RESTASIS MULTIDOSE™
(cyclosporine ophthalmic emulsion) 0.05% For topical ophthalmic use
Description for Restasis MultiDose
RESTASIS MULTIDOSE™ (cyclosporine ophthalmic emulsion) 0.05% contains a calcineurin inhibitor immunosuppressant 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:  Structural Formula
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Formula: C62H111N11O12 - Mol. Wt.: 1202.6
Cyclosporine is a fine white powder. RESTASIS MULTIDOSE™ 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 MULTIDOSE™ 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.
Uses for Restasis MultiDose
RESTASIS MULTIDOSE™ 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.
Dosage for Restasis MultiDose
Instill one drop of RESTASIS MULTIDOSE™ ophthalmic emulsion twice a day in each eye approximately 12 hours apart. RESTASIS MULTIDOSE™ can be used concomitantly with lubricant eye drops, allowing a 15-minute interval between products.
Preparation For First-Time Use
Step 1: Pull off the clear shipping cover by pulling straight up. Throw the shipping cover away. Do not use RESTASIS MULTIDOSE™ if shipping cover or pull tab are damaged or missing.
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Step 2: Remove the pull tab on the olive green colored protective cap by pulling the end of the pull tab away from the bottle then winding it counterclockwise. Throw away the pull tab.
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Step 3: Remove the olive green colored protective cap by pulling it straight up. Keep the colored protective cap.
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Step 4: Prime the bottle for first-time use by squeezing two drops onto a tissue. Do not let the bottle tip touch the tissue.
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Step 5: The bottle is now ready for use. After use, recap the bottle with the olive green colored protective cap by pushing it straight down onto the bottle.
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Preparation for Use
Step 6: Turn the bottle upside down a few times before giving your dose to make sure the medicine is mixed well.
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Step 7: Instill one drop in the affected eye. Replace the olive green colored protective cap.
HOW SUPPLIED
Dosage Forms And Strengths
Ophthalmic emulsion containing cyclosporine 0.5 mg/mL
Storage And Handling
RESTASIS MULTIDOSE™ ophthalmic emulsion is packaged in a sterile, multi-dose preservative-free bottle. Each bottle consists of a white opaque LDPE bottle, a white opaque polypropylene top with unidirectional valve and air filter, a protective olive green polypropylene cap, and a clear disposable shipping cover over the colored cap.
5.5 mL in 10-mL bottle - NDC 0023-5301-05
Storage
Store at 15-25 °C (59-77 °F).
Irvine, CA 92612, U.S.A. Revised: Oct 2016
Side Effects for Restasis MultiDose
The following serious adverse reactions are described elsewhere in the labeling:
- Potential for Eye Injury and Contamination [see WARNINGS AND PRECAUTIONS]
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 cyclosporine ophthalmic emulsion, 0.05% 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).
Post-marketing Experience
The following adverse reactions have been identified during post approval use of cyclosporine ophthalmic emulsion, 0.05%. 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 bottle tip touching the eye during administration).
Drug Interactions for Restasis MultiDose
No Information provided
Clinical Pharmacology for Restasis MultiDose
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 cyclosporine ophthalmic emulsion, 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 cyclosporine ophthalmic emulsion, 0.05%.
Clinical Studies
Four multicenter, randomized, adequate and well-controlled clinical studies were performed in approximately 1,200 patients with moderate to severe keratoconjunctivitis sicca. Cyclosporine ophthalmic emulsion, 0.05% 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 cyclosporine ophthalmic emulsion, 0.05%-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 cyclosporine ophthalmic emulsion, 0.05%.
Patient Information for Restasis MultiDose
INSTRUCTIONS FOR USE
RESTASIS MULTIDOSE™
(Re stay’ sis Mul tee dos)  (cyclosporine ophthalmic emulsion) 0.05%
Read this Instructions for Use before you start using RESTASIS MULTIDOSE™ and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment.
Important:
- RESTASIS MULTIDOSE™ is for use in the eye
- Wash your hands before using RESTASIS MULTIDOSE™.
- Do not let the bottle tip touch the eye or any other surfaces to avoid contamination or injury to your eye.
- Use 1 drop of RESTASIS MULTIDOSE™ in each eye, 2 times each day, about 12 hours apart.
- If you wear contact lenses, remove them before using RESTASIS MULTIDOSE™. Wait for at least 15 minutes before placing them back in your eyes.
- RESTASIS MULTIDOSE™ can be used with lubricant eye drops, but you should wait at least 15 minutes between using each product.
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PREPARING THE BOTTLE FOR FIRST-TIME USE:
Step 1: Pull off shipping cover by pulling straight up. Throw the shipping cover away. Do not use RESTASIS MULTIDOSE™ if shipping cover or pull tab are damaged or missing.
 |
Step 2: Remove the pull tab on the olive green colored protective cap by pulling the end of the pull tab away from the bottle then winding it counterclockwise. Throw away the pull tab.
 |
Step 3: Remove the olive green colored protective cap by pulling it straight up. Keep the colored protective cap.
 |
Step 4: Prime the bottle for first time use by squeezing 2 drops onto a tissue. Do not let the bottle tip touch the tissue.
 |
Step 5: The bottle is now ready for use. After use, recap the bottle with the olive green colored protective cap by pushing straight down onto the bottle.
 |
GIVING YOUR DOSE:
Step 6: Turn the bottle upside down a few times before giving your dose to make sure the medicine is mixed well.
Step 7: Instill one drop in the affected eye. Replace the olive green colored protective cap.
How do I store RESTASIS MULTIDOSE™?
- Store RESTASIS MULTIDOSE™ between 15-25 °C (59-77 °F).
Keep RESTASIS MULTIDOSE™ and all medicines out of the reach of children.
This Instructions for Use has been approved by the Food and Drug Administration.
From 
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