CYSTADROPS is a cystine-depleting agent indicated for the treatment of corneal cystine crystal deposits in adults and children with cystinosis.

{ "type": "p", "children": [], "text": "CYSTADROPS is a cystine-depleting agent indicated for the treatment of corneal cystine crystal deposits in adults and children with cystinosis. " }

Instill one drop of CYSTADROPS in each eye, 4 times a day during waking hours.

Do not touch dropper tip to the eyelids, surrounding areas, or any surface, as this may contaminate the solution.

In case of concomitant therapy with other topical ocular products, an interval of 10 minutes should be allowed between successive applications. Eye ointments should be administered last.

If the patient misses an instillation, the patient should be told to administer a dose as soon as feasible and then continue the treatment with the next scheduled instillation.  Discard bottle 7 days after first opening.

Ophthalmic solution containing 3.8 mg/mL of cysteamine (0.37%).

{ "type": "p", "children": [], "text": "Ophthalmic solution containing 3.8 mg/mL of cysteamine (0.37%)." }

None.

{ "type": "p", "children": [], "text": "None." }

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.

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.

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

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in 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 most common adverse reactions (≥ 10%) reported during clinical trials were eye pain, vision blurred, eye irritation, ocular hyperaemia, instillation site discomfort, eye pruritus, lacrimation increased, and ocular deposits.

Risk Summary There are no adequate and well-controlled studies of ophthalmic cysteamine in pregnant women to inform any drug associated risks. Oral administration of cysteamine to pregnant rats throughout the period of organogenesis was teratogenic at doses 240 to 960 times the recommended human ophthalmic dose (based on body surface area) [see Data]. CYSTADROPS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal data Teratology studies have been performed in rats at oral doses in the range of 37.5 mg/kg/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.

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.

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.

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. 

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.

CYSTADROPS is a sterile, viscous, ophthalmic solution containing 3.8 mg/mL of cysteamine (0.37%) equivalent to 5.6 mg/mL of cysteamine hydrochloride (0.55%). Cysteamine is a cystine- depleting agent which lowers the cystine content of cells in patients with cystinosis.

{ "type": "p", "children": [], "text": "CYSTADROPS is a sterile, viscous, ophthalmic solution containing 3.8 mg/mL of cysteamine (0.37%) equivalent to 5.6 mg/mL of cysteamine hydrochloride (0.55%). Cysteamine is a cystine- depleting agent which lowers the cystine content of cells in patients with cystinosis.\n\n" }

Molecular Formula: C2H7NS HCl

{ "type": "p", "children": [], "text": "Molecular Formula: C2H7NS HCl " }

Molecular Weight: 113.61

{ "type": "p", "children": [], "text": "Molecular Weight: 113.61" }

Each milliliter of CYSTADROPS contains: Active: cysteamine 3.8 mg (equivalent to cysteamine hydrochloride 5.6 mg); Preservative: benzalkonium chloride 0.1 mg; Inactive Ingredients: carmellose sodium, citric acid monohydrate, disodium edetate dihydrate, hydrochloric acid and sodium hydroxide (to adjust pH to 4.6-5.4), and water for injection.

{ "type": "p", "children": [], "text": "Each milliliter of CYSTADROPS contains: Active: cysteamine 3.8 mg (equivalent to cysteamine hydrochloride 5.6 mg); Preservative: benzalkonium chloride 0.1 mg; Inactive Ingredients: carmellose sodium, citric acid monohydrate, disodium edetate dihydrate, hydrochloric acid and sodium hydroxide (to adjust pH to 4.6-5.4), and water for injection." }

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

The peak plasma concentration of cysteamine following ocular administration of cysteamine ophthalmic solution in humans is unknown, because all patients concomitantly received oral cysteamine and the total daily ophthalmic dose is less than 4% of the recommended oral daily dose of cysteamine.

Carcinogenesis Cysteamine has not been tested for its carcinogenic potential in long-term animal studies.

Mutagenesis Cysteamine was not mutagenic in the Ames test. It produced a negative response in an in vitro sister chromatid exchange assay in human lymphocytes but a positive response in a similar assay in hamster ovarian cells.

Impairment of Fertility Repeat breeding reproduction studies were conducted in male and female rats. Cysteamine was found to have no effect on fertility and reproductive performance at an oral dose of 75 mg/kg/day (480 times the recommended human ophthalmic dose based on body surface area). At an oral dose of 375 mg/kg/day (2,400 times the recommended human ophthalmic dose based on body surface area), it reduced the fertility of the adult rats and the survival of their offspring.

Clinical safety and efficacy of CYSTADROPS were assessed in two studies: a single-arm study conducted for 5 years (OCT-1) and a randomized controlled study conducted for 90 days (CHOC).

{ "type": "p", "children": [], "text": "Clinical safety and efficacy of CYSTADROPS were assessed in two studies: a single-arm study conducted for 5 years (OCT-1) and a randomized controlled study conducted for 90 days (CHOC). " }

In the OCT-1 study, 8 patients with cystinosis (2 males and 6 females) with a mean age of 12.1 ± 4.6 (range: 7.0 – 21.0) were enrolled and received a median of 4 drops/eye/day of CYSTADROPS. In CHOC study, 32 patients with cystinosis (15 males and 17 females) with a mean age of 17.1 ± 13.0 (range: 2.9 – 62.6) were enrolled and received a median of 4 drops/eye/day. Fifteen patients were exposed to CYSTADROPS and 16 were exposed to cysteamine hydrochloride 0.1% (control arm).

{ "type": "p", "children": [], "text": "In the OCT-1 study, 8 patients with cystinosis (2 males and 6 females) with a mean age of 12.1 ± 4.6 (range: 7.0 – 21.0) were enrolled and received a median of 4 drops/eye/day of CYSTADROPS. In CHOC study, 32 patients with cystinosis (15 males and 17 females) with a mean age of 17.1 ± 13.0 (range: 2.9 – 62.6) were enrolled and received a median of 4 drops/eye/day. Fifteen patients were exposed to CYSTADROPS and 16 were exposed to cysteamine hydrochloride 0.1% (control arm). " }

Efficacy was assessed with In-Vivo Confocal Microscopy total score (IVCM score) by quantifying the cystine crystals in the cornea. A decrease in IVCM total score from baseline indicated a reduction in corneal crystals.

{ "type": "p", "children": [], "text": "Efficacy was assessed with In-Vivo Confocal Microscopy total score (IVCM score) by quantifying the cystine crystals in the cornea. A decrease in IVCM total score from baseline indicated a reduction in corneal crystals. " }

In the CHOC study, after 30 and 90 days of treatment with CYSTADROPS, 12% and 40% 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)).

{ "type": "p", "children": [], "text": "In the CHOC study, after 30 and 90 days of treatment with CYSTADROPS, 12% and 40% 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.

{ "type": "p", "children": [], "text": "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." }

CYSTADROPS (cysteamine ophthalmic solution) 0.37% is supplied as a 5 mL sterile viscous solution in a 10 mL amber glass bottle closed by a bromobutyl stopper and sealed with an aluminum tear-off cap.  A PVC dropper applicator with HDPE closure is packed separately and included in each carton box.

{ "type": "p", "children": [], "text": "CYSTADROPS (cysteamine ophthalmic solution) 0.37% is supplied as a 5 mL sterile viscous solution in a 10 mL amber glass bottle closed by a bromobutyl stopper and sealed with an aluminum tear-off cap.  A PVC dropper applicator with HDPE closure is packed separately and included in each carton box." }

Each carton box (NDC 55292-410-05) contains 1 bottle (NDC 55292-410-05) and 1 dropper applicator individually wrapped.

{ "type": "p", "children": [], "text": "Each carton box (NDC 55292-410-05) contains 1 bottle (NDC 55292-410-05) and 1 dropper applicator individually wrapped." }

Before First Opening: Before opening, store new, unopened CYSTADROPS in the refrigerator between 36°F to 46°F (2°C to 8°C). Keep the bottle in the outer carton in order to protect from light.

{ "type": "p", "children": [], "text": "\nBefore First Opening: Before opening, store new, unopened CYSTADROPS in the refrigerator between 36°F to 46°F (2°C to 8°C). Keep the bottle in the outer carton in order to protect from light." }

After First Opening: After opening, store opened CYSTADROPS at room temperature between 68°F to 77°F (20°C to 25°C). Do not refrigerate after opening. Keep the dropper bottle tightly closed in the outer carton in order to protect from light. Discard 7 days after first opening.

{ "type": "p", "children": [], "text": "\nAfter First Opening: After opening, store opened CYSTADROPS at room temperature between 68°F to 77°F (20°C to 25°C). Do not refrigerate after opening. Keep the dropper bottle tightly closed in the outer carton in order to protect from light. Discard 7 days after first opening." }

Advise the patient to read the FDA-approved patient labeling (Instructions for Use).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Instructions for Use)." }

Preparation for Administration and Storage of Bottles

{ "type": "p", "children": [], "text": "\nPreparation for Administration and Storage of Bottles\n" }

{ "type": "", "children": [], "text": "" }

{ "type": "", "children": [], "text": "" }

Risk of Contamination

{ "type": "p", "children": [], "text": "\nRisk of Contamination\n" }

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.

{ "type": "p", "children": [], "text": "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

{ "type": "p", "children": [], "text": "\nContact Lens Use\n" }

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)].

{ "type": "p", "children": [], "text": "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

{ "type": "p", "children": [], "text": "\nTopical Ophthalmic Use\n" }

Advise patients that CYSTADROPS is for topical ophthalmic use.

{ "type": "p", "children": [], "text": "Advise patients that CYSTADROPS is for topical ophthalmic use." }

Missed Dose

{ "type": "p", "children": [], "text": "\nMissed Dose\n" }

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.

{ "type": "p", "children": [], "text": "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

{ "type": "p", "children": [], "text": "Manufactured by: Baccinex SA, 2822 Courroux, Switzerland" }

Manufactured for: Recordati Rare Diseases Inc., Bridgewater, NJ 08807, U.S.A.

{ "type": "p", "children": [], "text": "Manufactured for: Recordati Rare Diseases Inc., Bridgewater, NJ 08807, U.S.A." }

This product label may have been updated. For the most recent prescribing information, please visit www.recordatirarediseases.com/us.

{ "type": "p", "children": [], "text": "This product label may have been updated. For the most recent prescribing information, please visit www.recordatirarediseases.com/us." }

