CYSTARAN

Cystinosis Agents
Other Ophthalmologicals, Topical

Immediate-release capsules (Cystagon)
May administer without regard to meals.
For patients 6 years of age and older, administer capsules intact.
For children younger than 6 years of age, do not administer the intact capsule. To avoid risk of aspiration, open the capsules and then sprinkle the contents on food.
MISSED DOSE: Administer a missed dose as soon as possible. If it is within 2 hours of the next dose, skip the missed dose and go back to the regular dosing schedule. Do not double the dose.[49354]
 
Delayed-release capsules or oral granules (Procysbi)
Administer capsules whole if possible. Patients should not crush or chew capsules, capsule contents, or oral granules.
Administer capsules with fruit juice (NOT grapefruit juice) or water.
For patients who have difficulty swallowing or are taking the oral granules, sprinkle the entire packet or capsule contents of intact granules 1) on approximately 4 ounces of applesauce or berry jelly, or 2) into approximately 4 ounces of fruit juice (NOT grapefruit juice). Consume the entire contents within 30 minutes of mixing. Do not chew the granules. Do not save for future use.
Ideally, advise patients to not eat for at least 2 hours before and 30 minutes after capsule or oral granule administration. If the patient is unable to take cysteamine without eating, limit the amount of food to approximately 4 ounces within 1 hour before and 1 hour after the dose. Administer doses consistently in relation to food and avoid high-fat food close to dosing.
Administer capsules or oral granules at least 1 hour before or 1 hour after medications containing bicarbonate or carbonate.
Feeding Tube Administration: Flush the gastrostomy (G) tube (14 French or larger) with 5 mL of water. Open the capsule(s) or packet(s) and mix intact granules into approximately 4 ounces of strained applesauce (no chunks). A minimum of 1 ounce of applesauce may be used for patients weighing 25 kg or less and receiving a dose of 1 or 2 capsules or packets. Draw the mixture up into a syringe and deliver into the G-tube within 30 minutes of preparation. Flush with a minimum of 10 mL fruit juice (NOT grapefruit juice) or water to clear the tube.
MISSED DOSE: Administer a missed dose as soon as possible up to 8 hours after the scheduled time. If it is within 4 hours of the next dose, skip the missed dose and administer the next regularly scheduled dose. Do not double the dose.[54560]

0.44% ophthalmic solution:
Ensure the bottle has been thawed prior to use (see below).
Have the patient remove contact lenses prior to administration; lenses may be reinserted 15 minutes after administration of ophthalmic drops.
Tilt the patient's head back slightly and pull the lower eyelid down with the index finger to form a pouch. Squeeze the prescribed number of drops into the pouch and have the patient gently close eyes for 1 to 2 minutes. Do not blink.
Care should be taken to avoid contamination. Do not touch the tip of the dropper to the eye, fingertips, or other surfaces.
Storage: Advise patients to store bottles in the freezer in the original carton; remove 1 new bottle from the freezer each week and allow it to thaw completely for approximately 24 hours prior to use. Record a discard date of 7 days from the day the bottle is thawed on the bottle label. Store thawed bottle at 2 to 25 degrees C (36 to 77 degrees F) for up to 1 week; do not refreeze.
 
0.37% ophthalmic solution:
Preparing the bottle for administration.
Wash hands in order to prevent contamination.
Remove the green protective cap, the metal seal, and the gray stopper from the bottle. Do not touch the opening of the bottle after removing the gray stopper.
Remove the dropper from its packaging without touching the end to be attached to the bottle.
Attach the dropper to the bottle. The dropper must not be removed once attached.
Ensure the small white cap remains tightly closed on the top of the dropper when not in use.
Prior to administration, have the patient remove contact lenses; lenses may be reinserted 15 minutes after administration of ophthalmic drops.
Tilt the patient's head back slightly and pull the lower eyelid down with the index finger to form a pouch. Squeeze the prescribed number of drops into the pouch and have the patient gently close eyes for 1 to 2 minutes. Do not blink.
If the patient misses an instillation, instruct the patient to administer the dose as soon as feasible and then continue the treatment with the next scheduled dose.
In case of concomitant therapy with other ophthalmic products, an interval of 10 minutes between applications should be observed. Ophthalmic ointments should be administered last.
Care should be taken to avoid contamination. Do not touch the tip of the dropper to the eye, fingertips, or other surfaces.
Storage: Advise patients to store unopened bottles in the refrigerator between 2 to 8 degrees C (36 to 46 degrees F) in the original carton. Each week, remove 1 new bottle from the refrigerator. Write the date the bottle was opened in the space on the carton; discard the bottle 7 days after opening. After opening the bottle, it should be stored at room temperature between 20 to 25 degrees C (68 to 77 degrees F); do not refrigerate the bottle after opening.

