VERKAZIA

1 Dosing Considerations • There are no special dosing considerations which need to be taken into account prior to initiating therapy with Verkazia (cyclosporine) ophthalmic emulsion. Efficacy and safety of Verkazia has not been studied beyond 12 months.

• Verkazia eye drops should not be used until at least 15 minutes after any other eye drops are used. 2 Recommended Dose and Dosage Adjustment Children from 4 years of age through adolescence: The recommended dose is one drop of Verkazia 4 times a day (morning, noon, afternoon and Verkazia Page 5 of 22 evening) to be applied to each affected eye.

The treatment should be discontinued if no improvement in signs and symptoms of Vernal Keratoconjunctivitis is observed. The treatment can be maintained at the recommended dose or decreased to one drop twice daily once adequate control of signs and symptoms is achieved.

Treatment should be discontinued after signs and symptoms are resolved and reinitiated upon their recurrence. Verkazia is not approved for use in children below 4 years of age. 3 Administration Patients should be instructed to wash their hands before instilling Verkazia into the eye(s).

Prior to administration, the single-dose container of Verkazia should be gently shaken. Patients should be instructed to use nasolacrimal occlusion and to close the eyelids for 2 minutes after instillation, to reduce the systemic absorption.

This may result in a decrease in systemic undesirable effects and an increase in local activity. Each single-dose container of Verkazia is sufficient to treat both eyes. For single-use only. Any unused emulsion after opening the vial should be discarded immediately.

4 Missed Dose If a dose is missed, treatment should be continued on the next instillation as normal. Patients should be advised not to instill more than one drop for each instillation in the affected eye(s).

1 Adverse Reaction Overview The most common adverse drug reactions following the use of Verkazia (cyclosporine) are eye pain and eye pruritus which are usually non-serious, transitory and occur during instillation. Most of the known adverse reactions following the use of Verkazia occur in or around the eye.

2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, 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 Verkazia Page 8 of 22 clinical trials is useful for identifying drug-related adverse events and for approximating rates. 1% (n=111) during the 4-month, randomized, double-masked period when the comparison to Vehicle (n=58) was possible.

The majority of suspected adverse drug reactions reported in clinical studies and related to the use of Verkazia were ocular and mild or moderate in severity. 7%)

General Verkazia (cyclosporine) is for ophthalmic use only. Driving and Operating Machinery Due caution should be exercised when driving or operating a vehicle or potentially dangerous machinery. Verkazia has moderate influence on the ability to drive and use machines.

This medicinal product may induce temporary blurred vision or other visual disturbances which may affect the ability to drive or use machines. Patients should be advised not to drive or use machines until their vision has cleared. Ophthalmologic Ophthalmic medicinal products, which affect the immune system, including cyclosporine, may affect host defences against local infections and malignancies.

Therefore, regular monitoring of the eye(s) is recommended when Verkazia is used long-term.

Contact lenses:

Patients wearing contact lenses have not been studied. Therefore, the use of Verkazia with contact lenses is not recommended.

Concomitant Ophthalmic therapy:

Co-administration of Verkazia with eye drops containing corticosteroids may potentiate the effects of Verkazia on the immune system. Hepatic The effect of Verkazia has not been studied in patients with hepatic impairment. However, no special dose adjustment is needed in this population as systemic exposure to cyclosporine is negligible (see Action and Clinical Pharmacology).

Renal The effect of Verkazia has not been studied in patients with renal impairment. However, no special dose adjustment is needed in this population as systemic exposure to cyclosporine is negligible (see Action and Clinical Pharmacology).

Skin Verkazia has not been studied in patients with an active orofacial herpes simplex infection, a history of ocular herpes, varicella-zoster, or vaccinia virus infection and should therefore be used with caution in such patients.

Verkazia 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 Dosage Forms, Strengths, Composition and Packaging.

• Patients with active or suspected ocular or peri-ocular infection. • Patients with ocular malignancies or premalignant conditions.