NDC 0065-0325 Emadine

Emedastine Difumarate

NDC Product Code 0065-0325

NDC 0065-0325-05

Package Description: 1 BOTTLE, PLASTIC in 1 CARTON > 5 mL in 1 BOTTLE, PLASTIC

NDC Product Information

Emadine with NDC 0065-0325 is a a human prescription drug product labeled by Alcon Laboratories, Inc.. The generic name of Emadine is emedastine difumarate. The product's dosage form is solution/ drops and is administered via ophthalmic form.

Labeler Name: Alcon Laboratories, Inc.

Dosage Form: Solution/ Drops - A solution which is usually administered in a drop-wise fashion.

Product Type: Human Prescription Drug What 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.

Emadine Active Ingredient(s)

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

  • EMEDASTINE DIFUMARATE .5 mg/mL

Inactive Ingredient(s)

About 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.

  • TROMETHAMINE (UNII: 023C2WHX2V)
  • SODIUM CHLORIDE (UNII: 451W47IQ8X)
  • HYDROCHLORIC ACID (UNII: QTT17582CB)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)
  • WATER (UNII: 059QF0KO0R)
  • HYPROMELLOSES (UNII: 3NXW29V3WO)
  • BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7)

Administration Route(s)

What 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.
  • Ophthalmic - Administration to the external eye.

Pharmacological Class(es)

What 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 Inhibitor - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Alcon Laboratories, Inc.
Labeler Code: 0065
FDA Application Number: NDA020706 What 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. What 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: 02-15-1998 What 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 What 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 What 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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Emadine 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

Description

EMADINE® (emedastine difumarate ophthalmic solution) 0.05% is a sterile ophthalmic solution containing emedastine, a relatively selective, H1-receptor antagonist for topical administration to the eyes. Emedastine difumarate is a white, crystalline, water-soluble fine powder with a molecular weight of 534.57. The chemical structure is presented below:Structural Formula:Chemical Name:1H-benzimidazole,1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl),(E)-2-butenedioate (1:2)Each mL of EMADINE® (emedastine difumarate ophthalmic solution) 0.05% contains: Active: 0.884 mg emedastine difumarate equivalent to 0.5 mg emedastine. Preservative: benzalkonium chloride 0.01%. Inactives: tromethamine; sodium chloride; hypromellose; hydrochloric acid/sodium hydroxide (adjust pH); and purified water. It has a pH of approximately 7.4 and an osmolality of approximately 300 mOsm/kg.

Clinical Pharmacology

Emedastine is a relatively selective, histamine H1 antagonist. In vitro examinations of emedastine's affinity for histamine receptors (H1: Ki = 1.3 nM, H2: Ki = 49,067 nM, and H3: Ki = 12,430 nM) demonstrate relative selectivity for the H1-histamine receptor. In vivo studies have shown concentration-dependent inhibition of histamine-stimulated vascular permeability in the conjunctiva following topical ocular administration.Emedastine appears to be devoid of effects on adrenergic, dopaminergic and serotonin receptors.
Following topical administration in man, emedastine was shown to have low systemic exposure. In a study involving 10 normal volunteers dosed bilaterally twice daily for 15 days with emedastine ophthalmic solution 0.05%, plasma concentrations of the parent compound were generally below the quantitation limit of the assay (less than 0.3 ng/mL).Samples in which emedastine was quantifiable, ranged from 0.30 to 0.49 ng/mL. The elimination half-life of oral emedastine in plasma is 3-4 hours. Approximately 44% of the oral dose is recovered in the urine over 24 hours with only 3.6% of the dose excreted as parent drug. Two primary metabolites, 5- and 6-hydroxyemedastine, are excreted in the urine as both free and conjugated forms. The 5’-oxoanalogs of 5- and 6-hydroxyemedastine and the N-oxide are also formed as minor metabolites.In an environmental study, patients with allergic conjunctivitis were treated with EMADINE® (emedastine difumarate ophthalmic solution) 0.05% for six weeks. The results demonstrated that EMADINE® (emedastine difumarate ophthalmic solution) 0.05% provides relief of the signs and symptoms of allergic conjunctivitis. In conjunctival antigen challenge studies, in which subjects were challenged with antigen both initially and up to four hours after dosing, EMADINE® (emedastine difumarate ophthalmic solution) 0.05% was demonstrated to be significantly more effective than placebo in preventing ocular itching associated with allergic conjunctivitis.

Indications And Usage

EMADINE® (emedastine difumarate ophthalmic solution) 0.05% is indicated for the temporary relief of the signs and symptoms of allergic conjunctivitis.

Contraindications

EMADINE® (emedastine difumarate ophthalmic solution) 0.05% is contraindicated in persons with a known hypersensitivity to emedastine difumarate or any of its components.

Warnings

FOR TOPICAL OPHTHALMIC USE ONLY - NOT FOR INJECTION OR ORAL USE.