visual impairment / Early / 10.0
hearing loss / Delayed / Incidence not known
seizures / Delayed / Incidence not known
papilledema / Delayed / Incidence not known
increased intracranial pressure / Early / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
fibrosing colonopathy / Delayed / Incidence not known
GI perforation / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known

conjunctivitis / Delayed / 15.0
conjunctival hyperemia / Early / 10.0
blurred vision / Early / 10.0
dehydration / Delayed / 15.0
encephalopathy / Delayed / Incidence not known
ataxia / Delayed / Incidence not known
confusion / Early / Incidence not known
pseudotumor cerebri / Delayed / Incidence not known
osteopenia / Delayed / Incidence not known
constipation / Delayed / Incidence not known
hallucinations / Early / Incidence not known
depression / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
anemia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
hypertension / Early / Incidence not known

vomiting / Early / 7.0-77.0
nausea / Early / 7.0-77.0
diarrhea / Early / 16.0-35.0
anorexia / Delayed / 2.0-31.0
halitosis / Early / 24.0-24.0
fever / Early / 22.0-22.0
lethargy / Early / 11.0-11.0
dizziness / Early / 5.0-5.0
drowsiness / Early / 0-5.0
headache / Early / 0.1
lacrimation / Early / 10.0
ocular irritation / Rapid / 10.0
ocular pain / Early / 10.0
ocular pruritus / Rapid / 10.0
fatigue / Early / 15.0
rash / Early / 5.0
abdominal pain / Early / 14.0
arthralgia / Delayed / 15.0
infection / Delayed / 15.0
pharyngitis / Delayed / 15.0
cough / Delayed / 15.0
influenza / Delayed / 15.0
hyperkinesis / Delayed / Incidence not known
tremor / Early / Incidence not known
diplopia / Early / Incidence not known
dyspepsia / Early / Incidence not known
nightmares / Early / Incidence not known
emotional lability / Early / Incidence not known
urticaria / Rapid / Incidence not known
drug-induced body odor / Delayed / Incidence not known

Cystadrops, Cystagon, CYSTARAN, PROCYSBI

Rx

Cystine-depleting agent
Administered orally for the treatment of nephropathic cystinosis
Ophthalmic preparations are used for the treatment of corneal cystine crystal accumulation in patients with cystinosis

Initiate therapy at one-fourth to one-sixth the maintenance dose and gradually escalate over 4 to 6 weeks. The recommended maintenance dose is 500 mg cysteamine free base every 6 hours (2 g/day). The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; Max: 1.95 g/m2/day. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the proper dose.

Initiate therapy at one-fourth to one-sixth the maintenance dose and gradually escalate over 4 to 6 weeks. The recommended maintenance dose is 500 mg cysteamine free base every 6 hours (2 g/day). The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; Max: 1.95 g/m2/day. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the proper dose.

Initiate therapy at one-fourth to one-sixth the maintenance dose and gradually escalate over 4 to 6 weeks. The recommended maintenance dose is 450 mg cysteamine free base every 6 hours (1.3 g/m2/day). The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; Max: 1.95 g/m2/day. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the proper dose.

Initiate therapy at one-fourth to one-sixth the maintenance dose and gradually escalate over 4 to 6 weeks. The recommended maintenance dose is 400 mg cysteamine free base every 6 hours (1.3 g/m2/day). The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; Max: 1.95 g/m2/day. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the proper dose.

