BIMATOPROST solution/ drops
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1. What Is Hypotrichosis Of The Eyelashes?
2. What Is Bimatoprost Ophthalmic Solution?
3. Who Should Not Take Bimatoprost Ophthalmic Solution?
4. Are There Any Special Warnings Associated With Bimatoprost Ophthalmic Solution Use?
5. Who Should I Tell That I Am Using Bimatoprost Ophthalmic Solution?
6. What Should I Do If I Get Bimatoprost Ophthalmic Solution In My Eye?
7. What Are The Possible Side Effects Of Bimatoprost Ophthalmic Solution?
8. How Do I Use Bimatoprost Ophthalmic Solution?
9. Active Ingredient:
10. Inactive Ingredients:
11. Patient Information
12. Manufactured By:

What Is Hypotrichosis Of The Eyelashes? ⮝

Hypotrichosis is another name for having inadequate or not enough eyelashes.

What Is Bimatoprost Ophthalmic Solution? ⮝

Bimatoprost ophthalmic solution is a prescription treatment for hypotrichosis used to grow eyelashes, making them longer, thicker and darker.

Who Should Not Take Bimatoprost Ophthalmic Solution? ⮝

Do not use bimatoprost ophthalmic solution if you are allergic to one of its ingredients.

Are There Any Special Warnings Associated With Bimatoprost Ophthalmic Solution Use? ⮝

Bimatoprost ophthalmic solution is intended foruse on the skin of the upper eyelid margins at the base of the eyelashes. Refer to Illustration 2 below.DO NOT APPLYto the lower eyelid. If you are using Lumiganor other products in the same class for elevated intraocular pressure (IOP), or if you have a history of abnormal IOP, you should only use bimatoprost ophthalmic solution under the close supervision of your physician.

Bimatoprost ophthalmic solution use may cause darkening of the eyelid skin which may be reversible. Bimatoprost ophthalmic solution use may also cause increased brown pigmentation of the colored part of the eye which is likely to be permanent.

It is possible for hair growth to occur in other areas of your skin that bimatoprost ophthalmic solution frequently touches. Any excess solution outside the upper eyelid margin should be blotted with a tissue or other absorbent material to reduce the chance of this from happening. It is also possible for a difference in eyelash length, thickness, fullness, pigmentation, number of eyelash hairs, and/or direction of eyelash growth to occur between eyes. These differences, should they occur, will usually go away if you stop using bimatoprost ophthalmic solution.

Who Should I Tell That I Am Using Bimatoprost Ophthalmic Solution? ⮝

You should tell your physician you are using bimatoprost ophthalmic solution especially if you have a history of eye pressure problems.

You should also tell anyone conducting an eye pressure screening that you are using bimatoprost ophthalmic solution.

What Should I Do If I Get Bimatoprost Ophthalmic Solution In My Eye? ⮝

Bimatoprost ophthalmic solution is an ophthalmic drug product. Bimatoprost ophthalmic solution is not expected to cause harm if it gets into the eye proper. Do not attempt to rinse your eye in this situation.

What Are The Possible Side Effects Of Bimatoprost Ophthalmic Solution? ⮝

The most common side effects after using bimatoprost ophthalmic solution are an itching sensation in the eyes and/or eye redness. This was reported in approximately 4% of patients. Bimatoprost ophthalmic solution may cause other less common side effects which typically occur on the skin close to where bimatoprost ophthalmic solution is applied, or in the eyes. These include skin darkening, eye irritation, dryness of the eyes, and redness of the eyelids.

If you develop a new ocular condition (e.g., trauma or infection), experience a sudden decrease in visual acuity, have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, you should immediately

If you stop using bimatoprost ophthalmic solution, your eyelashes are expected to return to their previous appearance over several weeks to months.

Any eyelid skin darkening is expected to reverse after several weeks to months.

Any darkening of the colored part of the eye known as the iris is NOT expected to reverse and is likely permanent.

How Do I Use Bimatoprost Ophthalmic Solution? ⮝

The recommended dosage is one application nightly to the skin of the upper eyelid margin at the base of the eyelashes only.

Once nightly, start by ensuring your face is clean, makeup and contact lenses are removed. Remove an applicator from its tray. Then, holding the sterile applicator horizontally, place one drop of bimatoprost ophthalmic solution on the area of the applicator closest to the tip but not on the tip (

Active Ingredient: ⮝

bimatoprost

Inactive Ingredients: ⮝

benzalkonium chloride, citric acid, purified water, sodium chloride and sodium phosphate dibasic. Sodium hydroxide and/or hydrochloric acid may be added to adjust pH. The pH during its shelf life ranges from 6.8 to 7.8.

Lumiganis a registered trademark of Allergan, Inc.

Manufactured by Alcon Laboratories, Inc.
Fort Worth, Texas 76134 for
Sandoz Inc.
Princeton, NJ 08540

Rev. September 2019

Patient Information ⮝

17.1 Potential for Pigmentation

Advise patients about the potential for increased brown pigmentation of the iris, which may be permanent. Also inform patients about the possibility of eyelid skin darkening, which may be reversible after discontinuation of bimatoprost ophthalmic solution, 0.03%.