<div class="scrollingtable"><table cellpadding="4" class="Noautorules" width="100%"> <colgroup> <col valign="top" width="1%"/> <col valign="top" width="99%"/> </colgroup> <tbody class="Headless"> <tr> <td align="center" colspan="2" valign="top"><span class="Bold"><span class="Bold"> INSTRUCTIONS FOR USE</span>   <br/> </span>CYSTADROPS<span class="Sup">® </span>(sys-tah-drops) <br/>(cysteamine ophthalmic solution) <br/>for topical ophthalmic use</td> </tr> <tr> <td colspan="2" valign="top"> </td> </tr> <tr> <td colspan="2" valign="top"> Read this Instructions for Use carefully before you start using CYSTADROPS and each time you get a refill; there may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment.  </td> </tr> <tr> <td colspan="2" valign="top"> </td> </tr> <tr> <td colspan="2" valign="top"><span class="Bold">Important information:</span></td> </tr> <tr> <td valign="top"><span class="Bold">• </span></td><td valign="top">Use CYSTADROPS exactly as your healthcare provider tells you to use it.  </td> </tr> <tr> <td valign="top">• </td><td valign="top">CYSTADROPS is for use in the eyes.</td> </tr> <tr> <td valign="top">• </td><td valign="top">Wash your hands before each use.</td> </tr> <tr> <td valign="top">• </td><td valign="top">If you use CYSTADROPS with other eye medicines, you should wait at least 10 minutes between using CYSTADROPS and your other eye medicines.</td> </tr> <tr> <td valign="top">• </td><td valign="top">If you wear contact lenses, remove them before using CYSTADROPS. You should wait at least 15 minutes after using CYSTADROPS, before placing your contact lenses back in your eyes.</td> </tr> <tr> <td valign="top">• </td><td valign="top"><span class="Bold">Do not</span> let the CYSTADROPS dropper touch your eyelids or any other surfaces.</td> </tr> <tr> <td colspan="2" valign="top"> </td> </tr> <tr> <td colspan="2" valign="top"><span class="Bold">Storing CYSTADROPS:</span></td> </tr> <tr> <td valign="top">• </td><td valign="top">Before opening, store new, unopened CYSTADROPS in the refrigerator between 36°F to 46°F (2°C to 8°C).</td> </tr> <tr> <td valign="top">• </td><td valign="top">After first opening, store opened CYSTADROPS at room temperature between 68°F to 77°F (20°C to 25°C). <span class="Bold">Do not</span> refrigerate after opening.</td> </tr> <tr> <td valign="top">• </td><td valign="top">Keep CYSTADROPS in the original carton to protect from light.</td> </tr> <tr> <td valign="top">• </td><td valign="top">Keep the CYSTADROPS dropper bottle tightly closed when not in use.</td> </tr> <tr> <td valign="top">• </td><td valign="top">Throw away any unused CYSTADROPS 7 days after opening.</td> </tr> <tr> <td valign="top">• </td><td valign="top"><span class="Bold">Keep CYSTADROPS and all medicines out of the reach of children. </span></td> </tr> <tr> <td valign="top">  </td><td valign="top"> </td> </tr> <tr> <td colspan="2" valign="top"><span class="Bold">Supplies needed:</span></td> </tr> <tr> <td valign="top">• </td><td valign="top">CYSTADROPS bottle and dropper</td> </tr> <tr> <td valign="top">• </td><td valign="top">mirror</td> </tr> <tr> <td valign="top">• </td><td valign="top">tissue </td> </tr> <tr> <td colspan="2" valign="top"> </td> </tr> <tr> <td colspan="2" valign="top"><span class="Bold">Using CYSTADROPS:</span></td> </tr> <tr> <td valign="top">• </td><td valign="top">Use 1 drop in each eye, four times a day.</td> </tr> <tr> <td valign="top">• </td><td valign="top">If you miss a dose, administer the missed dose as soon as possible and then use the drops at your next regular scheduled time.</td> </tr> <tr> <td colspan="2" valign="top"> </td> </tr> <tr> <td colspan="2" valign="top"><span class="Bold">Step 1: Before using a CYSTADROPS bottle for the first time</span></td> </tr> <tr> <td valign="top">• </td><td valign="top">Check the expiration date on the CYSTADROPS bottle before use. <span class="Bold">Do </span><span class="Bold">not</span> use CYSTADROPS if the expiration date has passed.</td> </tr> <tr> <td valign="top">• </td><td valign="top">After opening a CYSTADROPS bottle, allow it to reach room temperature before using it for the first time.</td> </tr> <tr> <td valign="top">• </td><td valign="top">After opening a CYSTADROPS bottle for the first time, write the date of opening in the space provided on the carton.</td> </tr> <tr> <td valign="top">• </td><td valign="top">Wash your hands carefully in order to avoid contamination of the contents in the bottle.</td> </tr> <tr> <td valign="top">• </td><td valign="top">Remove the green protective cap (Figure A).</td> </tr> <tr> <td valign="top">• </td><td valign="top">Remove the metal seal (Figure B).</td> </tr> <tr> <td valign="top">• </td><td valign="top">Remove the gray stopper (Figure C).</td> </tr> <tr> <td valign="top">• </td><td valign="top"><span class="Bold">Do not</span> touch the opening of the bottle after removing the gray stopper.</td> </tr> <tr> <td valign="top">• </td><td valign="top">Place the opened bottle on a flat surface.</td> </tr> <tr> <td colspan="2" valign="top"> </td> </tr> <tr> <td align="center" colspan="2" valign="top"><img alt="Figures A, B, C" src="/dailymed/image.cfm?name=figABC.jpg&amp;setid=5d2bcce3-9b89-4141-aeb7-db00449047f5"/></td> </tr> <tr> <td valign="top">• </td><td valign="top">Take the dropper out of its packaging. <span class="Bold">Do </span><span class="Bold">not</span> 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, <span class="Bold">do not</span> remove the dropper from the bottle (Figure E).</td> </tr> <tr> <td align="center" colspan="2" valign="top"><img alt="Figures D, E" src="/dailymed/image.cfm?name=figDE.jpg&amp;setid=5d2bcce3-9b89-4141-aeb7-db00449047f5"/> </td> </tr> <tr> <td valign="top">• </td><td valign="top">Make sure that you do not lose the small white cap (Figure E) that comes on the top of the dropper.</td> </tr> <tr> <td colspan="2" valign="top"> </td> </tr> <tr> <td colspan="2" valign="top"><span class="Bold">Step 2: Before using CYSTADROPS</span></td> </tr> <tr> <td valign="top">• </td><td valign="top">Check the opening date that you wrote down on the carton. <span class="Bold">Do not</span> use CYSTADROPS if more than 7 days have passed since the opening date.</td> </tr> <tr> <td valign="top">• </td><td valign="top">Get the CYSTADROPS dropper bottle, mirror, and tissue.</td> </tr> <tr> <td valign="top">• </td><td valign="top">Wash your hands.</td> </tr> <tr> <td colspan="2" valign="top"> </td> </tr> <tr> <td colspan="2" valign="top"><span class="Bold">Step 3: Using the CYSTADROPS dropper bottle</span></td> </tr> <tr> <td valign="top">• </td><td valign="top">Twist the small white cap to remove it from the dropper. <span class="Bold">Do </span><span class="Bold">not</span> throw the small white cap away. </td> </tr> <tr> <td valign="top">• </td><td valign="top">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.</td> </tr> <tr> <td valign="top">• </td><td valign="top">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.</td> </tr> <tr> <td align="center" colspan="2" valign="top"><img alt="figure F" src="/dailymed/image.cfm?name=figF.jpg&amp;setid=5d2bcce3-9b89-4141-aeb7-db00449047f5"/></td> </tr> <tr> <td valign="top">• </td><td valign="top">Use the mirror to help you bring the dropper bottle tip close to the eye.</td> </tr> <tr> <td valign="top">• </td><td valign="top"><span class="Bold">Do not</span> let the CYSTADROPS dropper touch your eyelids or any other surfaces.</td> </tr> <tr> <td valign="top">• </td><td valign="top">Gently squeeze the dropper to release 1 drop of CYSTADROPS.</td> </tr> <tr> <td valign="top">• </td><td valign="top">If a drop misses your eye, try again.</td> </tr> <tr> <td valign="top">• </td><td valign="top">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.</td> </tr> <tr> <td align="center" colspan="2" valign="top"><img alt="Figure G" src="/dailymed/image.cfm?name=figG.jpg&amp;setid=5d2bcce3-9b89-4141-aeb7-db00449047f5"/></td> </tr> <tr> <td valign="top">• </td><td valign="top">Remove any medicine around the eye with a tissue (Figure H).</td> </tr> <tr> <td valign="top">• </td><td valign="top">Repeat Step 3 for the other eye.</td> </tr> <tr> <td valign="top">• </td><td valign="top">Replace the small white cap on the dropper immediately after use.</td> </tr> <tr> <td align="center" colspan="2" valign="top"><img alt="Figure H" src="/dailymed/image.cfm?name=figH.jpg&amp;setid=5d2bcce3-9b89-4141-aeb7-db00449047f5"/></td> </tr> <tr> <td colspan="2" valign="top"> This Instructions for Use has been approved by the U.S. Food and Drug Administration.</td> </tr> <tr> <td colspan="2" valign="top"> Manufactured by: Baccinex SA, 2822 Courroux, Switzerland</td> </tr> <tr> <td colspan="2" valign="top">Manufactured for: Recordati Rare Diseases Inc., Bridgewater, NJ 08807, U.S.A. </td> </tr> <tr> <td colspan="2" valign="top"><img alt="Logo" src="/dailymed/image.cfm?name=logo.jpg&amp;setid=5d2bcce3-9b89-4141-aeb7-db00449047f5"/></td> </tr> <tr> <td colspan="2" valign="top"> Approved: 08/2020</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"4\" class=\"Noautorules\" width=\"100%\">\n<colgroup>\n<col valign=\"top\" width=\"1%\"/>\n<col valign=\"top\" width=\"99%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\" colspan=\"2\" valign=\"top\"><span class=\"Bold\"><span class=\"Bold\"> INSTRUCTIONS FOR USE</span>   <br/>\n</span>CYSTADROPS<span class=\"Sup\">® </span>(sys-tah-drops) <br/>(cysteamine ophthalmic solution) <br/>for topical ophthalmic use</td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"> </td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"> Read this Instructions for Use carefully before you start using CYSTADROPS and each time you get a refill; there may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment.  </td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"> </td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"><span class=\"Bold\">Important information:</span></td>\n</tr>\n<tr>\n<td valign=\"top\"><span class=\"Bold\">• </span></td><td valign=\"top\">Use CYSTADROPS exactly as your healthcare provider tells you to use it.  </td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">CYSTADROPS is for use in the eyes.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Wash your hands before each use.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">If you use CYSTADROPS with other eye medicines, you should wait at least 10 minutes between using CYSTADROPS and your other eye medicines.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">If you wear contact lenses, remove them before using CYSTADROPS. You should wait at least 15 minutes after using CYSTADROPS, before placing your contact lenses back in your eyes.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\"><span class=\"Bold\">Do not</span> let the CYSTADROPS dropper touch your eyelids or any other surfaces.</td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"> </td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"><span class=\"Bold\">Storing CYSTADROPS:</span></td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Before opening, store new, unopened CYSTADROPS in the refrigerator between 36°F to 46°F (2°C to 8°C).</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">After first opening, store opened CYSTADROPS at room temperature between 68°F to 77°F (20°C to 25°C). <span class=\"Bold\">Do not</span> refrigerate after opening.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Keep CYSTADROPS in the original carton to protect from light.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Keep the CYSTADROPS dropper bottle tightly closed when not in use.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Throw away any unused CYSTADROPS 7 days after opening.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\"><span class=\"Bold\">Keep CYSTADROPS and all medicines out of the reach of children. </span></td>\n</tr>\n<tr>\n<td valign=\"top\">  </td><td valign=\"top\"> </td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"><span class=\"Bold\">Supplies needed:</span></td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">CYSTADROPS bottle and dropper</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">mirror</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">tissue </td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"> </td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"><span class=\"Bold\">Using CYSTADROPS:</span></td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Use 1 drop in each eye, four times a day.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">If you miss a dose, administer the missed dose as soon as possible and then use the drops at your next regular scheduled time.</td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"> </td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"><span class=\"Bold\">Step 1: Before using a CYSTADROPS bottle for the first time</span></td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Check the expiration date on the CYSTADROPS bottle before use. <span class=\"Bold\">Do </span><span class=\"Bold\">not</span> use CYSTADROPS if the expiration date has passed.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">After opening a CYSTADROPS bottle, allow it to reach room temperature before using it for the first time.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">After opening a CYSTADROPS bottle for the first time, write the date of opening in the space provided on the carton.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Wash your hands carefully in order to avoid contamination of the contents in the bottle.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Remove the green protective cap (Figure A).</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Remove the metal seal (Figure B).</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Remove the gray stopper (Figure C).</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\"><span class=\"Bold\">Do not</span> touch the opening of the bottle after removing the gray stopper.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Place the opened bottle on a flat surface.</td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"> </td>\n</tr>\n<tr>\n<td align=\"center\" colspan=\"2\" valign=\"top\"><img alt=\"Figures A, B, C\" src=\"/dailymed/image.cfm?name=figABC.jpg&amp;setid=5d2bcce3-9b89-4141-aeb7-db00449047f5\"/></td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Take the dropper out of its packaging. <span class=\"Bold\">Do </span><span class=\"Bold\">not</span> 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, <span class=\"Bold\">do not</span> remove the dropper from the bottle (Figure E).</td>\n</tr>\n<tr>\n<td align=\"center\" colspan=\"2\" valign=\"top\"><img alt=\"Figures D, E\" src=\"/dailymed/image.cfm?name=figDE.jpg&amp;setid=5d2bcce3-9b89-4141-aeb7-db00449047f5\"/> </td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Make sure that you do not lose the small white cap (Figure E) that comes on the top of the dropper.</td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"> </td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"><span class=\"Bold\">Step 2: Before using CYSTADROPS</span></td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Check the opening date that you wrote down on the carton. <span class=\"Bold\">Do not</span> use CYSTADROPS if more than 7 days have passed since the opening date.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Get the CYSTADROPS dropper bottle, mirror, and tissue.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Wash your hands.</td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"> </td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"><span class=\"Bold\">Step 3: Using the CYSTADROPS dropper bottle</span></td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Twist the small white cap to remove it from the dropper. <span class=\"Bold\">Do </span><span class=\"Bold\">not</span> throw the small white cap away. </td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">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.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">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.</td>\n</tr>\n<tr>\n<td align=\"center\" colspan=\"2\" valign=\"top\"><img alt=\"figure F\" src=\"/dailymed/image.cfm?name=figF.jpg&amp;setid=5d2bcce3-9b89-4141-aeb7-db00449047f5\"/></td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Use the mirror to help you bring the dropper bottle tip close to the eye.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\"><span class=\"Bold\">Do not</span> let the CYSTADROPS dropper touch your eyelids or any other surfaces.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Gently squeeze the dropper to release 1 drop of CYSTADROPS.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">If a drop misses your eye, try again.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">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.</td>\n</tr>\n<tr>\n<td align=\"center\" colspan=\"2\" valign=\"top\"><img alt=\"Figure G\" src=\"/dailymed/image.cfm?name=figG.jpg&amp;setid=5d2bcce3-9b89-4141-aeb7-db00449047f5\"/></td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Remove any medicine around the eye with a tissue (Figure H).</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Repeat Step 3 for the other eye.</td>\n</tr>\n<tr>\n<td valign=\"top\">• </td><td valign=\"top\">Replace the small white cap on the dropper immediately after use.</td>\n</tr>\n<tr>\n<td align=\"center\" colspan=\"2\" valign=\"top\"><img alt=\"Figure H\" src=\"/dailymed/image.cfm?name=figH.jpg&amp;setid=5d2bcce3-9b89-4141-aeb7-db00449047f5\"/></td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"> This Instructions for Use has been approved by the U.S. Food and Drug Administration.</td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"> Manufactured by: Baccinex SA, 2822 Courroux, Switzerland</td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\">Manufactured for: Recordati Rare Diseases Inc., Bridgewater, NJ 08807, U.S.A. </td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"><img alt=\"Logo\" src=\"/dailymed/image.cfm?name=logo.jpg&amp;setid=5d2bcce3-9b89-4141-aeb7-db00449047f5\"/></td>\n</tr>\n<tr>\n<td colspan=\"2\" valign=\"top\"> Approved: 08/2020</td>\n</tr>\n</tbody>\n</table></div>" }

NDC 55292-410-05

{ "type": "p", "children": [], "text": "NDC 55292-410-05" }

Cystadrops® (cysteamine ophthalmic solution)

{ "type": "p", "children": [], "text": "Cystadrops®\n(cysteamine ophthalmic solution)" }

0.37 %

{ "type": "p", "children": [], "text": "0.37 %" }

For Topical Ophthalmic Use

{ "type": "p", "children": [], "text": "For Topical Ophthalmic Use" }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

1 x 5 mL sterile

{ "type": "p", "children": [], "text": "1 x 5 mL sterile" }

RECORDATI RARE DISEASESGROUP

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NDC 55292-410-05 Rx only Cystadrops® (cysteamine ophthalmic solution) 0.37 %  5 mL sterile Recordati Rare Diseases Inc. CDRLBL Lot: EXP: YYYY/MM

{ "type": "p", "children": [], "text": "NDC 55292-410-05 \nRx only\n\nCystadrops®\n(cysteamine ophthalmic solution) \n\n\n0.37 % \n5 mL \nsterile\n\nRecordati Rare Diseases Inc. CDRLBL\n Lot: \nEXP: YYYY/MM" }

PROCYSBI is indicated for the treatment of nephropathic cystinosis in adults and pediatric patients 1 year of age and older.

{ "type": "p", "children": [], "text": "PROCYSBI is indicated for the treatment of nephropathic cystinosis in adults and pediatric patients 1 year of age and older." }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: Starting and Maintenance Dosage of PROCYSBI by Body Weight in Cysteamine-Naïve Patients 1 Year of Age and Older (Dosage Rounded Using Available Strengths of Capsules or Packets of Oral Granules)</span> </caption> <col align="center" valign="middle" width="30%"/> <col align="center" valign="middle" width="20%"/> <col align="center" valign="middle" width="20%"/> <col align="center" valign="middle" width="30%"/> <thead> <tr class="Botrule First"> <th align="center" class="Lrule Rrule" rowspan="2">Weight in kilograms</th><th align="center" class="Rrule" colspan="2">Starting PROCYSBI Dosage in mg every 12 hours, as a Fraction of the Maintenance Dosage</th><th align="center" class="Rrule" rowspan="2">Maintenance PROCYSBI Dosage in mg every 12 hours<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></th> </tr> <tr class="Last"> <th align="center" class="Rrule">⅙ of dosage</th><th align="center" class="Rrule">¼ of dosage</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Higher dosages may be required to achieve target therapeutic WBC cystine concentration <span class="Italics">[see <a href="#S2.4">Dosage and Administration (2.4)</a>]</span>.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">5 or less</td><td align="center" class="Rrule">25</td><td align="center" class="Rrule">50</td><td align="center" class="Rrule">200</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">6 to 10</td><td align="center" class="Rrule">50</td><td align="center" class="Rrule">75</td><td align="center" class="Rrule">300</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">11 to 15</td><td align="center" class="Rrule">75</td><td align="center" class="Rrule">100</td><td align="center" class="Rrule">400</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">16 to 20</td><td align="center" class="Rrule">100</td><td align="center" class="Rrule">125</td><td align="center" class="Rrule">500</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">21 to 25</td><td align="center" class="Rrule">100</td><td align="center" class="Rrule">150</td><td align="center" class="Rrule">600</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">26 to 30</td><td align="center" class="Rrule">125</td><td align="center" class="Rrule">175</td><td align="center" class="Rrule">700</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">31 to 40</td><td align="center" class="Rrule">125</td><td align="center" class="Rrule">200</td><td align="center" class="Rrule">800</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">41 to 50</td><td align="center" class="Rrule">150</td><td align="center" class="Rrule">225</td><td align="center" class="Rrule">900</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">51 kg and greater</td><td align="center" class="Rrule">175</td><td align="center" class="Rrule">250</td><td align="center" class="Rrule">1000</td> </tr> </tbody> </table></div>

Oral Administration in Food or Liquid

Administration of PROCYSBI capsules or oral granules with foods and liquids not included below has not been studied clinically and is not recommended.