Initiate therapy at one-fourth to one-sixth the maintenance dose and gradually escalate over 4 to 6 weeks. The recommended maintenance dose is 350 mg cysteamine free base every 6 hours (1.3 g/m2/day). The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; Max: 1.95 g/m2/day. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the proper dose.

Initiate therapy at one-fourth to one-sixth the maintenance dose and gradually escalate over 4 to 6 weeks. The recommended maintenance dose is 300 mg cysteamine free base every 6 hours (1.3 g/m2/day). The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; Max: 1.95 g/m2/day. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the proper dose.

Initiate therapy at one-fourth to one-sixth the maintenance dose and gradually escalate over 4 to 6 weeks. The recommended maintenance dose is 250 mg cysteamine free base every 6 hours (1.3 g/m2/day). The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; Max: 1.95 g/m2/day. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the proper dose.

Initiate therapy at one-fourth to one-sixth the maintenance dose and gradually escalate over 4 to 6 weeks. The recommended maintenance dose is 200 mg cysteamine free base every 6 hours (1.3 g/m2/day). The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; Max: 1.95 g/m2/day. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the proper dose.

Initiate therapy at one-fourth to one-sixth the maintenance dose and gradually escalate over 4 to 6 weeks. The recommended maintenance dose is 150 mg cysteamine free base every 6 hours (1.3 g/m2/day). The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; Max: 1.95 g/m2/day. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the proper dose.

Initiate therapy at one-fourth to one-sixth the maintenance dose and gradually escalate over 4 to 6 weeks. The recommended maintenance dose is 100 mg cysteamine free base every 6 hours (1.3 g/m2/day). The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; Max: 1.95 g/m2/day. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the proper dose.

Initiate therapy at one-fourth to one-sixth the maintenance dose and gradually escalate over 4 to 6 weeks. The recommended maintenance dose is 150 mg cysteamine free base every 6 hours (1.3 g/m2/day). The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; Max: 1.95 g/m2/day. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the proper dose.

Initiate therapy at one-fourth to one-sixth the maintenance dose and gradually escalate over 4 to 6 weeks. The recommended maintenance dose is 100 mg cysteamine free base every 6 hours (1.3 g/m2/day). The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; Max: 1.95 g/m2/day. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the proper dose.

Initiate therapy at 175 mg or 250 mg PO every 12 hours (one-sixth or one-fourth maintenance) in cysteamine-naive patients; gradually increase the dose over 4 to 6 weeks to 1,000 mg PO every 12 hours (1.3 g/m2/day maintenance dose). If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the maintenance dose. For patients switching from immediate-release cysteamine, initiate delayed-release cysteamine at a dosage equal to the same total daily dose; divide by 2 and administer every 12 hours. If intolerance occurs, decrease the dose and gradually increase to the maintenance dose. The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; increase the dosage by 10% and round dose calculations to the nearest incremental dosage (use only whole capsules or packets of oral granules). Max: 1.95 g/m2/day.

Initiate therapy at 175 mg or 250 mg PO every 12 hours (one-sixth or one-fourth maintenance) in cysteamine-naive patients; gradually increase the dose over 4 to 6 weeks to 1,000 mg PO every 12 hours (1.3 g/m2/day maintenance dose). If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the maintenance dose. For patients switching from immediate-release cysteamine, initiate delayed-release cysteamine at a dosage equal to the same total daily dose; divide by 2 and administer every 12 hours. If intolerance occurs, decrease the dose and gradually increase to the maintenance dose. The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; increase the dosage by 10% and round dose calculations to the nearest incremental dosage (use only whole capsules or packets of oral granules). Max: 1.95 g/m2/day.[54560]