17.2 Potential for Eyelash Changes

Inform patients of the possibility of eyelash and vellus hair changes in the treated eye during treatment with bimatoprost ophthalmic solution, 0.03%. These changes may result in a disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. Eyelash changes are usually reversible upon discontinuation of treatment.

17.3 Handling the Container

Instruct patients 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.

17.4 When to Seek Physician Advice

Advise patients that if they develop an intercurrent ocular condition (e.g., trauma or infection), have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician's advice concerning the continued use of bimatoprost ophthalmic solution, 0.03%.

17.5 Use with Contact Lenses

Advise patients that bimatoprost ophthalmic solution, 0.03% contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of bimatoprost ophthalmic solution, 0.03% and may be reinserted 15 minutes following its administration.

17.6 Use with Other Ophthalmic Drugs

Advise patients that if more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes between applications.

Marketed by:

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States

Manufactured By: ⮝

Lupin Limited

Pithampur (M.P.) - 454 775

India

March 2015 ID#: 239313

1. No Title 1572554401
2. 1 Indications And Usage
3. 2 Dosage And Administration
4. 3 Dosage Forms And Strengths
5. 4 Contraindications
6. 5 Warnings And Precautions
7. 11 Description
8. 12 Clinical Pharmacology
9. 14 Clinical Studies
10. 16 How Supplied/storage And Handling
11. Bimatoprost Ophthalmic Solution 0.03%, Carton
12. Highlights Of Prescribing Information
13. Recent Major Changes
14. Indications And Usage
15. Dosage And Administration
16. Dosage Forms And Strengths
17. Contraindications
18. Warnings And Precautions
19. Adverse Reactions
20. Use In Specific Populations
21. 1 Indications And Usage
22. 2 Dosage And Administration
23. 3 Dosage Forms And Strengths
24. 4 Contraindications
25. 5 Warnings And Precautions
26. 6 Adverse Reactions
27. 8 Use In Specific Populations
28. 10 Overdosage
29. 11 Description
30. 12 Clinical Pharmacology
31. 13 Nonclinical Toxicology
32. 14 Clinical Studies
33. 16 How Supplied/storage And Handling
34. Package/label Display Panel
35. 1 Indications And Usage
36. 2 Dosage And Administration
37. 3 Dosage Forms And Strengths
38. 6 Adverse Reactions
39. 8 Use In Specific Populations
40. 10 Overdosage
41. 13 Nonclinical Toxicology
42. Package Label.principal Display Panel
43. 1 Indications & Usage
44. 2 Dosage & Administration
45. 3 Dosage Forms & Strengths
46. No Title 1572456460

No Title 1572554401 ⮝

Manufactured by:																																																													Manufactured for:
Apotex Inc.																																																													Apotex Corp.
Toronto, Ontario																																																													Weston, FL
Canada M9L 1T9																																																													USA 33326

Revised: February 2018

Apotex Corp.

NDC 60505-0583-4

Rx Only

Bimatoprost Ophthalmic Solution

0.03%

2.5 mL sterile

Apotex Corp.

NDC 60505-0583-4

Bimatoprost Ophthalmic Solution

0.03%

Rx Only

2.5 mL sterile

BIMATOPROST bimatoprost solution/ drops

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:60505-0583 Route of Administration OPHTHALMIC

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength bimatoprost (UNII: QXS94885MZ) (bimatoprost - UNII:QXS94885MZ) bimatoprost 0.3 mg in 1 mL

Inactive Ingredients Ingredient Name Strength Sodium chloride (UNII: 451W47IQ8X) benzalkonium chloride (UNII: F5UM2KM3W7) SODIUM PHOSPHATE, DIBASIC, ANHYDROUS (UNII: 22ADO53M6F) Citric Acid Monohydrate (UNII: 2968PHW8QP) water (UNII: 059QF0KO0R) Sodium hydroxide (UNII: 55X04QC32I) hydrochloric acid (UNII: QTT17582CB)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:60505-0583-4 1 in 1 CARTON 10/08/2018 1 2.5 mL in 1 BOTTLE, DROPPER; Type 0: Not a Combination Product 2 NDC:60505-0583-1 1 in 1 CARTON 10/08/2018 2 5 mL in 1 BOTTLE, DROPPER; Type 0: Not a Combination Product 3 NDC:60505-0583-5 1 in 1 CARTON 10/08/2018 3 7.5 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 ANDA090449 10/08/2018

Labeler - Apotex Corp. (845263701)

Revised: 10/2018 Document Id: db6ed929-29d4-3e7c-bfef-df0a276c1292 34391-3 Set id: f5c1c8c6-2a7f-482b-6ecf-9cabd3a6a5c1 Version: 2 Effective Time: 20181015 Apotex Corp.

1 Indications And Usage ⮝

Bimatoprost ophthalmic solution, 0.03% is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension.

2 Dosage And Administration ⮝

The recommended dosage is one drop in the affected eye(s) once daily in the evening.

Bimatoprost ophthalmic solution, 0.03% should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect.

Reduction of the intraocular pressure starts approximately 4 hours after the first administration with maximum effect reached within approximately 8 to 12 hours.

Bimatoprost ophthalmic solution, 0.03% may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.

3 Dosage Forms And Strengths ⮝

Ophthalmic solution containing bimatoprost 0.3 mg/mL.