Administration in Applesauce or Berry Jelly:

Administration in Fruit Juice (except grapefruit juice):

Administration in Applesauce via a Gastrostomy (G) Tube (14 French or larger)

A bolus (straight) feeding tube is recommended.

Missed Doses

PROCYSBI delayed-release capsules:

{ "type": "p", "children": [], "text": "PROCYSBI delayed-release capsules:" }

{ "type": "ul", "children": [ "25 mg cysteamine: the capsules have a light blue opaque cap imprinted with \"PRO\" in white ink and a light blue opaque body imprinted with \"25 mg\" in white ink.", "75 mg cysteamine: the capsules have a dark blue opaque cap imprinted with \"PRO\" in white ink and a light blue opaque body imprinted with \"75 mg\" in white ink." ], "text": "" }

PROCYSBI delayed-release oral granules:

{ "type": "p", "children": [], "text": "PROCYSBI delayed-release oral granules:" }

{ "type": "ul", "children": [ "75 mg cysteamine: white to off-white granules in single-use packets ", "300 mg cysteamine: white to off-white granules in single-use packets " ], "text": "" }

The use of PROCYSBI is contraindicated in patients with a serious hypersensitivity reaction, including anaphylaxis, to penicillamine or cysteamine.

{ "type": "p", "children": [], "text": "The use of PROCYSBI is contraindicated in patients with a serious hypersensitivity reaction, including anaphylaxis, to penicillamine or cysteamine." }

Skin and bone lesions that resemble clinical findings for Ehlers-Danlos-like syndrome have been reported in patients treated with high doses of immediate-release cysteamine bitartrate or other cysteamine salts. These include molluscoid pseudotumors (purplish hemorrhagic lesions), skin striae, bone lesions (including osteopenia, compression fractures, scoliosis and genu valgum), leg pain, and joint hyperextension. One patient on immediate-release cysteamine bitartrate with serious skin lesions subsequently died of acute cerebral ischemia with marked vasculopathy. Monitor patients for development of skin or bone lesions and interrupt PROCYSBI dosing if patients develop these lesions. PROCYSBI may be restarted at a lower dose under close supervision, then slowly increase to the appropriate therapeutic dose [see Dosage and Administration (2.1, 2.4)].

Severe skin rashes such as erythema multiforme bullosa or toxic epidermal necrolysis have been reported in patients receiving immediate-release cysteamine bitartrate. If severe skin rashes develop, permanently discontinue use of PROCYSBI [see Contraindications (4)].

Gastrointestinal (GI) ulceration and bleeding have been reported in patients receiving immediate-release cysteamine bitartrate. GI tract symptoms including nausea, vomiting, anorexia and abdominal pain, sometimes severe, have been associated with cysteamine. If severe GI tract symptoms develop, consider decreasing the dose of PROCYSBI [see Dosage and Administration (2.1, 2.4)].

Fibrosing colonopathy, including colonic stricture formation, has been reported with postmarketing use of PROCYSBI in pediatric and young adult patients with nephropathic cystinosis. Some of these patients had been treated with PROCYSBI for prolonged periods of time. Reported symptoms include: abdominal pain, vomiting, bloody or persistent diarrhea, and fecal incontinence. Evaluate patients with severe, persistent, and/or worsening abdominal symptoms for fibrosing colonopathy. If the diagnosis is confirmed, permanently discontinue PROCYSBI and switch to immediate-release cysteamine bitartrate capsules. An association between methacrylic acid-ethyl acrylate copolymer (an inactive ingredient in PROCYSBI) and fibrosing colonopathy cannot be ruled out.

Central Nervous System (CNS) symptoms such as seizures, lethargy, somnolence, depression, and encephalopathy have been associated with immediate-release cysteamine. Neurological complications have also been described in some patients with cystinosis who have not been treated with cysteamine. Carefully evaluate and monitor patients who develop CNS symptoms. Interrupt medication or adjust the dose as necessary for patients with severe symptoms or with symptoms that persist or progress. Inform patients that PROCYSBI may impair their ability to perform tasks such as driving or operating machinery.

Cysteamine has been associated with reversible leukopenia and elevated alkaline phosphatase levels. Monitor white blood cell counts and alkaline phosphatase levels. If tests values remain elevated, consider decreasing the dose or discontinuing the drug until values revert to normal.

Benign intracranial hypertension (pseudotumor cerebri; PTC) and/or papilledema have been reported in patients receiving immediate-release cysteamine bitartrate treatment. Monitor patients for signs and symptoms of PTC, including headache, tinnitus, dizziness, nausea, diplopia, blurry vision, loss of vision, pain behind the eye or pain with eye movement. If signs/symptoms persist, interrupt dosing or decrease the dose and refer the patient to an ophthalmologist. If the diagnosis is confirmed, permanently discontinue use of PROCYSBI.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The data described below reflect exposure to cysteamine in 345 patients with nephropathic cystinosis (246 patients receiving immediate-release cysteamine as cysteamine hydrochloride or phosphocysteamine, and 80 patients receiving PROCYSBI) in open-label clinical trials.

Clinical Trials Experience with PROCYSBI in Patients Switched from Immediate-Release Cysteamine Bitartrate

Sixty-two patients with nephropathic cystinosis (38 males and 24 females) received PROCYSBI in two clinical trials at doses ranging from 0.29 grams/m2 per day to 2.19 grams/m2 per day [see Clinical Studies (14.2)]. All patients were switched from immediate-release cysteamine to PROCYSBI. Forty-three patients, ages 6 to 26 years old, received PROCYSBI in an 8-week, open-label, randomized, cross-over trial comparing PROCYSBI to immediate-release cysteamine bitartrate. Forty of 43 patients continued PROCYSBI treatment in an open-label extension trial (36 patients were treated with PROCYSBI for longer than 2 years, and 20 patients were treated for longer than 5 years). An additional 19 patients (6 renal transplanted patients and 13 patients aged 2 to 6 years) were enrolled directly into this trial (12 patients were treated with PROCYSBI for longer than 2 years, and 9 patients were treated for longer than 5 years).

In the open-label, randomized, cross-over trial, a higher incidence of adverse reactions was reported in patients during the PROCYSBI treatment period compared with the immediate-release cysteamine bitartrate treatment period (see Table 2). Other significant adverse reactions reported during clinical trials included hypersensitivity reactions, including anaphylaxis.

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 2: Adverse Reactions in ≥5% of Patients with Nephropathic Cystinosis in a Randomized, Cross-Over Trial</span> </caption> <col align="left" valign="top" width="34%"/> <col align="center" valign="middle" width="33%"/> <col align="center" valign="middle" width="33%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule" rowspan="2" valign="middle">Adverse Reaction</th><th align="center" class="Lrule Rrule">Immediate-Release Cysteamine</th><th align="center" class="Lrule Rrule">PROCYSBI</th> </tr> <tr class="Last"> <th align="center" class="Lrule Rrule">(n = 41)<br/>%</th><th align="center" class="Lrule Rrule">(n = 43)<br/>%</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Vomiting/emesis</td><td align="center" class="Rrule">12</td><td align="center" class="Rrule">19</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Nausea</td><td align="center" class="Rrule">7</td><td align="center" class="Rrule">16</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Abdominal pain/discomfort</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule">14</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Headache</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule">9</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Dizziness</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule">5</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Anorexia/loss of appetite</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">2</td> </tr> </tbody> </table></div>

In the open-label extension trial (N=59), the most commonly reported adverse reactions (>15%) were vomiting, headache, diarrhea, nausea, conjunctivitis, influenza, gastroenteritis, nasopharyngitis, abdominal pain, dehydration, ear infection, upper respiratory tract infection, fatigue, arthralgia, cough, and pain in extremity.

Clinical Trials Experience with PROCYSBI in Cysteamine-Naïve Patients

Seventeen cysteamine-naïve patients (fifteen patients between the ages of 1 and 5 years, one 9-year old and one 22-year old) received PROCYSBI in an open-label clinical trial [see Clinical Studies (14.2)]. Serious adverse reactions occurring in at least 2 patients (>10%) were: gastroenteritis/viral gastroenteritis (n=6), vomiting (n=4), and electrolyte imbalance (n=2). Three patients with serious adverse reactions of gastroenteritis also had dehydration. Common adverse reactions reported at a frequency of >10% (occurring in at least 2 patients) are shown in Table 3.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 3: Adverse Reactions in &gt;10% of Patients with Nephropathic Cystinosis Naïve to Cysteamine Treatment in an Open-Label Trial </span> </caption> <col align="left" valign="top" width="50%"/> <col align="left" valign="top" width="50%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">Adverse Reaction</th><th align="left" class="Rrule">PROCYSBI<br/>N = 17<br/>n (%)</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Vomiting</td><td align="left" class="Rrule">13 (77)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Gastroenteritis/viral gastroenteritis</td><td align="left" class="Rrule">9 (53)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Diarrhea</td><td align="left" class="Rrule">6 (35)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Breath odor</td><td align="left" class="Rrule">4 (24)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Nausea</td><td align="left" class="Rrule">3 (18)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Electrolyte imbalance</td><td align="left" class="Rrule">2 (12)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Headache</td><td align="left" class="Rrule">2 (12)</td> </tr> </tbody> </table></div>

Clinical Trials Experience with Immediate-Release Cysteamine

The most frequent adverse reactions involved the gastrointestinal and central nervous systems and were especially prominent at the initiation of cysteamine therapy. Most patients were able to resume therapy at lower doses. The most common reactions (>5%) were vomiting, anorexia, fever, diarrhea, lethargy, and rash. Other adverse reactions included nausea, bad breath, abdominal pain, headache, dizziness, and urticaria.

Withdrawals due to intolerance, vomiting, anorexia, lethargy, and fever occurred more frequently in those patients receiving 1.95 grams/m2 per day as compared with 1.3 grams/m2 per day of immediate-release cysteamine bitartrate.

The following adverse reactions have been identified during post-approval use of cysteamine bitartrate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Drugs that increase the gastric pH (e.g., medications containing bicarbonate or carbonate) may alter the pharmacokinetics of cysteamine due to the premature release of cysteamine from PROCYSBI and increase WBC cystine concentration. Concomitant administration of 20 mg omeprazole did not affect the pharmacokinetics of cysteamine when PROCYSBI was administered with 240 mL of orange juice or with 240 mL of water [see Clinical Pharmacology (12.3)]. Monitor WBC cystine concentration when drugs that increase the gastric pH are concomitantly used [see Dosage and Administration (2.5)].

Consumption of alcohol with PROCYSBI may increase the rate of cysteamine release and/or adversely alter the pharmacokinetic properties, as well as the effectiveness and safety of PROCYSBI. Therefore, do not consume alcoholic beverages during treatment with PROCYSBI [see Dosage and Administration (2.6)].

PROCYSBI can be administered with other electrolyte and mineral replacements necessary for management of Fanconi syndrome, as well as vitamin D and thyroid hormone.

Risk Summary

There are no available data on PROCYSBI use in pregnant women to inform any drug-associated risks for birth defects or miscarriage [see Data]. Cysteamine (administered as cysteamine bitartrate) was teratogenic and fetotoxic in rats at doses less than the recommended human maintenance dose.

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Advise pregnant women of the potential risk to a fetus.

Data

Animal Data

Embryo-fetal development studies were conducted in rats using oral administration of cysteamine bitartrate, with a dose range of 37.5 to 150 mg/kg per day of cysteamine equivalent (about 0.2 to 0.7 times the recommended human maintenance dose based on body surface area). Cysteamine bitartrate was fetotoxic and produced adverse developmental effects. Observed teratogenic findings were cleft palate, kyphosis, heart ventricular septal defects, microcephaly and exencephaly.

Risk Summary

There is no information on the presence of cysteamine in human milk, the effects on the breast-fed infant, or the effects on milk production. Cysteamine is present in the milk of lactating rats [see Data]. Because of the potential for serious adverse reactions in breastfed infants from cysteamine, breastfeeding is not recommended.

Data

A decrease in survival occurred in neonatal rats nursed by mothers receiving cysteamine [see Nonclinical Toxicology (13)].

The safety and effectiveness of PROCYSBI have been established in pediatric patients 1 year of age and older for the treatment of nephropathic cystinosis. Use of PROCYSBI is supported by evidence from patients switched to PROCYSBI from immediate-release cysteamine bitartrate in two trials: an open-label, randomized, cross-over trial in adults and pediatric patients aged 6 years and older (n=43) and an open-label extension trial in pediatric patients aged 2 years and older (n=59). Another open-label trial was conducted in cysteamine naïve pediatric patients 1 year to less than 6 years of age (n=15) [see Clinical Trials (14.2)]. The safety profile in pediatric patients was similar to adults. In patients less than 6 years of age, vomiting occurred in 12/15 cysteamine treatment naïve patients compared to 11/13 patients switched from immediate-release cysteamine to PROCYSBI.

The safety and effectiveness of PROCYSBI have not been established in patients less than 1 year of age.

No studies with PROCYSBI have been conducted in geriatric patients.

One case of overdosing with PROCYSBI has been reported. A 16-year-old male patient suffered nausea and vomiting after he mistakenly took a second dose of PROCYSBI 30 minutes after his usual dose.

{ "type": "p", "children": [], "text": "One case of overdosing with PROCYSBI has been reported. A 16-year-old male patient suffered nausea and vomiting after he mistakenly took a second dose of PROCYSBI 30 minutes after his usual dose." }

Two cases of overdosing with immediate-release cysteamine bitartrate have been reported in two patients. In the first case, the patient immediately vomited after ingesting an unknown dose and did not develop any symptoms. The second case involved an accidental ingestion of a 200 to 250 mg/kg dose by a healthy 13-month-old child. Vomiting and dehydration were experienced. The child was hospitalized and fluids were administered. The patient fully recovered from the overdosing.

