Approved Use RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% helps increase your eyes’ natural ability to produce tears, which may be reduced by inflammation due to Chronic Dry Eye. RESTASIS® did not increase tear production in patients using anti-inflammatory eye drops or tear duct plugs.

Important Safety Information Do not use RESTASIS® Ophthalmic Emulsion if you are allergic to any of the ingredients. To help avoid eye injury and contamination, do not touch the vial tip to your eye or other surfaces. RESTASIS® should not be used while wearing contact lenses. If contact lenses are worn, they should be removed prior to the use.

The most common side effect is a temporary burning sensation. Other side effects include eye redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please click here for full Product Information.

Making Your Own Real Tears Matters:

Alison Tendler MD RESTASIS® User, Eye Doctor

Your Guide to RESTASIS® Therapy

Congratulations! You’ve started the journey to making more of your own tears with RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05%, the only prescription available to treat Chronic Dry Eye disease caused by decreased tear production due to inflammation. I use RESTASIS® myself and I prescribe it for my patients who have the same type of Chronic Dry Eye disease that I have.

We’re not alone on this journey. In this guidebook, you’ll meet other people just like you who are on their way to making more of their own real tears. And you’ll learn about what you can expect throughout your treatment with RESTASIS® Ophthalmic Emulsion.

Approved Use RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% helps increase your eyes’ natural ability to produce tears, which may be reduced by inflammation due to Chronic Dry Eye. RESTASIS® did not increase tear production in patients using anti-inflammatory eye drops or tear duct plugs.

Important Safety InformationDo not use RESTASIS® Ophthalmic Emulsion if you are allergic to any of the ingredients. To help avoid eye injury and contamination, do not touch the vial tip to your eye or other surfaces. RESTASIS® should not be used while wearing contact lenses. If contact lenses are worn, they should be removed prior to the use.

The most common side effect is a temporary burning sensation. Other side effects include eye redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please click here for full Product Information.

Starting on Your RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% JourneyYou’ve taken the first important step in taking charge of your eye health! You’ve spoken to your eye doctor, who diagnosed you with Chronic Dry Eye disease caused by decreased tear production due to inflammation and gave you a prescription for RESTASIS®.

You’re not alone—many people suffer from this type of Chronic Dry Eye disease. Gwen is one of those people. She was using artificial tears constantly to treat her dry eye. Like you, Gwen took action and went to her doctor.

Her doctor explained that RESTASIS® is the only prescription eye drop that helps increase your eyes’ natural ability to produce tears, which may be reduced by inflammation due to Chronic Dry Eye disease. RESTASIS® Ophthalmic Emulsion did not increase tear production in patients using anti-inflammatory eye drops or tear duct plugs.

Meet other patients like you who are on the same journey to increased tear production.

Jenny Mark Toni

Gwen

Ask your eye doctor for a 90-day prescription and join My Tears, My Rewards® today!

GETTInG STARTEd

Approved Use RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% helps increase your eyes’ natural ability to produce tears, which may be reduced by inflammation due to Chronic Dry Eye. RESTASIS® did not increase tear production in patients using anti-inflammatory eye drops or tear duct plugs.

Important Safety InformationDo not use RESTASIS® Ophthalmic Emulsion if you are allergic to any of the ingredients. To help avoid eye injury and contamination, do not touch the vial tip to your eye or other surfaces. RESTASIS® should not be used while wearing contact lenses. If contact lenses are worn, they should be removed prior to the use.

The most common side effect is a temporary burning sensation. Other side effects include eye redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please click here for full Product Information.

How RESTASIS® Is DifferentWith continued use, 1 drop, twice a day in each eye, 12 hours apart, every day, RESTASIS® Ophthalmic Emulsion is the only prescription eye drop that helps you make more of your own tears when your ability to make them has been reduced by inflammation due to Chronic Dry Eye disease.

It’s important to understand that RESTASIS® is not an over-the-counter product like an artificial tear. It is a prescription medicine. Artificial tears are helpful for temporary relief, but they do not increase the eyes’ ability to produce their own tears; only prescription RESTASIS® Ophthalmic Emulsion can.

RESTASIS® can be used with artificial tears, such as REFRESH® OPTIVE™ Advanced Lubricant Eye Drops. Allow for 15 minutes between products.

