Ciclesonideside effects

The following clinically significant adverse reactions are described elsewhere in the labeling: Oropharyngeal Candidiasis Immunosuppression and Risk of Infections Hypercorticism and Adrenal Suppression Reduction in Bone Mineral Density Growth Effects Glaucoma and Cataracts Most common adverse reactions (≥ 3%) are headache, nasopharyngitis, sinusitis, pharyngolaryngeal pain, upper respiratory infection, arthralgia, nasal congestion, pain in extremity and back pain. Other adverse reactions have been reported. To report SUSPECTED ADVERSE REACTIONS, contact Covis Pharma at 1-877-411-2510 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trial Experience The safety data described below for adult and pediatric patients 12 years of age and older reflect exposure to ALVESCO in doses ranging from 80 mcg to 640 mcg twice daily in five double-blind placebo-controlled clinical trials. Studies with once daily dosing are omitted from the safety database because the doses studied once daily are lower than the highest recommended twice daily doses. The five studies were of 12 to 16 weeks treatment duration, one of which included a safety extension follow-up of one year. In the 12 to 16 week treatment studies, 720 patients (298 males and 422 females) aged 12 years and older were exposed to ALVESCO. In the long-term safety trial, 197 patients (82 males and 115 females) with severe persistent asthma from one of the 12-week trials were re-randomized and treated for up to one year with ALVESCO 320 mcg twice daily. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults and Pediatric Patients 12 Years of Age and Older Four of the five trials included a total of 624 patients ages 12 years and older (359 females and 265 males) with asthma of varying severity who were treated with ALVESCO 80 mcg, 160 mcg, or 320 mcg twice daily for 12 to 16 weeks. These studies included patients previously using either controller therapy (predominantly inhaled corticosteroids) or reliever therapy (bronchodilator therapy alone). In these trials, the mean age was 39.1 years, and the majority of the patients (79.0%) were Caucasian. In these trials, 52.3%, 59.8% and 54.1% of the patients in the ALVESCO 80 mcg, 160 mcg, and 320 mcg treatment groups, respectively, had at least one adverse event compared to 58.0% in the placebo group. Table 2 includes adverse reactions for the recommended doses of ALVESCO that occurred at an incidence of ≥ 3% in any of the ALVESCO groups and which were more frequent with ALVESCO compared to placebo.

Table 2: Adverse Reactions with ≥ 3% Incidence Reported in Patients ≥ 12 Years of Age with ALVESCO in US Placebo-Controlled Clinical Trials in Patients Previously on Bronchodilators and/or Inhaled Corticosteroids Adverse Reaction Placebo (N=507) % ALVESCO 80 mcg BID (N=325) % 160 mcg BID (N=127) % 320 mcg BID (N=172) % Headache 7.3 4.9 11.0 8.7 Nasopharyngitis 7.5 10.5 8.7 7.0 Sinusitis 3.0 3.1 5.5 5.2 Pharyngolaryngeal pain 4.3 4.3 2.4

4.7 Upper respiratory

Inf. 6.5 7.1 8.7 4.1 Arthralgia 1.0 0.9 2.4 3.5 Nasal congestion 1.6 1.8 5.5 2.9 Pain in extremity 1.0 0.3 3.1 2.3 Back pain 2.0 0.6 3.1 1.2 The following adverse reactions occurred in these clinical trials using ALVESCO with an incidence of less than 1% and occurred at a greater incidence with ALVESCO than with placebo.

Infections and Infestations: Oral candidiasis Respiratory Disorders: Cough Gastrointestinal Disorders: Dry mouth, nausea General Disorders and Administrative Site Conditions: Chest discomfort Respiratory, Thoracic, and Mediastinal Disorders: Dysphonia, dry throat The fifth study was a 12-week clinical trial in asthma patients 12 years of age and older who previously required oral corticosteroids (average daily dose of oral prednisone of 12 mg/day), in which the effects of ALVESCO 320 mcg twice daily (n = 47) and 640 mcg twice daily (n = 49) were compared with placebo (n = 45) for the frequency of reported adverse reactions. The following adverse reactions occurred at an incidence of ≥ 3% in the ALVESCO-treated patients and were more frequent compared to placebo: sinusitis, hoarseness, oral candidiasis, influenza, pneumonia, nasopharyngitis, arthralgia, back pain, musculoskeletal chest pain, headache, urticaria, dizziness, gastroenteritis, face edema, fatigue, and conjunctivitis. Long-Term Clinical Trials Experience A total of 197 patients 12 years of age and older (82 males and 115 females) from one of the 12-week treatment placebo-controlled studies were re-randomized to ciclesonide 320 mcg twice daily and followed for one year. The safety profile from the one-year follow-up was similar to that seen in the 12- and 16-week treatment studies.

6.2 Post-marketing

Experience In addition to adverse reactions identified from clinical trials, the following adverse reactions have been identified during worldwide post-marketing use of ciclesonide oral inhalation. 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.

Immune System Disorders: Immediate or delayed hypersensitivity reactions such as angioedema with swelling of the lips, tongue and pharynx.