1 Adverse Reaction Overview Long-acting beta2-adrenergic agonists such as vilanterol, one of the active ingredients of ANORO ELLIPTA increase the risk of asthma-related death. ANORO ELLIPTA is not indicated for the treatment of asthma (See 1 INDICATIONS and 3 SERIOUS WARNINGS AND PRECAUTIONS BOX).
ANORO ELLIPTA is a combination of a long-acting muscarinic antagonist and a long-acting beta2-agonist. Adverse reactions to ANORO ELLIPTA are expected to be similar in nature to other muscarinic antagonists and beta2-agonists. Adverse reactions that have been associated with other muscarinic antagonists include cardiovascular effects (atrial arrhythmias and tachycardia), ocular disorders (blurred vision), urinary retention, gastrointestinal disorders, dry mouth and cough.
Adverse reactions that have been associated with other beta2-agonists include immediate hypersensitivity reactions (urticaria, rash, bronchospasm, edema, angioedema, and anaphylactic shock or anaphylactic reaction), cardiovascular effects (tachycardia, arrhythmia, palpitations, myocardial ischemia, angina pectoris, hypertension or hypotension), hypokalemia, hyperglycemia, and metabolic acidosis, headache, nervousness, insomnia, PrANORO ELLIPTA (umeclidinium/vilanterol) Page 12 of 38 dizziness, nausea, muscle spasms, fatigue, malaise, and tremor.
2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. 5/25 mcg or greater for up to one year during clinical studies. 5/25 mcg and 1,330 patients who received 125/25 mcg, all once-daily.
Patients were excluded from clinical studies if they had clinically significant cardiovascular abnormalities that were uncontrolled or a significant ECG finding from the 12-lead ECG conducted at the study entry. 24-week studies A total of 1,674 subjects (518 females and 1,156 males) with COPD were treated once daily with ANORO ELLIPTA or umeclidinium/vilanterol 125/25 mcg.
Other treatments included the individual components (umeclidinium or vilanterol), placebo, or active comparator (tiotropium bromide). Table 2 shows all adverse events that occurred with a frequency of equal to or greater than 1% in patients receiving ANORO ELLIPTA in the four 24-week well-controlled studies where the rates in patients receiving ANORO ELLIPTA exceeded placebo.
5 mcg (n=418) Vilanterol 25 mcg (n=1,034) % % % % Infections and Infestations Pharyngitis Sinusitis Lower respiratory tract infection <1 <1 <1 2 1 1 1 <1 <1 2 1 <1 Gastrointestinal Disorders Diarrhea Constipation 1 <1 2 1 <1 <1 2 <1 Musculoskeletal and Connective Tissue Disorders Pain in extremity Muscle spasms Neck pain 1 <1 <1 2 1 1 <1 <1 <1 2 <1 <1 General disorders and administration site conditions Chest pain <1 1 <1 <1 Studies DB2113361, DB2113373, DB2113360, and DB2113374 Incidence boundaries are applied prior to rounding percentages for presentation in the table.
12-month study In a long-term safety study, 335 subjects were treated for up to 12 months with umeclidinium/vilanterol 125/25 mcg or placebo. The demographic and baseline characteristics of the long-term safety study were PrANORO ELLIPTA (umeclidinium/vilanterol) Page 13 of 38 similar to those of the placebo-controlled efficacy studies.
Patients with an abnormal/significant ECG finding or 24-hour Holter monitoring finding during the study withdrew from the study. Adverse events that occurred with a frequency of equal to or greater than 1% in the group receiving 125/25 mcg and exceeded placebo in this study were: headache, back pain, sinusitis, cough, urinary tract infection, arthralgia, nausea, vertigo, abdominal pain, pleuritic pain, respiratory tract infection viral, toothache and diabetes mellitus.
3 Less Common Clinical Trial Adverse Reactions (<1%) Cardiac disorders: atrial fibrillation, atrial flutter, ECG PR prolongation, increased heart rate, palpitation, tachycardia, supraventricular extrasystoles, supraventricular tachycardia (SVT), ectopic supraventricular rhythm, and cardiac ischemia.
Gastrointestinal disorders: dry mouth. Respiratory, Thoracic and Mediastinal Disorders: cough. 5 Post-Market Adverse Reactions The following relevant adverse reactions have been identified from post-approval use of ANORO ELLIPTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune System Disorders: hypersensitivity reactions including rash (uncommon), anaphylaxis (rare), angioedema (rare), and urticaria (rare) Psychiatric Disorders: anxiety (uncommon) Nervous System Disorders: tremor (uncommon), dysgeusia (uncommon) Eye Disorders: vision blurred (rare), glaucoma (rare), intraocular pressure increased (rare), eye pain (rare) Respiratory, Thoracic and Mediastinal Disorders: paradoxical bronchospasm (rare), dysphonia (rare) Renal and Urinary Disorders: urinary retention (rare), dysuria (rare)