Activities Requiring Mental Alertness: In clinical trials, the occurrence of somnolence has been reported in some patients taking Cetirizine dihydrochloride, due caution should therefore be exercised when driving a car or operating potentially dangerous machinery. Concurrent use of Cetirizine dihydrochloride with alcohol or other CNS depressants should be avoided because additional reductions in alertness and additional impairment of CNS performance may occur.
Drug-Drug Interactions: No clinically significant drug interactions have been found with theophylline at a low dose, azithromycin, pseudoephedrine, ketoconazole, or erythromycin. There was a small decrease in the clearance of cetirizine caused by a 400-mg dose of theophylline, it is possible that larger theophylline doses could have a greater effect.
Carcinogenesis, Mutagenesis and Impairment of Fertility: 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 on a mg/m2 basis, or approximately 7 times the maximum recommended daily oral dose in infants on a mg/m2 basis). In a 2-year carcinogenicity study in mice, cetirizine caused an increased incidence of benign liver tumors in males at a dietary dose of 16 mg/kg (approximately 6 times the maximum recommended daily oral dose in adults on a mg/m2 basis, or approximately 3 times the maximum recommended daily oral dose in infants on a mg/m2 basis). No increase in the incidence of liver tumors was observed in mice at a dietary dose of 4 mg/kg (approximately 2 times the recommended maximum daily oral dose the maximum recommended daily dose in adults on a mg/m2 basis or approximately 3 times the maximum recommended daily oral dose in infants on a mg/m2 basis). The clinical significance of these findings during long-term use of Cetirizine dihydrochloride is not known.
Cetirizine 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 rats.
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 maximum recommended daily oral dose in adults on a mg/m2 basis).
Pregnancy Category B: In mice, rats and rabbits, cetirizine was not teratogenic at oral doses up to 96, 225, and 135 mg/kg, respectively (approximately 40, 180, and 220 times the maximum recommended daily oral dose in adults on a mg/m2) basis. There are no adequate and well-controlled studies in pregnant women.
Because animal studies are not always predictive of human response, Cetirizine dihydrochloride should be used in pregnancy only if clearly needed.
Nursing Mothers: In mice, cetirizine caused retarded pup weight gain during lactation at an oral dose in dams of 96 mg/kg (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 was excreted in milk. Cetirizine has been reported to be excreted in human breast milk. Because many drugs are excreted in human breast milk, use of Cetirizine dihydrochloride in nursing mothers is not recommended.
Use in Children: The safety of Cetirizine dihydrochloride has been demonstrated in pediatric patients aged 6 months to 11 years. The safety of Cetirizine dihydrochloride, at daily doses of 5 or 10 mg, has been demonstrated in 376 pediatric patients aged 6 to 11 years in placebo-controlled trials of up to 4 weeks and in 254 patients in a non-placebo-controlled 12-week trial. The safety of cetirizine has been demonstrated in 168 patients received between 0.2 and 0.4 mg/kg of cetirizine HCl. The safety of cetirizine in 399 patients aged 12 to 24 months has been demonstrated in a placebo-controlled 18-month trial, in which the average dose was 0.25 mg/kg bid, corresponding to a range of 4 to 11 mg/day. The safety of Cetirizine dihydrochloride syrup has been demonstrated in 42 patients aged 6 to 11 months in a placebo-controlled 7-day trial. The prescribed dose was 0.25 mg/kg, which corresponded to a mean of 4.5 mg/day with a range of 3.4 to 6.2 mg/day.
The effectiveness of Cetirizine dihydrochloride for the treatment of allergic rhinitis and chronic idiopathic urticaria in pediatric patient aged 6 to 11 years is based on an extrapolation of the demonstrated efficacy of Cetirizine dihydrochloride in adults with these conditions and the likelihood the disease course, pathophysiology and the drug's effect are substantially similar between these two populations. Efficacy is extrapolated down to 6 months of age for perennial allergic rhinitis and down to 2 years of age for seasonal allergic rhinitis because these diseases are thought to occur down to these ages in children. The recommended doses for the pediatric population are based on cross-study comparisons of the pharmacokinetics and pharmacodynamics of cetirizine in adults and pediatric subjects and on the safety profile of cetirizine in both adult and pediatric patients at doses equal to or higher than the recommended doses. The cetirizine AUC and Cmax in pediatric subjects aged 6 to 11 years who received single dose of 20 mg of cetirizine tablets.
The saftey and effectiveness of cetirizine in pediatric patients under the age of 6 months have not been established.
Use in Elderly: Of the total number of patients in clinical studies of Cetirizine dihydrochloride, 186 patients were 65 years and older, and 39 patients were 75 years and older. No overall differences in safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. With regards to efficacy, clinical studies of Cetirizine 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.
Cetirizine dihydrochloride is known to be substantially excreted by the kidney and the risk of toxic reactions to the 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.