Anoro Ellipta

• Store Anoro Ellipta at room temperature between 68°F and 77°F (20°C and 25°C). Keep in a dry place away from heat and sunlight. 
• Store Anoro Ellipta in the unopened foil tray and only open when ready for use. 
• Safely throw away Anoro Ellipta in the trash 6 weeks after you open the foil tray or when the counter reads “0”, whichever comes first. Write the date you open the tray on the label on the inhaler. 
• Keep Anoro Ellipta and all medicines out of the reach of children

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include fast heart rate, and feeling shaky or short of breath.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Use of umeclidinium and vilanterol combination is not recommended in children. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of umeclidinium and vilanterol combination in the elderly.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Bepridil
• Cisapride
• Dronedarone
• Fluconazole
• Ketoconazole
• Mesoridazine
• Nelfinavir
• Pimozide
• Piperaquine
• Posaconazole
• Saquinavir
• Sparfloxacin
• Terfenadine
• Thioridazine
• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amineptine
• Amiodarone
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Anagrelide
• Aripiprazole
• Aripiprazole Lauroxil
• Atazanavir
• Boceprevir
• Bupropion
• Buserelin
• Butriptyline
• Ceritinib
• Clarithromycin
• Clomipramine
• Clozapine
• Cobicistat
• Conivaptan
• Crizotinib
• Dabrafenib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Deutetrabenazine
• Dibenzepin
• Donepezil
• Dothiepin
• Doxepin
• Efavirenz
• Escitalopram
• Foscarnet
• Gonadorelin
• Goserelin
• Histrelin
• Hydroxychloroquine
• Hydroxyzine
• Idelalisib
• Imipramine
• Indinavir
• Iprindole
• Itraconazole
• Ivabradine
• Leuprolide
• Levofloxacin
• Lofepramine
• Lopinavir
• Melitracen
• Methadone
• Metronidazole
• Nafarelin
• Nefazodone
• Nilotinib
• Nortriptyline
• Opipramol
• Panobinostat
• Pasireotide
• Pimavanserin
• Pitolisant
• Propizepine
• Protriptyline
• Quetiapine
• Ribociclib
• Ritonavir
• Sotalol
• Sulpiride
• Tacrolimus
• Telaprevir
• Telithromycin
• Tianeptine
• Tiotropium
• Tipranavir
• Trimipramine
• Triptorelin
• Troleandomycin
• Vemurafenib
• Vinflunine
• Voriconazole
• Zuclopenthixol

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergy to milk proteins—Should not be used in patients with these conditions.

• Bladder blockage or
• Diabetes or
• Enlarged prostate (BPH, prostatic hyperplasia) or
• Heart or blood vessel disease or
• Heart rhythm problems (eg, arrhythmia, prolonged QT interval) or
• Hypertension (high blood pressure) or
• Hyperthyroidism (overactive thyroid) or
• Hypokalemia (low potassium in the blood) or
• Ketoacidosis (high ketones in the blood) or
• Narrow-angle glaucoma or
• Problems passing urine or
• Seizures—Use with caution. May make these conditions worse.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Sore throat.
• Runny nose.
• Cough.
• Throat irritation.
• Muscle spasm.
• Pain in arms or legs.
• Hard stools (constipation).
• Loose stools (diarrhea).
• Neck pain.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Anoro Ellipta (umeclidinium/vilanterol 62.5 mcg/25 mcg) should be administered as 1 inhalation once daily by the orally inhaled route only.

Anoro Ellipta should be used at the same time every day. Do not use Anoro Ellipta more than 1 time every 24 hours.

No dosage adjustment is required for geriatric patients, patients with renal impairment, or patients with moderate hepatic impairment [see Clinical Pharmacology (12.3)].

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:

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 Ellipta 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 Ellipta (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 white. 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 postbronchodilator percent predicted forced expiratory volume in 1 second (FEV1) was 48% (range: 13% to 76%), the mean postbronchodilator 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 Placebo in Subjects with Chronic Obstructive Pulmonary Disease

Other adverse reactions with Anoro Ellipta observed with an incidence less than 1% but more common than 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.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of Anoro Ellipta. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to Anoro Ellipta or a combination of these factors.

Cardiac Disorders

Palpitations.

Eye Disorders

Blurred vision, glaucoma, increased intraocular pressure.

Immune System Disorders

Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria.

Nervous System Disorders

Dysgeusia, tremor.

Psychiatric Disorders

Anxiety.

Renal and Urinary Disorders

Dysuria, urinary retention.

Respiratory, Thoracic, and Mediastinal Disorders

Paradoxical bronchospasm.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Anoro Ellipta

No studies of carcinogenicity, mutagenicity, or impairment of fertility were conducted with Anoro Ellipta; however, studies are available for the individual components, umeclidinium and vilanterol, as described below.

Umeclidinium

Umeclidinium produced no treatment-related increases in the incidence of tumors in 2-year inhalation studies in rats and mice at inhaled doses up to 137 and 295/200 mcg/kg/day (male/female), respectively (approximately 20 and 25/20 times the MRHDID in adults on an AUC basis, respectively).

Umeclidinium tested negative in the following genotoxicity assays: the in vitro Ames assay, in vitro mouse lymphoma assay, and in vivo rat bone marrow micronucleus assay.