Let’s talk about the right way for you to get started with RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% treatment

RESTASIS® works when you use it exactly as prescribed.

• To use RESTASIS® Ophthalmic Emulsion, invert the unit dose vial a few times to obtain a uniform, white, opaque emulsion before using

• Place 1 drop of RESTASIS® twice a day in each eye, 12 hours apart, every day

• RESTASIS® Ophthalmic Emulsion is packaged in single-use vials because it doesn’t contain any preservatives. So it’s important that 1 vial be used each time and immediately discarded after each use

• Be sure to get a full 30-day supply (60 vials total) or 90-day supply (180 vials total) from your pharmacist

• If you are a contact lens wearer, you can still use RESTASIS® Ophthalmic Emulsion. Just make sure to not use RESTASIS® while your contact lenses are on your eyes. Remove your contact lenses before using RESTASIS® Ophthalmic Emulsion, and wait 15 minutes after applying RESTASIS® before putting your contact lenses back on

REMEMBER: It’s important to use RESTASIS® as directed, twice a day, every day.

GETTInG STARTEd

Approved Use RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% helps increase your eyes’ natural ability to produce tears, which may be reduced by inflammation due to Chronic Dry Eye. RESTASIS® did not increase tear production in patients using anti-inflammatory eye drops or tear duct plugs.

Important Safety InformationDo not use RESTASIS® Ophthalmic Emulsion if you are allergic to any of the ingredients. To help avoid eye injury and contamination, do not touch the vial tip to your eye or other surfaces. RESTASIS® should not be used while wearing contact lenses. If contact lenses are worn, they should be removed prior to the use.

The most common side effect is a temporary burning sensation. Other side effects include eye redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please click here for full Product Information.

What You Can Expect With RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05%

“ Remember: It took a while for your Chronic Dry Eye disease to develop. And it’s going to take a while before you can tell that you’re getting increased tear production with RESTASIS ®. As a physician, I knew what to expect, but it still took patience to keep putting in the RESTASIS ® drops twice a day, 12 hours apart, every day. But then I started seeing results, so it’s important that I continue with treatment.”

Just as it took time for you to develop Chronic Dry Eye disease, it will take time for RESTASIS® to help you produce your own real tears. Be patient because it could take 3 to 6 months after beginning therapy for you to notice an increase in tear production.

Give RESTASIS® Ophthalmic Emulsion time to help you make more of your own real tears. When you use RESTASIS®, you may experience a temporary burning sensation. This might be a response to treatment. If this persists, or you are considering discontinuing treatment, talk to your eye doctor immediately.

– Alison Tendler MD, RESTASIS® User, Eye Doctor

SETTInG ExpEcTATIonS

Approved Use RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% helps increase your eyes’ natural ability to produce tears, which may be reduced by inflammation due to Chronic Dry Eye. RESTASIS® did not increase tear production in patients using anti-inflammatory eye drops or tear duct plugs.

Important Safety InformationDo not use RESTASIS® Ophthalmic Emulsion if you are allergic to any of the ingredients. To help avoid eye injury and contamination, do not touch the vial tip to your eye or other surfaces. RESTASIS® should not be used while wearing contact lenses. If contact lenses are worn, they should be removed prior to the use.

The most common side effect is a temporary burning sensation. Other side effects include eye redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please click here for full Product Information.

Tracking Your Progress With RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05%

WITH CONTINUED USE:Keep up the good work—your eyes should be producing more of their own real tears. As long as you continuously use RESTASIS® Ophthalmic Emulsion, you may continue to make more of your own real tears.

Individual results may vary.

1 MONTH:Your eyes may begin producing more of their own real tears.

Ask your eye doctor for a 90-day prescription and join My Tears, My Rewards ® for continuous savings and support throughout your RESTASIS® journey.

3 MONTHS:You may begin to notice an increase in tear production. Stick with your treatment—you should make more of your own real tears within a few months.

6 MONTHS:You may experience a significant increase in tear production and may rely less on artificial tears. Ask your eye doctor about how you are doing on RESTASIS®.

Getting Started

Mo. 1 Mo. 2 Mo. 3 Mo. 4 Mo. 5 Mo. 6 Continued Use

SETTInG ExpEcTATIonS

Approved Use RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% helps increase your eyes’ natural ability to produce tears, which may be reduced by inflammation due to Chronic Dry Eye. RESTASIS® did not increase tear production in patients using anti-inflammatory eye drops or tear duct plugs.

