EPINASTINE HYDROCHLORIDE solution/ drops
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Patient Information

17.1 Sterility of Dropper Tip

Patients should be advised not to touch dropper tip to any surface, as this may contaminate the contents (seeWARNINGS AND PRECAUTIONS, 5.1).

17.2 Concomitant Use of Contact Lenses

Patients should be advised not to wear a contact lens if their eye is red. Patients should be advised thatEpinastine HCl Ophthalmic Solution 0.05%should not be used to treat contact lens-related irritation. Patients should also be advised to remove contact lenses prior to instillation ofEpinastine HCl Ophthalmic Solution 0.05%. The preservative inEpinastine HCl Ophthalmic Solution 0.05%, benzalkonium chloride, may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration ofEpinastine HCl Ophthalmic Solution 0.05%

17.3 Topical Ophthalmic Use Only

For topical ophthalmic administration only.

Rx only
Distributed by:
Breckenridge Pharmaceutical, Inc.
Boca Raton, FL 33487

Manufactured by:
PrimaPharma, Inc.
San Diego, CA 92121

Rev: 08/2017

1. Highlights Of Prescribing Information
2. Indications And Usage
3. Dosage And Administration
4. Dosage Forms And Strengths
5. Contraindications
6. Warnings And Precautions
7. Adverse Reactions
8. 1 Indications And Usage
9. 2 Dosage And Administration
10. 3 Dosage Forms And Strengths
11. 4 Contraindications
12. 5 Warnings And Precautions
13. 6 Adverse Reactions
14. 8 Use In Specific Populations
15. 11 Description
16. 12 Clinical Pharmacology
17. 13 Nonclinical Toxicology
18. 14 Clinical Studies
19. 16 How Supplied/storage And Handling
20. Package Label.principal Display Panel
21. Epinastine Hydrochloride
22. Principal Display Panel - 5 Ml Bottle Carton

Highlights Of Prescribing Information ⮝

These highlights do not include all the information needed to use EPINASTINE HCL OPHTHALMIC SOLUTION, 0.05% safely and effectively. See full prescribing information for EPINASTINE HCL OPHTHALMIC SOLUTION, 0.05%

EPINASTINE HCL ophthalmic solution, 0.05%
Initial U.S. Approval: 2003

Indications And Usage ⮝

Epinastine HCl Ophthalmic Solution 0.05% is an H1 histamine receptor antagonist indicated for the prevention of itching associated with allergic conjunctivitis. (1)

Dosage And Administration ⮝

The recommended dosage is one drop in each eye twice a day. (2)

Dosage Forms And Strengths ⮝

Ophthalmic solution containing 0.5 mg/mL epinastine HCl. (3)

Contraindications ⮝

None (4)

Warnings And Precautions ⮝

• To minimize the risk of contamination, do not touch dropper tip to any surface. Keep bottle tightly closed when not in use. (5.1)
• Epinastine HCl Ophthalmic Solution 0.05% should not be used to treat contact lens-related irritation. (5.2)
• Remove contact lenses prior to instillation of Epinastine HCl Ophthalmic Solution 0.05%. (5.2)

Adverse Reactions ⮝

The most common ocular adverse reactions (incidence occurring in approximately 1% - 10% of Epinastine HCl Ophthalmic Solution 0.05% - treated eyes were burning sensation in the eye, folliculosis, hyperemia, and pruritus. The most common non-ocular adverse reactions, occurring in 10% of Epinastine HCl Ophthalmic Solution 0.05% -treated eyes, were infection (cold symptoms and upper respiratory infections). (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Breckenridge Pharmaceutical, Inc. at 1-800-367-3395 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 8/2017

1 Indications And Usage ⮝

Epinastine HCl Ophthalmic Solution 0.05% is indicated for the prevention of itching associated with allergic conjunctivitis.

2 Dosage And Administration ⮝

The recommended dosage is one drop in each eye twice a day.

Treatment should be continued throughout the period of exposure (i.e., until the pollen season is over or until exposure to the offending allergen is terminated), even when symptoms are absent.