{ "type": "p", "children": [], "text": "Two cases of overdosing with immediate-release cysteamine bitartrate have been reported in two patients. In the first case, the patient immediately vomited after ingesting an unknown dose and did not develop any symptoms. The second case involved an accidental ingestion of a 200 to 250 mg/kg dose by a healthy 13-month-old child. Vomiting and dehydration were experienced. The child was hospitalized and fluids were administered. The patient fully recovered from the overdosing." }

Should overdosing occur, the respiratory and cardiovascular systems should be supported appropriately. No specific antidote is known. Hemodialysis may be considered since cysteamine is poorly bound to plasma proteins.

{ "type": "p", "children": [], "text": "Should overdosing occur, the respiratory and cardiovascular systems should be supported appropriately. No specific antidote is known. Hemodialysis may be considered since cysteamine is poorly bound to plasma proteins." }

PROCYSBI, for oral administration, is a cystine-depleting agent that lowers the cystine content of cells in patients with nephropathic cystinosis, an inherited defect of lysosomal transport.

{ "type": "p", "children": [], "text": "PROCYSBI, for oral administration, is a cystine-depleting agent that lowers the cystine content of cells in patients with nephropathic cystinosis, an inherited defect of lysosomal transport." }

PROCYSBI contains the bitartrate salt of cysteamine. The chemical name for cysteamine bitartrate is ethanethiol, 2-amino, (2R,3R)-2,3-dihydroxybutanedioate (1:1) (salt). Cysteamine bitartrate is a highly water soluble white powder with a molecular weight of 227.24 and the molecular formula C2H7NS ∙ C4H6O6. It has the following chemical structure:

{ "type": "p", "children": [], "text": "PROCYSBI contains the bitartrate salt of cysteamine. The chemical name for cysteamine bitartrate is ethanethiol, 2-amino, (2R,3R)-2,3-dihydroxybutanedioate (1:1) (salt). Cysteamine bitartrate is a highly water soluble white powder with a molecular weight of 227.24 and the molecular formula C2H7NS ∙ C4H6O6. It has the following chemical structure:" }

Each PROCYSBI delayed-release capsule contains either 25 mg cysteamine (equivalent to 74 mg cysteamine bitartrate) or 75 mg cysteamine (equivalent to 221 mg cysteamine bitartrate).

{ "type": "p", "children": [], "text": "Each PROCYSBI delayed-release capsule contains either 25 mg cysteamine (equivalent to 74 mg cysteamine bitartrate) or 75 mg cysteamine (equivalent to 221 mg cysteamine bitartrate)." }

Each packet of PROCYSBI delayed-release oral granules contains either 75 mg cysteamine (equivalent to 221 mg cysteamine bitartrate) or 300 mg cysteamine (equivalent to 884 mg cysteamine bitartrate).

{ "type": "p", "children": [], "text": "Each packet of PROCYSBI delayed-release oral granules contains either 75 mg cysteamine (equivalent to 221 mg cysteamine bitartrate) or 300 mg cysteamine (equivalent to 884 mg cysteamine bitartrate)." }

PROCYSBI delayed release granules contain the following inactive ingredients: Eudragit® L 30 D-55 (methacrylic acid-ethyl acrylate copolymer), hypromellose, microcrystalline cellulose, purified water, sodium lauryl sulfate, talc, and triethyl citrate. Additionally the capsule shell contains the following inactive ingredients: gelatin, ink (blue and white), and titanium dioxide.

{ "type": "p", "children": [], "text": "PROCYSBI delayed release granules contain the following inactive ingredients: Eudragit® L 30 D-55 (methacrylic acid-ethyl acrylate copolymer), hypromellose, microcrystalline cellulose, purified water, sodium lauryl sulfate, talc, and triethyl citrate. Additionally the capsule shell contains the following inactive ingredients: gelatin, ink (blue and white), and titanium dioxide." }

Cysteamine is an aminothiol that participates within lysosomes in a thiol-disulfide interchange reaction converting cystine into cysteine and cysteine-cysteamine mixed disulfide, both of which can exit the lysosome in patients with cystinosis.

Normal individuals and persons heterozygous for cystinosis have WBC cystine concentrations of less than 0.2 and usually below 1 nmol ½ cystine/mg protein, respectively, when measured using the mixed leukocyte assay. Untreated patients with nephropathic cystinosis have elevations of WBC cystine concentration above 2 nmol ½ cystine/mg protein.

After the administration of a single dose of PROCYSBI, peak concentrations of cysteamine were observed at 3 hours post-dose. The nadir of WBC cystine closely followed the peak concentrations at 3.5 hours post-dose, and returned to baseline WBC concentrations at 12 hours-post dose. The cystine concentration in WBC lysate was measured with LC/MS/MS and total protein content in human WBC lysate was measured using the bicinchoninic acid (BCA) assay. A correction factor was applied to the total protein content for the difference in results from the Lowry method. The cystine concentration in nmol ½ cystine/mg protein was calculated by multiplying nmol cystine/mg protein by 2 [see Dosage and Administration (2.5)].

The pharmacokinetics of cysteamine with administration of PROCYSBI were evaluated in 43 patients age ranged from 6 to 26 years (mean age 12 years) with cystinosis and with an estimated glomerular filtration rate of greater than 30 mL/minutes/1.73 m2. Table 4 shows the mean pharmacokinetic parameters for PROCYSBI and immediate-release cysteamine bitartrate at steady state. The mean (± SD) dose for PROCYSBI was 656 ± 144 mg/m2 (given every 12 hours) and for immediate-release cysteamine bitartrate was 404 ± 88 mg/m2 (given every 6 hours).

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 4: Pharmacokinetic parameters for cysteamine at steady state* after administration of PROCYSBI or immediate-release cysteamine bitartrate </span> </caption> <col align="left" valign="middle" width="34%"/> <col align="center" valign="middle" width="33%"/> <col align="center" valign="middle" width="33%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">Immediate-release cysteamine bitartrate given every 6 hours</th><th align="center" class="Rrule" valign="top">PROCYSBI given every 12 hours</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">C<span class="Sub">max</span> (mg/L)</td><td align="center" class="Rrule">2.7 ± 1.4</td><td align="center" class="Rrule">3.6 ± 1.8</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">AUC<span class="Sub">0-6h</span> (min*mg/L)</td><td align="center" class="Rrule">351 ± 153</td><td align="center" class="Rrule">NA</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">AUC<span class="Sub">0-12h</span> (min*mg/L)</td><td align="center" class="Rrule">NA</td><td align="center" class="Rrule">726 ± 339</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">AUC<span class="Sub">inf</span> (min*mg/L)</td><td align="center" class="Rrule">380 ± 157</td><td align="center" class="Rrule">785 ± 358</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">T<span class="Sub">max</span> (min)</td><td align="center" class="Rrule">73 ± 31</td><td align="center" class="Rrule">188 ± 88</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">t½ (min)</td><td align="center" class="Rrule">90 ± 24</td><td align="center" class="Rrule">253 ± 403</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">CL/F (L/min)</td><td align="center" class="Rrule">1.4 ± 0.8</td><td align="center" class="Rrule">1.2 ± 0.8</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Vd/F (L)</td><td align="center" class="Rrule">198 ± 159</td><td align="center" class="Rrule">382 ± 404</td> </tr> </tbody> </table></div>

Absorption

The pharmacokinetics of cysteamine with administration of PROCYSBI are consistent with a delayed-release formulation; the mean Tmax for cysteamine was 188 minutes with PROCYSBI compared with 73 minutes for immediate-release cysteamine bitartrate.

The mean plasma cysteamine peak and AUC were similar when a single PROCYSBI dose of 600 mg was administered with 240 mL orange juice or with 240 mL water. The systemic exposure to cysteamine was similar when PROCYSBI was administered with orange juice as a whole capsule and sprinkled in applesauce in the fasted state. In a food effect study conducted in healthy subjects (n=20), administration of a meal 30 minutes following PROCYSBI administration (intact capsules) decreased Cmax by 34% and AUC0-t by 32% compared to administration of a meal 2 hours post-dose [see Dosage and Administration (2.6)].

Distribution

Cysteamine was moderately bound to human plasma proteins, predominantly to albumin, with mean protein binding of about 52%. Plasma protein binding was independent of concentration over the concentration range achieved clinically with the recommended doses. The volume of distribution (Vd/F) was 382 L for PROCYSBI compared with 198 L for immediate-release cysteamine bitartrate.

Elimination

After each dose of PROCYSBI the cysteamine concentration in the blood continues to decline for approximately 30 minutes and the WBC cystine concentration increases accordingly.

The apparent clearance (Cl/F) of cysteamine was similar between PROCYSBI (1.2 ± 0.8 L/min) and immediate-release cysteamine bitartrate (1.4 ± 0.8 L/min).

The half-life was 253 minutes for PROCYSBI and 90 minutes for immediate-release cysteamine bitartrate.

Specific Populations

Pediatric patients 1 year to less than 6 years of age

The pharmacokinetics of cysteamine with administration of PROCYSBI at steady state were evaluated in 11 cysteamine treatment naïve patients between the ages of 1 and 5 years of age with nephropathic cystinosis. A mean (± SD) Cmax of 1.26 ± 0.86 mg/L was reached at an average Tmax of 199 ± 138 minutes and the mean (± SD) dose was 242 ± 93 mg/m2. The mean exposure was calculated to be 206 ± 113 minutes*mg/L (AUClast) and 231 ± 123 minutes*mg/L (AUCinf). The mean CLss/F was estimated to be 0.69 ± 0.37 L/minutes with an average half-life (t½) of 270 ± 56 minutes. Overall, the pharmacokinetics in patients between the ages of 1 and 5 years of age is comparable with those in older children and adults.

Patients with Renal Impairment

The pharmacokinetics of cysteamine with administration of a single oral dose of 600 mg PROCYSBI were evaluated in non-cystinosis subjects with renal impairment and healthy subjects with normal renal function (eGFR >90 mL/min/1.73m2) matched for age, body mass index and sex.

The mean AUCinf and mean Cmax for cysteamine were 8%, and 3% lower, respectively, in subjects with mild renal impairment (eGFR 60 to 89 mL/min/1.73m2) compared to healthy subjects. In subjects with moderate renal impairment (eGFR 30 to 59 mL/min/1.73m2) and severe renal impairment (≤29 mL/min/1.73m2), the mean AUCinf was 49% and 35% higher and the mean Cmax was 27% and 11% higher, respectively compared to healthy subjects. The mean t½ was 7 hours, 8.3 hours, and 8.8 hours in subjects with mild, moderate, and severe renal impairment, respectively and ranged from 6.6 to 7.5 hours in healthy subjects. The mean CL/F was 1.57, 1.08, and 1.09 L/min in mild, moderate, and severe renal impairment subjects compared to 1.40 to 1.60 L/min in healthy subjects.

In subjects with end-stage renal disease receiving 4 hours of hemodialysis, the geometric mean Cmax and AUCinf of cysteamine was 60% higher when PROCYSBI was administered 3 hours before hemodialysis, and 22% higher when administered 1 hour after completion of hemodialysis compared to healthy subjects. Approximately 4.3% (25.6 mg) of the 600 mg PROCYSBI dose was removed from the body with hemodialysis. The apparent clearance of cysteamine in subjects who received PROCYSBI before hemodialysis was approximately 65 mL/min.

The increased exposure to cysteamine in patients with renal impairment compared to healthy subjects is not considered to be clinically meaningful.

Drug Interaction Studies

An in vitro study indicates cysteamine bitartrate is not an inhibitor of CYP enzymes (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4). The potential for cysteamine to affect the pharmacokinetics of other drugs via these enzymes is low.

Omeprazole

The effect of concomitant omeprazole on the pharmacokinetics of cysteamine was evaluated following co-administration of single PROCYSBI dose of 600 mg with 20 mg of omeprazole in comparison to administration of PROCYSBI alone in healthy subjects in two separate studies. In both studies omeprazole was dosed once daily for 5 days before co-administration with PROCYSBI and single dose PROCYSBI was given either with 240 mL orange juice in one study or with 240 mL water in another study. The pharmacokinetic parameters of cysteamine were not significantly different when PROCYSBI was administered with omeprazole compared to when PROCYSBI was administered alone, regardless whether PROCYSI was administered with orange juice or water [see Dosage and Administration (2.6), Drug Interactions (7.1)].

Cysteamine has not been tested for its carcinogenic potential in long-term animal studies.

PROCYSBI was not mutagenic in the Ames test. It produced a negative response in an in-vitro sister chromatid exchange assay in human lymphocytes, but a positive response in a similar assay in hamster ovarian cells.

Repeat breeding reproduction studies were conducted in male and female rats. Cysteamine was found to have no effect on fertility and reproductive performance at an oral dose of 75 mg/kg per day (450 mg/m2 per day, 0.4 times the recommended human dose based on body surface area). At an oral dose of 375 mg/kg per day (2250 mg/m2 per day, 1.7 times the recommended human maintenance dose based on body surface area), it reduced the fertility of the adult rats and the survival of their offspring.

Efficacy of immediate-release cysteamine bitartrate was demonstrated in open-label clinical trials of cysteamine hydrochloride and phosphocysteamine.

An open-label clinical trial of cysteamine hydrochloride was conducted in 94 pediatric patients (mainly from the United States) with nephropathic cystinosis. Patients were treated with increasing doses of cysteamine hydrochloride (mean dose 54 mg/kg per day) to attain WBC cystine concentrations of less than 2 nmol ½ cystine/mg protein 5 to 6 hours post-dose. The clinical outcomes were compared with a historical control group of 17 pediatric patients who had been in the placebo group of a randomized placebo-controlled trial of ascorbic acid. Cysteamine-treated patients had been diagnosed at a mean age of 22 months and had a mean age of 46 months old at study entry; placebo patients had been diagnosed at about 29 months and had a mean age of about 52 months old at trial entry. The principal measures of effectiveness were serum creatinine and calculated creatinine clearance and growth (height).

The average median WBC cystine concentration during treatment was 1.7 ± 0.2 nmol ½ cystine/mg protein. There were 70 cysteamine-treated patients with a baseline serum creatinine of less than 2 mg/dL who were followed for at least 1 year, and 17 placebo patients. Twelve of the 94 cysteamine-treated patients required early dialysis or renal transplant. Median follow-up of cysteamine patients was over 32 months, and 20% were followed more than 5 years. Median follow-up of the placebo group was 20 months; only 1 patient was followed more than 24 months. Glomerular function among cysteamine-treated patients was maintained over time. Placebo-treated patients experienced a gradual rise in serum creatinine. Renal tubular function was not affected by treatment.