Important Safety InformationDo not use RESTASIS® Ophthalmic Emulsion if you are allergic to any of the ingredients. To help avoid eye injury and contamination, do not touch the vial tip to your eye or other surfaces. RESTASIS® should not be used while wearing contact lenses. If contact lenses are worn, they should be removed prior to the use.

The most common side effect is a temporary burning sensation. Other side effects include eye redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please click here for full Product Information.

Stay on the Path to Increased Tear Production With RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05%

REMEMBER:

“ When I started RESTASIS ®, the waiting was the hardest part. After a month or so, I hadn’t noticed any change. The truth? I was ready to give up. So I spoke to my doctor—she told me to give RESTASIS ® time to work and that in 3 to 6 months I should notice a difference. So I decided to keep using it. And one day I realized it was working for me. I was so glad I hung in there!”

– Michelle, RESTASIS® Patient

The doctor reminded Michelle that Chronic Dry Eye is a chronic disease and there’s no permanent cure for it. As with Michelle, you will need to continue to use RESTASIS® Ophthalmic Emulsion twice a day in each eye, 12 hours apart, every day, in order to experience increased tear production.

After you’ve used RESTASIS® for a while, you may start to notice that your eyes are making more of their own real tears. If so, congratulations! However, if you feel like there hasn’t been much of a change yet, continue with it!

Michelle is a patient who’s been using RESTASIS® Ophthalmic Emulsion for some time. She decided to check with her doctor about the progress she was making in producing more of her own real tears.

Always ask your eye doctor about any questions you have and always follow your doctor’s instructions.

MonThS

1-3

Approved Use RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% helps increase your eyes’ natural ability to produce tears, which may be reduced by inflammation due to Chronic Dry Eye. RESTASIS® did not increase tear production in patients using anti-inflammatory eye drops or tear duct plugs.

Important Safety InformationDo not use RESTASIS® Ophthalmic Emulsion if you are allergic to any of the ingredients. To help avoid eye injury and contamination, do not touch the vial tip to your eye or other surfaces. RESTASIS® should not be used while wearing contact lenses. If contact lenses are worn, they should be removed prior to the use.

The most common side effect is a temporary burning sensation. Other side effects include eye redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please click here for full Product Information.

Once she was in her third month of treatment, Andrea had already noticed an increase in tear production. She continued using RESTASIS®. If you haven’t noticed much of a change in tear production at 3 months, be patient. You should make more of your own real tears within a few months.

If you’re like Andrea, you began to notice a significant increase in tear production by 6 months. You can continue to use RESTASIS® Ophthalmic Emulsion with artificial tears, such as REFRESH® OPTIVE™ Advanced Lubricant Eye Drops. Allow for 15 minutes between products. But by 6 months, you may notice that you’re using artificial tears less.

Even though you’re on your way to making more of your own real tears, it’s important to keep using RESTASIS® as prescribed by your doctor.

REMEMBER: With continued use twice a day in each eye, 12 hours apart, every day, RESTASIS® helps you make more of your own real tears.

Talk to your eye doctor about how you are doing on RESTASIS® Ophthalmic Emulsion.

“ RESTASIS® worked for me, so after 6 months, I asked my doctor if I could stop using it. The doctor said for my type of Chronic Dry Eye, in order for me to continue making more of my own tears, I have to continuously use RESTASIS®. You can bet I will!”

– Andrea, RESTASIS® Patient

Staying With RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% Matters

MonThS

3-6

Approved Use RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% helps increase your eyes’ natural ability to produce tears, which may be reduced by inflammation due to Chronic Dry Eye. RESTASIS® did not increase tear production in patients using anti-inflammatory eye drops or tear duct plugs.

Important Safety InformationDo not use RESTASIS® Ophthalmic Emulsion if you are allergic to any of the ingredients. To help avoid eye injury and contamination, do not touch the vial tip to your eye or other surfaces. RESTASIS® should not be used while wearing contact lenses. If contact lenses are worn, they should be removed prior to the use.

The most common side effect is a temporary burning sensation. Other side effects include eye redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please click here for full Product Information.

Keep Up the Good Work!

REMEMBER: Maintaining treatment success with RESTASIS® matters.