Initiate therapy at 150 mg or 225 mg PO every 12 hours (one-sixth or one-fourth maintenance) in cysteamine-naive patients; gradually increase the dose over 4 to 6 weeks to 900 mg PO every 12 hours (1.3 g/m2/day maintenance dose). If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the maintenance dose. For patients switching from immediate-release cysteamine, initiate delayed-release cysteamine at a dosage equal to the same total daily dose; divide by 2 and administer every 12 hours. If intolerance occurs, decrease the dose and gradually increase to the maintenance dose. The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; increase the dosage by 10% and round dose calculations to the nearest incremental dosage (use only whole capsules or packets of oral granules). Max: 1.95 g/m2/day.[54560]

Initiate therapy at 125 mg or 200 mg PO every 12 hours (one-sixth or one-fourth maintenance) in cysteamine-naive patients and gradually increase to 800 mg PO every 12 hours (1.3 g/m2/day maintenance dose). For patients 1 to 5 years, increase the dosage in 10% increments, while monitoring WBC cystine concentrations, allowing a minimum of 2 weeks between adjustments. If a patient achieves the therapeutic target WBC cystine concentration at a dosage below the recommended weight-based maintenance dosage, then stop dosage escalation. For patients 6 years and older, gradually increase the dose over 4 to 6 weeks. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the maintenance dose. For patients switching from immediate-release cysteamine, initiate delayed-release cysteamine at a dosage equal to the same total daily dose; divide by 2 and administer every 12 hours. If intolerance occurs, decrease the dose and gradually increase to the maintenance dose. The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; increase the dosage by 10% and round dose calculations to the nearest incremental dosage (use only whole capsules or packets of oral granules). Max: 1.95 g/m2/day.[54560]

Initiate therapy at 125 mg or 175 mg PO every 12 hours (one-sixth or one-fourth maintenance) in cysteamine-naive patients and gradually increase to 700 mg PO every 12 hours (1.3 g/m2/day maintenance dose). For patients 1 to 5 years, increase the dosage in 10% increments, while monitoring WBC cystine concentrations, allowing a minimum of 2 weeks between adjustments. If a patient achieves the therapeutic target WBC cystine concentration at a dosage below the recommended weight-based maintenance dosage, then stop dosage escalation. For patients 6 years and older, gradually increase the dose over 4 to 6 weeks. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the maintenance dose. For patients switching from immediate-release cysteamine, initiate delayed-release cysteamine at a dosage equal to the same total daily dose; divide by 2 and administer every 12 hours. If intolerance occurs, decrease the dose and gradually increase to the maintenance dose. The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; increase the dosage by 10% and round dose calculations to the nearest incremental dosage (use only whole capsules or packets of oral granules). Max: 1.95 g/m2/day.[54560]

Initiate therapy at 100 mg or 150 mg PO every 12 hours (one-sixth or one-fourth maintenance) in cysteamine-naive patients and gradually increase to 600 mg PO every 12 hours (1.3 g/m2/day maintenance dose). For patients 1 to 5 years, increase the dosage in 10% increments, while monitoring WBC cystine concentrations, allowing a minimum of 2 weeks between adjustments. If a patient achieves the therapeutic target WBC cystine concentration at a dosage below the recommended weight-based maintenance dosage, then stop dosage escalation. For patients 6 years and older, gradually increase the dose over 4 to 6 weeks. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the maintenance dose. For patients switching from immediate-release cysteamine, initiate delayed-release cysteamine at a dosage equal to the same total daily dose; divide by 2 and administer every 12 hours. If intolerance occurs, decrease the dose and gradually increase to the maintenance dose. The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; increase the dosage by 10% and round dose calculations to the nearest incremental dosage (use only whole capsules or packets of oral granules). Max: 1.95 g/m2/day.[54560]

