Levocetirizine dihydrochloride tablets are a histamine H 1 -receptor antagonist indicated for: The treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria ( 1.2 )
1.2Chronic Idiopathic Urticaria
Levocetirizine dihydrochloride tablets are indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 years of age and older.
Contraindications
The use of levocetirizine dihydrochloride tablets is contraindicated in: Patients with a known hypersensitivity to levocetirizine or any of the ingredients of levocetirizine dihydrochloride tablets or to cetirizine ( 4.1 ) Patients with end-stage renal disease at less than 10 mL/min creatinine clearance or patients undergoing hemodialysis ( 4.2 ) Children 6 months to 11 years of age with renal impairment ( 4.3 )
4.1Patients with Known Hypersensitivity Patients
with known hypersensitivity to levocetirizine or any of the ingredients of levocetirizine dihydrochloride tablets, or to cetirizine. Observed reactions range from urticaria to anaphylaxis [see Adverse Reactions ( 6.2 )] .
4.2Patients with End-Stage Renal Disease Patients
with end-stage renal disease (CL CR < 10 mL/min) and patients undergoing hemodialysis.
4.3Pediatric Patients with Impaired Renal Function Children
6 months to 11 years of age with impaired renal function.
Warnings and precautions
Avoid engaging in hazardous occupations requiring complete mental alertness such as driving or operating machinery when taking levocetirizine dihydrochloride ( 5.1 ). Avoid concurrent use of alcohol or other central nervous system depressants with levocetirizine dihydrochloride ( 5.1 ). Use with caution in patients with predisposing factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia). Discontinue levocetirizine dihydrochloride if urinary retention occurs ( 5.2 ).
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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.
5.2Urinary Retention
Urinary retention has been reported postmarketing with levocetirizine dihydrochloride. Levocetirizine dihydrochloride should be used with caution in patients with predisposing factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia) as levocetirizine dihydrochloride may increase the risk of urinary retention. Discontinue levocetirizine dihydrochloride if urinary retention occurs.
Interactions
In vitro data indicate that levocetirizine is unlikely to produce pharmacokinetic interactions through inhibition or induction of liver drug-metabolizing enzymes. No in vivo drug-drug interaction studies have been performed with levocetirizine. Drug interaction studies have been performed with racemic cetirizine.
7.1Antipyrine, Azithromycin, Cimetidine, Erythromycin, Ketoconazole, Theophylline, and Pseudoephedrine
Pharmacokinetic interaction studies performed with racemic cetirizine demonstrated that cetirizine did not interact with antipyrine, pseudoephedrine, erythromycin, azithromycin, ketoconazole, and cimetidine. There was a small decrease (~ 16%) in the clearance of cetirizine caused by a 400 mg dose of theophylline. It is possible that higher theophylline doses could have a greater effect.
7.2Ritonavir
Ritonavir increased the plasma AUC of cetirizine by about 42% accompanied by an increase in half-life (53%) and a decrease in clearance (29%) of cetirizine. The disposition of ritonavir was not altered by concomitant cetirizine administration.
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary
Available data from published literature and postmarketing experience with levocetirizine use in pregnant women are insufficient to identify any drug-associated risks of miscarriage, birth defects, or adverse maternal or fetal outcomes. In animal reproduction studies, there was no evidence of fetal harm with administration of levocetirizine by the oral route to pregnant rats and rabbits, during the period of organogenesis, at doses up to 390 times and 470 times, respectively, the maximum recommended human dose (MRHD) in adults.
In rats treated during late gestation and the lactation period, cetirizine had no effects on pup development at oral doses up to approximately 60 times the MRHD in adults. In mice treated during late gestation and the lactation period, cetirizine administered by the oral route to the dams had no effects on pup development at a dose that was approximately 25 times the MRHD in adults; however, lower pup weight gain during lactation was observed at a dose that was 95 times the MRHD in adults [see Data] .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal data In embryo-fetal development studies, pregnant rats received daily doses of levocetirizine up to 200 mg/kg/day from gestation days 6 to 15 and pregnant rabbits received daily doses of levocetirizine up to 120 mg/kg/day from gestation days 6 to 18.
Levocetirizine produced no evidence of fetal harm in rats and rabbits at doses up to 390 and 470 times the MRHD, respectively (on a mg/m 2 basis with maternal oral doses of 200 and 120 mg/kg/day in rats and rabbits, respectively). No prenatal and postnatal development (PPND) studies in animals have been conducted with levocetirizine. In a PPND study conducted in mice, cetirizine was administered at oral doses up to 96 mg/kg/day from gestation day 15 through lactation day 21.