“ I’ve continued using RESTASIS ® because I know I have a specific type of chronic disease. I’m making more of my own real tears thanks to RESTASIS ®. I want to keep it that way! My doctor told me that as long as I continuously use RESTASIS®, I may continue to make my own real tears. So I’m going to continue with my treatment.”

– Michelle, RESTASIS® Patient

With continued use comes continued benefits. Here’s a list of resources to help you stay on your RESTASIS® Ophthalmic Emulsion journey:

RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% will help your eyes keep producing more of your own real tears with continued use. Individual results may vary.

a. Call the RESTASIS® Patient Support Center at 1-866-572-5931. Trained representatives and nurses can answer your questions about treatment and address any concerns you may have.

b. Go to mytearsmyrewards.com for more information on support and savings!

c. Go to restasis.com to meet patients just like you

MonThS

6& BEyOnd

Approved Use RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% helps increase your eyes’ natural ability to produce tears, which may be reduced by inflammation due to Chronic Dry Eye. RESTASIS® did not increase tear production in patients using anti-inflammatory eye drops or tear duct plugs.

Important Safety InformationDo not use RESTASIS® Ophthalmic Emulsion if you are allergic to any of the ingredients. To help avoid eye injury and contamination, do not touch the vial tip to your eye or other surfaces. RESTASIS® should not be used while wearing contact lenses. If contact lenses are worn, they should be removed prior to the use.

The most common side effect is a temporary burning sensation. Other side effects include eye redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please click here for full Product Information.

RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% Support and Savings

REMEMBER: Support every step of the way matters. Go to mytearsmyrewards.com and join today.

“ It takes dedication to use something twice a day, every day. The RESTASIS ® program I joined really helps. With the My Tears, My Rewards ® Program, I automatically get savings every time I refill my prescription, and those savings add up. And in addition to saving money, I get regular e-mails with information on taking care of my Chronic Dry Eye disease along with other health tips that are really useful.”

– Michelle, RESTASIS® Patient

Your type of Chronic Dry Eye disease that causes inflammation and reduces tear production requires continuous prescription medication. To support and reward your commitment to staying on RESTASIS® therapy, Allergan has created the My Tears, My Rewards ® (MTMR) Program.

To enroll in the MTMR Program, you will need a RESTASIS® Advantage Patient Support Pack which you can obtain from a participating eye doctor’s office, or by going to mytearsmyrewards.com. This pack contains information about RESTASIS® Ophthalmic Emulsion and the MTMR Program. It also contains the RESTASIS® MTMR Card, which provides entry into the program to earn instant

prescription savings and rewards with your RESTASIS® prescription.

SuppoRT & SAvInG

Approved Use RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% helps increase your eyes’ natural ability to produce tears, which may be reduced by inflammation due to Chronic Dry Eye. RESTASIS® did not increase tear production in patients using anti-inflammatory eye drops or tear duct plugs.

Important Safety InformationDo not use RESTASIS® Ophthalmic Emulsion if you are allergic to any of the ingredients. To help avoid eye injury and contamination, do not touch the vial tip to your eye or other surfaces. RESTASIS® should not be used while wearing contact lenses. If contact lenses are worn, they should be removed prior to the use.

The most common side effect is a temporary burning sensation. Other side effects include eye redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please click here for full Product Information.

Join MyTearsMyRewards.com Today to Receive Valuable Savings and Ongoing Support!

Dr. Tendler, Andrea Robinson, and Michelle Carmichael are actual RESTASIS® patients and are compensated for appearing in this guidebook.

® and ™ marks owned by Allergan, Inc. ©2013 Allergan, Inc., Irvine, CA 92612, U.S.A. APC35BO12

By joining the MTMR Program, you will qualify for

• Continuous rebates that give you the opportunity to reduce costs on RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% prescriptions*

– For potential savings of hundreds of dollars a year*†

– Including extra savings on 90-day prescriptions of RESTASIS®*†

• Ongoing information and counseling

– Regular e-mails and MTMR Program Guide

– Access to the RESTASIS® Patient Support Center

– Helping you manage your type of Chronic Dry Eye disease and get the most out of your RESTASIS® Ophthalmic Emulsion treatment

– Providing you with other information and tips about eye health-related issues

* The actual reimbursement for a member’s out-of-pocket costs for RESTASIS® will vary according to refill quantity, personal healthcare insurance coverage, and adherence to FDA dosing guidelines. Please review the RESTASIS® My Tears, My Rewards ® Program guidelines to learn about the savings you may be eligible for.

