NDC 71776-024 Zerviate

Cetirizine

NDC Product Code 71776-024

NDC Product Information

Zerviate with NDC 71776-024 is a a human prescription drug product labeled by Eyevance Pharmaceuticals. The generic name of Zerviate is cetirizine. The product's dosage form is solution, gel forming / drops and is administered via ophthalmic form.

Labeler Name: Eyevance Pharmaceuticals

Dosage Form: Solution, Gel Forming / Drops - A solution, which after usually being administered in a drop-wise fashion, forms a gel.

Product Type: Human Prescription Drug Additional informationCallout TooltipWhat kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.


Zerviate Active Ingredient(s)

Additional informationCallout TooltipWhat is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • CETIRIZINE 2.4 mg/mL

Inactive Ingredient(s)

Additional informationCallout TooltipAbout the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7)
  • EDETATE DISODIUM (UNII: 7FLD91C86K)
  • GLYCERIN (UNII: PDC6A3C0OX)
  • HYPROMELLOSE 2910 (4000 MPA.S) (UNII: RN3152OP35)
  • POLYETHYLENE GLYCOL 400 (UNII: B697894SGQ)
  • POLYSORBATE 80 (UNII: 6OZP39ZG8H)
  • SODIUM PHOSPHATE, DIBASIC (UNII: GR686LBA74)
  • HYDROCHLORIC ACID (UNII: QTT17582CB)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)
  • WATER (UNII: 059QF0KO0R)

Administration Route(s)

Additional informationCallout TooltipWhat are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Ophthalmic - Administration to the external eye.

Pharmacological Class(es)

Additional informationCallout TooltipWhat is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Histamine H1 Receptor Antagonists - [MoA] (Mechanism of Action)
  • Histamine-1 Receptor Antagonist - [EPC] (Established Pharmacologic Class)
  • Histamine H1 Receptor Antagonists - [MoA] (Mechanism of Action)
  • Histamine-1 Receptor Antagonist - [EPC] (Established Pharmacologic Class)

Product Labeler Information

Additional informationCallout TooltipWhat is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Eyevance Pharmaceuticals
Labeler Code: 71776
FDA Application Number: NDA208694 Additional informationCallout TooltipWhat is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. Additional informationCallout TooltipWhat is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 02-19-2019 Additional informationCallout TooltipWhat is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 Additional informationCallout TooltipWhat is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N Additional informationCallout TooltipWhat is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

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Zerviate Product Label Images

Zerviate Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

ZERVIATE™ (cetirizine ophthalmic solution) 0.24% is indicated for the treatment of ocular itching associated with allergic conjunctivitis.

2 Dosage And Administration

The recommended dosage of ZERVIATE is to instill one drop in each affected eye twice daily (approximately 8 hours apart).

3 Dosage Forms And Strengths

Cetirizine ophthalmic solution, 0.24% is a sterile, buffered, clear, colorless aqueous solution containing cetirizine 0.24% (equivalent to cetirizine hydrochloride 0.29%).

4 Contraindications

None.

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 dropper tip of the bottle to prevent contaminating the tip and solution. Keep the bottle closed when not in use.

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 after 10 minutes following administration of ZERVIATE.

6 Adverse Reactions

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.

Risk Summary

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 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.

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).

8.4 Pediatric Use

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.

8.5 Geriatric Use

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

11 Description

ZERVIATE is a sterile opthalmic solution containing cetirizene, which is a histamine-1 (H1) receptor antagonist, for topical administration to the eyes.  Cetirizine hydrochloride is a white, crystalline, water-soluble powder with a molecular weight of 461.8 and a molecular formula of C21H25CIN203•2HCl.  The chemical structure is presented below:Chemical Name:  (

RS)-2-[2-[4-[(4-Chlorophenyl) phenylmethyl] piperazin-1-yl] ethoxy] acetic acid, dihydrochloride

Each mL of ZERVIATE contains an active ingredient [cetirizine 2.40 mg (equivalent to 2.85 mg of cetirizine hydrochloride)] and the following inactive ingredients: benzalkonium chloride 0.010% (preservative); glycerin; sodium phosphate, dibasic; edetate disodium; polyethylene glycol 400; polysorbate 80; hypromellose; hydrochloric acid/sodium hydroxide (to adjust pH); and water for injection. ZERVIATE solution has a pH of approximately 7.0 and osmolality of approximately 300 mOsm/kg.

12.1 Mechanism Of Action

ZERVIATE is a histamine-1 (H1) receptor antagonist (antihistamine) and an inhibitor of release of histamine from mast cells. Its effects are mediated via selective inhibition of H


1 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.