Cetirizine lowered pup body weight gain during lactation at an oral dose in dams that was approximately 95 times the MRHD (on a mg/m 2 basis with a maternal oral dose of 96 mg/kg/day); however, there were no effects on pup weight gain at an oral dose in dams that was approximately 25 times the MRHD (on a mg/m 2 basis with a maternal oral dose of 24 mg/kg/day). In a PPND study conducted in rats, cetirizine was administered at oral doses up to 180 mg/kg/day from gestation day 17 to lactation day 22.
Cetirizine did not have any adverse effects on rat dams or offspring development at doses up to approximately 60 times the MRHD (on a mg/m 2 basis with a maternal oral dose of 30 mg/kg/day). Cetirizine caused excessive maternal toxicity at an oral dose in dams that was approximately 350 times the MRHD (on a mg/m 2 basis with a maternal oral dose of 180 mg/kg/day).
Adverse reactions
Use of levocetirizine dihydrochloride has been associated with somnolence, fatigue, asthenia, and urinary retention [see Warnings and Precautions ( 5 )]. The most common adverse reactions (rate ≥2% and > placebo) were somnolence, nasopharyngitis, fatigue, dry mouth, and pharyngitis in subjects 12 years of age and older, and pyrexia, somnolence, cough, and epistaxis in children 6 to 12 years of age. In subjects 1 to 5 years of age, the most common adverse reactions (rate ≥2% and > placebo) were pyrexia, diarrhea, vomiting, and otitis media.
In subjects 6 to 11 months of age, the most common adverse reactions (rate ≥3% and > placebo) were diarrhea and constipation. ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals USA, Inc . at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience
The safety data described below reflect exposure to levocetirizine dihydrochloride in 2708 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 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 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 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 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 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 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.
Table 1: Adverse Reactions Reported in ≥2%* of Subjects Aged 12 Years and Older Exposed to Levocetirizine Dihydrochloride 2.5 mg or 5 mg Once Daily in Placebo-Controlled Clinical Trials 1 to 6 Weeks in Duration Adverse Reactions Levocetirizine Dihydrochloride 2.5 mg (n = 421) Levocetirizine Dihydrochloride 5 mg (n = 1070) Placebo (n = 912) Somnolence 22 (5%) 61 (6%) 16 (2%) Nasopharyngitis 25 (6%) 40 (4%) 28 (3%) Fatigue 5 (1%) 46 (4%) 20 (2%) Dry Mouth 12 (3%) 26 (2%) 11 (1%) Pharyngitis 10 (2%) 12 (1%) 9 (1%) * Rounded to the closest unit percentage 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.
Table 2: Adverse Reactions Reported in ≥2%* of Subjects Aged 6 to 12 Years Exposed to Levocetirizine Dihydrochloride 5 mg Once Daily in Placebo-Controlled Clinical Trials 4 and 6 Weeks in Duration Adverse Reactions Levocetirizine Dihydrochloride 5 mg (n = 243) Placebo (n = 240) Pyrexia 10 (4%) 5 (2%) Cough 8 (3%) 2 (<1%) Somnolence 7 (3%) 1 (<1%) Epistaxis 6 (2%) 1 (<1%) * Rounded to the closest unit percentage 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. Table 3: Adverse Reactions Reported in ≥2%* of Subjects Aged 1 to 5 Years Exposed to Levocetirizine Dihydrochloride 1.25 mg Twice Daily in a 2-Week Placebo-Controlled Clinical Trial Adverse Reactions Levocetirizine Dihydrochloride 1.25 mg Twice Daily (n = 114) Placebo (n = 59) Pyrexia 5 (4%) 1 (2%) Diarrhea 4 (4%) 2 (3%) Vomiting 4 (4%) 2 (3%) Otitis Media 3 (3%) 0 (0%) * Rounded to the closest unit percentage 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 constipation which were reported in 6 (13%) and 1 (4%) and 3 (7%) and 1 (4%) children in the levocetirizine dihydrochloride and 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 dihydrochloride 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 dihydrochloride discontinued because of somnolence, fatigue or asthenia compared to 2 (<1%) in the placebo g
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
LEVOCETIRIZINE DIHYDROCHLORIDE 5MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
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