† MTMR members with 30-day prescriptions may enjoy paying no out-of-pocket expenses up to $75 on every 4th RESTASIS® Ophthalmic Emulsion prescription refill. MTMR members with 90-day prescriptions may enjoy paying no out-of-pocket expenses on RESTASIS® prescriptions up to $90.

Watch stories about how RESTASIS® helps increase tear production in people like you who have a certain type of Chronic dry Eye disease.

SuppoRT & SAvInG

Approved Use RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% helps increase your eyes’ natural ability to produce tears, which may be reduced by inflammation due to Chronic Dry Eye. RESTASIS® did not increase tear production in patients using anti-inflammatory eye drops or tear duct plugs.

Important Safety InformationDo not use RESTASIS® Ophthalmic Emulsion if you are allergic to any of the ingredients. To help avoid eye injury and contamination, do not touch the vial tip to your eye or other surfaces. RESTASIS® should not be used while wearing contact lenses. If contact lenses are worn, they should be removed prior to the use.

The most common side effect is a temporary burning sensation. Other side effects include eye redness, discharge, watery eyes, eye pain, foreign body sensation, itching, stinging, and blurred vision.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please click here for full Product Information.

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use RESTASIS® 0.05% safely and effectively. See full prescribing information for RESTASIS®.

RESTASIS® (cyclosporine ophthalmic emulsion) 0.05% Initial U.S. Approval: 1983

INDICATIONS AND USAGERESTASIS® is a topical immunomodulator indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca. Increased tear production was not seen in patients currently taking topical anti-inflammatory drugs or using punctal plugs. (1)

DOSAGE AND ADMINISTRATIONInstill one drop of RESTASIS® ophthalmic emulsion twice a day in each eye approximately 12 hours apart. (2)

DOSAGE FORMS AND STRENGTHSOphthalmic emulsion containing cyclosporine 0.5 mg/mL (3)

CONTRAINDICATIONS• Hypersensitivity (4)

WARNINGS AND PRECAUTIONS• To avoid the potential for eye injury and contamination, be careful not

to touch the vial tip to your eye or other surfaces. (5.1)

ADVERSE REACTIONSThe most common adverse reaction following the use of RESTASIS® was ocular burning (17%). (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Allergan, Inc. at 1-800-433-8871 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

See 17 for PATIENT COUNSELING INFORMATION

Revised: 12/2012

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Potential for Eye Injury and Contamination

5.2 Use with Contact Lenses

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Post-marketing Experience

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

17.1 Handling the Container

17.2 Use with Contact Lenses

17.3 Administration

* Sections or subsections omitted from the full prescribing information are not listed

FULL PRESCRIBING INFORMATION1 INDICATIONS AND USAGERESTASIS® ophthalmic emulsion is indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca. Increased tear production was not seen in patients currently taking topical anti-inflammatory drugs or using punctal plugs.2 DOSAGE AND ADMINISTRATIONInvert the unit dose vial a few times to obtain a uniform, white, opaque emulsion before using. Instill one drop of RESTASIS® ophthalmic emulsion twice a day in each eye approximately 12 hours apart. RESTASIS® can be used concomitantly with artificial tears, allowing a 15 minute interval between products. Discard vial immediately after use.

3 DOSAGE FORMS AND STRENGTHSOphthalmic emulsion containing cyclosporine 0.5 mg/mL

4 CONTRAINDICATIONSRESTASIS® is contraindicated in patients with known or suspected hypersensitivity to any of the ingredients in the formulation.

5 WARNINGS AND PRECAUTIONS5.1 Potential for Eye Injury and ContaminationTo avoid the potential for eye injury and contamination, be careful not to touch the vial tip to your eye or other surfaces.

5.2 Use with Contact LensesRESTASIS® should not be administered while wearing contact lenses. Patients with decreased tear production typically should not wear contact lenses. If contact lenses are worn, they should be removed prior to the administration of the emulsion. Lenses may be reinserted 15 minutes following administration of RESTASIS® ophthalmic emulsion.

