short-acting bronchodilator; ANORO ELLIPTA should be discontinued immediately;
and alternative therapy should be instituted.
5. 6 Hypersensitivity Reactions
Hypersensitivity reactions may occur after administration of ANORO ELLIPTA. There have been reports of anaphylactic
reactions in patients with severe milk protein allergy after inhalation of other powder products containing lactose;
therefore, patients with severe milk protein allergy should not use ANORO ELLIP TA [see Contraindications ( 4)].
5. 7 Cardiovascular Effects
Vilanterol, like other beta2-agonists, can produce a clinically significant cardiovascular effect in some patients as
measured by increases in pulse rate, systolic or diastolic blood pressure, or symptoms [see Clinical Pharmacology
( 12. 2) of full Prescribing Information]. If such effects occur, ANORO ELLIPTA may need to be discontinued. In
addition, beta-agonists have been reported to produce electrocardiographic changes, such as flattening of the
T wave, prolongation of the QTc interval, and ST segment depression, although the clinical significance of these
findings is unknown.
Therefore, ANORO ELLIPTA should be used with caution in patients with cardiovascular disorders, especially coronary
insufficiency, cardiac arrhythmias, and hypertension.
ANORO ELLIPTA, like all medicines containing sympathomimetic amines, should be used with caution in patients
with convulsive disorders or thyrotoxicosis and in those who are unusually responsive to sympathomimetic amines.
Doses of the related beta2-adrenoceptor agonist albuterol, when administered intravenously, have been reported to
aggravate preexisting diabetes mellitus and ketoacidosis.
5. 9 Worsening of Narrow-Angle Glaucoma
ANORO ELLIPTA should be used with caution in patients with narrow-angle glaucoma. Prescribers and patients
should be alert for signs and symptoms of acute narrow-angle glaucoma (e.g., eye pain or discomfort, blurred
vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal
edema). Instruct patients to consult a physician immediately should any of these signs or symptoms develop.
5. 10 Worsening of Urinary Retention
ANORO ELLIP TA should be used with caution in patients with urinary retention. Prescribers and patients should
be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination), especially in
patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to consult a physician immediately
should any of these signs or symptoms develop.
5. 11 Hypokalemia and Hyperglycemia
Beta-adrenergic agonist medicines may produce significant hypokalemia in some patients, possibly through
intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease in serum
potassium is usually transient, not requiring supplementation. Beta-agonist medicines may produce transient
hyperglycemia in some patients. In 4 clinical trials of 6-month duration evaluating ANORO ELLIPTA in subjects
with COPD, there was no evidence of a treatment effect on serum glucose or potassium.
6 ADVERSE REACTIONS
LABA, such as vilanterol, one of the active ingredients in ANORO ELLIPTA, increase the risk of asthma-related
death. ANORO ELLIPTA is not indicated for the treatment of asthma. [See Boxed Warning and Warnings and
Precautions ( 5. 1).]
The following adverse reactions are described in greater detail in other sections:
• Paradoxical bronchospasm [see Warnings and Precautions ( 5. 5)]
• Cardiovascular effects [see Warnings and Precautions ( 5. 7)]
• Worsening of narrow-angle glaucoma [see Warnings and Precautions ( 5. 9)]
• Worsening of urinary retention [see Warnings and Precautions ( 5. 10)]
6. 1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the
clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not
reflect the rates observed in practice.
The clinical program for ANORO ELLIP TA included 8,138 subjects with COPD in four 6-month lung function trials,
one 12-month long-term safety study, and 9 other trials of shorter duration. A total of 1,124 subjects have received
at least 1 dose of ANORO ELLIP TA (umeclidinium/vilanterol 62.5 mcg/25 mcg), and 1,330 subjects have received a
higher dose of umeclidinium/vilanterol (125 mcg/25 mcg). The safety data described below are based on the four
6-month and the one 12-month trials. Adverse reactions observed in the other trials were similar to those observed
in the confirmatory trials.
6-Month Trials: The incidence of adverse reactions associated with ANORO ELLIPTA in Table 1 is based on four
6-month trials: 2 placebo-controlled trials (Trials 1 and 2; n = 1,532 and n = 1,489, respectively) and 2 active-controlled trials (Trials 3 and 4; n = 843 and n = 869, respectively). Of the 4,733 subjects, 68% were male and
84% were Caucasian. They had a mean age of 63 years and an average smoking history of 45 pack-years, with
50% identified as current smokers. At screening, the mean post-bronchodilator percent predicted forced expiratory
volume in 1 second (FEV1) was 48% (range: 13% to 76%), the mean post-bronchodilator FEV1/forced vital capacity
(FVC) ratio was 0.47 (range: 0.13 to 0.78), and the mean percent reversibility was 14% (range: -45% to 109%).
Subjects received 1 dose once daily of the following: ANORO ELLIPTA, umeclidinium/vilanterol 125 mcg/25 mcg,
umeclidinium 62.5 mcg, umeclidinium 125 mcg, vilanterol 25 mcg, active control, or placebo.
Table 1. Adverse Reactions With ANORO ELLIPTA With ≥1% Incidence and More Common Than With Placebo
in Subjects With Chronic Obstructive Pulmonary Disease
(n = 555)
(n = 842)
(n = 418)
(n = 1,034)
Infections and infestations
Lower respiratory tract infection
Musculoskeletal and connective
Pain in extremity
General disorders and
administration site conditions
Chest pain < 1 1 < 1 < 1
Other adverse reactions with ANORO ELLIPTA observed with an incidence less than 1% but more common than with
placebo included the following: productive cough, dry mouth, dyspepsia, abdominal pain, gastroesophageal reflux
disease, vomiting, musculoskeletal chest pain, chest discomfort, asthenia, atrial fibrillation, ventricular extrasystoles,
supraventricular extrasystoles, myocardial infarction, pruritus, rash, and conjunctivitis.
12-Month Trial: In a long-term safety trial, 335 subjects were treated for up to 12 months with umeclidinium/
vilanterol 125 mcg/25 mcg or placebo. The demographic and baseline characteristics of the long-term safety trial
were similar to those of the placebo-controlled efficacy trials described above. Adverse reactions that occurred with
a frequency of greater than or equal to 1% in the group receiving umeclidinium/vilanterol 125 mcg/25 mcg that
exceeded that in placebo in this trial were: headache, back pain, sinusitis, cough, urinary tract infection, arthralgia,
nausea, vertigo, abdominal pain, pleuritic pain, viral respiratory tract infection, toothache, and diabetes mellitus.
7 DRUG INTERACTIONS
Vilanterol, a component of ANORO ELLIPTA, is a substrate of CYP3A4. Concomitant administration of the strong
CYP3A4 inhibitor ketoconazole increases the systemic exposure to vilanterol. Caution should be exercised when