Calculated creatinine clearances were evaluated for two groups of pediatric patients, one with poor WBC cystine depletion (defined as median WBC cystine concentrations greater than 3 nmol ½ cystine/mg protein or WBC cystine concentrations not measured at least 2 times per year) and one with good WBC cystine depletion. The final mean creatinine clearance of the good depletion group was 20.8 mL/min/1.73 m2 greater than the mean for the poor-depletion group.

Height-for-age measurements of treated patients were compared with height-for-age measurements of 143 patients initially screened for inclusion in the trial. Patients on treatment maintained growth (i.e., did not show increasing growth failure compared with normal scales) although growth velocity did not increase enough to allow patients to catch up to age norms for height.

In another open-label clinical trial, 46 patients who had completed the clinical trial of cysteamine hydrochloride (averaging 6.5 years of treatment) and 93 treatment naïve patients were treated with either cysteamine hydrochloride or phosphocysteamine (patient's choice). Patients had cystinosis diagnosed by elevated WBC cystine (mean 3.63 nmol ½ cystine/mg). Newly enrolled patients and the 46 continuing patients were required to have serum creatinine less than 3 mg/dL and 4 mg/dL, respectively. Patients were randomized to doses of 1.3 or 1.95 grams/m2 per day and stratified according to whether the serum creatinine was above 1.2 mg/dL or not. Doses could be raised if WBC cystine concentrations were approximately 2 nmol ½ cystine/mg protein and lowered due to intolerance. The mean age of the newly enrolled patients was about 49 months for the cysteamine group and about 34 months for the phosphocysteamine group. The mean age of the patients in the long-term follow-up group was about 9 years.

Mean doses were 1.27 grams/m2 per day and 1.87 grams/m2 per day in the two groups and WBC cystine concentrations averaged 1.72 ± 1.65 nmol ½ cystine/mg protein and 1.86 ± 0.92 nmol ½ cystine/mg protein in the 1.3 grams/m2 per day and 1.95 grams/m2 per day in the two groups, respectively. In new patients, serum creatinine was essentially unchanged over the period of follow-up (about half of the patients were followed for 24 months) and phosphocysteamine and cysteamine hydrochloride had similar effects. The long-term follow-up group also had essentially no change in renal function (almost 80% were followed at least 2 years). In four studies of patients with untreated cystinosis, renal death (need for transplant or dialysis) occurred at median age of less than 10 years. Both new patients and patients in the long-term follow-up group maintained height (although they did not catch up from baseline). There was no apparent difference in height maintenance between the two doses.

Multi-Center, Open-Label, Randomized Clinical Trial in Patients Receiving Immediate-Release Cysteamine Bitartrate

A clinical trial comparing immediate-release cysteamine bitartrate and PROCYSBI was conducted in 43 (40 pediatric and 3 adult) patients with nephropathic cystinosis (Study RP103-03; NCT01000961). Patient age ranged from 6 to 26 years (mean age 12 years) and 56% were male. Patients with WBC cystine concentrations greater than 2 nmol ½ cystine/mg protein (measured using the mixed leukocyte assay) and estimated glomerular filtration rate (eGFR corrected for body surface area) less than 30 mL/minute/1.73 m2 at the time of screening were excluded from the trial. Prior to randomization, patients were to be on a stable dose of immediate-release cysteamine bitartrate administered every six hours. PROCYSBI dose adjustments of up to approximately 100% of the total daily dose of immediate-release cysteamine bitartrate were allowed by trial criteria. The average total daily dose of PROCYSBI for patients completing the clinical trial was approximately 91% of the average total daily dose of immediate-release cysteamine bitartrate for patients at trial entry.

This trial demonstrated that at steady-state, PROCYSBI administered every 12 hours was non-inferior to immediate-release cysteamine bitartrate administered every 6 hours with respect to the depletion of WBC cystine concentrations (Table 5). Using a linear mixed effects statistical analysis model, the least-square-mean value of WBC cystine was 0.52 ± 0.06 nmol ½ cystine/mg protein after 12 hours under PROCYSBI and 0.44 ± 0.06 nmol ½ cystine/mg protein after 6 hours under immediate-release cysteamine; a difference of 0.08 ± 0.03 nmol ½ cystine/mg protein (95.8% Confidence Interval = 0.01 to 0.15).

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 5: Comparison of WBC cystine concentrations in open-label, randomized, cross-over clinical trial participants, who were on a stable dose of immediate-release cysteamine prior to randomization, with WBC cystine less than 2 nmol ½ cystine/mg protein throughout the trial<a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a></span> </caption> <col align="center" valign="middle" width="46%"/> <col align="center" valign="middle" width="27%"/> <col align="center" valign="middle" width="27%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule"></th><th align="center" class="Rrule" valign="middle">Immediate-release cysteamine bitartrate</th><th align="center" class="Rrule" valign="middle">PROCYSBI</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>Per–Protocol (PP) Population (N=39)</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">WBC cystine concentration in nmol ½ cystine/mg protein<br/> (LS Mean ± SE)</td><td align="center" class="Rrule">0.44 ± 0.06</td><td align="center" class="Rrule">0.52 ± 0.06</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">Difference in Treatment effect<br/>(LS mean ± SE)<br/> [95.8% CI; p-value]</td><td align="center" class="Rrule" colspan="2">0.08 ± 0.03<br/> [0.01 to 0.15; &lt;0.0001]</td> </tr> </tbody> </table></div>

Multi-Center, Single-Arm, Open-Label, Long-Term Extension Clinical Trial of PROCYSBI

Forty of the 41 patients completing the randomized trial continued treatment with PROCYSBI in an open-label extension trial, for a total treatment duration ranging from 1 month to 6.7 years in the study (Study RP103-03-04; NCT01197378). Thirty-six of the 40 patients continued treatment with PROCYSBI for at least 24 months and 20 patients continued treatment for longer than 60 months in the extension trial, and maintained their mean WBC cystine concentrations below 1 nmol ½ cystine/mg protein (measured using the mixed leukocyte assay) over this time period.

Thirteen pediatric patients, aged 2 to 6 years, were also enrolled in the extension trial and treated with PROCYSBI. All of them were on treatment with immediate-release cysteamine bitartrate at the time of enrollment. All 13 patients received at least 18 months of treatment with PROCYSBI, and their mean ± SD WBC cystine concentration (measured using the mixed leukocyte assay) decreased from 1.41 ± 1.03 nmol ½ cystine/mg protein at baseline to 1.22 ± 1.40 nmol ½ cystine/mg protein after 18 months of treatment. Seven of these pediatric patients were able to achieve a WBC cystine concentration (measured using the mixed leukocyte assay) of less than 1.0 nmol ½ cystine/mg protein after 18 months of treatment; their mean ± SD dose of PROCYSBI increased from 0.81 ± 0.25 grams/m2 per day at baseline to 0.90 ± 0.25 grams/m2 per day after 18 months of treatment.

During extended treatment with PROCYSBI, mean estimates of renal function, as measured by the eGFR, were maintained.

Multi-Center, Open-Label, Clinical Trial in Cysteamine Naïve Patients Less than 6 Years of Age

A clinical trial of PROCYSBI (Study RP103-08; NCT01744782) was conducted in 17 patients with a documented diagnosis of nephropathic cystinosis who were naïve to cysteamine treatment (15 patients between the ages of 1 and 5 years, one 9-year old and one 22-year old). The PROCYSBI starting dose was ¼ the maintenance dose of 1 gram/m2/day (actual dosing was based on weight bands using the available capsule strengths, as shown in (Table 1) and the dosage was gradually increased by 10% every 2 weeks. Dosage adjustment was allowed throughout the trial and was based on subject-specific factors (e.g., weight, tolerability) and WBC cystine concentrations. WBC cystine concentrations were obtained 30 minutes after the morning dose collected bi-monthly until the patient's WBC cystine concentration (using the mixed leukocyte assay) was < 1 nmol ½ cystine/mg protein. Treatment duration was at least 12 months.

Fourteen of the 15 patients between 1 year and less than 6 years of age completed 12 months of treatment, and 10 patients completed 18 months of treatment. Thirteen of the 14 patients achieved their highest total daily dosage of PROCYSBI following the 9-month visit (9-month visit for 8 subjects, 12-month visit for 4 subjects, and 18-month visit for 1 subject).

Some patients did not have WBC cystine samples collected at each visit or results were not reportable due to laboratory errors. Thus, the numbers of patients with available WBC cystine data varied across the time points analyzed. In patients with missing samples, dose escalation was continued if the patient's last reported WBC cystine concentration was > 1 nmol ½ cystine/mg protein.

In patients 1 year to less than 6 years, the mean (±SD) WBC cystine concentration on Day 1, 30 minutes following the first dose, was 3.17±2.95 nmol ½ cystine/mg protein (n=15 patients). At 12 months (13 patients with samples), the mean WBC cystine concentration was 0.80 ± 0.60 nmol ½ cystine/mg protein at 30 minutes post dose. At 18 months (9 patients with samples) the mean WBC cystine concentration was 0.74 ± 0.64 nmol ½ cystine/mg protein at 30 minutes post dose.

In patients 1 year to less than 6 years, the mean (±SD) weight percentiles at Day 1 (n=14), 12 months (n=13) and 18 months (n=10) were 3.5 ± 11.1, 11.9 ± 18.3, and 30.1 ± 28.2, respectively, and patient weight z-scores were -4.0 ± 2.1, -2.2 ± 1.7, and -1.3 ± 2.0, respectively. In the same patients, similar trends were observed for height.

How Supplied

PROCYSBI (cysteamine bitartrate) delayed-release capsules

PROCYSBI (cysteamine bitartrate) delayed-release oral granules

Storage and Handling

Instructions for the Patient

Ehlers-Danlos-like Syndrome

Advise patients and caregivers that PROCYSBI may cause abnormalities of the skin, bones, and joints. Advise patients to report any skin changes or problems with their bones or joints to their physician [see Warnings and Precautions (5.1)].

Skin Rash

Advise patients and caregivers to contact their physician immediately if they experience a skin rash [see Warnings and Precautions (5.2)].

Gastrointestinal Ulcers and Bleeding

Advise patients and caregivers that PROCYSBI may cause ulcers and bleeding. Advise patients to contact their physician immediately if they experience stomach pain, nausea, vomiting, loss of appetite, or are vomiting blood [see Warnings and Precautions (5.3)].

Fibrosing Colonopathy

Advise patients and caregivers that fibrosing colonopathy has been reported with PROCYSBI. Advise patients to contact their physician immediately if they experience severe, persistent and/or worsening stomach pain, vomiting, bloody or persistent diarrhea, or inability to control bowel movements [see Warnings and Precautions (5.4)].

Central Nervous System Symptoms

Advise patients and caregivers that PROCYSBI may impair their ability to perform tasks such as driving or operating machinery. Advise patients to contact their physician immediately if they experience seizures, lethargy, somnolence, depression, and encephalopathy [see Warnings and Precautions (5.5)].

Benign Intracranial Hypertension

Advise patients and caregivers that PROCYSBI may cause benign intracranial hypertension. Advise patients to contact their physician immediately if they experience headache, tinnitus, dizziness, nausea, double vision, blurry vision, loss of vision, or eye pain [see Warnings and Precautions (5.7)].

Use by Pregnant Women

Advise patients and to contact their physician immediately if they suspect they may be pregnant. Discuss with the patient the individual risks and benefits of continuing PROCYSBI during pregnancy [see Use in Specific Populations (8.1)].

Breastfeeding

Advise patients that breastfeeding is not recommended while taking PROCYSBI [see Use in Specific Populations (8.2)].

Laboratory Monitoring

Discuss with the patient and caregivers the importance of required laboratory testing to determine the correct dose of PROCYSBI [see Dosage and Administration (2.5)].

Administration

Storage

Advise patients and caregivers to keep PROCYSBI in a dry place. Protect from moisture. For bottles, keep PROCYSBI delayed-release capsules in the original bottle. Do not remove the dessicant or oxygen absorber from the bottle. Do not store PROCYSBI delayed-release oral granules in opened packets [see How Supplied/Storage and Handling (16)].

AMGEN Horizon Therapeutics USA, Inc.Deerfield, IL 60015

{ "type": "p", "children": [], "text": "\nAMGEN\nHorizon Therapeutics USA, Inc.Deerfield, IL 60015" }

© 2025 Amgen Inc. All rights reserved.

{ "type": "p", "children": [], "text": "© 2025 Amgen Inc. All rights reserved." }