Information For Patients:

To prevent contaminating the dropper tip and solution, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle. Keep the bottle tightly closed when not in use. Do not use if the solution has become discolored.Patients should be advised not to wear a contact lens if their eye is red. EMADINE® (emedastine difumarate ophthalmic solution) 0.05% should not be used to treat contact lens related irritation. The preservative in EMADINE® (emedastine difumarate ophthalmic solution) 0.05%, benzalkonium chloride, may be absorbed by soft contact lenses. Patients who wear soft contact lenses and whose eyes are not red, should be instructed to wait at least ten minutes after instilling EMADINE® (emedastine difumarate ophthalmic solution) 0.05% before they insert their contact lenses.

Carcinogenesis, Mutagenesis, Impairment Of Fertility:

Emedastine difumarate demonstrated no carcinogenicity effects in lifetime studies in mice and rats at dietary doses more than 80,000 times and more than 26,000 times the maximum recommended ocular human use level of 0.002 mg/kg/day for a 50 kg adult, respectively. Higher dose levels were not tested. Emedastine difumarate was determined to be nonmutagenic in an in vitro bacterial reverse mutation (Ames) test, an in vitro modification of the Ames test, an in vitro mammalian chromosome aberration test, an in vitro mammalian forward mutation test, an in vitro mammalian DNA repair synthesis test, an in vivo mammalian sister chromatid exchange test and an in vivo mouse micronucleus test. There was no evidence of impaired fertility or reproductive capacity in rats at 15,000 times the maximum recommended ocular human use level.

Pregnancy:

Teratology and peri- and post-natal studies have been conducted with emedastine difumarate in rats and rabbits. At 15,000 times the maximum recommended ocular human use level, emedastine difumarate was shown not to be teratogenic in rats and rabbits and no effects on peri/post-natal development were observed in rats. However, at 70,000 times the maximum recommended ocular human use level, emedastine difumarate was shown to increase the incidence of external, visceral and skeletal anomalies in rats. There are, however, no adequate and well controlled studies in pregnant women. Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers:

Emedastine has been identified in breast milk in rats following oral administration. It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in breast milk. Nevertheless, caution should be exercised when EMADINE® (emedastine difumarate ophthalmic solution) 0.05% is administered to a nursing mother.

Pediatric Use:

Safety and effectiveness in pediatric patients below the age of 3 years have not been established.

Geriatric Use:

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

Adverse Reactions

In controlled clinical studies of EMADINE® (emedastine difumarate ophthalmic solution) 0.05% lasting for 42 days, the most frequent adverse reaction was headache 11%. The following adverse experiences were reported in less than 5% of patients: Abnormal dreams, asthenia, bad taste, blurred vision, burning or stinging, corneal infiltrates, corneal staining, dermatitis, discomfort, dry eye, foreign body sensation, hyperemia, keratitis, pruritus, rhinitis, sinusitis and tearing. Some of these events were similar to the underlying disease being studied.

Overdosage

Somnolence and malaise have been reported following daily oral administration. Oral ingestion of the contents of a 15 mL DROP-TAINER® dispenser would be equivalent to 7.5 mg. In case of overdosage, treatment is symptomatic and supportive.

Dosage And Administration

The recommended dose is one drop in the affected eye up to four times daily.

How Supplied

EMADINE® (emedastine difumarate ophthalmic solution) 0.05% is supplied as follows:5 mL in opaque, plastic DROP-TAINER® dispenser.5 mL: NDC 0065-0325-05STORAGE: Store at 4°C to 30°C (39°F-86°F).Rx Only©2002, 2003, 2009, 2018 Novartis Distributed by:ALCON LABORATORIES, INC.Fort Worth, Texas 76134 USAAlcon®a Novartis companyRevised: April 2018T2018-34

Principle Display Panel

NDC 0065-0325-05Alcon®Emadine®(emedastine difumarate ophthalmic solution) 0.05% 5 mLSterile Rx OnlyFOR TOPICAL OPHTHALMIC USE ONLYWARNING: Do not touch dropper tip to any surface, as this may contaminate the solution.USUAL DOSAGE: Read enclosed insert.EACH mL CONTAINS:Active: emedastine difumarate 0.884 mg equivalent to emadastine 0.5 mg.Preservative: benzalkonium chloride, 0.01%.Inactives: tromethamine, sodium chloride, hypromellose, hydrochloric acid and/or sodium hydroxide (to adjust pH), and purified water.Storage: Store at 4º-30ºC (39º-86ºF).U.S. Pat. Nos. 5,441,958ALCON®ALCON LABORATORIES, INC.Fort Worth, Texas 76134 USAPrinted in USA©2002, 2003, 2009 Alcon, Inc.350928-0109LOT:EXP.:NDC 0065-0325-05Alcon®Emadine®(emedastine difumarate ophthalmic solution) 0.05% Sterile 5 mLRx OnlyEach mL Contains: emedastine 0.5 mgUSUAL DOSAGE: Read enclosed insert.FOR TOPICAL OPHTHALMIC USE ONLY.STORAGE: Store at 4º-30ºC (39º-86ºF).U.S. Pat. Nos. 4,430,343 and 5,441,958ALCON LABORATORIES, INC.Fort Worth, Texas 76134 USAPrinted in USA©2002, 2004 Alcon, Inc.LOT:EXP.:H13153-1113

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