4 Contraindications ⮝

None

5 Warnings And Precautions ⮝

5.1 Pigmentation

Bimatoprost ophthalmic solution has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes. Pigmentation is expected to increase as long as bimatoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of bimatoprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The long term effects of increased pigmentation are not known.

Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. While treatment with bimatoprost ophthalmic solution, 0.03% can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly [see PATIENT COUNSELING INFORMATION, (17.1)].

5.2 Eyelash Changes

Bimatoprost ophthalmic solution, 0.03% may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, thickness, and number of lashes. Eyelash changes are usually reversible upon discontinuation of treatment.

5.3 Intraocular Inflammation

Prostaglandin analogs, including bimatoprost, have been reported to cause intraocular inflammation. In addition, because these products may exacerbate inflammation, caution should be used in patients with active intraocular inflammation (e.g., uveitis).

5.4 Macular Edema

Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic solution. Bimatoprost ophthalmic solution, 0.03% should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema.

5.5 Bacterial Keratitis

There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface [see PATIENT COUNSELING INFORMATION, (17.3)].

5.6 Use with Contact Lenses

Contact lenses should be removed prior to instillation of bimatoprost ophthalmic solution, 0.03% and may be reinserted 15 minutes following its administration.

11 Description ⮝

Bimatoprost ophthalmic solution, 0.03% is a synthetic prostamide analog with ocular hypotensive activity. Its chemical name is (Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenyl-1-pentenyl]cyclopentyl]-5-N-ethylheptenamide, and its molecular weight is 415.58. Its molecular formula is C25H37NO4. Its chemical structure is:

Bimatoprost is a powder, which is freely soluble in alcohol. Bimatoprost ophthalmic solution, 0.03% is a clear, isotonic, colorless, sterile ophthalmic solution with an osmolality of approximately 290 mOsmol/kg.

Bimatoprost ophthalmic solution, 0.03% contains Active: bimatoprost 0.3 mg/mL; Inactives: benzalkonium chloride 0.05 mg/mL; disodium hydrogen phosphate heptahydrate, citric acid monohydrate, sodium chloride and water for injection. Sodium hydroxide and/or hydrochloric acid may be added to adjust pH. The pH during its shelf life ranges from 6.9 to 7.6.

12 Clinical Pharmacology ⮝

12.1 Mechanism of Action

Bimatoprost, a prostaglandin analog, is a synthetic structural analog of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost is believed to lower intraocular pressure (IOP) in humans by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.

12.3 Pharmacokinetics

Absorption

After one drop of bimatoprost ophthalmic solution, 0.03% was administered once daily to both eyes of 15 healthy subjects for two weeks, blood concentrations peaked within 10 minutes after dosing and were below the lower limit of detection (0.025 ng/mL) in most subjects within 1.5 hours after dosing. Mean Cmax and AUC0-24hr values were similar on days 7 and 14 at approximately 0.08 ng/mL and 0.09 ng hr/mL, respectively, indicating that steady state was reached during the first week of ocular dosing. There was no significant systemic drug accumulation over time.

Distribution

Bimatoprost is moderately distributed into body tissues with a steady-state volume of distribution of 0.67 L/kg. In human blood, bimatoprost resides mainly in the plasma. Approximately 12% of bimatoprost remains unbound in human plasma.

Metabolism

Bimatoprost is the major circulating species in the blood once it reaches the systemic circulation following ocular dosing. Bimatoprost then undergoes oxidation, N-deethylation and glucuronidation to form a diverse variety of metabolites.

Elimination

Following an intravenous dose of radiolabeled bimatoprost (3.12 mcg/kg) to six healthy subjects, the maximum blood concentration of unchanged drug was 12.2 ng/mL and decreased rapidly with an elimination half-life of approximately 45 minutes. The total blood clearance of bimatoprost was 1.5 L/hr/kg. Up to 67% of the administered dose was excreted in the urine while 25% of the dose was recovered in the feces.

14 Clinical Studies ⮝

In clinical studies of patients with open angle glaucoma or ocular hypertension with a mean baseline IOP of 26 mmHg, the IOP-lowering effect of bimatoprost ophthalmic solution, 0.03% once daily (in the evening) was 7 to 8 mmHg.

16 How Supplied/storage And Handling ⮝

Bimatoprost ophthalmic solution, 0.03% is supplied sterile in opaque white low density polyethylene bottle which is closed with white low density polyethylene nozzle and then with turquoise colored high density polyethylene cap in the following sizes:

2.5 mL fill in a 5 mL container - NDC 68180-429-01

5 mL fill in a 10 mL container - NDC 68180-429-02

7.5 mL fill in a 10 mL container - NDC 68180-429-03

Storage: Bimatoprost ophthalmic solution, 0.03% should be stored at 2 to 25 C (36 to 77 F).