1XXXXXX-V3

{ "type": "p", "children": [], "text": "\n1XXXXXX-V3\n" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="bottom" width="30%"/> <col align="left" valign="bottom" width="30%"/> <col align="left" valign="bottom" width="40%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule" colspan="3">PATIENT INFORMATION<br/>PROCYSBI<span class="Sup">®</span> (Pro-CIS-bee)<br/>(cysteamine bitartrate)<br/>delayed-release capsules and delayed-release oral granules</th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="2" valign="top">This Patient Information has been approved by the U.S. Food and Drug Administration. </td><td align="right" valign="top">Revised: 12/2024     </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What is PROCYSBI?</span> <br/>PROCYSBI is a prescription medicine used to treat nephropathic cystinosis in adults and children 1 year of age and older.<br/>It is not known if PROCYSBI is safe and effective in children under 1 year of age.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Do not</span> take PROCYSBI if you are allergic to penicillamine or cysteamine.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Before taking PROCYSBI, tell your doctor about all of your medical conditions, including if you</span>:<ul class="Disc"> <li>drink alcohol.</li> <li>have a skin rash or bone problems.</li> <li>have or have had stomach or bowel (intestinal) problems including ulcers or bleeding.</li> <li>have a history of seizures, lack of energy, unusual sleepiness, depression, or changes in your ability to think clearly.</li> <li>have liver or blood problems.</li> <li>are pregnant or plan to become pregnant. It is not known if PROCYSBI will harm your unborn baby. Tell your doctor right away if you think that you are pregnant. Talk with your doctor about the benefits and risks of taking PROCYSBI during pregnancy.</li> <li>are breastfeeding or plan to breastfeed. You should not breastfeed during treatment with PROCYSBI. Talk with your doctor about the best way to feed your baby if you take PROCYSBI.</li> </ul> <span class="Bold">Tell your doctor about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements.<br/>Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">How should I take PROCYSBI?</span> <ul class="Disc"> <li>Read the "<span class="Bold">Instructions for Use</span>" that comes with PROCYSBI for information about the right way to prepare and take PROCYSBI.</li> <li>Take PROCYSBI exactly as your doctor tells you to.</li> <li>Your doctor may start you on a low dose of PROCYSBI and slowly increase your dose to help avoid side effects, especially if you have not taken a medicine that contains cysteamine bitartrate before.</li> <li>Do not change your dose of PROCYSBI unless your doctor tells you to.</li> <li>PROCYSBI is taken 2 times each day, every 12 hours.</li> <li>Take PROCYSBI the same way each time, either without eating or with a small amount of food, as follows:<ul class="Circle"> <li> <span class="Bold">If you take PROCYSBI without eating,</span> do not eat for at least 2 hours before taking PROCYSBI and at least 30 minutes after taking PROCYSBI.</li> <li> <span class="Bold">If you are not able to take PROCYSBI without eating,</span> you can eat a small amount of food (½ cup) within 1 hour before you take PROCYSBI through 1 hour after you take it.</li> <li>Avoid eating foods that are high in fat close to the time that you will take a dose of PROCYSBI.</li> </ul> </li> <li>Talk to your doctor or pharmacist if you have questions about how to take PROCYSBI.</li> <li> <span class="Bold">PROCYSBI is available as capsules in a bottle and oral granules in packets</span>.<br/> <span class="Bold">Capsules</span>: <ul class="Circle"> <li>Swallow PROCYSBI capsules whole. Do not crush or chew capsules or capsule contents.</li> <li>Take the PROCYSBI capsule whole with fruit juice (except for grapefruit juice) or water.</li> <li>If PROSCYBI capsules cannot be swallowed whole, the capsule may be opened and the contents sprinkled on and mixed in applesauce, berry jelly or fruit juice (except grapefruit juice) and taken by mouth.</li> <li>Read the "<span class="Bold">Instructions for Use</span>" if you have a gastrostomy tube (G-tube).</li> </ul> <span class="Bold">Granules</span>: <ul class="Circle"> <li>Sprinkle and mix PROCYSBI oral granules on applesauce, berry jelly or fruit juice (except grapefruit juice) and take by mouth. Do not crush or chew oral granules.</li> <li>Read the "<span class="Bold">Instructions for Use</span>" if you have a gastrostomy tube (G-tube).</li> </ul> </li> <li>Take PROCYSBI at least 1 hour before or 1 hour after you take medicines that contain bicarbonate or carbonate.</li> <li>If you miss a dose, take it as soon as possible, up to 8 hours after the scheduled time of the missed dose. If it is less than 4 hours of the time the next dose is due, skip the missed dose. Take the next dose at your regularly scheduled time. Do not take 2 doses at one time to make up for a missed dose.</li> <li>If you take too much PROCYSBI, call your doctor or go to the nearest hospital emergency room right away.</li> <li>Your doctor should do blood tests to measure the amount of cystine inside your white blood cells or to measure the amount of PROCYSBI in your blood before you start taking it and regularly during treatment with PROCYSBI. This will help your doctor to prescribe the dose of PROCYSBI that is right for you.</li> <li>Take supplements if prescribed by your doctor, such as salt or mineral replacement supplements, vitamin D, or thyroid hormone.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What should I avoid while taking PROCYSBI?</span> <ul class="Disc"> <li>Do not drive or operate machinery until you know how PROCYSBI affects you. PROCYSBI can make you sleepy or less alert than normal.</li> <li>Do not drink alcohol if you take PROCYSBI. Drinking alcohol while taking PROCYSBI may change how PROCYSBI works and may cause an increase in the amount of PROCYSBI in your blood that may cause serious side effects.</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What are the possible side effects of PROCYSBI?</span> <br/> <span class="Bold">PROCYSBI can cause serious side effects, including:</span> <ul class="Disc"> <li> <span class="Bold">Skin, bone, and joint problems.</span> People treated with high doses of cysteamine bitartrate may develop abnormal changes of their skin and bones. These changes may include stretch marks, bone injuries (such as fractures), bone deformities, and joint problems. Check your skin while taking PROCYSBI. Tell your doctor if you notice any skin changes or problems with your bones or joints. Your doctor will check you for these problems.</li> <li> <span class="Bold">Skin rash.</span> Skin rash is common with cysteamine bitartrate and may sometimes be severe. <span class="Bold">Tell your doctor right away if you get a skin rash.</span> Your dose of PROCYSBI may need to be decreased until the rash goes away. If the rash is severe, your doctor may tell you to stop taking PROCYSBI.</li> <li> <span class="Bold">Stomach and bowel (intestinal) problems.</span> Some people who take other medicines that contain cysteamine bitartrate may develop ulcers and bleeding in their stomach or bowel. People treated with PROCYSBI may also develop abnormal swelling and narrowing of the large bowel which must be treated right away. <span class="Bold">Tell your doctor right away</span> if you get abdominal pain, nausea, vomiting, loss of appetite, weight loss, bloody or persistent diarrhea, or are vomiting blood or have bowel moments that you cannot control.</li> <li> <span class="Bold">Central nervous system symptoms.</span> Some people who take other medicines that contain cysteamine bitartrate develop seizures, depression, and become very sleepy. The medicine may affect how your brain is working (encephalopathy). <span class="Bold">Tell your doctor right away</span> if you develop any of these symptoms.</li> <li> <span class="Bold">Low white blood cell count and certain abnormal liver function blood tests.</span> Your doctor should check you for these problems.</li> <li> <span class="Bold">Benign intracranial hypertension</span> (pseudotumor cerebri) has happened in some people who take immediate-release cysteamine bitartrate. This is a condition where there is high pressure in the fluid around the brain. Your doctor should do eye examinations to find and treat this problem early.<br/> <span class="Bold">Tell your doctor right away if you develop any of the following symptoms while taking PROCYSBI:</span> headache, buzzing or "whooshing" sound in the ear, dizziness, nausea, double vision, blurry vision, loss of vision, pain behind the eye, or pain with eye movement.</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">The most common side effects with PROCYSBI include:</span></td> </tr> <tr> <td align="left" class="Lrule" valign="top"> <dl> <dt> </dt> <dd> <ul class="Disc"> <li>vomiting</li> <li>pink eye</li> <li>tiredness</li> <li>problems with body salts or electrolytes</li> </ul> </dd> </dl> </td><td align="left" valign="top"> <ul class="Disc"> <li>nausea</li> <li>diarrhea</li> <li>flu</li> <li>infection of ear, nose or throat</li> </ul> </td><td align="left" class="Rrule" valign="top"> <ul class="Disc"> <li>stomach (abdominal) pain</li> <li>cold</li> <li>headache</li> <li>joint pain</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3">These are not all the possible side effects of PROCYSBI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">General information about the safe and effective use of PROCYSBI.</span> <br/>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use PROCYSBI for a condition for which it was not prescribed. Do not give PROCYSBI to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about PROCYSBI that is written for health professionals. </td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What are the ingredients in PROCYSBI?</span> <br/> <span class="Bold">Active ingredients</span>: cysteamine bitartrate<br/> <span class="Bold">Inactive ingredients</span>: Eudragit<span class="Sup">®</span> L 30 D-55, hypromellose, microcrystalline cellulose, purified water, sodium lauryl sulfate, talc, and triethyl citrate. Capsule shell ingredients: gelatin, titanium dioxide, blue ink and white ink.<br/>Horizon Therapeutics USA, Inc., Deerfield, IL 60015<br/>For more information go to www.PROCYSBI.com or call 1 800 77 AMGEN (1 800 772 6436)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"30%\"/>\n<col align=\"left\" valign=\"bottom\" width=\"30%\"/>\n<col align=\"left\" valign=\"bottom\" width=\"40%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"center\" class=\"Lrule Rrule\" colspan=\"3\">PATIENT INFORMATION<br/>PROCYSBI<span class=\"Sup\">®</span> (Pro-CIS-bee)<br/>(cysteamine bitartrate)<br/>delayed-release capsules and delayed-release oral granules</th>\n</tr>\n</thead>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"2\" valign=\"top\">This Patient Information has been approved by the U.S. Food and Drug Administration. </td><td align=\"right\" valign=\"top\">Revised: 12/2024     </td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What is PROCYSBI?</span>\n<br/>PROCYSBI is a prescription medicine used to treat nephropathic cystinosis in adults and children 1 year of age and older.<br/>It is not known if PROCYSBI is safe and effective in children under 1 year of age.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Do not</span> take PROCYSBI if you are allergic to penicillamine or cysteamine.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Before taking PROCYSBI, tell your doctor about all of your medical conditions, including if you</span>:<ul class=\"Disc\">\n<li>drink alcohol.</li>\n<li>have a skin rash or bone problems.</li>\n<li>have or have had stomach or bowel (intestinal) problems including ulcers or bleeding.</li>\n<li>have a history of seizures, lack of energy, unusual sleepiness, depression, or changes in your ability to think clearly.</li>\n<li>have liver or blood problems.</li>\n<li>are pregnant or plan to become pregnant. It is not known if PROCYSBI will harm your unborn baby. Tell your doctor right away if you think that you are pregnant. Talk with your doctor about the benefits and risks of taking PROCYSBI during pregnancy.</li>\n<li>are breastfeeding or plan to breastfeed. You should not breastfeed during treatment with PROCYSBI. Talk with your doctor about the best way to feed your baby if you take PROCYSBI.</li>\n</ul>\n<span class=\"Bold\">Tell your doctor about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements.<br/>Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">How should I take PROCYSBI?</span>\n<ul class=\"Disc\">\n<li>Read the \"<span class=\"Bold\">Instructions for Use</span>\" that comes with PROCYSBI for information about the right way to prepare and take PROCYSBI.</li>\n<li>Take PROCYSBI exactly as your doctor tells you to.</li>\n<li>Your doctor may start you on a low dose of PROCYSBI and slowly increase your dose to help avoid side effects, especially if you have not taken a medicine that contains cysteamine bitartrate before.</li>\n<li>Do not change your dose of PROCYSBI unless your doctor tells you to.</li>\n<li>PROCYSBI is taken 2 times each day, every 12 hours.</li>\n<li>Take PROCYSBI the same way each time, either without eating or with a small amount of food, as follows:<ul class=\"Circle\">\n<li>\n<span class=\"Bold\">If you take PROCYSBI without eating,</span> do not eat for at least 2 hours before taking PROCYSBI and at least 30 minutes after taking PROCYSBI.</li>\n<li>\n<span class=\"Bold\">If you are not able to take PROCYSBI without eating,</span> you can eat a small amount of food (½ cup) within 1 hour before you take PROCYSBI through 1 hour after you take it.</li>\n<li>Avoid eating foods that are high in fat close to the time that you will take a dose of PROCYSBI.</li>\n</ul>\n</li>\n<li>Talk to your doctor or pharmacist if you have questions about how to take PROCYSBI.</li>\n<li>\n<span class=\"Bold\">PROCYSBI is available as capsules in a bottle and oral granules in packets</span>.<br/>\n<span class=\"Bold\">Capsules</span>: \t\t\t\t\t\t\t\t\t\t\t<ul class=\"Circle\">\n<li>Swallow PROCYSBI capsules whole. Do not crush or chew capsules or capsule contents.</li>\n<li>Take the PROCYSBI capsule whole with fruit juice (except for grapefruit juice) or water.</li>\n<li>If PROSCYBI capsules cannot be swallowed whole, the capsule may be opened and the contents sprinkled on and mixed in applesauce, berry jelly or fruit juice (except grapefruit juice) and taken by mouth.</li>\n<li>Read the \"<span class=\"Bold\">Instructions for Use</span>\" if you have a gastrostomy tube (G-tube).</li>\n</ul>\n<span class=\"Bold\">Granules</span>: \t\t\t\t\t\t\t\t\t\t\t<ul class=\"Circle\">\n<li>Sprinkle and mix PROCYSBI oral granules on applesauce, berry jelly or fruit juice (except grapefruit juice) and take by mouth. Do not crush or chew oral granules.</li>\n<li>Read the \"<span class=\"Bold\">Instructions for Use</span>\" if you have a gastrostomy tube (G-tube).</li>\n</ul>\n</li>\n<li>Take PROCYSBI at least 1 hour before or 1 hour after you take medicines that contain bicarbonate or carbonate.</li>\n<li>If you miss a dose, take it as soon as possible, up to 8 hours after the scheduled time of the missed dose. If it is less than 4 hours of the time the next dose is due, skip the missed dose. Take the next dose at your regularly scheduled time. Do not take 2 doses at one time to make up for a missed dose.</li>\n<li>If you take too much PROCYSBI, call your doctor or go to the nearest hospital emergency room right away.</li>\n<li>Your doctor should do blood tests to measure the amount of cystine inside your white blood cells or to measure the amount of PROCYSBI in your blood before you start taking it and regularly during treatment with PROCYSBI. This will help your doctor to prescribe the dose of PROCYSBI that is right for you.</li>\n<li>Take supplements if prescribed by your doctor, such as salt or mineral replacement supplements, vitamin D, or thyroid hormone.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What should I avoid while taking PROCYSBI?</span>\n<ul class=\"Disc\">\n<li>Do not drive or operate machinery until you know how PROCYSBI affects you. PROCYSBI can make you sleepy or less alert than normal.</li>\n<li>Do not drink alcohol if you take PROCYSBI. Drinking alcohol while taking PROCYSBI may change how PROCYSBI works and may cause an increase in the amount of PROCYSBI in your blood that may cause serious side effects.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What are the possible side effects of PROCYSBI?</span>\n<br/>\n<span class=\"Bold\">PROCYSBI can cause serious side effects, including:</span>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Skin, bone, and joint problems.</span> People treated with high doses of cysteamine bitartrate may develop abnormal changes of their skin and bones. These changes may include stretch marks, bone injuries (such as fractures), bone deformities, and joint problems. Check your skin while taking PROCYSBI. Tell your doctor if you notice any skin changes or problems with your bones or joints. Your doctor will check you for these problems.</li>\n<li>\n<span class=\"Bold\">Skin rash.</span> Skin rash is common with cysteamine bitartrate and may sometimes be severe. <span class=\"Bold\">Tell your doctor right away if you get a skin rash.</span> Your dose of PROCYSBI may need to be decreased until the rash goes away. If the rash is severe, your doctor may tell you to stop taking PROCYSBI.</li>\n<li>\n<span class=\"Bold\">Stomach and bowel (intestinal) problems.</span> Some people who take other medicines that contain cysteamine bitartrate may develop ulcers and bleeding in their stomach or bowel. People treated with PROCYSBI may also develop abnormal swelling and narrowing of the large bowel which must be treated right away. <span class=\"Bold\">Tell your doctor right away</span> if you get abdominal pain, nausea, vomiting, loss of appetite, weight loss, bloody or persistent diarrhea, or are vomiting blood or have bowel moments that you cannot control.</li>\n<li>\n<span class=\"Bold\">Central nervous system symptoms.</span> Some people who take other medicines that contain cysteamine bitartrate develop seizures, depression, and become very sleepy. The medicine may affect how your brain is working (encephalopathy). <span class=\"Bold\">Tell your doctor right away</span> if you develop any of these symptoms.</li>\n<li>\n<span class=\"Bold\">Low white blood cell count and certain abnormal liver function blood tests.</span> Your doctor should check you for these problems.</li>\n<li>\n<span class=\"Bold\">Benign intracranial hypertension</span> (pseudotumor cerebri) has happened in some people who take immediate-release cysteamine bitartrate. This is a condition where there is high pressure in the fluid around the brain. Your doctor should do eye examinations to find and treat this problem early.<br/>\n<span class=\"Bold\">Tell your doctor right away if you develop any of the following symptoms while taking PROCYSBI:</span> headache, buzzing or \"whooshing\" sound in the ear, dizziness, nausea, double vision, blurry vision, loss of vision, pain behind the eye, or pain with eye movement.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">The most common side effects with PROCYSBI include:</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\">\n<dl>\n<dt> </dt>\n<dd>\n<ul class=\"Disc\">\n<li>vomiting</li>\n<li>pink eye</li>\n<li>tiredness</li>\n<li>problems with body salts or electrolytes</li>\n</ul>\n</dd>\n</dl>\n</td><td align=\"left\" valign=\"top\">\n<ul class=\"Disc\">\n<li>nausea</li>\n<li>diarrhea</li>\n<li>flu</li>\n<li>infection of ear, nose or throat</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" valign=\"top\">\n<ul class=\"Disc\">\n<li>stomach (abdominal) pain</li>\n<li>cold</li>\n<li>headache</li>\n<li>joint pain</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\">These are not all the possible side effects of PROCYSBI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">General information about the safe and effective use of PROCYSBI.</span>\n<br/>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use PROCYSBI for a condition for which it was not prescribed. Do not give PROCYSBI to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about PROCYSBI that is written for health professionals. \t\t\t\t\t\t\t\t\t</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What are the ingredients in PROCYSBI?</span>\n<br/>\n<span class=\"Bold\">Active ingredients</span>: cysteamine bitartrate<br/>\n<span class=\"Bold\">Inactive ingredients</span>: Eudragit<span class=\"Sup\">®</span> L 30 D-55, hypromellose, microcrystalline cellulose, purified water, sodium lauryl sulfate, talc, and triethyl citrate. Capsule shell ingredients: gelatin, titanium dioxide, blue ink and white ink.<br/>Horizon Therapeutics USA, Inc., Deerfield, IL 60015<br/>For more information go to www.PROCYSBI.com or call 1 800 77 AMGEN (1 800 772 6436)</td>\n</tr>\n</tbody>\n</table></div>" }

