6 ADVERSE REACTIONS The most common adverse reactions (≥ 2%) in subjects age 12 years and older were headache, back pain, dizziness, stomach discomfort, and pain in extremity. In subjects aged 6 to 11 years, cough, upper respiratory tract infection, pyrexia and otitis media were more frequently reported. In subjects aged 6 months to 5 years, vomiting, diarrhea, somnolence/fatigue and rhinorrhea were more frequently reported. ( 6.1 ) Other adverse reactions have been reported. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan Pharmaceuticals Inc. at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Studies 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described below reflect exposure to fexofenadine hydrochloride in 5,083 patients in trials for allergic rhinitis and chronic idiopathic urticaria. In these trials, 3,010 patients 12 years of age and older with seasonal allergic rhinitis were exposed to fexofenadine hydrochloride at doses of 20 mg to 240 mg twice daily or 120 mg to 180 mg once daily. A total of 646 patients 6 to 11 years of age with seasonal allergic rhinitis were exposed to fexofenadine hydrochloride at doses of 15 mg to 60 mg twice daily. The duration of treatment in these trials was 2 weeks. A total of 534 patients 6 months to 5 years of age with allergic rhinitis were exposed to fexofenadine hydrochloride at doses of 15 mg to 30 mg twice daily. The duration of treatment in these trials ranged from one day to 2 weeks. There were 893 patients 12 years of age and older with chronic idiopathic urticaria exposed to fexofenadine hydrochloride at doses of 20 mg to 240 mg twice daily or 180 mg once daily. The duration of treatment in these trials was 4 weeks. Seasonal Allergic Rhinitis Adults and Adolescents In placebo-controlled seasonal allergic rhinitis clinical trials in subjects 12 years of age and older, 2,439 subjects received fexofenadine hydrochloride capsules at doses of 20 mg to 240 mg twice daily. All adverse reactions that were reported by greater than 1% of subjects who received the recommended daily dose of fexofenadine hydrochloride (60 mg capsules twice daily) are listed in Table 1. In another placebo-controlled clinical study in the United States, 571 subjects aged 12 years and older received fexofenadine hydrochloride tablets at doses of 120 mg or 180 mg once daily. Table 1 also lists adverse reactions that were reported by greater than 2% of subjects treated with fexofenadine hydrochloride tablets at doses of 180 mg once daily. The incidence of adverse reactions, including somnolence/fatigue, was not dose related and was similar across subgroups defined by age, gender, and race. Table 1 Adverse Reactions in Subjects Aged 12 Years and Older Reported in Placebo-Controlled Seasonal Allergic Rhinitis Clinical Trials in the United States Twice Daily Dosing with Fexofenadine Capsules at Rates of Greater Than 1% Adverse reaction Fexofenadine 60 mg Twice Daily (n=680) Placebo Twice Daily (n=674) Frequency Frequency Dysmenorrhea 1.5% 0.3% Once Daily Dosing with Fexofenadine Hydrochloride Tablets at Rates of Greater Than 2% Adverse reaction Fexofenadine 180 mg Once Daily (n=283) Placebo (n=293) Frequency Frequency Headache 10.3% 7.2% Back Pain 2.5% 1.4% The frequency and magnitude of laboratory abnormalities were similar in fexofenadine hydrochloride- and placebo-treated subjects. Pediatrics Table 2 lists adverse reactions in subjects aged 6 years to 11 years of age which were reported by greater than 2% of subjects treated with fexofenadine hydrochloride tablets at a dose of 30 mg twice daily in placebo-controlled seasonal allergic rhinitis studies in the United States and Canada. Table 2 Adverse Reactions Reported in Placebo-Controlled Seasonal Allergic Rhinitis Studies in Pediatric Subjects Aged 6 Years to 11 Years in the United States and Canada at Rates of Greater Than 2% Adverse reaction Fexofenadine 30 mg Twice Daily (n = 209) Frequency Placebo (n = 229) Frequency Cough 3.8% 1.3% Upper Respiratory Tract Infection 2.9% 0.9% Pyrexia 2.4% 0.9% Otitis Media 2.4% 0.0% Table 3 lists adverse reactions in subjects 6 months to 5 years of age which were reported by greater than 2% of subjects treated with fexofenadine hydrochloride in three open single and multiple dose pharmacokinetic studies and three placebo-controlled safety studies with fexofenadine hydrochloride capsule content (484 subjects) and suspension (50 subjects) at doses of 15 mg (108 subjects) and 30 mg (426 subjects) given twice a day. Table 3 Adverse Reactions Reported in Placebo-Controlled Studies in Pediatric Subjects with Allergic Rhinitis Aged 6 Months to 5 Years of Age at Rates Greater Than 2% Adverse reaction Fexofenadine 15 mg Twice Daily (n = 108) Frequency Fexofenadine 30 mg Twice Daily (n = 426) Frequency Fexofenadine Total Twice Daily (n = 534) Frequency Placebo (n = 430) Frequency Vomiting 12% 4.2% 5.8% 8.6% Diarrhea 3.7% 2.8% 3% 2.6% Somnolence/Fatigue 2.8% 0.9% 1.3% 0.2% Rhinorrhea 0.9% 2.1% 1.9% 0.9% Chronic Idiopathic Urticaria Adverse reactions reported by subjects 12 years of age and older in placebo-controlled chronic idiopathic urticaria studies were similar to those reported in placebo-controlled seasonal allergic rhinitis studies. In placebo-controlled chronic idiopathic urticaria clinical trials, 726 subjects 12 years of age and older received fexofenadine hydrochloride tablets at doses of 20 mg to 240 mg twice daily. Table 4 lists adverse reactions in subjects aged 12 years and older which were reported by greater than 2% of subjects treated with fexofenadine hydrochloride 60 mg tablets twice daily in controlled clinical studies in the United States and Canada. In a placebo-controlled clinical study in the United States, 167 subjects aged 12 years and older received fexofenadine hydrochloride 180 mg tablets. Table 4 also lists adverse reactions that were reported by greater than 2% of subjects treated with fexofenadine hydrochloride tablets at doses of 180 mg once daily. Table 4 Adverse Reactions Reported in Subjects 12 years of Age and Older in Placebo-Controlled Chronic Idiopathic Urticaria Studies Twice-Daily Dosing with Fexofenadine Hydrochloride in Studies in the United States and Canada at Rates of Greater than 2% Adverse reaction Fexofenadine 60 mg Twice Daily (n = 191) Frequency Placebo (n = 183) Frequency Dizziness 2.1% 1.1% Back Pain 2.1% 1.1% Stomach discomfort 2.1% 0.6% Pain in extremity 2.1% 0% Once-Daily Dosing with Fexofenadine Hydrochloride in a Study in the United States at Rates of Greater than 2% Adverse reaction Fexofenadine 180 mg Once Daily (n = 167) Frequency Placebo (n = 92) Frequency Headache 4.8% 3.3% The safety of fexofenadine hydrochloride in the treatment of chronic idiopathic urticaria in pediatric patients 6 months to 11 years of age is based on the safety profile of fexofenadine hydrochloride in adults and pediatric patients at doses equal to or higher than the recommended dose [see Use in Specific Populations (8.4) ]. 6.2 Post-Marketing Experience In addition to the adverse reactions reported during clinical studies and listed above, the following adverse events have been identified during post-approval use of fexofenadine hydrochloride tablets. Because these events 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. Events that have been reported rarely during post-marketing experience include: insomnia, nervousness, sleep disorders or paroniria, and hypersensitivity reactions (including anaphylaxis, urticaria, angioedema, chest tightness, dyspnea, flushing, pruritis, and rash).