Initiate therapy at 100 mg or 125 mg PO every 12 hours (one-sixth or one-fourth maintenance) in cysteamine-naive patients and gradually increase to 500 mg PO every 12 hours (1.3 g/m2/day maintenance dose). For patients 1 to 5 years, increase the dosage in 10% increments, while monitoring WBC cystine concentrations, allowing a minimum of 2 weeks between adjustments. If a patient achieves the therapeutic target WBC cystine concentration at a dosage below the recommended weight-based maintenance dosage, then stop dosage escalation. For patients 6 years and older, gradually increase the dose over 4 to 6 weeks. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the maintenance dose. For patients switching from immediate-release cysteamine, initiate delayed-release cysteamine at a dosage equal to the same total daily dose; divide by 2 and administer every 12 hours. If intolerance occurs, decrease the dose and gradually increase to the maintenance dose. The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; increase the dosage by 10% and round dose calculations to the nearest incremental dosage (use only whole capsules or packets of oral granules). Max: 1.95 g/m2/day.[54560]

Initiate therapy at 75 mg or 100 mg PO every 12 hours (one-sixth or one-fourth maintenance) in cysteamine-naive patients and gradually increase to 400 mg PO every 12 hours (1.3 g/m2/day maintenance dose). For patients 1 to 5 years, increase the dosage in 10% increments, while monitoring WBC cystine concentrations, allowing a minimum of 2 weeks between adjustments. If a patient achieves the therapeutic target WBC cystine concentration at a dosage below the recommended weight-based maintenance dosage, then stop dosage escalation. For patients 6 years and older, gradually increase the dose over 4 to 6 weeks. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the maintenance dose. For patients switching from immediate-release cysteamine, initiate delayed-release cysteamine at a dosage equal to the same total daily dose; divide by 2 and administer every 12 hours. If intolerance occurs, decrease the dose and gradually increase to the maintenance dose. The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; increase the dosage by 10% and round dose calculations to the nearest incremental dosage (use only whole capsules or packets of oral granules). Max: 1.95 g/m2/day.[54560]

Initiate therapy at 50 mg or 75 mg PO every 12 hours (one-sixth or one-fourth maintenance) in cysteamine-naive patients and gradually increase to 300 mg PO every 12 hours (1.3 g/m2/day maintenance dose). For patients 1 to 5 years, increase the dosage in 10% increments, while monitoring WBC cystine concentrations, allowing a minimum of 2 weeks between adjustments. If a patient achieves the therapeutic target WBC cystine concentration at a dosage below the recommended weight-based maintenance dosage, then stop dosage escalation. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the maintenance dose. For patients switching from immediate-release cysteamine, initiate delayed-release cysteamine at a dosage equal to the same total daily dose; divide by 2 and administer every 12 hours. If intolerance occurs, decrease the dose and gradually increase to the maintenance dose. The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; increase the dosage by 10% and round dose calculations to the nearest incremental dosage (use only whole capsules or packets of oral granules). Max: 1.95 g/m2/day.[54560]

Initiate therapy at 25 mg or 50 mg PO every 12 hours (one-sixth or one-fourth maintenance) in cysteamine-naive patients and gradually increase to 200 mg PO every 12 hours (1.3 g/m2/day maintenance dose). For patients 1 to 5 years, increase the dosage in 10% increments, while monitoring WBC cystine concentrations, allowing a minimum of 2 weeks between adjustments. If a patient achieves the therapeutic target WBC cystine concentration at a dosage below the recommended weight-based maintenance dosage, then stop dosage escalation. If intolerance occurs, temporarily stop therapy, re-institute at a lower dose, and gradually increase to the maintenance dose. For patients switching from immediate-release cysteamine, initiate delayed-release cysteamine at a dosage equal to the same total daily dose; divide by 2 and administer every 12 hours. If intolerance occurs, decrease the dose and gradually increase to the maintenance dose. The dosage may be further increased to achieve a therapeutic target WBC cystine concentration; increase the dosage by 10% and round dose calculations to the nearest incremental dosage (use only whole capsules or packets of oral granules). Max: 1.95 g/m2/day.[54560]

Instill 1 drop in each eye, every waking hour.

Instill 1 drop in each eye, every waking hour.

Instill 1 drop in each eye, every waking hour.

Instill 1 drop in each eye 4 times daily during waking hours.

Instill 1 drop in each eye 4 times daily during waking hours.

Instill 1 drop in each eye 4 times daily during waking hours.