PROCYSBI is available as:

{ "type": "p", "children": [], "text": "\nPROCYSBI is available as:" }

{ "type": "ul", "children": [ "Capsules in bottles (see \"Taking PROCYSBI Capsules\")", "Oral granules in packets (see \"Taking PROCYSBI Oral Granules\")" ], "text": "" }

Your doctor will tell you the number of capsules or packets of oral granules you need to take for each dose. If you have any questions, talk to your doctor.

{ "type": "p", "children": [], "text": "Your doctor will tell you the number of capsules or packets of oral granules you need to take for each dose. If you have any questions, talk to your doctor." }

Taking PROCYSBI capsules

{ "type": "p", "children": [], "text": "\nTaking PROCYSBI capsules\n" }

PROCYSBI capsules should be swallowed whole with fruit juice (except grapefruit juice) or water. If you cannot swallow the capsule whole, you can open each capsule and take the capsule contents with certain foods and juices, or the capsule contents can be given through a gastrostomy tube (G-tube).

{ "type": "p", "children": [], "text": "PROCYSBI capsules should be swallowed whole with fruit juice (except grapefruit juice) or water. If you cannot swallow the capsule whole, you can open each capsule and take the capsule contents with certain foods and juices, or the capsule contents can be given through a gastrostomy tube (G-tube)." }

Opening PROCYSBI capsules:

{ "type": "p", "children": [], "text": "\nOpening PROCYSBI capsules:\n" }

{ "type": "ul", "children": [ "Do not pinch the PROCYSBI capsule in the center.", "Do not crush or chew the PROCYSBI capsule.", "Use both hands to open the PROCYSBI capsule.", "Hold each end of the PROCYSBI capsule with your thumb and index (pointer) fingers and gently twist the two ends in opposite directions to open." ], "text": "" }

Taking PROCYSBI with applesauce or berry jelly:

{ "type": "p", "children": [], "text": "\nTaking PROCYSBI with applesauce or berry jelly:\n" }

Do not take PROCYSBI with any food other than applesauce or berry jelly.

{ "type": "p", "children": [], "text": "\nDo not take PROCYSBI with any food other than applesauce or berry jelly.\n" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="top" width="8%"/> <col align="left" valign="top" width="92%"/> <tbody class="Headless"> <tr> <td align="left">Step 1<span class="Bold">:</span></td><td align="left">Place about ½ cup (4 ounces) of applesauce or berry jelly into a clean container. If needed, use a smaller amount you can finish in one feeding. Do not use any other food.</td> </tr> <tr> <td align="left">Step 2:</td><td align="left">Open the PROCYSBI capsule. See "<span class="Bold"><a href="#openCaps">Opening PROCYSBI capsules</a></span>" above. You may need to use more than 1 PROCYSBI capsule for the dose prescribed by your doctor.</td> </tr> <tr> <td align="left">Step 3:</td><td align="left">Sprinkle the granules that are inside the capsule onto the applesauce or berry jelly.</td> </tr> <tr> <td align="left">Step 4:</td><td align="left">Mix the granules with the applesauce or berry jelly. Do not crush the granules.</td> </tr> <tr> <td align="left">Step 5:</td><td align="left">Swallow the applesauce or berry jelly and granules mixture within 30 minutes after preparing. Do not chew the granules. Do not save the applesauce or berry jelly and granules for later use.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"8%\"/>\n<col align=\"left\" valign=\"top\" width=\"92%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\">Step 1<span class=\"Bold\">:</span></td><td align=\"left\">Place about ½ cup (4 ounces) of applesauce or berry jelly into a clean container. If needed, use a smaller amount you can finish in one feeding. Do not use any other food.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 2:</td><td align=\"left\">Open the PROCYSBI capsule. See \"<span class=\"Bold\"><a href=\"#openCaps\">Opening PROCYSBI capsules</a></span>\" above. You may need to use more than 1 PROCYSBI capsule for the dose prescribed by your doctor.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 3:</td><td align=\"left\">Sprinkle the granules that are inside the capsule onto the applesauce or berry jelly.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 4:</td><td align=\"left\">Mix the granules with the applesauce or berry jelly. Do not crush the granules.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 5:</td><td align=\"left\">Swallow the applesauce or berry jelly and granules mixture within 30 minutes after preparing. Do not chew the granules. Do not save the applesauce or berry jelly and granules for later use.</td>\n</tr>\n</tbody>\n</table></div>" }

Taking PROCYSBI with fruit juice:

{ "type": "p", "children": [], "text": "\nTaking PROCYSBI with fruit juice:\n" }

Do not take PROCYSBI with grapefruit juice.

{ "type": "p", "children": [], "text": "\nDo not take PROCYSBI with grapefruit juice.\n" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="top" width="8%"/> <col align="left" valign="top" width="92%"/> <tbody class="Headless"> <tr> <td align="left">Step 1:</td><td align="left">Pour about ½ cup (4 ounces) of fruit juice into a clean cup.</td> </tr> <tr> <td align="left">Step 2:</td><td align="left">Open the PROCYSBI capsule. See "<span class="Bold"><a href="#openCaps">Opening PROCYSBI capsules</a></span>" above. You may need to use more than 1 PROCYSBI capsule for the dose prescribed by your doctor.</td> </tr> <tr> <td align="left">Step 3:</td><td align="left">Sprinkle all the granules that are inside the capsule into ½ cup (4 ounces) of fruit juice.</td> </tr> <tr> <td align="left">Step 4:</td><td align="left">Stir gently until mixed. Do not crush the granules.</td> </tr> <tr> <td align="left">Step 5:</td><td align="left">Drink all of the fruit juice and granules mixture within 30 minutes of mixing. Do not chew the granules. Do not save the fruit juice or water and granules mixture for later use.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"8%\"/>\n<col align=\"left\" valign=\"top\" width=\"92%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\">Step 1:</td><td align=\"left\">Pour about ½ cup (4 ounces) of fruit juice into a clean cup.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 2:</td><td align=\"left\">Open the PROCYSBI capsule. See \"<span class=\"Bold\"><a href=\"#openCaps\">Opening PROCYSBI capsules</a></span>\" above. You may need to use more than 1 PROCYSBI capsule for the dose prescribed by your doctor.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 3:</td><td align=\"left\">Sprinkle all the granules that are inside the capsule into ½ cup (4 ounces) of fruit juice.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 4:</td><td align=\"left\">Stir gently until mixed. Do not crush the granules.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 5:</td><td align=\"left\">Drink all of the fruit juice and granules mixture within 30 minutes of mixing. Do not chew the granules. Do not save the fruit juice or water and granules mixture for later use.</td>\n</tr>\n</tbody>\n</table></div>" }

Giving PROCYSBI through a gastrostomy tube (G-tube):

{ "type": "p", "children": [], "text": "\nGiving PROCYSBI through a gastrostomy tube (G-tube):\n" }

It is best to use a straight (bolus) feeding tube.

{ "type": "p", "children": [], "text": "It is best to use a straight (bolus) feeding tube." }

For people who have a gastrostomy tube (G-tube) that is size 14 French or larger, PROCYSBI may be given as follows:

{ "type": "p", "children": [], "text": "For people who have a gastrostomy tube (G-tube) that is size 14 French or larger, PROCYSBI may be given as follows:" }

Use only strained applesauce with no chunks when giving PROCYSBI through a gastrostomy tube (G-tube).

{ "type": "p", "children": [], "text": "\nUse only strained applesauce with no chunks when giving PROCYSBI through a gastrostomy tube (G-tube).\n" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="top" width="8%"/> <col align="left" valign="top" width="92%"/> <tbody class="Headless"> <tr> <td align="left">Step 1:</td><td align="left">Flush the gastrostomy tube button with 5 mL of water to clear the button.</td> </tr> <tr> <td align="left">Step 2:</td><td align="left">Place about ½ cup (4 ounces) of applesauce into a clean container. Children who weigh 55 pounds (25 kilograms) or less can take PROCYSBI with at least 1/8 cup (1 ounce) of applesauce. </td> </tr> <tr> <td align="left">Step 3:</td><td align="left">Open the PROCYSBI capsule. See "<span class="Bold"><a href="#openCaps">Opening PROCYSBI capsules</a></span>" above. You may need to use more than 1 PROCYSBI capsule for the dose prescribed by your doctor.</td> </tr> <tr> <td align="left">Step 4:</td><td align="left">Sprinkle the granules that are inside the capsule on the applesauce. Gently mix the granules with the applesauce. Do not crush the granules.</td> </tr> <tr> <td align="left">Step 5:</td><td align="left">Place the tip of a catheter tip syringe at the bottom of the container of applesauce and granules mixture. For an adult dose, draw up about 40 mL of the mixture. When giving to a child, draw up at least 10 mL of the mixture for doses of 1 or 2 capsules.</td> </tr> <tr> <td align="left">Step 6:</td><td align="left">Place the tip of the catheter tip syringe into the feeding tube that will be connected to the gastrostomy tube. Fill the feeding tube with the applesauce and granules mixture.</td> </tr> <tr> <td align="left">Step 7:</td><td align="left">Hold the feeding tube in a horizontal (straight across) position. Give the applesauce and granules mixture through the gastrostomy tube at a quick and steady rate of 10 mL over 10 seconds.</td> </tr> <tr> <td align="left">Step 8:</td><td align="left">Repeat Step 5 through Step 7 until all of the applesauce and granules mixture is given. <span class="Bold">Give all of the applesauce and granules mixture through the gastrostomy tube within 30 minutes of mixing.</span> Do not save the applesauce and granules mixture for later use.</td> </tr> <tr> <td align="left">Step 9:</td><td align="left">Draw up at least 10 mL of fruit juice or water into another catheter tip syringe. <span class="Bold">Do not use grapefruit juice.</span> Gently swirl the syringe. Flush the gastrostomy tube with the fruit juice or water. Use enough fruit juice or water to flush the gastrostomy tube so that there is no applesauce and granules mixture left in the gastrostomy tube.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"8%\"/>\n<col align=\"left\" valign=\"top\" width=\"92%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\">Step 1:</td><td align=\"left\">Flush the gastrostomy tube button with 5 mL of water to clear the button.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 2:</td><td align=\"left\">Place about ½ cup (4 ounces) of applesauce into a clean container. Children who weigh 55 pounds (25 kilograms) or less can take PROCYSBI with at least 1/8 cup (1 ounce) of applesauce. </td>\n</tr>\n<tr>\n<td align=\"left\">Step 3:</td><td align=\"left\">Open the PROCYSBI capsule. See \"<span class=\"Bold\"><a href=\"#openCaps\">Opening PROCYSBI capsules</a></span>\" above. You may need to use more than 1 PROCYSBI capsule for the dose prescribed by your doctor.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 4:</td><td align=\"left\">Sprinkle the granules that are inside the capsule on the applesauce. Gently mix the granules with the applesauce. Do not crush the granules.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 5:</td><td align=\"left\">Place the tip of a catheter tip syringe at the bottom of the container of applesauce and granules mixture. For an adult dose, draw up about 40 mL of the mixture. When giving to a child, draw up at least 10 mL of the mixture for doses of 1 or 2 capsules.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 6:</td><td align=\"left\">Place the tip of the catheter tip syringe into the feeding tube that will be connected to the gastrostomy tube. Fill the feeding tube with the applesauce and granules mixture.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 7:</td><td align=\"left\">Hold the feeding tube in a horizontal (straight across) position. Give the applesauce and granules mixture through the gastrostomy tube at a quick and steady rate of 10 mL over 10 seconds.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 8:</td><td align=\"left\">Repeat Step 5 through Step 7 until all of the applesauce and granules mixture is given. <span class=\"Bold\">Give all of the applesauce and granules mixture through the gastrostomy tube within 30 minutes of mixing.</span> Do not save the applesauce and granules mixture for later use.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 9:</td><td align=\"left\">Draw up at least 10 mL of fruit juice or water into another catheter tip syringe. <span class=\"Bold\">Do not use grapefruit juice.</span> Gently swirl the syringe. Flush the gastrostomy tube with the fruit juice or water. Use enough fruit juice or water to flush the gastrostomy tube so that there is no applesauce and granules mixture left in the gastrostomy tube.</td>\n</tr>\n</tbody>\n</table></div>" }

Taking PROCYSBI oral granules

{ "type": "p", "children": [], "text": "\nTaking PROCYSBI oral granules\n" }

You must mix the PROCYSBI oral granules in packets with certain foods and juices to take your PROCYSBI dose. PROCYSBI oral granules can also be given through a gastrostomy tube (G-tube).

