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Included as part of the PRECAUTIONS section.

Activities Requiring Mental Alertness

In clinical trials the occurrence of somnolence, fatigue, and asthenia has been reported in some patients under therapy with XYZAL (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 XYZAL (levocetirizine dihydrochloride) . Concurrent use of XYZAL (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.

Nonclinical Toxicology

Carcinogenesls, Mutagenesis, Impairment of Fertility

No carcinogenicity studies have been performed with levocetirizine. However, evaluation of cetirizine carcinogenicity studies are relevant for determination of the carcinogenic potential of levocetirizine. In a 2-year carcinogenicity study, in rats, cetirizine was not carcinogenic at dietary doses up to 20 mg/kg (approximately 15 times the maximum recommended daily oral dose in adults, approximately 10 times the maximum recommended daily oral dose in children 6 to 11 years of age and approximately 15 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m² basis). In a 2-year carcinogenicity study in mice, cetirizine caused an increased incidence of benign hepatic tumors in males at a dietary dose of 16 mg/kg (approximately 6 times the maximum recommended daily oral dose in adults, approximately 4 times the maximum recommended daily oral dose in children 6 to 11 years of age, and approximately 6 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m² basis). No increased incidence of benign tumors was observed at a dietary dose of 4 mg/kg (approximately 2 times the maximum recommended daily oral dose in adults, equivalent to the maximum recommended daily oral dose in children 6 to 11 years of age and approximately 2 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m² basis). The clinical significance of these findings during long-term use of XYZAL (levocetirizine dihydrochloride) is not known.

Levocetirizine was not mutagenic in the Ames test, and not clastogenic in the human lymphocyte assay, the mouse lymphoma assay, and in vivo micronucleus test in mice.

In a fertility and general reproductive performance study in mice, cetirizine did not impair fertility at an oral dose of 64 mg/kg (approximately 25 times the recommended daily oral dose in adults on a mg/m² basis).

Use In Specific Populations

Pregnancy

Pregnancy Category B

There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, XYZAL (levocetirizine dihydrochloride) should be used during pregnancy only if clearly needed.

Teratogenic Effects

In rats and rabbits, levocetirizine was not teratogenic at oral doses approximately 320 and 390, respectively, times the maximum recommended daily oral dose in adults on a mg/m² basis.

Nursing Mothers

No peri- and post-natal animal studies have been conducted with levocetirizine. In mice, cetirizine caused retarded pup weight gain during lactation at an oral dose in dams that was approximately 40 times the maximum recommended daily oral dose in adults on a mg/m² basis. Studies in beagle dogs indicated that approximately 3% of the dose of cetirizine was excreted in milk. Cetirizine has been reported to be excreted in human breast milk. Because levocetirizine is also expected to be excreted in human milk, use of XYZAL (levocetirizine dihydrochloride) in nursing mothers is not recommended.

Pediatrtc Use

The recommended dose of XYZAL (levocetirizine dihydrochloride) for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in patients 6 months to 17 years of age is based on extrapolation of efficacy from adults 18 years of age and older [see Clinical Studies].

The recommended dose of XYZAL (levocetirizine dihydrochloride) in patients 6 months to 11 years of age for the treatment of the symptoms of perennial allergic rhinitis and chronic idiopathic urticaria and in patients 2 to 11 years of age for the treatment of symptoms of seasonal allergic rhinitis is based on cross-study comparisons of the systemic exposure of XYZAL (levocetirizine dihydrochloride) in adults and pediatric patients and on the safety profile of XYZAL (levocetirizine dihydrochloride) in both adult and pediatric patients at doses equal to or higher than the recommended dose for patients 6 months to 11 years of age.

The safety of XYZAL (levocetirizine dihydrochloride) 5 mg once daily was evaluated in 243 pediatric patients 6 to 12 years of age in two placebo-controlled clinical trials lasting 4 and 6 weeks. The safety of XYZAL (levocetirizine dihydrochloride) 1.25 mg twice daily was evaluated in one 2-week clinical trial in 114 pediatric patients 1 to 5 years of age and the safety of XYZAL (levocetirizine dihydrochloride) 1.25 mg once daily was evaluated in one 2-week clinical trial in 45 pediatric patients 6 to 11 months of age [see ADVERSE REACTIONS] .

The effectiveness of XYZAL (levocetirizine dihydrochloride) 1.25 mg once daily (6 months to 5 years of age) and 2.5 mg once daily (6 to 11 years of age) for the treatment of the symptoms of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria is supported by the extrapolation of demonstrated efficacy of XYZAL (levocetirizine dihydrochloride) 5 mg once daily in patients 12 years of age and older based on the pharmacokinetic comparison between adults and children.

Cross-study comparisons indicate that administration of a 5 mg dose of XYZAL (levocetirizine dihydrochloride) to 6 to 12 year old pediatric seasonal allergic rhinitis patients resulted in about 2-fold the systemic exposure (AUC) observed when 5 mg of XYZAL (levocetirizine dihydrochloride) was administered to healthy adults. Therefore, in children 6 to 11 years of age the recommended dose of 2.5 mg once daily should not be exceeded. In a population pharmacokinetics study the administration of 1.25 mg once daily in children 6 months to 5 years of age resulted in systemic exposure comparable to 5 mg once daily in adults, [see DOSAGE AND ADMINISRATION; Clinical Studies; and CLINICAL PHARMACOLOGY].

Geriatric Use

Clinical studies of XYZAL (levocetirizine dihydrochloride) for each approved indication did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Renal Impairment

XYZAL (levocetirizine dihydrochloride) is known to be substantially excreted by the kidneys and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].

Hepatic Impairment

As levocetirizine is mainly excreted unchanged by the kidneys, it is unlikely that the clearance of levocetirizine is significantly decreased in patients with solely hepatic impairment [see CLINICAL PHARMACOLOGY].

Last reviewed on RxList: 5/2/2011
This monograph has been modified to include the generic and brand name in many instances.