ay be reinserted 15 minutes following its administration [see patient counseling information ( 17 )] .

tients are to write the date the bottle was opened in the space on the carton. after first opening, store opened cystadrops at room temperature between 68°f to 77°f (20°c to 25°c). do not refrigerate after opening. patients are to wash their hands carefully in order to avoid microbiological contamination of the content in the bottle. remove the green protective cap (see figure a ). remove the metal seal (see figure b ). remove the gray stopper (see figure c ) from the bottle. do not touch the opening of the bottle after removing the gray stopper. take the dropper out of its packaging, without touching the end intended to be attached to the bottle, attach it (see figure d ) to the bottle and do not remove it. patients should be advised not to lose the small white cap that comes on the top of the dropper (see figure e ). keep the small white cap tightly closed when not in use. instill one drop of cystadrops in each eye, 4 times a day during waking hours. at the end of 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 7 days after first opening.

day to 150 mg/kg/day (240 to 960 times the recommended human ophthalmic dose based on body surface area) and have shown cysteamine bitartrate to be teratogenic. observed teratogenic findings were intrauterine death, cleft palate, kyphosis, heart ventricular septal defects, microcephaly, exencephaly, and growth deficits. 8.2 lactation risk summary there is no information regarding the presence of cysteamine in human milk, the effects on the breastfed infants, or the effects on milk production. cysteamine administered orally is present in milk of lactating rats. it is not known whether measurable levels of cysteamine would be present in maternal milk following topical ocular administration of cystadrops. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for cystadrops and any potential adverse effects on the breastfed child from cystadrops or from the underlying maternal conditions. 8.4 pediatric use the safety and effectiveness of cystadrops has been established in pediatric patients. use of cystadrops is supported by adequate and well controlled trials in pediatric patients and additional experience supporting the safety of cystadrops. 8.5 geriatric use clinical studies of cystadrops did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. 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. clearance of cysteamine from the conjunctival sac of the eye is not dependent on renal function and the total systemic dose is negligible, so impaired renal function is unlikely to affect total body clearance. the total daily ophthalmic dose is less than 4% of the recommended oral daily dose of cysteamine; thus, the systemic exposure following ophthalmic administration is expected to be negligible compared to oral administration.

60 times the recommended human ophthalmic dose based on body surface area) and have shown cysteamine bitartrate to be teratogenic. observed teratogenic findings were intrauterine death, cleft palate, kyphosis, heart ventricular septal defects, microcephaly, exencephaly, and growth deficits.

% reduction in the total ivcm total score across all corneal layers was observed from baseline, respectively. cystadrops demonstrated greater reduction compared to the control arm at 90 days. the average reduction in ivcm total score was 4.6 in the cystadrops arm and 0.5 in the control arm, mean difference 3.8 (95% ci: (2.1, 5.6)). in the oct-1 study, a mean decrease in corneal cystine crystal deposits of 30%, in comparison with baseline, was maintained over the 60 month period of the study.

do not remove it. patients should be advised not to lose the small white cap (see figure e) that comes on the top of the dropper. keep the small white cap tightly closed when not in use. instill one drop of cystadrops in each eye, 4 times a day during waking hours. instruct patients to discard the bottle at the end of 7 days. there may be medication left in the bottle; however, the bottle must be discarded by the patient because the medication is only stable for 7 days after first opening. risk of contamination advise patients 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. contact lens use advise patients that contact lenses should be removed prior to application of cystadrops. contact lenses may be reinserted 15 minutes following cystadrops administration [see warnings and precautions ( 5.3 )] . topical ophthalmic use advise patients that cystadrops is for topical ophthalmic use. missed dose if the patient misses an instillation, instruct the patient to administer a dose as soon as feasible and then to continue the treatment with the next scheduled instillation. manufactured by: baccinex sa, 2822 courroux, switzerland manufactured for: recordati rare diseases inc., lebanon, nj 08833, u.s.a. this product label may have been updated. for the most recent prescribing information, please visit www.recordatirarediseases.com/us.

e opening, store new, unopened cystadrops in the refrigerator between 36°f to 46°f (2°c to 8°c). • after first opening, store opened cystadrops at room temperature between 68°f to 77°f (20°c to 25°c). do not refrigerate after opening. • keep cystadrops in the original carton to protect from light. • keep the cystadrops dropper bottle tightly closed when not in use. • throw away any unused cystadrops 7 days after opening. • keep cystadrops and all medicines out of the reach of children. supplies needed: • cystadrops bottle and dropper • mirror • tissue using cystadrops: • use 1 drop in each eye, four times a day. • if you miss a dose, administer the missed dose as soon as possible and then use the drops at your next regular scheduled time. step 1: before using a cystadrops bottle for the first time • check the expiration date on the cystadrops bottle before use. do not use cystadrops if the expiration date has passed. • after opening a cystadrops bottle, allow it to reach room temperature before using it for the first time. • after opening a cystadrops bottle for the first time, write the date of opening in the space provided on the carton. • wash your hands carefully in order to avoid contamination of the contents in the bottle. • remove the green protective cap (figure a). • remove the metal seal (figure b). • remove the gray stopper (figure c). • do not touch the opening of the bottle after removing the gray stopper. • place the opened bottle on a flat surface. • take the dropper out of its packaging. do not touch the end of the dropper that will be attached to the bottle. attach the dropper (figure d) to the bottle. after attaching the dropper to the bottle, do not remove the dropper from the bottle (figure e). • make sure that you do not lose the small white cap (figure e) that comes on the top of the dropper. step 2: before using cystadrops • check the opening date that you wrote down on the carton. do not use cystadrops if more than 7 days have passed since the opening date. • get the cystadrops dropper bottle, mirror, and tissue. • wash your hands. step 3: using the cystadrops dropper bottle • twist the small white cap to remove it from the dropper. do not throw the small white cap away. • hold the cystadrops dropper bottle with the dropper pointing down, between your thumb and fingers. if no medicine fills the dropper, move the cystadrops dropper bottle up and down until medicine fills the dropper. • tilt your head back. pull down your lower eyelid with a clean finger and look up (figure f). the medicine will go into the space between your lower eyelid and your eye. • use the mirror to help you bring the dropper bottle tip close to the eye. • do not let the cystadrops dropper touch your eyelids or any other surfaces. • gently squeeze the dropper to release 1 drop of cystadrops. • if a drop misses your eye, try again. • after using cystadrops, close your eye and press a finger into the corner of your eye by the nose (figure g), then gently massage your upper eyelid to spread the cystadrops over the eye. • remove any medicine around the eye with a tissue (figure h). • repeat step 3 for the other eye. • replace the small white cap on the dropper immediately after use. this instructions for use has been approved by the u.s. food and drug administration. manufactured by: baccinex sa, 2822 courroux, switzerland manufactured for: recordati rare diseases inc., lebanon, nj 08833, u.s.a. approved: 08/2020