Specific guidelines for dosage adjustments in hepatic impairment are not available; however, cysteamine should be used with caution in patients with hepatic disease. Cysteamine has been associated with reversible elevated hepatic enzyme concentrations.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Aluminum Hydroxide; Magnesium Carbonate: (Major) In general, cysteamine may be administered with electrolyte and mineral replacements necessary for managing Fanconi syndrome, as well as with vitamin D and thyroid hormone. However, delayed-release cysteamine (Procysbi) should be administered at least 1 hour before or 1 after medications that increase gastric pH, including those containing bicarbonate or carbonate (i.e., magnesium carbonate). Drugs that increase the gastric pH, such as bicarbonate and carbonate, may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) In general, cysteamine may be administered with electrolyte and mineral replacements necessary for managing Fanconi syndrome, as well as with vitamin D and thyroid hormone. However, delayed-release cysteamine (Procysbi) should be administered at least 1 hour before or 1 after medications that increase gastric pH, including those containing bicarbonate or carbonate (i.e., sodium bicarbonate). Drugs that increase the gastric pH, such as bicarbonate and carbonate, may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Aspirin, ASA; Omeprazole: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
Calcium Carbonate: (Major) In general, cysteamine may be administered with electrolyte and mineral replacements necessary for managing Fanconi syndrome, as well as with vitamin D and thyroid hormone. However, delayed-release cysteamine (Procysbi) should be administered at least 1 hour before or 1 after medications that increase gastric pH, including those containing bicarbonate or carbonate (i.e.calcium carbonate). Drugs that increase the gastric pH, such as bicarbonate and carbonate, may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) In general, cysteamine may be administered with electrolyte and mineral replacements necessary for managing Fanconi syndrome, as well as with vitamin D and thyroid hormone. However, delayed-release cysteamine (Procysbi) should be administered at least 1 hour before or 1 after medications that increase gastric pH, including those containing bicarbonate or carbonate (i.e.calcium carbonate). Drugs that increase the gastric pH, such as bicarbonate and carbonate, may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with H2-blockers. Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Calcium Carbonate; Magnesium Hydroxide: (Major) In general, cysteamine may be administered with electrolyte and mineral replacements necessary for managing Fanconi syndrome, as well as with vitamin D and thyroid hormone. However, delayed-release cysteamine (Procysbi) should be administered at least 1 hour before or 1 after medications that increase gastric pH, including those containing bicarbonate or carbonate (i.e.calcium carbonate). Drugs that increase the gastric pH, such as bicarbonate and carbonate, may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Major) In general, cysteamine may be administered with electrolyte and mineral replacements necessary for managing Fanconi syndrome, as well as with vitamin D and thyroid hormone. However, delayed-release cysteamine (Procysbi) should be administered at least 1 hour before or 1 after medications that increase gastric pH, including those containing bicarbonate or carbonate (i.e.calcium carbonate). Drugs that increase the gastric pH, such as bicarbonate and carbonate, may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Calcium Carbonate; Simethicone: (Major) In general, cysteamine may be administered with electrolyte and mineral replacements necessary for managing Fanconi syndrome, as well as with vitamin D and thyroid hormone. However, delayed-release cysteamine (Procysbi) should be administered at least 1 hour before or 1 after medications that increase gastric pH, including those containing bicarbonate or carbonate (i.e.calcium carbonate). Drugs that increase the gastric pH, such as bicarbonate and carbonate, may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Calcium; Vitamin D: (Major) In general, cysteamine may be administered with electrolyte and mineral replacements necessary for managing Fanconi syndrome, as well as with vitamin D and thyroid hormone. However, delayed-release cysteamine (Procysbi) should be administered at least 1 hour before or 1 after medications that increase gastric pH, including those containing bicarbonate or carbonate (i.e.calcium carbonate). Drugs that increase the gastric pH, such as bicarbonate and carbonate, may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Cimetidine: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with H2-blockers. Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Dexlansoprazole: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
Esomeprazole: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
Ethanol: (Major) Avoid alcohol ingestion during treatment with cysteamine. Consumption of alcohol may increase the rate of cysteamine release and/or adversely affect the pharmacokinetics of cysteamine, altering the safety and effectiveness.
Famotidine: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with H2-blockers. Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
H2-blockers: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with H2-blockers. Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Ibuprofen; Famotidine: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with H2-blockers. Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Lansoprazole: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
Lanthanum Carbonate: (Major) In general, cysteamine may be administered with electrolyte and mineral replacements necessary for managing Fanconi syndrome, as well as with vitamin D and thyroid hormone. However, delayed-release cysteamine (Procysbi) should be administered at least 1 hour before or 1 after medications that increase gastric pH, including those containing bicarbonate or carbonate (i.e., lanthanum carbonate). Drugs that increase the gastric pH, such as bicarbonate and carbonate, may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Naproxen; Esomeprazole: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
Nizatidine: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with H2-blockers. Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Omeprazole: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
Omeprazole; Amoxicillin; Rifabutin: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
Omeprazole; Sodium Bicarbonate: (Major) In general, cysteamine may be administered with electrolyte and mineral replacements necessary for managing Fanconi syndrome, as well as with vitamin D and thyroid hormone. However, delayed-release cysteamine (Procysbi) should be administered at least 1 hour before or 1 after medications that increase gastric pH, including those containing bicarbonate or carbonate (i.e., sodium bicarbonate). Drugs that increase the gastric pH, such as bicarbonate and carbonate, may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
Pantoprazole: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
Proton pump inhibitors: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
Rabeprazole: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with proton pump inhibitors (PPIs). Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. Concomitant administration of omeprazole 20 mg did not alter the pharmacokinetics of delayed-release cysteamine when administered with orange juice; however, the effect of omeprazole on the pharmacokinetics of delayed-release cysteamine when administered with water have not been studied.
Ranitidine: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with H2-blockers. Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Sodium Bicarbonate: (Major) In general, cysteamine may be administered with electrolyte and mineral replacements necessary for managing Fanconi syndrome, as well as with vitamin D and thyroid hormone. However, delayed-release cysteamine (Procysbi) should be administered at least 1 hour before or 1 after medications that increase gastric pH, including those containing bicarbonate or carbonate (i.e., sodium bicarbonate). Drugs that increase the gastric pH, such as bicarbonate and carbonate, may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.

