1 INDICATIONS AND USAGE

1.1 Seasonal Allergic Rhinitis

Levocetirizine Dihydrochloride is indicated for the relief of symptoms associated with seasonal allergic rhinitis in adults and children 2 years of age and older.

1.2 Perennial Allergic Rhinitis

Levocetirizine Dihydrochloride is indicated for the relief of symptoms associated with perennial allergic rhinitis in adults and children 6 months of age and older.

1.3 Chronic Idiopathic Urticaria

Levocetirizine Dihydrochloride is indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 months of age and older.

2 DOSAGE AND ADMINISTRATION

Levocetirizine Dihydrochloride is available as 2.5 mg/5 mL (0.5 mg/mL) oral solution and as 5 mg breakable (scored) tablets, allowing for the administration of 2.5 mg, if needed. Levocetirizine Dihydrochloride can be taken without regard to food consumption.

2.1 Adults and Children 12 Years of Age and Older

The recommended dose of Levocetirizine Dihydrochloride is 5 mg (1 tablet or 2 teaspoons [10 mL] oral solution) once daily in the evening. Some patients may be adequately controlled by 2.5 mg (1/2 tablet or 1 teaspoon [5 mL] oral solution) once daily in the evening.

2.2 Children 6 to 11 Years of Age

The recommended dose of Levocetirizine Dihydrochloride is 2.5 mg (1/2 tablet or 1 teaspoon [5 mL] oral solution) once daily in the evening. The 2.5 mg dose should not be exceeded because the systemic exposure with 5 mg is approximately twice that of adults [see Clinical Pharmacology (12.3)].

2.3 Children 6 months to 5 Years of Age

The recommended initial dose of Levocetirizine Dihydrochloride is 1.25 mg (1/2 teaspoon oral solution) [2.5mL] once daily in the evening. The 1.25 mg once daily dose should not be exceeded based on comparable exposure to adults receiving 5 mg [see Clinical Pharmacology (12.3)].

2.4 Dose Adjustment for Renal and Hepatic Impairment

In adults and children 12 years of age and older with:

• Mild renal impairment (creatinine clearance [CLCR] = 50-80 mL/min): a dose of 2.5 mg once daily is recommended;
• Moderate renal impairment (CLCR = 30-50 mL/min): a dose of 2.5 mg once every other day is recommended;
• Severe renal impairment (CLCR = 10-30 mL/min): a dose of 2.5 mg twice weekly (administered once every 3-4 days) is recommended;
• End-stage renal disease patients (CLCR < 10 mL/min) and patients undergoing hemodialysis should not receive Levocetirizine Dihydrochloride .

No dose adjustment is needed in patients with solely hepatic impairment. In patients with both hepatic impairment and renal impairment, adjustment of the dose is recommended.

3 DOSAGE FORMS AND STRENGTHS

Levocetirizine Dihydrochloride oral solution is a clear, colorless liquid containing 0.5 mg of levocetirizine dihydrochloride per mL

Levocetirizine Dihydrochloride tablets are white, film-coated, oval-shaped, scored, imprinted (with the letter Y in red color on both halves of the scored tablet) and contain 5 mg levocetirizine dihydrochloride.

4 CONTRAINDICATIONS

The use of Levocetirizine Dihydrochloride is contraindicated in:

4.1 Patients with known hypersensitivity

Patients with known hypersensitivity to levocetirizine or any of the ingredients of Levocetirizine Dihydrochloride or to cetirizine. Observed reactions range from urticaria to anaphylaxis [see Adverse Reactions (6.2)].

4.2 Patients with end-stage renal disease

Patients with end-stage renal disease (CLCR < 10 mL/min) and patients undergoing hemodialysis

4.3 Pediatric patients with impaired renal function

Children 6 months to 11 years of age with impaired renal function

5 WARNINGS AND PRECAUTIONS

5.1 Activities Requiring Mental Alertness

In clinical trials the occurrence of somnolence, fatigue, and asthenia has been reported in some patients under therapy with Levocetirizine Dihydrochloride. Patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness, and motor coordination such as operating machinery or driving a motor vehicle after ingestion of Levocetirizine Dihydrochloride. Concurrent use of Levocetirizine Dihydrochloride with alcohol or other central nervous system depressants should be avoided because additional reductions in alertness and additional impairment of central nervous system performance may occur.

6 ADVERSE REACTIONS

Use of Levocetirizine Dihydrochloride has been associated with somnolence, fatigue, and asthenia [see Warnings and Precautions (5.1)].

6.1 Clinical Trials Experience

The safety data described below reflect exposure to Levocetirizine Dihydrochloride in 2708 patients with seasonal or perennial 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 Dihydrochloride 2.5, 5, 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 seasonal or perennial allergic rhinitis (162 males and 81 females 6 to 12 years of age) were treated with Levocetirizine Dihydrochloride 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 Dihydrochloride 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 Dihydrochloride 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 Dihydrochloride 5 mg once daily. Long term safety data are also available from an 18-month trial in 255 Levocetirizine Dihydrochloride - treated subjects 12-24 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 Dihydrochloride 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 1-6 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 Dihydrochloride showed dose ordering between tested doses of 2.5, 5 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 Dihydrochloride 2.5 mg or 5 mg in eight placebo-controlled clinical trials and that were more common with Levocetirizine Dihydrochloride 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 Dihydrochloride 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 Dihydrochloride 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 Dihydrochloride 5 mg in placebo-controlled clinical trials and that were more common with Levocetirizine Dihydrochloride than placebo.

Pediatric Patients 1 to 5 Years of Age

A total of 114 pediatric patients 1 to 5 years of age received Levocetirizine Dihydrochloride 1.25 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 Levocetirizine Dihydrochloride 1.25 mg twice daily in the placebo-controlled safety trial and that were more common with Levocetirizine Dihydrochloride than placebo

Pediatric Patients 6 to 11 Months of Age

A total of 45 pediatric patients 6 to 11 months of age received Levocetirizine Dihydrochloride 1.25 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 Levocetirizine Dihydrochloride 1.25 mg once daily in the placebo-controlled safety trial and that were more common with Levocetirizine Dihydrochloride than placebo included diarrhea and constipati