Cysteamine is used orally to treat nephropathic cystinosis. Cysteamine ophthalmic solutions are used to treat the corneal cystine crystal accumulation that occurs in patients with cystinosis. Nephropathic cystinosis is a rare autosomal recessive disease involving the defective transport of cystine across the lysosomal membrane. The defective transport of cystine out of lysosomes results in free cystine accumulation and crystallization within the lysosomes, which destroys various tissues and damages organs, especially the kidney. An example of kidney damage includes renal tubular Fanconi Syndrome, which is characterized by polyuria, polydipsia, electrolyte imbalance, dehydration, rickets, and growth failure. If left untreated, progressive glomerular failure and end-stage renal failure, usually occurring by 10 years of age, also are possible. Other sequelae of untreated cystinosis include photophobia, retinal blindness, hypothyroidism, pulmonary dysfunction, and male hypogonadism. For patients with cystinosis, treatment with cysteamine early in life has been shown to slow the rate of renal failure progression, increase growth in affected patients, obviate the need for levothyroxine replacement, and decrease corneal cystine deposits.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
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.
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.
Ophthalmic Administration
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.
Causality of adverse events sometimes is difficult to determine based on the development of symptoms with cystinosis. In US trials, adverse reactions or intolerance to immediate-release cysteamine caused termination of therapy in 8% of patients.
Frequently reported ocular adverse events occurring in 10% or more of patients treated with cysteamine ophthalmic solution include: sensitivity to light, ocular and conjunctival hyperemia, ocular pain or ocular irritation, instillation site discomfort, ocular pruritus, increased lacrimation, ocular deposits, visual field defects (visual impairment), and headache. Patients are commonly receiving concurrent oral cysteamine treatment, which may also cause headaches and is reported in 5% or less of patients receiving immediate-release cysteamine and in 9% to more than 15% of patients receiving delayed-release cysteamine. Conjunctivitis has been reported in more than 15% of patients receiving delayed-release cysteamine.
Central nervous system related adverse reactions are common with oral cysteamine therapy and are especially prominent at the initiation of therapy. Suspending treatment and then gradual reintroduction of cysteamine may be effective in improving tolerance. In clinical evaluation of immediate-release cysteamine, CNS adverse reactions occurring in more than 5% of patients include lethargy (11%). Other CNS reactions reported in less than 5% of patients include: drowsiness or somnolence, encephalopathy, seizures, ataxia, confusion, tremor, hyperkinesis, hearing loss, dizziness, and jitteriness; exact incidence rates are not reported. In clinical evaluation of delayed-release cysteamine, dizziness (5%) and fatigue (more than 15%) were also commonly reported. Neurological complications are associated with cystinosis and have been described in patients not taking cysteamine. If CNS symptoms develop, the patient should be clinically evaluated and the cysteamine dose adjusted as necessary. Discontinuation of drug therapy secondary to lethargy occurred more often in patients taking higher cysteamine doses of 1.95 g/m2/day compared to 1.3 g/m2/day.
Pseudotumor cerebri (PTC) (benign increased intracranial pressure) and/or papilledema have occurred during systemic cysteamine therapy, causing symptoms such as headache, tinnitus, dizziness, nausea, diplopia, blurred vision, visual impairment, and pain behind the eye or with eye movement. There have also been reports associated with ophthalmic use of cysteamine; however, all of these patients were on concurrent oral cysteamine. The condition resolves with the initiation of diuretic therapy. PTC may occur more commonly in cystinotic patients because of renal transplantation and concurrent medications. Although a causal relationship between PTC and cysteamine has not been established, clinicians should monitor patients receiving cysteamine for PTC. In addition, patients should receive periodic eye examinations for early identification and timely treatment of this condition to prevent vision loss. Patients should be instructed to promptly report any symptoms associated with PTC. If symptoms persist, interrupt therapy or decrease the dose of cysteamine and refer the patient to an ophthalmologist. If the diagnosis of PTC and/or papilledema is confirmed, discontinue cysteamine therapy permanently.
Dermatologic reactions are possible with oral cysteamine therapy. Skin rash has been reported as a frequent adverse reaction in 7% of patients receiving immediate-release cysteamine and in 5% or more of patients receiving delayed-release cysteamine. If a skin rash develops, therapy with cysteamine should be withheld until the rash resolves. Cysteamine may then be restarted, under close supervision, at a lower dose and slowly titrated to the therapeutic dose. If a severe skin rash develops, such as erythema multiforme bullosa or toxic epidermal necrolysis, cysteamine therapy should not be reinitiated. In addition, serious skin lesions have been reported in some patients receiving high doses of cysteamine. These skin lesions are purplish hemorrhagic lesions over the elbow area on both arms and have been described as molluscoid pseudotumors. Skin striae and bone lesions (described as osteopenia, compression fractures, scoliosis, and genu valgum) along with leg pain and joint hyperextension also may be present. These skin and bone reactions have responded to cysteamine dose reduction. Monitor patients closely for skin and bone abnormalities, and if such abnormalities occur, the dose of cysteamine should be reduced.