{ "type": "p", "children": [], "text": "You must mix the PROCYSBI oral granules in packets with certain foods and juices to take your PROCYSBI dose. PROCYSBI oral granules can also be given through a gastrostomy tube (G-tube).\n" }

Opening PROCYSBI oral granules in packets:

{ "type": "p", "children": [], "text": "\nOpening PROCYSBI oral granules in packets:\n" }

{ "type": "ul", "children": [ "Tear open the packet along the dotted (perforated) line.", "Do not store granules in opened packets for your next dose." ], "text": "" }

Taking PROCYSBI with applesauce or berry jelly:

{ "type": "p", "children": [], "text": "\nTaking PROCYSBI with applesauce or berry jelly:\n" }

Do not take PROCYSBI with any food other than applesauce or berry jelly.

{ "type": "p", "children": [], "text": "\nDo not take PROCYSBI with any food other than applesauce or berry jelly.\n" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="top" width="8%"/> <col align="left" valign="top" width="92%"/> <tbody class="Headless"> <tr> <td align="left">Step 1:</td><td align="left">Place about ½ cup (4 ounces) of applesauce or berry jelly into a clean container. Do not use any other food.</td> </tr> <tr> <td align="left">Step 2:</td><td align="left">Open the packet of PROCYSBI oral granules. See "<span class="Bold"><a href="#openOral">Opening PROCYSBI oral granules in packets</a></span>" above. You may need to use more than 1 packet of PROCYSBI oral granules for the dose prescribed by your doctor.</td> </tr> <tr> <td align="left">Step 3:</td><td align="left">Sprinkle all the granules that are inside the packet onto the applesauce or berry jelly.</td> </tr> <tr> <td align="left">Step 4:</td><td align="left">Mix the granules with the applesauce or berry jelly. Do not crush the granules.</td> </tr> <tr> <td align="left">Step 5:</td><td align="left">Swallow the applesauce or berry jelly and granules mixture within 30 minutes after preparing. Do not chew the granules. Do not save the applesauce or berry jelly and granules for later use.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"8%\"/>\n<col align=\"left\" valign=\"top\" width=\"92%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\">Step 1:</td><td align=\"left\">Place about ½ cup (4 ounces) of applesauce or berry jelly into a clean container. Do not use any other food.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 2:</td><td align=\"left\">Open the packet of PROCYSBI oral granules. See \"<span class=\"Bold\"><a href=\"#openOral\">Opening PROCYSBI oral granules in packets</a></span>\" above. You may need to use more than 1 packet of PROCYSBI oral granules for the dose prescribed by your doctor.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 3:</td><td align=\"left\">Sprinkle all the granules that are inside the packet onto the applesauce or berry jelly.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 4:</td><td align=\"left\">Mix the granules with the applesauce or berry jelly. Do not crush the granules.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 5:</td><td align=\"left\">Swallow the applesauce or berry jelly and granules mixture within 30 minutes after preparing. Do not chew the granules. Do not save the applesauce or berry jelly and granules for later use.</td>\n</tr>\n</tbody>\n</table></div>" }

Taking PROCYSBI with fruit juice:

{ "type": "p", "children": [], "text": "\nTaking PROCYSBI with fruit juice:\n" }

Do not take PROCYSBI with grapefruit juice.

{ "type": "p", "children": [], "text": "\nDo not take PROCYSBI with grapefruit juice.\n" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="top" width="8%"/> <col align="left" valign="top" width="92%"/> <tbody class="Headless"> <tr> <td align="left">Step 1:</td><td align="left">Pour about ½ cup (4 ounces) of fruit juice into a clean cup.</td> </tr> <tr> <td align="left">Step 2:</td><td align="left">Open the PROCYSBI packet. See "<span class="Bold"><a href="#openOral">Opening PROCYSBI oral granules in packets</a></span>" above. You may need to use more than 1 packet of PROCYSBI oral granules for the dose prescribed by your doctor.</td> </tr> <tr> <td align="left">Step 3:</td><td align="left">Sprinkle all the granules that are inside the packet into ½ cup (4 ounces) of fruit juice.</td> </tr> <tr> <td align="left">Step 4:</td><td align="left">Stir gently until mixed. Do not crush the granules.</td> </tr> <tr> <td align="left">Step 5:</td><td align="left">Drink all of the fruit juice and granules mixture within 30 minutes of mixing. Do not chew the granules. Do not save the fruit juice and granules for later use.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"8%\"/>\n<col align=\"left\" valign=\"top\" width=\"92%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\">Step 1:</td><td align=\"left\">Pour about ½ cup (4 ounces) of fruit juice into a clean cup.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 2:</td><td align=\"left\">Open the PROCYSBI packet. See \"<span class=\"Bold\"><a href=\"#openOral\">Opening PROCYSBI oral granules in packets</a></span>\" above. You may need to use more than 1 packet of PROCYSBI oral granules for the dose prescribed by your doctor.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 3:</td><td align=\"left\">Sprinkle all the granules that are inside the packet into ½ cup (4 ounces) of fruit juice.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 4:</td><td align=\"left\">Stir gently until mixed. Do not crush the granules.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 5:</td><td align=\"left\">Drink all of the fruit juice and granules mixture within 30 minutes of mixing. Do not chew the granules. Do not save the fruit juice and granules for later use.</td>\n</tr>\n</tbody>\n</table></div>" }

Giving PROCYSBI through a gastrostomy tube (G-tube):

{ "type": "p", "children": [], "text": "\nGiving PROCYSBI through a gastrostomy tube (G-tube):\n" }

It is best to use a straight (bolus) feeding tube.

{ "type": "p", "children": [], "text": "It is best to use a straight (bolus) feeding tube." }

For people who have a gastrostomy tube (G-tube) that is size 14 French or larger, PROCYSBI may be given as follows:

{ "type": "p", "children": [], "text": "For people who have a gastrostomy tube (G-tube) that is size 14 French or larger, PROCYSBI may be given as follows:" }

Use only strained applesauce with no chunks when giving PROCYSBI through a gastrostomy tube (G-tube).

{ "type": "p", "children": [], "text": "\nUse only strained applesauce with no chunks when giving PROCYSBI through a gastrostomy tube (G-tube).\n" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="top" width="8%"/> <col align="left" valign="top" width="92%"/> <tbody class="Headless"> <tr> <td align="left">Step 1:</td><td align="left">Flush the gastrostomy tube button with 5 mL of water to clear the button.</td> </tr> <tr> <td align="left">Step 2:</td><td align="left">Place about ½ cup (4 ounces) of applesauce into a clean container. Children who weigh 55 pounds (25 kilograms) or less can take PROCYSBI with at least 1/8 cup (1 ounce) of applesauce. </td> </tr> <tr> <td align="left">Step 3:</td><td align="left">Open the packet of PROCYSBI oral granules. See "<span class="Bold"><a href="#openOral">Opening PROCYSBI oral granules in packets</a></span>" above. You may need to use more than 1 packet of PROCYSBI oral granules for the dose prescribed by your doctor.</td> </tr> <tr> <td align="left">Step 4:</td><td align="left">Sprinkle all the granules that are inside the packet on the applesauce. Gently mix the granules with the applesauce. Do not crush the granules.</td> </tr> <tr> <td align="left">Step 5:</td><td align="left">Place the tip of a catheter tip syringe at the bottom of the container of applesauce and granules mixture. For an adult dose, draw up about 40 mL of the mixture. When giving to a child, draw up at least 10 mL of the mixture for doses of 1 or 2 packets.</td> </tr> <tr> <td align="left">Step 6:</td><td align="left">Place the tip of the catheter tip syringe into the feeding tube that will be connected to the gastrostomy tube. Fill the feeding tube with the applesauce and granules mixture.</td> </tr> <tr> <td align="left">Step 7:</td><td align="left">Hold the feeding tube in a horizontal (straight across) position. Give the applesauce and granules mixture through the gastrostomy tube at a quick and steady rate of 10 mL over 10 seconds.</td> </tr> <tr> <td align="left">Step 8:</td><td align="left">Repeat Step 5 through Step 7 until all of the applesauce and granules mixture is given. Give all of the applesauce and granules mixture through the gastrostomy tube within 30 minutes of mixing. Do not save the applesauce and granules mixture for later use. </td> </tr> <tr> <td align="left">Step 9:</td><td align="left">Draw up at least 10 mL of fruit juice into another catheter tip syringe. <span class="Bold">Do not use grapefruit juice.</span> Gently swirl the syringe. Flush the gastrostomy tube with the fruit juice. Use enough fruit juice to flush the gastrostomy tube so that there is no applesauce and granules mixture left in the gastrostomy tube.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"8%\"/>\n<col align=\"left\" valign=\"top\" width=\"92%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\">Step 1:</td><td align=\"left\">Flush the gastrostomy tube button with 5 mL of water to clear the button.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 2:</td><td align=\"left\">Place about ½ cup (4 ounces) of applesauce into a clean container. Children who weigh 55 pounds (25 kilograms) or less can take PROCYSBI with at least 1/8 cup (1 ounce) of applesauce. </td>\n</tr>\n<tr>\n<td align=\"left\">Step 3:</td><td align=\"left\">Open the packet of PROCYSBI oral granules. See \"<span class=\"Bold\"><a href=\"#openOral\">Opening PROCYSBI oral granules in packets</a></span>\" above. You may need to use more than 1 packet of PROCYSBI oral granules for the dose prescribed by your doctor.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 4:</td><td align=\"left\">Sprinkle all the granules that are inside the packet on the applesauce. Gently mix the granules with the applesauce. Do not crush the granules.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 5:</td><td align=\"left\">Place the tip of a catheter tip syringe at the bottom of the container of applesauce and granules mixture. For an adult dose, draw up about 40 mL of the mixture. When giving to a child, draw up at least 10 mL of the mixture for doses of 1 or 2 packets.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 6:</td><td align=\"left\">Place the tip of the catheter tip syringe into the feeding tube that will be connected to the gastrostomy tube. Fill the feeding tube with the applesauce and granules mixture.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 7:</td><td align=\"left\">Hold the feeding tube in a horizontal (straight across) position. Give the applesauce and granules mixture through the gastrostomy tube at a quick and steady rate of 10 mL over 10 seconds.</td>\n</tr>\n<tr>\n<td align=\"left\">Step 8:</td><td align=\"left\">Repeat Step 5 through Step 7 until all of the applesauce and granules mixture is given. Give all of the applesauce and granules mixture through the gastrostomy tube within 30 minutes of mixing. Do not save the applesauce and granules mixture for later use. </td>\n</tr>\n<tr>\n<td align=\"left\">Step 9:</td><td align=\"left\">Draw up at least 10 mL of fruit juice into another catheter tip syringe. <span class=\"Bold\">Do not use grapefruit juice.</span> Gently swirl the syringe. Flush the gastrostomy tube with the fruit juice. Use enough fruit juice to flush the gastrostomy tube so that there is no applesauce and granules mixture left in the gastrostomy tube.</td>\n</tr>\n</tbody>\n</table></div>" }

How should I store PROCYSBI?

{ "type": "p", "children": [], "text": "\nHow should I store PROCYSBI?\n" }

{ "type": "ul", "children": [ "Store PROCYSBI capsules and PROCYSBI oral granules at room temperature between 68°F to 77°F (20°C to 25°C).", "Keep PROCYSBI in the original packaging. Do not put PROCYSBI in another container (repackage).", "Keep PROCYSBI in a dry place to protect from moisture.", "The PROCYSBI bottle contains a desiccant to help keep the medicine dry (protect it from moisture). Do not remove the desiccant from the bottle.", "Protect from light.", "Do not store opened packets of PROCYSBI oral granules for later use.", "Throw away (dispose of) any unused PROCYSBI by the \"discard after\" date on the bottle or carton." ], "text": "" }

Keep PROCYSBI and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep PROCYSBI and all medicines out of the reach of children.\n" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration." }

Horizon Therapeutics USA, Inc., Deerfield, IL 60015

{ "type": "p", "children": [], "text": "Horizon Therapeutics USA, Inc., Deerfield, IL 60015" }

Revised: December 2024

{ "type": "p", "children": [], "text": "Revised: December 2024" }

NDC # 75987-100-04

{ "type": "p", "children": [], "text": "NDC # 75987-100-04" }

Dispense only in original packaging

{ "type": "p", "children": [], "text": "Dispense only in original packaging" }

25 mg

{ "type": "p", "children": [], "text": "25 mg" }

PROCYSBI® (cysteamine bitartrate)delayed-release capsules

{ "type": "p", "children": [], "text": "PROCYSBI®\n(cysteamine bitartrate)delayed-release capsules" }

60 capsules

{ "type": "p", "children": [], "text": "60 capsules" }

Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }

Horizon Therapeutics USA, Inc.Deerfield, IL 60015© 2025 Amgen Inc. All rights reserved.Country of origin: Italy

{ "type": "p", "children": [], "text": "Horizon Therapeutics USA, Inc.Deerfield, IL 60015© 2025 Amgen Inc. All rights reserved.Country of origin: Italy" }

Discard after:

{ "type": "p", "children": [], "text": "Discard after:" }

AMGEN

{ "type": "p", "children": [], "text": "AMGEN" }

NDC # 75987-101-08

{ "type": "p", "children": [], "text": "NDC # 75987-101-08" }

Dispense only inoriginal packaging

{ "type": "p", "children": [], "text": "Dispense only inoriginal packaging" }

75 mg

{ "type": "p", "children": [], "text": "75 mg" }

PROCYSBI® (cysteamine bitartrate)delayed-release capsules

{ "type": "p", "children": [], "text": "PROCYSBI®\n(cysteamine bitartrate)delayed-release capsules" }

Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }

250 capsules

{ "type": "p", "children": [], "text": "250 capsules" }

Horizon Therapeutics USA, Inc.Deerfield, IL 60015© 2025 Amgen Inc. All rights reserved.Country of origin: Italy

{ "type": "p", "children": [], "text": "Horizon Therapeutics USA, Inc.Deerfield, IL 60015© 2025 Amgen Inc. All rights reserved.Country of origin: Italy" }

NDC: 75987-140-13

{ "type": "p", "children": [], "text": "NDC: 75987-140-13" }

PROCYSBI® (cysteamine bitartrate)delayed-release oral granules

{ "type": "p", "children": [], "text": "PROCYSBI®\n(cysteamine bitartrate)delayed-release oral granules" }

75 mg

{ "type": "p", "children": [], "text": "75 mg" }

Dispense only in original packaging

{ "type": "p", "children": [], "text": "Dispense only in original packaging" }

Contains 60 packets

{ "type": "p", "children": [], "text": "Contains 60 packets" }

Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }

NDC: 75987-145-13

{ "type": "p", "children": [], "text": "NDC: 75987-145-13" }

PROCYSBI® (cysteamine bitartrate)delayed-release oral granules

{ "type": "p", "children": [], "text": "PROCYSBI®\n(cysteamine bitartrate)delayed-release oral granules" }

300 mg

{ "type": "p", "children": [], "text": "300 mg" }

Dispense only in original packaging

{ "type": "p", "children": [], "text": "Dispense only in original packaging" }

Contains 60 packets

{ "type": "p", "children": [], "text": "Contains 60 packets" }

Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }