Cetirizine

ZERVIATE ® (cetirizine ophthalmic solution) 0.24% is indicated for the treatment of ocular itching associated with allergic conjunctivitis. ZERVIATE ® (cetirizine ophthalmic solution) 0.24% is a histamine-1 (H1) receptor antagonist indicated for treatment of ocular itching associated with allergic conjunctivitis. ( 1 )

Cetirizine ophthalmic solution, 0.24% is a sterile, buffered, clear, colorless aqueous solution containing cetirizine 0.24% (equivalent to cetirizine hydrochloride 0.29%). Ophthalmic solution: 2.4 mg cetirizine in 1 mL sterile solution (0.24%). ( 3 )

None. None. ( 4 )

Contamination of Tip and Solution. To prevent contaminating the dropper tip and solution, advise patients not to touch the eyelids or surrounding areas with the tip of the single-use container. ( 5.1 )

5.1 Contamination of Tip and Solution As with any eye drop, care should be taken not to touch the eyelids or surrounding areas with the tip of the single-use container in order to avoid injury to the eye and to prevent contaminating the tip and solution. Discard the single-use container after using in each eye.

5.2 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 10 minutes following administration of ZERVIATE ® .

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trial of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates in practice. In seven clinical trials, patients with allergic conjunctivitis or those at a risk of developing allergic conjunctivitis received one drop of either cetirizine (N=511) or vehicle (N=329) in one or both eyes. The most commonly reported adverse reactions occurred in approximately 1–7% of patients treated with either ZERVIATE ® or vehicle. These reactions were ocular hyperemia, instillation site pain, and visual acuity reduced. The most common adverse reactions (1–7%) were ocular hyperemia, instillation site pain, and visual acuity reduced. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Harrow at 1-833-4HARROW(427769) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Risk Summary There were no adequate or well-controlled studies with ZERVIATE ® in pregnant women. Cetirizine should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Data Animal Data 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/m 2 basis).

8.2 Lactation Risk Summary 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 C max = 311 ng/mL) that were 100 times higher than the observed human exposure (Mean C max = 3.1 ng/ mL) following twice daily administration of cetirizine ophthalmic solution 0.24% to both eyes for one week [see Clinical Pharmacology ( 12.3 )] . 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 ZERVIATE ® .

8.4 Pediatric Use The safety and effectiveness of ZERVIATE ® (cetirizine ophthalmic solution) 0.24% 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.

8.5 Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger patients.

ZERVIATE ® , an antihistamine, is a histamine-1 (H1) receptor antagonist. Its effects are mediated via selective inhibition of H1 histamine receptors. The antihistaminic activity of cetirizine has been documented in a variety of animal and human models. In vivo and ex vivo animal models have shown negligible anticholinergic and antiserotonergic activity. In vitro receptor binding studies have shown no measurable affinity for other than H1 receptors.