Included as part of the PRECAUTIONS section.
Contamination Of Tip And Solution
As with any eye drop, care should be taken not to touch
the eyelids or surrounding areas with the dropper tip of the bottle to prevent
contaminating the tip and solution. Keep the bottle closed when not in use.
Contact Lens Wear
Patients should be advised not to wear a contact lens if
their eye is red.
ZERVIATE should not be instilled while wearing contact
lenses. Remove contact lenses prior to instillation of ZERVIATE. The preservative
in ZERVIATE, benzalkonium chloride, may be absorbed by soft contact lenses.
Lenses may be reinserted after 10 minutes following administration of ZERVIATE.
Impairment Of Fertility
In a 2-year carcinogenicity study in rats, orally
administered cetirizine was not carcinogenic at dietary doses up to 20 mg/kg
(approximately 550 times the MRHOD, 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 220
times the MRHOD, 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 55
times the MRHOD, on a mg/m² basis). The clinical significance of these findings
during long-term use of cetirizine is not known.
Cetirizine was not mutagenic in
the Ames test or in an in vivo micronucleus test in rats. Cetirizine was not
clastogenic in the human lymphocyte assay or the mouse lymphoma assay.
Impairment of Fertility
In a fertility and general reproductive performance study
in mice, cetirizine did not impair fertility at an oral dose of 64 mg/kg
(approximately 875 times the MRHOD on a mg/m² basis).
Use In Specific Populations
There were no adequate or well-controlled studies with
ZERVIATE™ (cetirizine ophthalmic solution) 0.24% in pregnant women. Cetirizine
should be used in pregnancy only if the potential benefit justifies the
potential risk to the fetus.
Cetirizine was not teratogenic in mice, rats, or rabbits
at oral doses up to 96, 225, and 135 mg/kg, respectively (approximately 1300,
4930, and 7400 times the maximum recommended human ophthalmic dose (MRHOD), on
a mg/m² basis).
Cetirizine has been reported to be excreted in human
breast milk following oral administration. Multiple doses of oral dose
cetirizine (10 mg tablets once daily for 10 days) resulted in systemic levels
(Mean Cmax = 311 ng/mL) that were 100 times higher than the observed human
exposure (Mean Cmax = 3.1 ng/mL) following twice-daily administration of
cetirizine ophthalmic solution 0.24% to both eyes for one week [see CLINICAL
PHARMACOLOGY]. Comparable bioavailability has been found between the tablet
and syrup dosage forms. However, it is not known whether the systemic
absorption resulting from topical ocular administration of ZERVIATE could
produce detectable quantities in human breast milk.
There is no adequate information regarding the effects of
cetirizine on breastfed infants, or the effects on milk production to inform
risk of ZERVIATE to an infant during lactation. The developmental and health
benefits of breastfeeding should be considered along with the mother's clinical
need for ZERVIATE and any potential adverse effects on the breastfed child from
The safety and effectiveness of ZERVIATE has been
established in pediatric patients two years of age and older. Use of ZERVIATE
in these pediatric patients is supported by evidence from adequate and
well-controlled studies of ZERVIATE in pediatric and adult patients.
No overall differences in safety or effectiveness have
been observed between elderly and younger patients.