CYSTADROPS

1 Dosing Considerations Treatment with CYSTADROPS should be initiated under the supervision of a physician experienced in the management of cystinosis. 2 Recommended Dose and Dosage Adjustment The recommended dose is one drop in each eye, 4 times a day during waking hours.

The recommended interval between each instillation is 4 hours. The dose could be decreased progressively (to a minimum total daily dose of 1 drop in each eye) depending on the results of ophthalmic examination (such as corneal cystine crystal deposits, photophobia).

The dose should not exceed 4 drops a day in each eye. The accumulation of corneal cystine crystals increases if CYSTADROPS is discontinued. Pediatric Population CYSTADROPS may be used in pediatric patients from 2 years of age at the same dose as in adults (see Clinical Trials).

Page 4 of 22 The safety and efficacy of CYSTADROPS in children aged less than 2 years has not been established. No data are available. 3 Administration For ocular use. Before opening, the patient should be told to store CYSTADROPS in a refrigerator (2°C - 8°C).

Before the first administration, in order to facilitate the administration, the patient should be told to bring CYSTADROPS to room temperature. After first opening, the patient should be told to keep the dropper bottle at room temperature.

To avoid sticky eyes in the morning, the patient should be advised to apply the last drop of the day at least 30 minutes before going to bed. To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas, or other surfaces with the dropper tip of the dropper bottle.

The patient should be told to discard the dropper bottle after 7 days of use. In case of concomitant therapy with other topical ocular medicinal products, an interval of ten minutes should be allowed between successive applications.

Eye ointments should be administered last. 4 Missed Dose If the patient misses an instillation, the patient should be told to continue the treatment with the next instillation.

1 Adverse Reaction Overview The most common adverse reactions are eye pain, ocular hyperaemia, eye pruritus, lacrimation increased, blurred vision or eye irritation. The majority of these adverse reactions are transient and most are mild or moderate in severity.

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 clinical trials is useful for identifying drug-related adverse events and for approximating rates. The following adverse reactions were reported during clinical trials and the French Named Patient Use (NPU) program with CYSTADROPS.

Reported adverse reactions are listed below, by system organ class and by frequency (by patient). Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).

3 Clinical Trial Adverse Reactions (Pediatrics) Frequency, type and severity of adverse reactions in children are the same as in adults. 78 CYSTADROPS treated pediatric patients were followed through clinical trials and the French NPU program.

25 patients were under 6 years old, 22 between 6 and 12 years old, and 31 between 12 and 18 years old.

Driving and Operating Machinery CYSTADROPS may have a minor influence on the ability to drive and use machines. Temporary (less than 1 minute on average) blurred vision or other visual disturbances may affect the ability to drive or use machines.

If blurred vision occurs at instillation, the patient must wait until their vision clears before driving or using machines. Ophthalmologic CYSTADROPS contains benzalkonium chloride which may cause eye irritation. Benzalkonium chloride, which is commonly used as a preservative in ophthalmic products, has also been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy.

Monitoring is required. Contact Lenses Benzalkonium chloride is known to discolour soft contact lenses. Contact with soft contact lenses should be avoided. Patients should be instructed to remove contact lenses prior to the administration of the eye drops and wait at least 15 minutes before re-inserting contact lenses.

55% (w/w) cysteamine hydrochloride* Benzalkonium chloride (as preservative) Carmellose sodium Citric acid monohydrate Disodium edetate Hydrochloric acid (for pH adjustment) Sodium hydroxide (for pH adjustment) Water for injection Page 6 of 22 Sexual Health Fertility No data on the effect of cysteamine on human fertility are available.

Studies in animals with systemic cysteamine have shown a reduction of fertility (see Non-clinical Toxicology). 4% of the highest recommended dose of oral cysteamine in any age group. Systemic exposure of cysteamine following ocular administration is therefore lower than following oral administration.

There are no adequate data from the use of cysteamine in pregnant women. Studies in animals with oral cysteamine have shown reproductive toxicity, including teratogenesis (see Non-clinical Toxicology). The potential risk for humans is unknown.

If a pregnancy is diagnosed or planned, CYSTADROPS treatment should be carefully reconsidered and the patient must be advised of the possible teratogenic risk of cysteamine. 4% of the highest recommended dose of oral cysteamine in any age group.

CYSTADROPS 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.