3 Dosage Forms And Strengths ⮝

Solution containing 0.5 mg/mL epinastine HCl

4 Contraindications ⮝

None

5 Warnings And Precautions ⮝

5.1 Contamination of Tip and Solution

Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye, surrounding structures, fingers, or any other surface in order to avoid contamination of the solution by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.

Bottle should be kept tightly closed when not in use.

5.2 Use with Contact Lenses

Patients should be advised not to wear a contact lens if their eye is red. Epinastine HCl Ophthalmic Solution 0.05% should not be used to treat contact lens-related irritation.

The preservative in Epinastine HCl ophthalmic solution 0.05%, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of Epinastine HCl Ophthalmic Solution 0.05% and may be reinserted after 10 minutes following its administration.

5.3 Topical Ophthalmic Use Only

Epinastine HCl Ophthalmic Solution 0.05% is for topical ophthalmic use only and not for injection or oral use.

6 Adverse Reactions ⮝

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

The most frequently reported ocular adverse reactions occurring in approximately 1-10% of patients were burning sensation in the eye, folliculosis, hyperemia, and pruritus.

The most frequently reported non-ocular adverse reactions were infection (cold symptoms and upper respiratory infections), seen in approximately 10% of patients, and headache, rhinitis, sinusitis, increased cough, and pharyngitis, seen in approximately 1 - 3% of patients.

Some of these reactions were similar to the underlying disease being studied.

6.2 Postmarketing Experience

The following reactions have been identified during postmarketing use of Epinastine HCl Ophthalmic Solution 0.05% in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to Epinastine HCl Ophthalmic Solution 0.05%, or a combination of these factors, include: lacrimation increased.

8 Use In Specific Populations ⮝

8.1 Pregnancy

Teratogenic Effects

Pregnancy Category C

In an embryofetal developmental study in pregnant rats, maternal toxicity with no embryofetal effects was observed at an oral dose that was approximately 150,000 times the maximum recommended ocular human dose (MROHD) of 0.0014 mg/kg/day on a mg/kg basis. Total resorptions and abortion were observed in an embryofetal study in pregnant rabbits at an oral dose that was approximately 55,000 times the MROHD. In both studies, no drug-induced teratogenic effects were noted.

Epinastine reduced pup body weight gain following an oral dose to pregnant rats that was approximately 90,000 times the MROHD.

There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Epinastine HCl Ophthalmic Solution 0.05% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

8.3 Nursing Mothers

A study in lactating rats revealed excretion of epinastine in the breast milk. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Epinastine HCl Ophthalmic Solution 0.05% is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients below the age of 2 years have not been established.

8.5 Geriatric Use

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

11 Description ⮝

Epinastine HCl Ophthalmic Solution 0.05% is a clear, colorless, sterile isotonic solution containing epinastine HCl, an antihistamine and an inhibitor of histamine release from the mast cell for topical administration to the eyes.

Epinastine HCl is represented by the following structural formula:

C16H15N3HCl Mol. Wt. 285.78

Chemical Name:

3-Amino-9,13b-dihydro-1H-dibenz[c,f]imidazo[1,5-a]azepine hydrochloride

Each mL contains: Active: Epinastine HCl 0.05% (0.5 mg/mL) equivalent to epinastine 0.044% (0.44 mg/mL); Preservative: Benzalkonium chloride 0.01%; Inactives: Edetate disodium, dihydrate; purified water; sodium chloride; sodium phosphate, monobasic, anhydrous; and sodium hydroxide and/or hydrochloric acid (to adjust pH).

Epinastine HCl Ophthalmic Solution 0.05% has a pH of approximately 7 and an osmolality range of 250 to 310 mOsm/kg.

12 Clinical Pharmacology ⮝

12.1 Mechanism of Action

Epinastine is a topically active, direct H1-receptor antagonist and an inhibitor of the release of histamine from the mast cell. Epinastine is selective for the histamine H1-receptor and has affinity for the histamine H2 receptor. Epinastine also possesses affinity for the 1, 2-, and 5-HT2 receptors.

