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| Product NDC Code | 71776-024 | ||||||||
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| Drug Name | Zerviate |
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| Type | Brand | ||||||||
| Pharm Class | Histamine H1 Receptor Antagonists [MoA], Histamine-1 Receptor Antagonist [EPC] |
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| Active Ingredients |
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| Route | OPHTHALMIC | ||||||||
| Dosage Form | SOLUTION/ DROPS | ||||||||
| RxCUI drug identifier | 2119476, 2119481 |
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| Application Number | NDA208694 | ||||||||
| Labeler Name | Eyevance Pharmaceuticals | ||||||||
| Packages |
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Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.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. The most common adverse reactions (1–7%) were ocular hyperemia, instillation site pain, and visual acuity reduced. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Eyevance Pharmaceuticals, LLC at 1-844-390-0720 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action ZERVIATE, an antihistamine, is a histamine-1 (H1) receptor antagonist. 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.
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.12.1 Mechanism of Action ZERVIATE, an antihistamine, is a histamine-1 (H1) receptor antagonist. 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.
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.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.
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4 CONTRAINDICATIONS None. None. ( 4 )
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.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 C 21 H 25 ClN 2 0 3 •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. image description
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2 DOSAGE AND ADMINISTRATION The recommended dosage of ZERVIATE is to instill one drop in each affected eye twice daily (approximately 8 hours apart). │The single-use containers are to be used immediately after opening and can be used to dose both eyes. Discard the single-use container and any remaining contents after administration. The single-use │containers should be stored in the original foil pouch until ready to use. The recommended dose is one drop in each affected eye twice daily. ( 2 )
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.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%). Ophthalmic solution: 2.4 mg cetirizine in 1 mL sterile solution (0.24%). ( 3 )
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1 INDICATIONS AND USAGE 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 )
Spl product data elements
Usually a list of ingredients in a drug product.Zerviate Cetirizine BENZALKONIUM CHLORIDE EDETATE DISODIUM GLYCERIN HYPROMELLOSE 2910 (4000 MPA.S) POLYETHYLENE GLYCOL 400 POLYSORBATE 80 SODIUM PHOSPHATE, DIBASIC HYDROCHLORIC ACID SODIUM HYDROXIDE WATER CETIRIZINE CETIRIZINE
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity 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/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. Mutagenesis 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/m 2 basis).
Nonclinical toxicology
Information about toxicology in non-human subjects.13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity 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/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. Mutagenesis 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/m 2 basis).
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.image description image description image description image description image description image description
Recent major changes
A list of the section(s) that contain substantive changes that have been approved by FDA in the product labeling. The headings and subheadings, if appropriate, affected by the change are listed together with each section’s identifying number and the month and year on which the change was incorporated in the labeling.RECENT MAJOR CHANGES Dosage and Administration (2) 2/2020 Warnings and Precautions (5.1) 2/2020
Zerviate: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.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. Advise patients to discard single-use containers after each 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. Administration: Advise patients that the solution from one single-use container is to be used immediately after opening. Advise patients that the single-use container can be used to dose both eyes. Discard the single-use container and remaining contents immediately after administration. Storage of Single-use Containers: Instruct patients to store single-use containers in the original foil pouch until ready to use. ZPI0000 Rev 02/2020 Distributed by: Eyevance Pharmaceuticals, LLC. Fort Worth, TX 76102 U.S. Patents: 8,829,005; 9,254,286; 9,750,684; 9,993,471
Clinical studies
This field may contain references to clinical studies in place of detailed discussion in other sections of the labeling.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 Difference Study 1 Study 2 Statistics 15 minutes post-treatment 8 hours post-treatment 15 minutes post-treatment 8 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-CAC Mean 1.00 2.38 1.76 2.69 1.01 2.54 1.94 2.86 Treatment 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-CAC Mean 1.18 2.43 1.85 2.74 1.17 2.51 2.03 2.94 Treatment 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-CAC Mean 1.11 2.11 1.54 2.53 1.15 2.23 1.82 2.66 Treatment 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)*
| 1 Treatment difference values shown are the group mean active minus the group mean vehicle at each post-CAC time point. * p<0.05 | ||||||||
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.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).
8.5 Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger patients.
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.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.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy 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. 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).
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 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. 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 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.
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.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 a 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]. ZERVIATE is also supplied in 5 low-density polyethylene 0.2 mL single-use containers within a foil pouch. 5 mL fill in a 7.5 mL bottle NDC 71776-024-05 7.5 mL fill in a 10 mL bottle NDC 71776-024-08 Carton of 30 single-use containers NDC 71776-024-30 Storage: Store at 15°C to 25°C (59°F to 77°F). Single-use containers should be stored in the original foil pouch.
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API