Bimatoprost Ophthalmic Solution 0.03%, Carton  ⮝

NDC 0781-6206-93

Bimatoprost

Ophthalmic

Solution

0.03%

Rx only

FOR TOPICAL APPLICATION

TO THE UPPER EYE LID

Sterile

3 mL

SANDOZ

BIMATOPROST bimatoprost solution/ drops

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0781-6206 Route of Administration OPHTHALMIC

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength BIMATOPROST (UNII: QXS94885MZ) (BIMATOPROST - UNII:QXS94885MZ) BIMATOPROST 0.3 mg in 1 mL

Inactive Ingredients Ingredient Name Strength BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7) 0.05 mg in 1 mL CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP) HYDROCHLORIC ACID (UNII: QTT17582CB) SODIUM CHLORIDE (UNII: 451W47IQ8X) SODIUM HYDROXIDE (UNII: 55X04QC32I) SODIUM PHOSPHATE, DIBASIC, UNSPECIFIED FORM (UNII: GR686LBA74) WATER (UNII: 059QF0KO0R)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0781-6206-93 3 mL in 1 BOTTLE; Type 0: Not a Combination Product 12/06/2016 2 NDC:0781-6206-75 5 mL in 1 BOTTLE; Type 0: Not a Combination Product 12/06/2016

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA202719 12/06/2016

Labeler - Sandoz Inc (005387188)

Revised: 9/2019 Document Id: a57672b8-6e7c-4990-b218-0210d9f0ab67 34391-3 Set id: 27bef7e1-750a-4ac1-ab5f-e4c0121ffcbc Version: 15 Effective Time: 20190918 Sandoz Inc

Highlights Of Prescribing Information ⮝

These highlights do not include all the information needed to use Bimatoprost Ophthalmic Solution, 0.03% safely and effectively. See full prescribing information for Bimatoprost Ophthalmic Solution, 0.03%.

BIMATOPROST Ophthalmic Solution, 0.03%
for topical ophthalmic use
Initial U.S. Approval: 2001

Recent Major Changes ⮝

Warnings and Precautions, Intraocular Inflammation (5.3) 09/2014

Indications And Usage ⮝

Bimatoprost ophthalmic solution, 0.03% is a prostaglandin analog indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension. (1)

Dosage And Administration ⮝

One drop in the affected eye(s) once daily in the evening. (2)

Dosage Forms And Strengths ⮝

Solution containing 0.3 mg/mL bimatoprost. (3)

Contraindications ⮝

None. (4)

Warnings And Precautions ⮝

Pigmentation.

Pigmentation of the iris, periorbital tissue (eyelid) and eyelashes can occur. Iris pigmentation is likely to be permanent. (5.1)

Eyelash Changes.

Gradual change to eyelashes including increased length, thickness and number of lashes. Usually reversible. (5.2)

Adverse Reactions ⮝

Most common adverse reaction is conjunctival hyperemia (45%). (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Use In Specific Populations ⮝

Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use. (8.4)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 5/2016

1 Indications And Usage  ⮝

Bimatoprost ophthalmic solution, 0.03% is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension.

2 Dosage And Administration  ⮝

The recommended dosage is one drop in the affected eye(s) once daily in the evening. Bimatoprost ophthalmic solution, 0.03% should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect.

Reduction of the intraocular pressure starts approximately 4 hours after the first administration with maximum effect reached within approximately 8 to 12 hours.

Bimatoprost ophthalmic solution, 0.03% may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.

3 Dosage Forms And Strengths  ⮝

Ophthalmic solution containing bimatoprost 0.3 mg/mL.

4 Contraindications  ⮝

Bimatoprost ophthalmic solution, 0.03% is contraindicated in patients with hypersensitivity to bimatoprost or to any of the ingredients [see Adverse Reactions (6.2)].

5 Warnings And Precautions  ⮝

5.1 Pigmentation

Bimatoprost ophthalmic solution has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes. Pigmentation is expected to increase as long as bimatoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of bimatoprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The long term effects of increased pigmentation are not known.

Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. While treatment with bimatoprost ophthalmic solution, 0.03% can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly [see PATIENT COUNSELING INFORMATION (17.1)].

5.2 Eyelash Changes

Bimatoprost ophthalmic solution, 0.03% may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, thickness, and number of lashes. Eyelash changes are usually reversible upon discontinuation of treatment.

5.3 Intraocular Inflammation

Prostaglandin analogs, including bimatoprost, have been reported to cause intraocular inflammation. In addition, because these products may exacerbate inflammation, caution should be used in patients with active intraocular inflammation (e.g., uveitis).

5.4 Macular Edema

Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic solution. Bimatoprost ophthalmic solution, 0.03% should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema.

5.5 Bacterial Keratitis

There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface [see PATIENT COUNSELING INFORMATION (17.3)].

5.6 Use with Contact Lenses

Bimatoprost ophthalmic solution, 0.03% contains benzalkonium chloride, which may be absorbed by and cause discoloration of soft contact lenses. Contact lenses should be removed prior to instillation of bimatoprost ophthalmic solution, 0.03% and may be reinserted 15 minutes following its administration.

6 Adverse Reactions  ⮝

The following adverse reactions are described elsewhere in the labeling:

• Pigmentation [see Warnings and Precautions (5.1)]
• Eyelash Changes [see Warnings and Precautions (5.2)]
• Intraocular Inflammation [see Warnings and Precautions (5.3)]
• Macular Edema [see Warnings and Precautions (5.4)]
• Hypersensitivity [see Contraindications (4)]

6.1 Clinical Trials Experience

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

In clinical trials, the most frequent events associated with the use of bimatoprost ophthalmic solution, 0.03% occurring in approximately 15% to 45% of patients, in descending order of incidence, included conjunctival hyperemia, growth of eyelashes, and ocular pruritus. Approximately 3% of patients discontinued therapy due to conjunctival hyperemia.