No evidence of impairment of fertility was observed in male and female rats at subcutaneous doses up to 180 mcg/kg/day and inhaled doses up to 294 mcg/kg/day, respectively (approximately 100 and 50 times, respectively, the MRHDID in adults on an AUC basis).

Vilanterol

In a 2-year carcinogenicity study in mice, vilanterol caused a statistically significant increase in ovarian tubulostromal adenomas in females at an inhalation dose of 29,500 mcg/kg/day (approximately 7,800 times the MRHDID in adults on an AUC basis). No increase in tumors was seen at an inhalation dose of 615 mcg/kg/day (approximately 210 times the MRHDID in adults on an AUC basis).

In a 2-year carcinogenicity study in rats, vilanterol caused statistically significant increases in mesovarian leiomyomas in females and shortening of the latency of pituitary tumors at inhalation doses greater than or equal to 84.4 mcg/kg/day (greater than or equal to approximately 20 times the MRHDID in adults on an AUC basis). No tumors were seen at an inhalation dose of 10.5 mcg/kg/day (approximately 1 time the MRHDID in adults on an AUC basis).

These tumor findings in rodents are similar to those reported previously for other beta-adrenergic agonist drugs. The relevance of these findings to human use is unknown.

Vilanterol tested negative in the following genotoxicity assays: the in vitro Ames assay, in vivo rat bone marrow micronucleus assay, in vivo rat unscheduled DNA synthesis (UDS) assay, and in vitro Syrian hamster embryo (SHE) cell assay. Vilanterol tested equivocal in the in vitro mouse lymphoma assay.

No evidence of impairment of fertility was observed in reproductive studies conducted in male and female rats at inhaled vilanterol doses up to 31,500 and 37,100 mcg/kg/day, respectively (approximately 12,000 and 14,500 times, respectively, the MRHDID in adults on a mcg/m2 basis).

Use Anoro Ellipta exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Using this medicine improperly can cause death or serious side effects on the heart.

You may need to stop using other COPD medications you have been using in the past on a regular basis. Carefully follow your doctor's dosing instructions.

The usual dose of this medicine is 1 inhalation per day. Use the medicine at the same time each day, and not more than once in a 24-hour period.

Anoro Ellipta will not work fast enough to treat a bronchospasm attack. Use only a fast-acting inhalation medicine for an attack. Tell your doctor if any of your medicines seem to stop working as well in controlling your COPD.

Anoro Ellipta is a powder that comes with a special inhaler device preloaded with blister packs containing measured doses of the medicine. The device opens and loads a blister of Anoro Ellipta each time you use the inhaler. Follow the patient instructions provided with the inhaler device.

Seek medical attention if your breathing problems do not improve, or if your symptoms get worse quickly.

Store at room temperature away from moisture, heat, and light. Keep the inhaler device in the sealed foil tray until ready to start using it.

Throw the inhaler device away 6 weeks after you have taken it out of the foil pouch, or if the dose indicator shows a zero, whichever comes first.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose. Do not use more than 1 inhalation in a single day.

Applies to umeclidinium / vilanterol: inhalation powder

General

The most common adverse reaction was nasopharyngitis (9%).[Ref]

Endocrine

Common (1% to 10%): Diabetes Mellitus[Ref]

Gastrointestinal

Common (1% to 10%): Constipation, dry mouth, diarrhea, nausea, abdominal pain, toothache
Uncommon (0.1% to 1%): Dyspepsia, gastroesophageal reflux disease, vomiting[Ref]

Genitourinary

Common (1% to 10%): Urinary tract infection
Frequency not reported: Signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination)[Ref]

Musculoskeletal

Common (1% to 10%): Pain in extremity, muscle spasms, neck pain, back pain, arthralgia
Uncommon (0.1% to 1%): Musculoskeletal chest pain[Ref]

Nervous system

Common (1% to 10%): Headache
Postmarketing reports: Dysgeusia, tremor[Ref]

Other

Common (1% to 10%): Vertigo
Uncommon (0.1% to 1%): Asthenia[Ref]

Respiratory

Common (1% to 10%): Pharyngitis, sinusitis, nasopharyngitis, lower respiratory tract infection, upper respiratory tract infections, cough, chest pain, pleuritic pain, viral respiratory tract infection, oropharyngeal pain
Uncommon (0.1% to 1%): Productive cough, chest discomfort
Frequency not reported: Paradoxical bronchospasm[Ref]

Cardiovascular

Uncommon (0.1% to 1%): Atrial fibrillation, ventricular extrasystoles, supraventricular extrasystoles, myocardial infarction, rhythm idioventricular, tachycardia, supraventricular tachycardia
Frequency not reported: Symptoms of increases in pulse rate, systolic or diastolic blood pressure
Postmarketing reports: Palpitations[Ref]

Dermatologic

Uncommon (0.1% to 1%): Pruritus, rash[Ref]

Ocular

Uncommon (0.1% to 1%): Conjunctivitis
Frequency not reported: Worsening of 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)[Ref]

Hypersensitivity

Postmarketing reports: Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria

Psychiatric

Postmarketing reports: Anxiety

Some side effects of Anoro Ellipta may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.