6 ADVERSE REACTIONS6.1 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 common adverse reaction following the use of RESTASIS® was ocular burning (17%).

Other reactions reported in 1% to 5% of patients included conjunctival hyperemia, discharge, epiphora, eye pain, foreign body sensation, pruritus, stinging, and visual disturbance (most often blurring).

6.2 Post-marketing ExperienceThe following adverse reactions have been identified during post approval use of RESTASIS®. 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.

Reported reactions have included: hypersensitivity (including eye swelling, urticaria, rare cases of severe angioedema, face swelling, tongue swelling, pharyngeal edema, and dyspnea); and superficial injury of the eye (from the vial tip touching the eye during administration).

8 USE IN SPECIFIC POPULATIONS8.1 PregnancyTeratogenic Effects: Pregnancy Category C Adverse effects were seen in reproduction studies in rats and rabbits only at dose levels toxic to dams. At toxic doses (rats at 30 mg/kg/day and rabbits at 100 mg/kg/day), cyclosporine oral solution, USP, was embryo- and fetotoxic as indicated by increased pre- and postnatal mortality and reduced fetal weight together with related skeletal retardations. These doses are 5,000 and 32,000 times greater (normalized to body surface area), respectively, than the daily human dose of one drop (approximately 28 mcL) of 0.05% RESTASIS® twice daily into each eye of a 60 kg person (0.001 mg/kg/day), assuming that the entire dose is absorbed. No evidence of embryofetal toxicity was observed in rats or rabbits receiving cyclosporine at oral doses up to 17 mg/kg/day or 30 mg/kg/day, respectively, during organogenesis. These doses in rats and rabbits are approximately 3,000 and 10,000 times greater (normalized to body surface area), respectively, than the daily human dose.

pRoducT InfoRMATIon

Offspring of rats receiving a 45 mg/kg/day oral dose of cyclosporine from Day 15 of pregnancy until Day 21 postpartum, a maternally toxic level, exhibited an increase in postnatal mortality; this dose is 7,000 times greater than the daily human topical dose (0.001 mg/kg/day) normalized to body surface area assuming that the entire dose is absorbed. No adverse events were observed at oral doses up to 15 mg/kg/day (2,000 times greater than the daily human dose).

There are no adequate and well-controlled studies of RESTASIS® in pregnant women. RESTASIS® should be administered to a pregnant woman only if clearly needed.

8.3 Nursing MothersCyclosporine is known to be excreted in human milk following systemic administration, but excretion in human milk after topical treatment has not been investigated. Although blood concentrations are undetectable after topical administration of RESTASIS® ophthalmic emulsion, caution should be exercised when RESTASIS® is administered to a nursing woman.

8.4 Pediatric UseThe safety and efficacy of RESTASIS® ophthalmic emulsion have not been established in pediatric patients below the age of 16.

8.5 Geriatric UseNo overall difference in safety or effectiveness has been observed between elderly and younger patients.

11 DESCRIPTIONRESTASIS® (cyclosporine ophthalmic emulsion) 0.05% contains a topical immunomodulator with anti-inflammatory effects. Cyclosporine’s chemical name is Cyclo[[(E )-(2S,3R,4R)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl]-L-2-aminobutyryl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl] and it has the following structure:

Cyclosporine is a fine white powder. RESTASIS® appears as a white opaque to slightly translucent homogeneous emulsion. It has an osmolality of 230 to 320 mOsmol/kg and a pH of 6.5-8.0. Each mL of RESTASIS® ophthalmic emulsion contains: Active: cyclosporine 0.05%. Inactives: glycerin; castor oil; polysorbate 80; carbomer copolymer type A; purified water; and sodium hydroxide to adjust pH.

12 CLINICAL PHARMACOLOGY12.1 Mechanism of ActionCyclosporine is an immunosuppressive agent when administered systemically.

In patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca, cyclosporine emulsion is thought to act as a partial immunomodulator. The exact mechanism of action is not known.

12.3 PharmacokineticsBlood cyclosporine A concentrations were measured using a specific high pressure liquid chromatography-mass spectrometry assay. Blood concentrations of cyclosporine, in all the samples collected, after topical administration of RESTASIS® 0.05%, twice daily, in humans for up to 12 months, were below the quantitation limit of 0.1 ng/mL. There was no detectable drug accumulation in blood during 12 months of treatment with RESTASIS® ophthalmic emulsion.

