RESTASIS

1 Dosing Considerations  There are no special dosing considerations which need to be taken into account prior to initiating therapy with RESTASIS. 2 Recommended Dose and Dosage Adjustment  The recommended dose is one drop of RESTASIS, instilled twice a day in each eye approximately 12 hours apart.

This recommended dose is the maximum recommended dose and should be used both as the starting dose and throughout long term treatment. Dosage adjustments should not be necessary based on any co-morbid conditions, given the low systemic availability of the product.

Limited data from clinical studies exists for long term administration of RESTASIS (up to 40 months). It is expected that use of the product will continue long term. Health Canada has not authorized an indication for pediatric use. 3 Reconstitution Not applicable.

4 Administration The vial should be inverted a few times to obtain a uniform, white, opaque emulsion before using. 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.

Patients should be advised to avoid touching the tip of the vial to the eye or any surface, as this may contaminate the emulsion. To avoid the potential for injury to the eye, patients should also be advised not to touch the vial container to the eye.

RESTASIS should not be administered while the patient is wearing contact lenses. If contact lenses are worn, they should be removed prior to the administration of the emulsion. Lenses may be reinserted 15 minutes after the administration of RESTASIS.

RESTASIS may be used concomitantly with artificial tears. The patient should be advised to allow a 15- minute interval between administration of RESTASIS and the artificial tear product. 5 Missed Dose If a dose of this medication is missed, it should be taken as soon as possible.

However, if it is almost time for the next dose, the missed dose should be skipped and the regular dosing schedule resumed. Doses should not be doubled. The dose should not exceed two drops in the affected eye(s) daily.

1 Adverse Reaction Overview The most common adverse reaction following the use of RESTASIS is ocular burning. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. Therefore, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. In the combined data from the three key Phase 3 clinical studies, approximately 29% of treated patients experienced treatment-related adverse events (adverse reactions) in the first year.

The majority were ocular, mild or moderate in severity, and none were serious. The most commonly reported adverse reaction was eye burning, which was reported in approximately 17% of patients in the first year; the incidence of new reports decreased to 5% at 2 years.

The observed adverse drug reactions are provided below for those events observed at an incidence of ≥1% in the three vehicle- controlled clinical trials. 6%) Note that active events are reported over 12 months; vehicle events are reported for 6 month exposure period.

NOS – not otherwise specified The frequency of all adverse event reporting was generally highest shortly after initiation of RESTASIS treatment, but lessened as treatment continued. 05% treatment group in the three vehicle-controlled clinical trials over 12 months.

4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data Not applicable. 5 Post-Market Adverse Reactions Post-marketing reactions reported to date have been consistent with the events recorded during the vehicle-controlled clinical trials, with the majority of the reported events being ocular.

General For ophthalmic use only. Carcinogenesis and Mutagenesis See 16 NON-CLINICAL TOXICOLOGY. Driving and Operating Machinery RESTASIS may cause transient blurred vision due to its emulsion formulation. If patients experience blurred vision, they should be advised not to drive or operate machinery until vision has cleared.

Immune There is the potential to experience hypersensitivity to RESTASIS. Reactions of severe angioedema, face swelling, tongue swelling, pharyngeal oedema, dyspnea and urticaria have been reported with the use of RESTASIS. 5 Post-Market Adverse Drug Reactions.

If an allergic reaction occurs, patients should be advised to discontinue the drug. Ophthalmologic RESTASIS has not been studied in patients with a history of herpes keratitis, end stage lacrimal gland disease, keratoconjunctivitis sicca (KCS) secondary to the destruction of conjunctival goblet cells such as occurs with Vitamin A deficiency, or scarring, such as occurs with cicatricial pemphigoid, alkali burns, Stevens-Johnson syndrome, trachoma, or irradiation.

4 Administration for further information regarding the use of RESTASIS with respect to contamination, eye injury, and contact lens use. 1 Pregnant Women There are no adequate data from the use of RESTASIS in pregnant women. Studies in animals have shown reproductive toxicity at high maternotoxic doses.

See 16 NON-CLINICAL TOXICOLOGY. 05% w/v Carbomer Copolymer Type A, castor oil, glycerin, polysorbate 80, purified water and sodium hydroxide. RESTASIS (cyclosporine) Page 7 of 26 RESTASIS should not be used during pregnancy unless the benefits outweigh the risks.

2 Breast-feeding Cyclosporine is known to be excreted in human milk following systemic administration, but excretion in human milk after topical administration has not been investigated. Although blood concentrations are undetectable after topical administration of RESTASIS, caution should be exercised when RESTASIS is administered to a nursing woman.

 RESTASIS is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

 RESTASIS is contraindicated in patients with active ocular infections.