5.1 Contamination of Tip and Solution

To minimize contaminating the dropper tip and solution, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle. Keep bottle tightly closed when not in use.

5.2 Benign Intracranial Hypertension

There have been reports of benign intracranial hypertension (or pseudotumor cerebri) associated with oral cysteamine treatment that has resolved with the addition of diuretic therapy.

There have also been reports associated with ophthalmic use of cysteamine; however, all of these patients were on concurrent oral cysteamine.

5.3 Contact Lens Use

CYSTARAN contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to application of solution and may be reinserted 15 minutes following its administration [see Patient Counseling Information (17)] .

5.4 Topical Ophthalmic Use

CYSTARAN is for topical ophthalmic use.

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.

The safety data described below reflect exposure in controlled clinical trials of six months to 19 years duration in approximately 300 patients.

The most frequently reported ocular adverse reactions occurring in ≥10% of patients were sensitivity to light, redness, and eye pain/irritation, headache and visual field defects.

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

The safety and effectiveness of CYSTARAN (cysteamine ophthalmic solution) 0.44% have been established in pediatric patients.

8.5 Geriatric Use

When the clinical studies with CYSTARAN were conducted, the reduced life expectancy from cystinosis did not make it possible to include patients in the geriatric age range.

8.6 Renal Impairment

The effect of renal impairment on the pharmacokinetics of cysteamine following ophthalmic administration of cysteamine ophthalmic solution has not been evaluated because ophthalmic exposure compared to systemic exposure is negligible. The majority of the patients in the ophthalmic clinical studies are assumed to have had some degree of renal impairment due to their underlying systemic disease. The total daily ophthalmic dose is less than 2% of the recommended oral daily dose of cysteamine; thus, the systemic exposure following ophthalmic administration is expected to be negligible compared to oral administration.

12.1 Mechanism of Action

Cysteamine acts as a cystine-depleting agent by converting cystine to cysteine and cysteine-cysteamine mixed disulfides and reduces corneal cystine crystal accumulation.

12.3 Pharmacokinetics

The peak plasma concentration of cysteamine following ocular administration of cysteamine ophthalmic solution in humans is unknown, but it is expected to be substantially less than the peak plasma concentration following oral administration of cysteamine bitartrate.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Storage: Store in freezer at -25°C to -15°C (-13°F to 5°F) in the original carton. Thaw for approximately 24 hours before use. Store thawed bottle at 2°C to 25°C (36°F to 77°F) for up to 1 week. The thawed bottle does not require refrigeration between use. Do not refreeze the thawed medication. Discard after 1 week of use.

Storage of Bottles

1. Patients should be advised to store bottles in the freezer in the original carton.
2. Each week, one new bottle should be removed from the freezer.
3. Patients should be advised to allow the bottle to thaw completely (approximately 24 hours) prior to use.
4. After the bottle is completely thawed, the patient should record the discard date on the bottle label. The discard date is seven (7) days from the day the bottle is thawed.
5. Patients should be advised to store thawed bottle at 2°C to 25°C (36°F to 77°F) for up to 1 week. The thawed bottle does not require refrigeration between use and should not be refrozen.
6. At the end of 1 week (7 days), patients should discard the bottle. There may be medication left in the bottle; however, the bottle must be discarded by the patient because the medication is only stable for 1 week after thawing.

Risk of Contamination

Patients should be advised not to touch the eyelid or surrounding areas with the dropper tip of the bottle. The cap should remain on the bottle when not in use.

Use with Contact Lenses

Patients should be advised that contact lenses should be removed prior to application of CYSTARAN. Contact lenses may be reinserted 15 minutes following CYSTARAN administration.

Topical Ophthalmic Use

Patients should be advised that CYSTARAN is for topical ophthalmic use.