Ocular adverse events occurring in approximately 3 to 10% of patients, in descending order of incidence, included ocular dryness, visual disturbance, ocular burning, foreign body sensation, eye pain, pigmentation of the periocular skin, blepharitis, cataract, superficial punctate keratitis, periorbital erythema, ocular irritation, and eyelash darkening. The following ocular adverse events reported in approximately 1 to 3% of patients, in descending order of incidence, included: eye discharge, tearing, photophobia, allergic conjunctivitis, asthenopia, increases in iris pigmentation, and conjunctival edema. In less than 1% of patients, intraocular inflammation was reported as iritis.

Systemic adverse events reported in approximately 10% of patients were infections (primarily colds and upper respiratory tract infections). The following systemic adverse events reported in approximately 1 to 5% of patients, in descending order of incidence, included headaches, abnormal liver function tests, asthenia and hirsutism.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of bimatoprost ophthalmic solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to bimatoprost ophthalmic solution, or a combination of these factors, include: abnormal hair growth, asthma-like symptoms, dizziness, dyspnea, eyelid edema, hypersensitivity reaction including signs and symptoms of eye allergy and allergic dermatitis, hypertension, nausea, and periorbital and lid changes including deepening of the eyelid sulcus.

8 Use In Specific Populations  ⮝

8.1 Pregnancy

Risk Summary

There are no adequate and well-controlled studies of bimatoprost ophthalmic solution, 0.03% administration in pregnant women. There is no increase in the risk of major birth defects or miscarriages based on bimatoprost postmarketing experience.

In embryofetal developmental studies, administration of bimatoprost in pregnant mice and rats during organogensis, resulted in abortion and early delivery at oral doses at least 33 times (mice) or 94 times (rats) the human exposure at the recommended clinical dose (based on blood area under the curve [AUC] levels). These adverse effects were not observed at 2.6 times (mice) and 47 times (rats) the human exposure at the recommended clinical dose.

In pre/postnatal development studies, administration of bimatoprost to pregnant rats from organogenesis to the end of lactation resulted in reduced gestation length and fetal body weight, and increased fetal and pup mortality at oral doses at least 41 times the human systemic exposure at the recommended clinical dose (based on blood AUC levels). No adverse effects were observed in rat offspring at exposures estimated at 14 times the human exposure at the recommended clinical dose (based on blood AUC levels).

Because animal reproductive studies are not always predictive of human response bimatoprost ophthalmic solution, 0.03% should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Data

Animal Data

In an embryofetal development rat study, abortion was observed in pregnant rats administered bimatoprost orally during organogenesis at 0.6 mg/kg/day (94 times the human systemic exposure at the recommended human ophthalmic dose [RHOD], based on AUC). The No Observed Adverse Effect Level (NOAEL) for abortion was 0.3 mg/kg/day (estimated at 47 times the human systemic exposure at the RHOD, based on AUC). No abnormalities were observed in rat fetuses at doses up to 0.6 mg/kg/day.

In an embryofetal development mouse study, abortion and early delivery were observed in pregnant mice administered bimatoprost orally during organogenesis at doses greater than or equal to 0.3 mg/kg/day (33 times the human systemic exposure at the RHOD, based on AUC). The NOAEL for abortion and early delivery was 0.1 mg/kg/day (2.6 times the human systemic exposure at the RHOD, based on AUC). No abnormalities were observed in mouse fetuses at doses up to 0.6 mg/kg/day (72 times the human systemic exposure at the RHOD, based on AUC).

In a pre/postnatal development study, treatment of pregnant rats with bimatoprost orally from gestation day 7 to lactation day 20 resulted in reduced gestation length, increased late resorptions, fetal deaths, and postnatal pup mortality, and reduced pup body weight at doses greater than or equal to 0.3 mg/kg/day. These effects were observed at exposures at least 41 times the human systemic exposure at the RHOD, based on AUC. The NOAEL for postnatal development and mating performance of the offspring was 0.1 mg/kg/day (estimated at 14 times the human systemic exposure at the RHOD, based on AUC).

8.2 Lactation

Risk Summary

It is not known whether topical ocular treatment with bimatoprost ophthalmic solution, 0.03% could result in sufficient systemic absorption to produce detectable quantities in human milk. In animal studies, bimatoprost has been shown to be present in breast milk of lactating rats at an intravenous dose (i.e., 1 mg/kg) 324 times the RHOD (on a m2g/m basis), however no animal data is available at clinically relevant doses.

The developmental and health benefits of breastfeeding should be considered along with the mother s clinical need for bimatoprost ophthalmic solution, 0.03% and any potential adverse effects on the breastfed child from bimatoprost ophthalmic solution, 0.03%.

8.4 Pediatric Use

Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.

8.5 Geriatric Use

No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients.

10 Overdosage  ⮝

No information is available on overdosage in humans. If overdose with bimatoprost ophthalmic solution, 0.03% occurs, treatment should be symptomatic.