12.3 Pharmacokinetics

Fourteen subjects, with allergic conjunctivitis, received one drop of Epinastine HCl Ophthalmic Solution 0.05% in each eye twice daily for 7 days. On day 7, average maximum epinastine plasma concentrations of 0.04 0.014 ng/ml were reached after about two hours indicating low systemic exposure. While these concentrations represented an increase over those seen following a single dose, the day 1 and day 7 Area Under the Curve (AUC) values were unchanged indicating that there is no increase in systemic absorption with multiple dosing. Epinastine is 64% bound to plasma proteins. The total systemic clearance is approximately 56 L/hr and the terminal plasma elimination half-life is about 12 hours. Epinastine is mainly excreted unchanged. About 55% of an intravenous dose is recovered unchanged in the urine with about 30% in feces. Less than 10% is metabolized. The renal elimination is mainly via active tubular secretion.

13 Nonclinical Toxicology ⮝

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In 18-month or 2-year dietary carcinogenicity studies in mice or rats, respectively, epinastine was not carcinogenic at doses up to 40 mg/kg [approximately 30,000 times higher than the MROHD, assuming 100% absorption in humans and animals].

Epinastine in newly synthesized batches was negative for mutagenicity in the Ames/Salmonella assay and in vitro chromosome aberration assay using human lymphocytes. Positive results were seen with early batches of epinastine in two in vitro chromosomal aberration studies conducted in 1980s with human peripheral lymphocytes and with V79 cells, respectively. Epinastine was negative in the in vivo clastogenicity studies, including the mouse micronucleus assay and chromosome aberration assay in Chinese hamsters. Epinastine was also negative in the cell transformation assay using Syrian hamster embryo cells, V79/HGPRT mammalian cell point mutation assay, and in vivo/in vitro unscheduled DNA synthesis assay using rat primary hepatocytes.

Epinastine had no effect on fertility of male rats. Decreased fertility in female rats was observed at an oral dose up to approximately 90,000 times the MROHD.

14 Clinical Studies ⮝

Epinastine HCl 0.05% has been shown to be significantly superior to vehicle for improving ocular itching in patients with allergic conjunctivitis in clinical studies using two different models: (1) conjunctival antigen challenge (CAC) where patients were dosed and then received antigen instilled into the inferior conjunctival fornix; and (2) environmental field studies where patients were dosed and evaluated during allergy season in their natural habitat. Results demonstrated a rapid onset of action for epinastine HCl 0.05% within 3 to 5 minutes after conjunctival antigen challenge. Duration of effect was shown to be 8 hours, making a twice daily regimen suitable. This dosing regimen was shown to be safe and effective for up to 8 weeks, without evidence of tachyphylaxis.

16 How Supplied/storage And Handling ⮝

Epinastine HCl Ophthalmic Solution 0.05% is supplied sterile in opaque white LDPE plastic bottles with dropper tips and white polypropylene (PP) caps as follows:

5 mL in 10 mL bottle

NDC 51991-836-75

Storage: Store at 20-25 C (68-77 F) [see USP Controlled Room Temperature]. Keep bottle tightly closed and out of the reach of children.

Package Label.principal Display Panel ⮝

Container label

Carton label

EPINASTINE HYDROCHLORIDE epinastine hydrochloride solution/ drops

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:70069-008 Route of Administration OPHTHALMIC

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength EPINASTINE HYDROCHLORIDE (UNII: GFM415S5XL) (EPINASTINE - UNII:Q13WX941EF) EPINASTINE HYDROCHLORIDE 0.5 mg in 1 mL

Inactive Ingredients Ingredient Name Strength BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7) 0.1 mg in 1 mL EDETATE DISODIUM (UNII: 7FLD91C86K) SODIUM CHLORIDE (UNII: 451W47IQ8X) SODIUM PHOSPHATE, MONOBASIC (UNII: 3980JIH2SW) SODIUM HYDROXIDE (UNII: 55X04QC32I) HYDROCHLORIC ACID (UNII: QTT17582CB) WATER (UNII: 059QF0KO0R)

