levalbuterol inhalation

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Paradoxical bronchospasm [see Warnings and Precautions ( 5.1 ) ] Cardiovascular effects [see Warnings and Precautions ( 5.4 ) ] Immediate hypersensitivity reactions [see Warnings and Precautions ( 5.6 ) ] Hypokalemia [see Warnings and Precautions ( 5.8 ) ] Most common adverse reactions are: palpitations, chest pain, tachycardia, headache, dizziness, tremor and nervousness. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Cipla Ltd., India at 1-866-604-3268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of the drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults and Adolescents 12 Years of Age and Older: Adverse reaction information concerning Levalbuterol Inhalation Solution in adults and adolescents is derived from one 4-week, multicenter, randomized, double-blind, active-, and placebo-controlled trial in 362 patients with asthma 12 years of age and older. Adverse reactions reported in ≥2% of patients receiving Levalbuterol Inhalation Solution or racemic albuterol and more frequently than in patients receiving placebo are listed in Table 1. Table 1: Adverse Reactions Reported in a 4-Week, Controlled Clinical Trial in Adults and Adolescents ≥12 Years Old ­ a One treatment group, racemic albuterol 1.25 mg, with 68 subjects is omitted. ­ ­ Percent of Patients a ­ ­ Levalbuterol Levalbuterol Racemic albuterol Body System Placebo 1.25mg 0.63mg 2.5mg Preferred Term (n=75) (n=73) (n=72) (n=74) Body as a Whole ­ ­ ­ ­ Allergic reaction 1.3 0 0 2.7 Flu syndrome 0 1.4 4.2 2.7 Accidental injury 0 2.7 0 0 Pain 1.3 1.4 2.8 2.7 Back pain 0 0 0 2.7 Cardiovascular System Tachycardia 0 2.7 2.8 2.7 Migraine 0 2.7 0 0 Digestive System Dyspepsia 1.3 2.7 1.4 1.4 Musculoskeletal System Leg cramps 1.3 2.7 0 1.4 Central Nervous System Dizziness 1.3 2.7 1.4 0 Hypertonia 0 0 0 2.7 Nervousness 0 9.6 2.8 8.1 Tremor 0 6.8 0 2.7 Anxiety 0 2.7 0 0 Respiratory System Cough increased 2.7 4.1 1.4 2.7 Infection viral 9.3 12.3 6.9 12.2 Rhinitis 2.7 2.7 11.1 6.8 Sinusitis 2.7 1.4 4.2 2.7 Turbinate edema 0 1.4 2.8 0 The incidence of certain systemic beta-adrenergic adverse reactions (e.g., tremor, nervousness) was slightly less in the Levalbuterol Inhalation Solution 0.63 mg group compared with the other active treatment groups. The clinical significance of these small differences is unknown. Changes in heart rate 15 minutes after drug administration and in plasma glucose and potassium 1 hour after drug administration on day 1 and day 29 were clinically comparable in the Levalbuterol Inhalation Solution 1.25 mg and racemic albuterol 2.5 mg groups (see Table 2). Changes in heart rate and plasma glucose were slightly less in the Levalbuterol Inhalation Solution 0.63 mg group compared with the other active treatment groups (see Table 2). The clinical significance of these small differences is unknown. After 4 weeks, effects on heart rate, plasma glucose, and plasma potassium were generally diminished compared with day 1 in all active treatment groups. Table 2: Mean Changes from Baseline Heart Rate at 15 Minutes and Glucose and Potassium at 1 Hour after First Dose (Day 1) in Adults and Adolescents ≥12 Years Old ­ Mean Changes (day 1) ­ Heart Rate (bpm) Glucose (mg/dL) Potassium (mEq/L) Treatment ­ ­ ­ Levalbuterol 0.63mg, n=72 2.4 4.6 -0.2 Levalbuterol 1.25mg, n=73 6.9 10.3 -0.3 Racemic albuterol 2.5mg, n=74 5.7 8.2 -0.3 Placebo, n=75 -2.8 -0.2 -0.2 No other clinically relevant laboratory abnormalities related to administration of Levalbuterol Inhalation Solution were observed in this study. In the clinical trials, a slightly greater number of serious adverse events, discontinuations due to adverse events, and clinically significant ECG changes were reported in patients who received Levalbuterol 1.25 mg compared with the other active treatment groups. The following adverse reactions, considered potentially related to Levalbuterol, occurred in less than 2% of the 292 subjects who received Levalbuterol and more frequently than