In oral (by gavage) mouse and rat general toxicity studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m2 is at least 70 times higher than the accidental dose of one bottle of bimatoprost ophthalmic solution, 0.03% for a 10 kg child.

11 Description  ⮝

Bimatoprost ophthalmic solution, 0.03% is a synthetic prostamide analog with ocular hypotensive activity. Its chemical name is (Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenyl-1-pentenyl]cyclopentyl]-5-N-ethylheptenamide, and its molecular weight is 415.6 g/mol. Its molecular formula is C25H37NO4. Its chemical structure is:

Bimatoprost is a powder, which is very soluble in ethyl alcohol and methyl alcohol and slightly soluble in water. Bimatoprost ophthalmic solution, 0.03% is a clear, isotonic, colorless, sterile ophthalmic solution with an osmolality of approximately 290 mOsmol/kg.

Bimatoprost ophthalmic solution, 0.03% contains Active: bimatoprost 0.3 mg/mL; Inactives: benzalkonium chloride 0.05 mg/mL; citric acid; sodium chloride; sodium phosphate dibasic; and water for injection. Sodium hydroxide and/or hydrochloric acid may be added to adjust pH. The pH during its shelf life ranges from 6.8 to 7.8.

12 Clinical Pharmacology  ⮝

12.1 Mechanism of Action

Bimatoprost, a prostaglandin analog, is a synthetic structural analog of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost is believed to lower intraocular pressure (IOP) in humans by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.

12.3 Pharmacokinetics

Absorption

After one drop of bimatoprost ophthalmic solution, 0.03% was administered once daily to both eyes of 15 healthy subjects for two weeks, blood concentrations peaked within 10 minutes after dosing and were below the lower limit of detection (0.025 ng/mL) in most subjects within 1.5 hours after dosing. Mean Cmax and AUC0-24hr values were similar on days 7 and 14 at approximately 0.08 ng/mL and 0.09 ng hr/mL, respectively, indicating that steady state was reached during the first week of ocular dosing. There was no significant systemic drug accumulation over time.

Distribution

Bimatoprost is moderately distributed into body tissues with a steady-state volume of distribution of 0.67 L/kg. In human blood, bimatoprost resides mainly in the plasma. Approximately 12% of bimatoprost remains unbound in human plasma.

Metabolism

Bimatoprost is the major circulating species in the blood once it reaches the systemic circulation following ocular dosing. Bimatoprost then undergoes oxidation, N-deethylation and glucuronidation to form a diverse variety of metabolites.

Elimination

Following an intravenous dose of radiolabeled bimatoprost (3.12 mcg/kg) to six healthy subjects, the maximum blood concentration of unchanged drug was 12.2 ng/mL and decreased rapidly with an elimination half-life of approximately 45 minutes. The total blood clearance of bimatoprost was 1.5 L/hr/kg. Up to 67% of the administered dose was excreted in the urine while 25% of the dose was recovered in the feces.

13 Nonclinical Toxicology  ⮝

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage for 104 weeks at doses of up to 2 mg/kg/day and 1 mg/kg/day respectively (at least 192 and 291 times the human systemic exposure at the RHOD, respectively, based on blood AUC levels).

Mutagenesis

Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests.

Impairment of Fertility

Bimatoprost did not impair fertility in male or female rats at doses up to 0.6 mg/kg/day (at least 103 times the human systemic exposure at the RHOD, based on blood AUC levels).

14 Clinical Studies  ⮝

In clinical studies of patients with open angle glaucoma or ocular hypertension with a mean baseline IOP of 26 mmHg, the IOP-lowering effect of bimatoprost ophthalmic solution, 0.03% once daily (in the evening) was 7 to 8 mmHg.

16 How Supplied/storage And Handling  ⮝

Bimatoprost ophthalmic solution, 0.03% is supplied sterile in white opaque polypropylene bottles with translucent polypropylene droppers and turquoise opaque polypropylene caps in the following sizes:

2.5 mL fill in 5 mL container - NDC 60505-0583-4
5 mL fill in 5 mL container - NDC 60505-0583-1
7.5 mL fill in 10 mL container - NDC 60505-0583-5

Storage: Store at 2 C to 25 C (36 F to 77 F).

Package/label Display Panel  ⮝

AKORN

NDC 50383-908-07

Bimatoprost Ophthalmic Solution, 0.03%

For Topical Application in the Eye

Rx only

7.5 mL

Sterile

BIMATOPROST bimatoprost solution/ drops

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:50383-908 Route of Administration OPHTHALMIC

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength BIMATOPROST (UNII: QXS94885MZ) (BIMATOPROST - UNII:QXS94885MZ) BIMATOPROST 0.3 mg in 1 mL

Inactive Ingredients Ingredient Name Strength BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7) CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP) SODIUM CHLORIDE (UNII: 451W47IQ8X) SODIUM PHOSPHATE, DIBASIC, HEPTAHYDRATE (UNII: 70WT22SF4B) WATER (UNII: 059QF0KO0R) SODIUM HYDROXIDE (UNII: 55X04QC32I) HYDROCHLORIC ACID (UNII: QTT17582CB)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:50383-908-02 1 in 1 CARTON 11/12/2018 1 2.5 mL in 1 BOTTLE, DROPPER; Type 0: Not a Combination Product 2 NDC:50383-908-05 1 in 1 CARTON 11/12/2018 2 5 mL in 1 BOTTLE, DROPPER; Type 0: Not a Combination Product 3 NDC:50383-908-07 1 in 1 CARTON 11/12/2018 3 7.5 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 ANDA203299 11/12/2018