13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis: Systemic carcinogenicity studies were carried out in male and female mice and rats. In the 78-week oral (diet) mouse study, at doses of 1, 4, and 16 mg/kg/day, evidence of a statistically significant trend was found for lymphocytic lymphomas in females, and the incidence of hepatocellular carcinomas in mid-dose males significantly exceeded the control value.

In the 24-month oral (diet) rat study, conducted at 0.5, 2, and 8 mg/kg/day, pancreatic islet cell adenomas significantly exceeded the control rate in the low dose level. The hepatocellular carcinomas and pancreatic islet cell adenomas were not dose related. The low doses in mice and rats are approximately 80 times greater (normalized to body surface area) than the daily human dose of one drop (approximately 28 mcL) of 0.05% RESTASIS® twice daily into each eye of a 60 kg person (0.001 mg/kg/day), assuming that the entire dose is absorbed.

Mutagenesis: Cyclosporine has not been found to be mutagenic/genotoxic in the Ames Test, the V79-HGPRT Test, the micronucleus test in mice and Chinese hamsters, the chromosome-aberration tests in Chinese hamster bone-marrow, the mouse dominant lethal assay, and the DNA-repair test in sperm from treated mice. A study analyzing sister chromatid exchange (SCE) induction by cyclosporine using human lymphocytes in vitro gave indication of a positive effect (i.e., induction of SCE).

Impairment of Fertility: No impairment in fertility was demonstrated in studies in male and female rats receiving oral doses of cyclosporine up to 15 mg/kg/day (approximately 2,000 times the human daily dose of 0.001 mg/kg/day normalized to body surface area) for 9 weeks (male) and 2 weeks (female) prior to mating.

14 CLINICAL STUDIESFour multicenter, randomized, adequate and well-controlled clinical studies were performed in approximately 1,200 patients with moderate to severe keratoconjunctivitis sicca. RESTASIS® demonstrated statistically significant increases in Schirmer wetting of 10 mm versus vehicle at six months in patients whose tear production was presumed to be suppressed due to ocular inflammation. This effect was seen in approximately 15% of RESTASIS® ophthalmic emulsion-treated patients versus approximately 5% of vehicle-treated patients. Increased tear production was not seen in patients currently taking topical anti-inflammatory drugs or using punctal plugs.

No increase in bacterial or fungal ocular infections was reported following administration of RESTASIS®.

16 HOW SUPPLIED/STORAGE AND HANDLINGRESTASIS® ophthalmic emulsion is packaged in sterile, preservative-free single-use vials. Each vial contains 0.4 mL fill in a 0.9 mL LDPE vial; 30 vials are packaged in a polypropylene tray with an aluminum peelable lid. The entire contents of each tray (30 vials) must be dispensed intact. RESTASIS® is also provided in a 60 count (2 x 30) package (one month supply) that must be dispensed intact.

30 Vials 0.4 mL each - NDC 0023-9163-30 60 (2 x 30) Vials 0.4 mL each - NDC 0023-9163-60Storage: Store at 15-25°C (59-77°F).

17 PATIENT COUNSELING INFORMATION17.1 Handling the ContainerAdvise patients to not allow the tip of the vial to touch the eye or any surface, as this may contaminate the emulsion. To avoid the potential for injury to the eye, advise patients to not touch the vial tip to their eye [see Warnings and Precautions (5.1) ].

17.2 Use with Contact LensesRESTASIS® should not be administered while wearing contact lenses. Patients with decreased tear production typically should not wear contact lenses. Advise patients that if contact lenses are worn, they should be removed prior to the administration of the emulsion. Lenses may be reinserted 15 minutes following administration of RESTASIS® ophthalmic emulsion [see Warnings and Precautions (5.2) ].

17.3 AdministrationAdvise patients that the emulsion from one individual single-use vial is to be used immediately after opening for administration to one or both eyes, and the remaining contents should be discarded immediately after administration.

© 2013 Allergan, Inc. Irvine, CA 92612, U.S.A. ® marks owned by Allergan, Inc. Patented. See: www.allergan.com/products/patent_notices Made in the U.S.A. Based on 71876US15

APC10LK12

Formula: C62H111N11O12 Mol. Wt.: 1202.6

Structural Formula

pRoducT InfoRMATIon