in patients who received placebo in any clinical trial: Body as a Whole: chills, pain, chest pain Cardiovascular System: ECG abnormal, ECG change, hypertension, hypotension, syncope Digestive System: diarrhea, dry mouth, dry throat, dyspepsia, gastroenteritis, nausea Hemic and Lymphatic System: lymphadenopathy Musculoskeletal System: leg cramps, myalgia Nervous System: anxiety, hyperesthesia of the hand, insomnia, paresthesia, tremor Special Senses: eye itch The following reactions, considered potentially related to Levalbuterol, occurred in less than 2% of the treated subjects but at a frequency less than in patients who received placebo: asthma exacerbation, cough increased, wheezing, sweating, and vomiting. Pediatric Patients 6 to 11 Years of Age: Adverse reaction information concerning Levalbuterol Inhalation Solution in pediatric patients is derived from one 3-week, multicenter, randomized, double-blind, active-, and placebo-controlled trial in 316 pediatric patients 6 to 11 years of age. Adverse reactions reported in ≥2% of patients in any treatment group and more frequently than in patients receiving placebo are listed in Table 3. Table 3: Most Frequently Reported Adverse Reactions (≥2% in Any Treatment Group) and Those Reported More Frequently Than in Placebo during the Double-Blind Period (ITT Population, 6-11 Years Old) ­ Percent of Patients ­ ­ ­ ­ Racemic Racemic ­ ­ Levalbuterol Levalbuterol albuterol albuterol Body System Placebo 0.31mg 0.63mg 1.25mg 2.5mg Preferred Term (n=59) (n=66) (n=67) (n=64) (n=60) Body as a Whole ­ ­ ­ ­ ­ Abdominal pain 3.4 0 1.5 3.1 6.7 Accidental injury 3.4 6.1 4.5 3.1 5.0 Asthenia 0 3.0 3.0 1.6 1.7 Fever 5.1 9.1 3.0 1.6 6.7 Headache 8.5 7.6 11.9 9.4 3.3 Pain 3.4 3.0 1.5 4.7 6.7 Viral infection 5.1 7.6 9.0 4.7 8.3 Digestive System Diarrhea 0 1.5 6.0 1.6 0 Hemic and Lymphatic Lymphadenopathy 0 3.0 0 1.6 0 Musculoskeletal System ­ ­ ­ ­ ­ Myalgia 0 0 1.5 1.6 3.3 Respiratory System ­ ­ ­ ­ ­ Asthma 5.1 9.1 9.0 6.3 10.0 Pharyngitis 6.8 3.0 10.4 0 6.7 Rhinitis 1.7 6.1 10.4 3.1 5.0 Skin and Appendages ­ ­ ­ ­ ­ Eczema 0 0 0 0 3.3 Rash 0 0 7.5 1.6 0 Urticaria 0 0 3.0 0 0 Special Senses ­ ­ ­ ­ ­ Otitis media 1.7 0 0 0 3.3 Note: Subjects may have more than one adverse event per body system and preferred term. Changes in heart rate, plasma glucose, and serum potassium are shown in Table 4. The clinical significance of these small differences is unknown. Table 4: Mean Changes from Baseline Heart Rate at 30 Minutes and Glucose and Potassium at 1 Hour after First Dose (Day 1) and Last Dose (Day 21) in Children 6-11 Years Old ­ Mean Changes (day 1) ­ Heart Rate (bpm) Glucose (mg/dL) Potassium (mEq/L) Treatment ­ ­ ­ Levalbuterol 0.31mg, n=66 0.8 4.9 -0.31 Levalbuterol 0.63mg, n=67 6.7 5.2 -0.36 Racemic albuterol 1.25mg, n=64 6.4 8.0 -0.27 Racemic albuterol 2.5mg, n=60 10.9 10.8 -0.56 Placebo, n=59 -1.8 0.6 -0.05 ­ Mean Changes (day 21) ­ Heart Rate (bpm) Glucose (mg/dL) Potassium (mEq/L) Treatment ­ ­ ­ Levalbuterol 0.31mg, n=60 0 2.6 -0.32 Levalbuterol 0.63mg, n=66 3.8 5.8 -0.34 Racemic albuterol 1.25mg, n=62 5.8 1.7 -0.18 Racemic albuterol 2.5mg, n=54 5.7 11.8 -0.26 Placebo, n=55 -1.7 1.1 -0.04 6.2 Post-marketing Experience In addition to the adverse reactions reported in clinical trials, the following adverse reactions have been observed in postapproval use of Levalbuterol Inhalation Solution. 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 their seriousness, their frequency of reporting, or their likely beta-mediated mechanism: angioedema, anaphylaxis, arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles), asthma, chest pain, cough increased, dysphonia, dyspnea, gastrooesophageal reflux disease (GERD), metabolic acidosis, nausea, nervousness, rash, tachycardia, tremor, urticaria. In addition, Levalbuterol Inhalation Solution, like other sympathomimetic agents, can cause adverse reactions such as hypertension, angina, vertigo, central nervous system stimulation, sleeplessness, headache, and drying or irritation of the oropharynx.