Labeler - Hi-Tech Pharmacal Co., Inc. (101196749)

Establishment
Name	Address	ID/FEI	Business Operations
Hi-Tech Pharmacal Co., Inc.		101196749	MANUFACTURE(50383-908)

Revised: 11/2018 Document Id: 9f63a18e-5c90-49d1-863c-fa90cdbddcc0 34391-3 Set id: ce5c7f22-ade3-41ea-8dd8-3ec0399d3279 Version: 6 Effective Time: 20181112 Hi-Tech Pharmacal Co., Inc.

1 Indications And Usage ⮝

Bimatoprost ophthalmic solution, 0.03% is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension.

2 Dosage And Administration ⮝

The recommended dosage is one drop in the affected eye(s) once daily in the evening.
Bimatoprost ophthalmic solution, 0.03% should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect.
Reduction of the intraocular pressure starts approximately 4 hours after the first administration with maximum effect reached within approximately 8 to 12 hours.
Bimatoprost ophthalmic solution, 0.03% may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.

3 Dosage Forms And Strengths ⮝

Ophthalmic solution containing bimatoprost 0.3 mg/mL.

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.

In clinical trials, the most frequent events associated with the use of bimatoprost ophthalmic solution, 0.03% occurring in approximately 15% to 45% of patients, in descending order of incidence, included conjunctival hyperemia, growth of eyelashes, and ocular pruritus. Approximately 3% of patients discontinued therapy due to conjunctival hyperemia.

Ocular adverse events occurring in approximately 3 to 10% of patients, in descending order of incidence, included ocular dryness, visual disturbance, ocular burning, foreign body sensation, eye pain, pigmentation of the periocular skin, blepharitis, cataract, superficial punctate keratitis, periorbital erythema, ocular irritation, and eyelash darkening. The following ocular adverse events reported in approximately 1 to 3% of patients, in descending order of incidence, included: eye discharge, tearing, photophobia, allergic conjunctivitis, asthenopia, increases in iris pigmentation, and conjunctival edema. In less than 1% of patients, intraocular inflammation was reported as iritis.

Systemic adverse events reported in approximately 10% of patients were infections (primarily colds and upper respiratory tract infections). The following systemic adverse events reported in approximately 1 to 5% of patients, in descending order of incidence, included headaches, abnormal liver function tests, asthenia and hirsutism.

6.2 Postmarketing Experience

The following reactions have been identified during postmarketing use of bimatoprost ophthalmic solution, 0.03% 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 bimatoprost ophthalmic solution, or a combination of these factors, include: abnormal hair growth, dizziness, eyelid edema, hypertension, nausea, and periorbital and lid changes associated with a deepening of the eyelid sulcus.

8 Use In Specific Populations ⮝

8.1 Pregnancy

Pregnancy Category C

Teratogenic effects:

In embryo/fetal developmental studies in pregnant mice and rats, abortion was observed at oral doses of bimatoprost which achieved at least 33 or 97 times, respectively, the maximum intended human exposure based on blood AUC levels.

At doses at least 41 times the maximum intended human exposure based on blood AUC levels, the gestation length was reduced in the dams, the incidence of dead fetuses, late resorptions, peri- and postnatal pup mortality was increased, and pup body weights were reduced.

There are no adequate and well-controlled studies of bimatoprost ophthalmic solution, 0.03% administration in pregnant women. Because animal reproductive studies are not always predictive of human response. Bimatoprost ophthalmic solution, 0.03% should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.

8.3 Nursing Mothers

It is not known whether bimatoprost ophthalmic solution, 0.03% is excreted in human milk, although in animal studies, bimatoprost has been shown to be excreted in breast milk. Because many drugs are excreted in human milk, caution should be exercised when bimatoprost ophthalmic solution, 0.03% is administered to a nursing woman.

8.4 Pediatric Use

Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.

8.5 Geriatric Use

No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients.

8.6 Hepatic Impairment

In patients with a history of liver disease or abnormal ALT, AST and/or bilirubin at baseline, bimatoprost 0.03% had no adverse effect on liver function over 48 months.

10 Overdosage ⮝

No information is available on overdosage in humans. If overdose with bimatoprost ophthalmic solution, 0.03% occurs, treatment should be symptomatic.

In oral (by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m2 is at least 70 times higher than the accidental dose of one bottle of bimatoprost ophthalmic solution, 0.03% for a 10 kg child.

13 Nonclinical Toxicology ⮝

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses of up to 2 mg/kg/day and 1 mg/kg/day respectively (at least 192 and 291 times the recommended human exposure based on blood AUC levels respectively) for 104 weeks.

Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests.

Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day (at least 103 times the recommended human exposure based on blood AUC levels).