12.3 Pharmacokinetics

In healthy subjects, bilateral topical ocular dosing of one drop of ZERVIATE™ (cetirizine ophthalmic solution) 0.24% resulted in a mean cetirizine plasma C


max of 1.7 ng/mL following a single dose and 3.1 ng/mL after twice-daily dosing for one week. The observed mean terminal half-life of cetirizine was 8.6 hours following a single dose and 8.2 hours after twice-daily dosing of ZERVIATE for one week.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

CarcinogenicityIn 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/m


2 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/m


2 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/m


2 basis). The clinical significance of these findings during long-term use of cetirizine is not known.


MutagenesisCetirizine 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 FertilityIn 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/m


2 basis).

14 Clinical Studies

The efficacy of ZERVIATE was established in three randomized, double-masked, placebo-controlled, conjunctival allergen challenge (CAC) clinical trials in patients with a history of allergic conjunctivitis.Onset and duration of action were evaluated in two of these trials in which patients were randomized to receive ZERVIATE or vehicle ophthalmic solutions. Patients were evaluated with an ocular itching severity score ranging from 0 (no itching) to 4 (incapacitating itch) at several time points after CAC administration.


Table 1 displays data from the mean ocular itching severity scores after ocular administration of an antigen using the CAC model. A one unit difference compared to vehicle is considered a clinically meaningful change in the ocular itching severity score.


Patients treated with ZERVIATE demonstrated statistically and clinically significantly less ocular itching compared to vehicle at 15 minutes and 8 hours after treatment.Table 1 Itching Scores in the ITT Population by Treatment Group and Treatment DifferenceStudy 1Study 2Statistics15 minutes post-treatment8 hours post-treatment15 minutes post-treatment8 hours post-treatment  ZERVIATE  


N=50


  Vehicle  


N=50


  ZERVIATE  


N=50


  Vehicle  


N=50


  ZERVIATE  


N=51


  Vehicle  


N=50


  ZERVIATE  


N=51


  Vehicle  


N=50


1 Treatment difference values shown are the group mean active minus the group mean vehicle at each post-CAC time point.


* p<0.05


3 Minute Post-CACMean 1.002.381.762.691.012.541.942.86Treatment Difference     


(95% CI)


1-1.38 (-1.72, -1.05)*-0.93 (-1.26, -0.61)*-1.53 (-1.92, -1.15)*-0.92 (-1.25, -0.58)*5 Minute Post-CACMean1.182.431.852.741.172.512.031.82Treatment Difference


(95% CI)


1-1.25 (-1.58, -0.91)*-0.89 (-1.24, -0.54)*-1.34 (-1.71, -0.97)*-0.90 (-1.23, -0.57)*7 Minute Post-CACMean1.112.111.542.531.152.232.942.66Treatment Difference


(95% CI)


1-1.00 (-1.35, -0.65)*-0.99 (-1.40, -0.59)*-1.07 (-1.46, -0.69)*-0.84 (-1.21, -0.48)*

16 How Supplied/Storage And Handling

ZERVIATE is a sterile, buffered, clear, colorless aqueous solution containing cetirizine 0.24% (equivalent to cetirizine hydrochloride 0.29%) supplied in a white low-density polyethylene multi-dose ophthalmic bottle with a low-density polyethylene dropper tip and a white polypropylene cap. ZERVIATE is supplied in a 7.5 mL bottle that contains 5 mL and 10 mL bottle that contains 7.5 mL cetirizine ophthalmic solution, 2.40 mg [equivalent to 2.85 mg cetirizine hydrochloride in one mL solution].5 mL fill in a 7.5 mL bottle   NDC 71776-024-05


Storage: Store at 15°C to 25°C (59°F to 77°F).

17 Patient Counseling Information

•Risk of Contamination: Advise patients not to touch dropper tip to eyelids or surrounding areas, as this may contaminate the dropper tip and ophthalmic solution. Advise patients to keep the bottle closed when not in use.•Concomitant Use of Contact Lenses: Advise patients not to wear contact lenses if their eyes are red. Advise patients that ZERVIATE should not be used to treat contact lens-related irritation. Advise patients to remove contact lenses prior to instillation of ZERVIATE. The preservative in ZERVIATE solution, benzalkonium chloride, may be absorbed by soft contact lenses. Lenses may be reinserted ten minutes following administration of ZERVIATE.ZPI0000 Rev 06/2018Distributed by:Eyevance Pharmaceuticals, LLC.


Fort Worth, TX 76102U.S. Patents: 8,829,005; 9,254,286; 9,750,684; 9,993,471

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