Fluticasoneside effects

The following clinically significant adverse reactions are described elsewhere in labeling:

Serious Asthma-Related Events – Hospitalizations, Intubations, Death

Oropharyngeal Candidiasis

Increased Risk of Pneumonia in COPD

Immunosuppression and Risk of Infections

Hypercorticism and Adrenal Suppression

Paradoxical Bronchospasm

Cardiovascular Effects

Reduction in Bone Mineral Density

Worsening of Narrow-Angle Glaucoma

Worsening of Urinary Retention 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.

COPD: Most common adverse reactions (incidence ≥1%) are upper respiratory tract infection, pneumonia, bronchitis, oral candidiasis, headache, back pain, arthralgia, influenza, sinusitis, pharyngitis, rhinitis, dysgeusia, constipation, urinary tract infection, diarrhea, gastroenteritis, oropharyngeal pain, cough, and dysphonia.

Asthma: Most common adverse reactions (incidence ≥2%) are pharyngitis/nasopharyngitis, upper respiratory tract infection/viral upper respiratory tract infection, bronchitis, respiratory tract infection/viral respiratory tract infection, sinusitis/acute sinusitis, urinary tract infection, rhinitis, influenza, headache, and back pain. To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience in Chronic Obstructive Pulmonary Disease The safety of TRELEGY ELLIPTA in COPD is based on the safety data from two 12-week treatment trials with coadministration of umeclidinium and the fixed-dose combination of fluticasone furoate/vilanterol and a 52-week long-term trial of TRELEGY ELLIPTA 100/62.5/25 mcg compared with the fixed-dose combinations of fluticasone furoate/vilanterol and umeclidinium/vilanterol. Trials 1 and 2 Two 12-week treatment trials (Trial 1 and Trial 2) evaluated the coadministration of umeclidinium + fluticasone furoate/vilanterol, the components of TRELEGY ELLIPTA, compared with placebo + fluticasone furoate/vilanterol. A total of 824 subjects with COPD across two 12-week, randomized, double-blind clinical trials received at least 1 dose of umeclidinium 62.5 mcg + fluticasone furoate/vilanterol 100/25 mcg or placebo + fluticasone furoate/vilanterol 100/25 mcg administered once daily (mean age: 64 years, 92% White, 66% male across all treatments). The incidence of adverse reactions associated with the use of umeclidinium 62.5 mcg + fluticasone furoate/vilanterol 100/25 mcg presented in Table 2 is based on the two 12-week trials. Table 2. Adverse Reactions with Umeclidinium + Fluticasone Furoate/Vilanterol with ≥1% Incidence and More Common than Placebo + Fluticasone Furoate/Vilanterol in Subjects with COPD (Trials 1 and 2) Umec = Umeclidinium, FF/VI = Fluticasone Furoate/Vilanterol. Adverse Reaction Umec + FF/VI (n = 412) % Placebo + FF/VI (n = 412) % Nervous system disorders Headache 4 3 Dysgeusia 2 <1 Musculoskeletal and connective tissue disorders Back pain 4 2 Respiratory, thoracic, and mediastinal disorders Cough 1 <1 Oropharyngeal pain 1 0 Gastrointestinal disorders Diarrhea 2 <1 Infections and infestations Gastroenteritis 1 0 Trial 3 – Long-term Safety Data A 52-week trial (Trial 3) evaluated the long-term safety of TRELEGY ELLIPTA 100/62.5/25 mcg compared with the fixed-dose combinations of fluticasone furoate/vilanterol 100/25 mcg and umeclidinium/vilanterol 62.5/25 mcg. A total of 10,355 subjects with COPD with a history of moderate or severe exacerbations within the prior 12 months were randomized (2:2:1) to receive TRELEGY ELLIPTA 100/62.5/25 mcg, fluticasone furoate/vilanterol, or umeclidinium/vilanterol administered once daily in a double‑blind clinical trial (mean age: 65 years, 77% White, 66% male across all treatments). The incidence of adverse reactions in the long-term trial were consistent with those in Trials 1 and 2. However, in addition to the adverse reactions shown in Table 2, adverse reactions occurring in ≥1% of the subjects treated with TRELEGY ELLIPTA 100/62.5/25 mcg (n = 4,151) for up to 52 weeks also included upper respiratory tract infection, pneumonia, bronchitis, oral candidiasis, arthralgia, influenza, sinusitis, pharyngitis, rhinitis, constipation, urinary tract infection, and dysphonia.

6.2 Clinical

Trials Experience in Asthma The safety of TRELEGY ELLIPTA in asthma is based on a randomized, double-blind, parallel‑group, active-controlled trial of 24 to 52 weeks’ duration (Trial 4) that enrolled 2,436 adult subjects inadequately controlled on their current treatment of combination therapy (ICS plus a LABA). In the overall population, 62% were female and 80% were White; mean age was 53 years. The incidence of adverse reactions occurring in ≥1% of the subjects treated with TRELEGY ELLIPTA 100/62.5/25 mcg or TRELEGY ELLIPTA 200/62.5/25 mcg is shown in Table 3. Adverse reactions observed for the groups treated with TRELEGY ELLIPTA were similar to those observed for the fluticasone furoate/vilanterol arms. Table 3. Adverse Reactions with TRELEGY ELLIPTA with ≥1% Incidence in Subjects with Asthma (Trial 4) FF/VI = Fluticasone Furoate/Vilanterol. Adverse Reaction TRELEGY ELLIPTA 200/62.5/25 mcg (n = 408) % TRELEGY ELLIPTA 100/62.5/25 mcg (n =406) % FF/VI 200/25 mcg (n = 406) % FF/VI 100/25 mcg (n = 407) % Infections and infestations Pharyngitis/nasopharyngitis 15 17 16 16 Upper respiratory tract infection/viral upper respiratory tract infection 7 5 6 7 Bronchitis 5 4 5 3 Respiratory tract infection/viral respiratory tract infection 3 4 2 4 Sinusitis/acute sinusitis 3 2 2 3 Urinary tract infection 2 <1 <1 1 Rhinitis 1 2 2 3 Influenza 1 4 2 3 Pneumonia <1 1 2 2 Nervous system disorders Headache 5 9 6 7 Musculoskeletal and connective tissue disorders Back pain 2 3 1 4 Respiratory, thoracic, and mediastinal disorders Dysphonia 1 1 2 1 Oropharyngeal pain 1 1 <1 <1 Cough 1 <1 1 1

6.3 Postmarketing

Experience In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of TRELEGY 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 TRELEGY ELLIPTA or a combination of these factors. Cardiac Disorders Palpitations Eye Disorders Blurred vision, eye pain, glaucoma, and intraocular pressure increase Immune System Disorders Hypersensitivity reactions, including anaphylaxis, angioedema, rash, and urticaria Metabolism and Nutrition Disorders Hyperglycemia Musculoskeletal and Connective Tissue Disorders Muscle spasms Nervous System Disorders Tremor Psychiatric Disorders Anxiety Renal and Urinary Disorders Dysuria, urinary retention.