Making Your Own Real Tears Matters:

Transcription

1 Making Your Own Real Tears Matters: Your Guide to RESTASIS Therapy 0.05% helps increase your eyes natural ability did not increase tear production in patients using Alison Tendler MD RESTASIS User, Eye Doctor if you are allergic to any of the ingredients. To touch the vial tip to your eye or other surfaces. RESTASIS should not be used while wearing should be removed prior to the use. burning sensation. Other side effects include of prescription drugs to the FDA. Visit

2 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.

3 Getting Started Starting on Your RESTASIS (Cyclosporine Ophthalmic Emulsion) 0.05% Journey You 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 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!

4 Getting Started Let s talk about the right way for you to get started with 0.05% treatment How RESTASIS Is Different With 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. 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.

5 Setting Expectations What You Can Expect With RESTASIS (Cyclosporine Ophthalmic Emulsion) 0.05% 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. 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. Alison Tendler MD, RESTASIS User, Eye Doctor

6 Setting Expectations Tracking Your Progress With 0.05% Getting Started 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. Mo. 1 Mo. 2 Mo. 3 Mo. 4 Mo. 5 Mo. 6 Continued Use 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. 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. 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.

7 Months 1-3 Stay on the Path to Increased Tear Production With RESTASIS (Cyclosporine Ophthalmic Emulsion) 0.05% 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. 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. REMEMBER: Always ask your eye doctor about any questions you have and always follow your doctor s instructions.

8 Months 3-6 Staying With 0.05% Matters 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. 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 Talk to your eye doctor about how you are doing on RESTASIS Ophthalmic Emulsion. 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.

9 Months 6 & Beyond Keep Up the Good Work! 0.05% will help your eyes keep producing more of your own real tears with continued use. Individual results may vary. 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: a. Call the RESTASIS Patient Support Center at 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 REMEMBER: Maintaining treatment success with RESTASIS matters.

10 Support & Saving 0.05% Support and Savings 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. 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 s with information on taking care of my Chronic Dry Eye disease along with other health tips that are really useful. Michelle, RESTASIS Patient REMEMBER: 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 every step of the way matters. Go to mytearsmyrewards.com and join today.

11 Support & Saving Join MyTearsMyRewards.com Today to Receive Valuable Savings and Ongoing Support! 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 s 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. 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 Allergan, Inc., Irvine, CA 92612, U.S.A. APC35BO12

12 PRODUCT Information HIGHLIGHTS OF PRESCRIBING INFORMATION These 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 USAGE RESTASIS 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 ADMINISTRATION Instill one drop of RESTASIS ophthalmic emulsion twice a day in each eye approximately 12 hours apart. (2) DOSAGE FORMS AND STRENGTHS Ophthalmic 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 (5.1) ADVERSE REACTIONS The most common adverse reaction following the use of RESTASIS was ocular burning (17%). (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Allergan, Inc. at or FDA at FDA-1088 or 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 INFORMATION 1 INDICATIONS AND USAGE RESTASIS 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 antiinflammatory drugs or using punctal plugs. 2 DOSAGE AND ADMINISTRATION Invert 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 STRENGTHS Ophthalmic emulsion containing cyclosporine 0.5 mg/ml 4 CONTRAINDICATIONS RESTASIS is contraindicated in patients with known or suspected hypersensitivity to any of the ingredients in the formulation. 5 WARNINGS AND PRECAUTIONS 5.1 Potential for Eye Injury and Contamination To avoid the potential for eye injury and contamination, be careful not to 5.2 Use with Contact Lenses RESTASIS 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 REACTIONS 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 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 Experience The 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 POPULATIONS 8.1 Pregnancy Teratogenic 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 embryoand 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.

13 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 Mothers Cyclosporine 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 Use The safety and efficacy of RESTASIS ophthalmic emulsion have not been established in pediatric patients below the age of Geriatric Use No overall difference in safety or effectiveness has been observed between elderly and younger patients. 11 DESCRIPTION RESTASIS (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-nmethyl-l-leucyl-l-alanyl-d-alanyl-n-methyl-l-leucyl-n-methyl-l-leucyl-nmethyl-l-valyl] and it has the following structure: Structural Formula Formula: C 62 H 111 N 11 O 12 Mol. Wt.: 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 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 PHARMACOLOGY 12.1 Mechanism of Action Cyclosporine 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 Pharmacokinetics Blood 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 TOXICOLOGY 13.1 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 mg/kg/day normalized to body surface area) for 9 weeks (male) and 2 weeks (female) prior to mating. 14 CLINICAL STUDIES Four 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 antiinflammatory drugs or using punctal plugs. No increase in bacterial or fungal ocular infections was reported following administration of RESTASIS. 16 HOW SUPPLIED/STORAGE AND HANDLING RESTASIS ophthalmic emulsion is packaged in sterile, preservativefree 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 (2 x 30) Vials 0.4 ml each - NDC Storage: Store at C (59-77 F). 17 PATIENT COUNSELING INFORMATION 17.1 Handling the Container Advise 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)] Use with Contact Lenses RESTASIS 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)] Administration Advise 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 Allergan, Inc. Irvine, CA 92612, U.S.A. marks owned by Allergan, Inc. Patented. See: Made in the U.S.A. Based on 71876US15 APC10LK12