Use of levocetirizine has been associated with somnolence, fatigue, asthenia, and urinary retention [see Warnings and Precautions (5)].
6.1 Clinical Trials Experience
The safety data described below reflect exposure to levocetirizine in 2,708 patients with allergic rhinitis or chronic idiopathic urticaria in 14 controlled clinical trials of 1 week to 6 months duration.
The short-term (exposure up to 6 weeks) safety data for adults and adolescents are based upon eight clinical trials in which 1896 patients (825 males and 1071 females aged 12 years and older) were treated with levocetirizine 2.5 mg, 5 mg, or 10 mg once daily in the evening.
The short-term safety data from pediatric patients are based upon two clinical trials in which 243 children with allergic rhinitis (162 males and 81 females 6 to 12 years of age) were treated with levocetirizine 5 mg once daily for 4 to 6 weeks, one clinical trial in which 114 children (65 males and 49 females 1 to 5 years of age) with allergic rhinitis or chronic idiopathic urticaria were treated with levocetirizine 1.25 mg twice daily for 2 weeks, and one clinical trial in which 45 children (28 males and 17 females 6 to 11 months of age) with symptoms of allergic rhinitis or chronic urticaria were treated with levocetirizine 1.25 mg once daily for 2 weeks.
The long-term (exposure of 4 or 6 months) safety data in adults and adolescents are based upon two clinical trials in which 428 patients (190 males and 238 females) with allergic rhinitis were exposed to treatment with levocetirizine 5 mg once daily. Long term safety data are also available from an 18-month trial in 255 levocetirizine-treated subjects 12 to 24 months of age.
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 trial of another drug and may not reflect the rates observed in practice.
Adults and Adolescents 12 years of Age and Older
In studies up to 6 weeks in duration, the mean age of the adult and adolescent patients was 32 years, 44% of the patients were men and 56% were women, and the large majority (more than 90%) was Caucasian.
In these trials 43% and 42% of the subjects in the levocetirizine 2.5 mg and 5 mg groups, respectively, had at least one adverse event compared to 43% in the placebo group.
In placebo-controlled trials of 1 to 6 weeks in duration, the most common adverse reactions were somnolence, nasopharyngitis, fatigue, dry mouth, and pharyngitis, and most were mild to moderate in intensity. Somnolence with levocetirizine showed dose ordering between tested doses of 2.5 mg, 5 mg and 10 mg and was the most common adverse reaction leading to discontinuation (0.5%).
Table 1 lists adverse reactions that were reported in greater than or equal to 2% of subjects aged 12 years and older exposed to levocetirizine 2.5 mg or 5 mg in eight placebo-controlled clinical trials and that were more common with levocetirizine than placebo.
Additional adverse reactions of medical significance observed at a higher incidence than in placebo in adults and adolescents aged 12 years and older exposed to levocetirizine
are syncope (0.2%) and weight increased (0.5%).
Pediatric Patients 6 to 12 Years of Age
A total of 243 pediatric patients 6 to 12 years of age received levocetirizine
5 mg once daily in two short-term placebo controlled double-blind trials. The mean age of the patients was 9.8 years, 79 (32%) were 6 to 8 years of age, and 50% were Caucasian. Table 2 lists adverse reactions that were reported in greater than or equal to 2% of subjects aged 6 to 12 years exposed to levocetirizine
5 mg in placebo-controlled clinical trials and that were more common with levocetirizine
than placebo.
Pediatric Patients 1 to 5 Years of Age
A total of 114 pediatric patients 1 to 5 years of age received levocetirizine1.25 mg twice daily in a two week placebo-controlled double-blind safety trial. The mean age of the patients was 3.8 years, 32% were 1 to 2 years of age, 71% were Caucasian and 18% were Black. Table 3 lists adverse reactions that were reported in greater than or equal to 2% of subjects aged 1 to 5 years exposed to levocetirizine1.25 mg twice daily in the placebo-controlled safety trial and that were more common with levocetirizinethan placebo.
Pediatric Patients 6 to 11 Months of Age
A total of 45 pediatric patients 6 to 11 months of age received levocetirizine1.25 mg once daily in a two week placebo-controlled double-blind safety trial. The mean age of the patients was 9 months, 51% were Caucasian and 31% were Black. Adverse reactions that were reported in more than 1 subject (i.e. greater than or equal to 3% of subjects) aged 6 to 11 months exposed to levocetirizine1.25 mg once daily in the placebo-controlled safety trial and that were more common with levocetirizinethan placebo included diarrhea and constipation which were reported in 6 (13%) and 1 (4%) and 3 (7%) and 1 (4%) children in the levocetirizineand placebo-treated groups, respectively.
Long-Term Clinical Trials Experience
In two controlled clinical trials, 428 patients (190 males and 238 females) aged 12 years and older were treated with levocetirizine
5 mg once daily for 4 or 6 months. The patient characteristics and the safety profile were similar to that seen in the short-term studies. Ten (2.3%) patients treated with levocetirizine
discontinued because of somnolence, fatigue or asthenia compared to 2 (<1%) in the placebo group.
There are no long term clinical trials in children below 12 years of age with allergic rhinitis or chronic idiopathic urticaria.
Laboratory Test Abnormalities
Elevations of blood bilirubin and transaminases were reported in <1% of patients in the clinical trials. The elevations were transient and did not lead to discontinuation in any patient.
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