Product Characteristics Color WHITE (Clear Solution) Score Shape Size Flavor Imprint Code Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:70069-008-10 10 in 1 CARTON 09/14/2016 1 NDC:70069-008-01 1 in 1 CARTON 1 5 mL in 1 BOTTLE; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090951 09/14/2016

Labeler - Somerset Therapeutics, LLC (079947873)

Registrant - Somerset Therapeutics, LLC (079947873)

Establishment
Name	Address	ID/FEI	Business Operations
Wintac Limited		677236695	ANALYSIS(70069-008) , LABEL(70069-008) , MANUFACTURE(70069-008) , PACK(70069-008)

Revised: 11/2018 Document Id: 84ad9b83-cca6-42ea-b274-6563c0c262f6 34391-3 Set id: 0d4ee45c-e58f-4b7c-b389-898f5c27f54d Version: 2 Effective Time: 20181130 Somerset Therapeutics, LLC

Epinastine Hydrochloride ⮝

EPINASTINE HYDROCHLORIDE epinastine hydrochloride solution/ drops

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:50090-1635(NDC:51991-836) Route of Administration OPHTHALMIC

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength EPINASTINE HYDROCHLORIDE (UNII: GFM415S5XL) (EPINASTINE - UNII:Q13WX941EF) EPINASTINE HYDROCHLORIDE 0.5 mg in 1 mL

Inactive Ingredients Ingredient Name Strength benzalkonium chloride (UNII: F5UM2KM3W7) 0.1 mg in 1 mL edetate sodium (UNII: MP1J8420LU) water (UNII: 059QF0KO0R) sodium chloride (UNII: 451W47IQ8X) sodium phosphate, monobasic, anhydrous (UNII: KH7I04HPUU) sodium hydroxide (UNII: 55X04QC32I) hydrochloric acid (UNII: QTT17582CB)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:50090-1635-0 1 in 1 CARTON 01/15/2015 1 5 mL in 1 BOTTLE, DROPPER ; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090870 11/05/2013

Labeler - A-S Medication Solutions (830016429)

Establishment
Name	Address	ID/FEI	Business Operations
A-S Medication Solutions		830016429	RELABEL(50090-1635)

Revised: 11/2017 Document Id: 3592bbdc-acc8-40a6-b284-4fceca8ca464 34391-3 Set id: 6099119a-0cb4-4c63-a893-861a930686fe Version: 3 Effective Time: 20171128 A-S Medication Solutions

Principal Display Panel - 5 Ml Bottle Carton ⮝

NDC 51991-836-75

Epinastine HCl
Ophthalmic
Solution,
0.05%

FOR USE IN THE
EYES ONLY

sterile

Breckenridge
Pharmaceutical, Inc.
Rx Only
5 mL sterile

EPINASTINE HYDROCHLORIDE epinastine hydrochloride solution/ drops

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:51991-836 Route of Administration OPHTHALMIC

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Epinastine Hydrochloride (UNII: GFM415S5XL) (Epinastine - UNII:Q13WX941EF) Epinastine Hydrochloride 0.5 mg in 1 mL

Inactive Ingredients Ingredient Name Strength benzalkonium chloride (UNII: F5UM2KM3W7) 0.1 mg in 1 mL edetate sodium (UNII: MP1J8420LU) water (UNII: 059QF0KO0R) sodium chloride (UNII: 451W47IQ8X) sodium phosphate, monobasic, anhydrous (UNII: KH7I04HPUU) sodium hydroxide (UNII: 55X04QC32I) hydrochloric acid (UNII: QTT17582CB)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:51991-836-75 1 in 1 CARTON 11/05/2013 1 5 mL in 1 BOTTLE, DROPPER; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090870 11/05/2013

Labeler - Breckenridge Pharmaceutical, Inc. (150554335)

Establishment
Name	Address	ID/FEI	Business Operations
PrimaPharma, Inc.		079699106	MANUFACTURE(51991-836)

Revised: 1/2019 Document Id: 7b868a33-dbef-4470-97d5-26009b03dacb 34391-3 Set id: 8ff37968-22a1-4904-a139-977463790f12 Version: 6 Effective Time: 20190131 Breckenridge Pharmaceutical, Inc.