Cystadrops/CYSTARAN Ophthalmic Sol: 0.37%, 0.44%
Cystagon Oral Cap: 50mg, 150mg
PROCYSBI Intragastric Gran: 75mg, 300mg
PROCYSBI Oral Cap DR Pellets: 25mg, 75mg
PROCYSBI Oral Gran: 75mg, 300mg

1.95 g/m2/day PO for immediate-release capsules, delayed-release capsules, and delayed-release oral granules; 4 drops/eye/day for 0.37% ophthalmic solution; 1 drop/eye/hour during waking hours for 0.44% ophthalmic solution.

1.95 g/m2/day PO for immediate-release capsules, delayed-release capsules, and delayed-release oral granules; 4 drops/eye/day for 0.37% ophthalmic solution; 1 drop/eye/hour during waking hours for 0.44% ophthalmic solution.

1.95 g/m2/day PO for immediate-release capsules, delayed-release capsules, and delayed-release oral granules; 4 drops/eye/day for 0.37% ophthalmic solution; 1 drop/eye/hour during waking hours for 0.44% ophthalmic solution.

1.95 g/m2/day PO for immediate-release capsules, delayed-release capsules, and delayed-release oral granules; 4 drops/eye/day for 0.37% ophthalmic solution; 1 drop/eye/hour during waking hours for 0.44% ophthalmic solution.

1.95 g/m2/day PO for immediate-release capsules; 4 drops/eye/day for 0.37% ophthalmic solution; 1 drop/eye/hour during waking hours for 0.44% ophthalmic solution; safety and efficacy have not been established for delayed-release capsules and delayed-release oral granules.

1.95 g/m2/day PO for immediate-release capsules; 4 drops/eye/day for 0.37% ophthalmic solution; 1 drop/eye/hour during waking hours for 0.44% ophthalmic solution; safety and efficacy have not been established for delayed-release capsules and delayed-release oral granules.