Package Label.principal Display Panel ⮝

BIMATOPROST OPHTHALMIC SOLUTION

Rx Only

0.03%

NDC 68180-429-01

2.5 mL Bottle Label

BIMATOPROST OPHTHALMIC SOLUTION

Rx Only

0.03%

NDC 68180-429-01

2.5 mL Carton Label

BIMATOPROST OPHTHALMIC SOLUTION

Rx Only

0.03%

NDC 68180-429-02

5 mL Bottle Label

BIMATOPROST OPHTHALMIC SOLUTION

Rx Only

0.03%

NDC 68180-429-02

5 mL Carton Label

BIMATOPROST OPHTHALMIC SOLUTION

Rx Only

0.03%

NDC 68180-429-03

7.5 mL Bottle Label

BIMATOPROST OPHTHALMIC SOLUTION

Rx Only

0.03%

NDC 68180-429-03

7.5 mL Carton Label

BIMATOPROST bimatoprost solution/ drops

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:57297-429 Route of Administration OPHTHALMIC

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength BIMATOPROST (UNII: QXS94885MZ) (BIMATOPROST - UNII:QXS94885MZ) BIMATOPROST 0.3 mg in 1 mL

Inactive Ingredients Ingredient Name Strength BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7) CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP) HYDROCHLORIC ACID (UNII: QTT17582CB) SODIUM CHLORIDE (UNII: 451W47IQ8X) SODIUM HYDROXIDE (UNII: 55X04QC32I) SODIUM PHOSPHATE, DIBASIC, HEPTAHYDRATE (UNII: 70WT22SF4B) WATER (UNII: 059QF0KO0R)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:57297-429-02 1 in 1 CARTON 05/13/2015 1 5 mL in 1 BOTTLE, DROPPER; Type 0: Not a Combination Product 2 NDC:57297-429-03 1 in 1 CARTON 05/13/2015 2 7.5 mL in 1 BOTTLE, DROPPER; Type 0: Not a Combination Product 3 NDC:57297-429-01 1 in 1 CARTON 05/13/2015 3 2.5 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 ANDA203991 05/13/2015

Labeler - LUPIN LIMITED (675923163)

Registrant - LUPIN LIMITED (675923163)

Establishment
Name	Address	ID/FEI	Business Operations
LUPIN LIMITED		863645527	manufacture(57297-429) , pack(57297-429)

Revised: 5/2016 Document Id: 7e93fb29-97d9-4fa1-bdec-75eea81143c9 34391-3 Set id: 8a37cb8a-c698-490a-8e70-fa8d74eb0471 Version: 1 Effective Time: 20160504 LUPIN LIMITED

1 Indications & Usage ⮝

Bimatoprost ophthalmic solution, 0.03% is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension.

2 Dosage & Administration ⮝

The recommended dosage is one drop in the affected eye(s) once daily in the evening. Bimatoprost ophthalmic solution, 0.03% should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect.

Reduction of the intraocular pressure starts approximately 4 hours after the first administration with maximum effect reached within approximately 8 to 12 hours.

Bimatoprost ophthalmic solution, 0.03% may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.

3 Dosage Forms & Strengths ⮝

Ophthalmic solution containing bimatoprost 0.3 mg/mL.

No Title 1572456460 ⮝

Manufactured by:																																																													Manufactured for:
Apotex Inc.																																																													Apotex Corp.
Toronto, Ontario																																																													Weston, FL
Canada M9L 1T9																																																													USA 33326

Revised: February 2018

Apotex Corp.

NDC 60505-0583-4

Rx Only

Bimatoprost Ophthalmic Solution

0.03%

2.5 mL sterile

Apotex Corp.

NDC 60505-0583-4

Bimatoprost Ophthalmic Solution

0.03%

Rx Only

2.5 mL sterile

BIMATOPROST bimatoprost solution/ drops

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:60505-0583 Route of Administration OPHTHALMIC

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength bimatoprost (UNII: QXS94885MZ) (bimatoprost - UNII:QXS94885MZ) bimatoprost 0.3 mg in 1 mL

Inactive Ingredients Ingredient Name Strength Sodium chloride (UNII: 451W47IQ8X) benzalkonium chloride (UNII: F5UM2KM3W7) SODIUM PHOSPHATE, DIBASIC, ANHYDROUS (UNII: 22ADO53M6F) Citric Acid Monohydrate (UNII: 2968PHW8QP) water (UNII: 059QF0KO0R) Sodium hydroxide (UNII: 55X04QC32I) hydrochloric acid (UNII: QTT17582CB)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:60505-0583-4 1 in 1 CARTON 10/08/2018 1 2.5 mL in 1 BOTTLE, DROPPER; Type 0: Not a Combination Product 2 NDC:60505-0583-1 1 in 1 CARTON 10/08/2018 2 5 mL in 1 BOTTLE, DROPPER; Type 0: Not a Combination Product 3 NDC:60505-0583-5 1 in 1 CARTON 10/08/2018 3 7.5 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 ANDA090449 10/08/2018

Labeler - Apotex Corp. (845263701)

Revised: 10/2018 Document Id: db6ed929-29d4-3e7c-bfef-df0a276c1292 34391-3 Set id: f5c1c8c6-2a7f-482b-6ecf-9cabd3a6a5c1 Version: 2 Effective Time: 20181015 Apotex Corp.