Cysteamine, an aminothiol, decreases the amount of cystine in the lysosomes of patients with cystinosis. Exogenous cysteamine enters the cell and converts cystine to cysteine and a cysteine-cysteamine complex. Both cysteine and the cysteine-cysteamine complex are more readily transported out of the lysosome than cystine, resulting in a long-term depletion of lysosomal cystine. Clinically, the administration of cysteamine early in life slows the progression of renal failure, improves growth, obviates the need for levothyroxine replacement, and decreases corneal cystine deposits.

Cysteamine is administered orally and ophthalmically. Cysteamine bitartrate has been shown by the manufacturer to produce leukocyte cystine-lowering effects similar to those of the hydrochloride salt. Cysteamine is moderately bound to protein (52%), predominately to albumin. The maximum response after oral administration (measured as reduction of white cell cystine concentration) occurred approximately 1.8 hours post immediate-release cysteamine dose and returned to baseline 6 hours post dose.[49354] After each dose of delayed-release cysteamine, the cysteamine concentration in the blood continues to decline for approximately 1/2 hour, and the concentration of leukocyte cystine increases accordingly.[54560]

Cysteamine hydrochloride has an unpleasant taste and odor, and it binds to oral mucosa and dental fillings. For this reason, cysteamine is commercially available as capsules and oral granules in the bitartrate salt. The pharmacokinetics of delayed-release cysteamine have been studied in 43 patients ages 6 to 26 years. At steady state, the Cmax was lower for immediate- versus delayed-release cysteamine (2.7 +/- 1.7 mg/L vs. 3.6 +/- 1.8 mg/L, respectively); the AUC was also lower for immediate- versus delayed-release cysteamine and the Tmax for delayed-release cysteamine was 188 +/- 88 minutes. Bioequivalence has been demonstrated between whole capsule and sprinkle administration in the fasted state. Administration with food reduces the systemic exposure of delayed-release cysteamine. However, administration of capsule contents mixed with a small amount (4 ounces) of applesauce or orange juice has shown no effect on the rate and extent of cysteamine absorption as compared to administration of intact capsules.[54560]

Ophthalmic Route
Peak plasma concentrations of cysteamine following ophthalmic administration are unknown. Because the total daily ophthalmic dose is less than 4% of the recommended oral dose, systemic drug exposures occurring with ophthalmic administration are expected to be negligible compared to oral administration.[52497] [65845]

There are no adequate and well-controlled studies that have been conducted with cysteamine in pregnant women to inform any drug-associated risks. Teratology studies performed in rats at oral doses of approximately 0.2- to 0.7-times the recommended human oral maintenance dose and 86- to 960-times the recommended human ophthalmic dose have revealed cysteamine bitartrate to be teratogenic and fetotoxic. Teratogenic findings include intrauterine death, cleft palate, kyphosis, heart ventricular septal defects, microcephaly, growth deficits, and exencephaly. Oral cysteamine should be used during pregnancy only if the benefits to the mother outweigh the risks to the fetus. According to the FDA-approved product labeling, ophthalmic cysteamine should also be used during pregnancy only if the benefits to the mother outweigh the risks to the fetus; however, systemic exposure following ophthalmic exposure is expected to be negligible. Therefore, it is unlikely that ophthalmic administration would result in clinically significant exposure to the fetus.

It is unknown whether cysteamine is excreted in breast milk. Because animal studies have shown potential developmental toxicity, the manufacturer of immediate-release cysteamine capsules (Cystagon) recommends to either discontinue systemic cysteamine or discontinue breast-feeding. Similarly, the manufacturer of delayed-release capsules (Procysbi), recommends avoiding nursing during therapy. It is not known whether measurable concentrations of cysteamine would be present in human milk after ophthalmic administration of the drug; however, because the systemic exposure following ophthalmic administration is expected to be negligible compared to oral administration, it is unlikely that a clinically significant amount of drug would be excreted into breast-milk.  Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.