Gastrointestinal (GI) adverse reactions are common with oral cysteamine therapy and are especially prominent at the initiation of therapy. Suspending treatment and then gradual reintroduction of cysteamine may be effective in improving tolerance. The most common GI reactions are nausea and/or vomiting (7% to 77%), gastroenteritis (53%), halitosis (24%), diarrhea (16% to 35%), anorexia (2% to 31%), and abdominal pain (14% or more). Other less common GI adverse reactions reported include constipation, duodenitis, and dyspepsia. Halitosis occurs due to dimethylsulfide (DMS) generation, which is lower after administration of delayed-release cysteamine (vs. immediate-release administration). Some GI adverse reactions can be severe. GI bleeding and GI perforation have been reported in patients receiving cysteamine. If severe GI reactions develop, interrupt therapy and reduce the dose. During postmarketing use, fibrosing colonopathy, including colonic stricture formation, was reported in pediatric and young adult patients with nephropathic cystinosis receiving delayed-release cysteamine capsules or oral granules. Some patients had been treated with cysteamine for extended periods of time. Reported symptoms include abdominal pain, vomiting, bloody or persistent diarrhea, and fecal incontinence. If signs of fibrosing colonopathy occur, permanently discontinue delayed-release cysteamine and switch to immediate-release cysteamine capsules. Discontinuation of drug therapy secondary to vomiting and anorexia occurred more often in patients taking higher cysteamine doses of 1.95 g/m2/day compared to 1.3 g/m2/day.
Psychiatric adverse reactions including abnormal thinking, depression, emotional lability, hallucinations, nervousness, and nightmares have been reported in patients taking cysteamine.
Elevated hepatic enzymes have been reported with systemic cysteamine therapy. Liver function should be monitored during cysteamine therapy. If abnormal liver function tests persist, consider decreasing the dose or interrupting cysteamine therapy until values return to normal.
Electrolyte imbalance occurred in 12% of patients receiving delayed-release cysteamine. Anemia and leukopenia have been reported with systemic cysteamine therapy. Monitor complete blood counts during cysteamine therapy. If leukopenia persists, consider decreasing the dose or interrupting cysteamine therapy until values return to normal.
Adverse reactions associated with immediate-release cysteamine therapy include fever (22%), dehydration, hypertension, and urticaria. Skin odor (drug-induced body odor) has been reported. Dehydration, arthralgia, and pain in extremity have been reported in more than 15% of patients receiving delayed-release cysteamine. Discontinuation of drug therapy secondary to fever occurred more often in patients taking higher cysteamine doses of 1.95 g/m2/day compared to 1.3 g/m2/day.
One postmarketing report of interstitial nephritis with early renal failure (unspecified) has been reported with immediate-release cysteamine; however, a causal relationship between cysteamine systemic therapy and this event could not be established.
Influenza, naso-pharyngitis, ear infection, upper respiratory tract infection, and cough have been reported in more than 15% of patients receiving delayed-release cysteamine.
Systemic cysteamine is contraindicated in patients who have demonstrated cysteamine hypersensitivity or penicillamine hypersensitivity. The possible mechanism involves the presence of a sulfhydryl (-SH) group in the structure of cysteamine. This sulfhydryl group can cause a hypersensitivity reaction in patients who had previously shown a reaction to penicillamine.
Cases of pseudotumor cerebri (PTC) (benign increased intracranial pressure) and papilledema have been reported with oral cysteamine therapy. There have also been reports associated with the ophthalmic use of cysteamine; however, all of these patients were on concurrent oral cysteamine. PTC may occur more commonly in cystinotic patients because of renal transplantation and concurrent medications. Clinicians should monitor for PTC in patients receiving cysteamine, even though a causal relationship has not been established. In addition, to prevent vision loss, patients should receive periodic eye examinations for early identification and timely treatment of PTC and papilledema. Instruct patients to promptly report any of the symptoms associated with PTC or papilledema (such as headache, tinnitus, dizziness, nausea, diplopia, blurry vision, loss of vision, and pain behind the eye or with eye movement). If symptoms persist, interrupt therapy or decrease the dose of cysteamine and refer the patient to an ophthalmologist. If the diagnosis of PTC or papilledema is confirmed, discontinue cysteamine therapy permanently.
Systemic cysteamine may cause lethargy and somnolence. Advise patients to be cautious when engaging in hazardous activities such as driving or operating machinery until the effects of cysteamine are known.
Systemic cysteamine should be used with caution in patients with a history of blood disorders including anemia and leukopenia. Such blood dyscrasias rarely can develop as a result of cysteamine therapy. Monitor complete blood counts during oral cysteamine therapy. If leukopenia persists, consider decreasing the dose or interrupting cysteamine therapy until values return to normal.
Use systemic cysteamine with caution in patients with a history of seizures. Cysteamine therapy has been associated with seizures and may exacerbate the condition.
Use systemic cysteamine with caution in patients with hepatic disease. Cysteamine has been associated with abnormal liver function tests and may exacerbate hepatic impairment. Monitor liver function during oral cysteamine therapy. If abnormal liver function tests persist, consider decreasing the dose or interrupting cysteamine therapy until values return to normal. The total daily ophthalmic dose is less than 2% of the recommended oral daily dose of cysteamine; thus, the systemic exposure after ophthalmic administration is expected to be negligible compared to oral administration.
Use systemic cysteamine with caution in patients with a history of GI disease. Oral cysteamine has been associated with GI toxicity, sometimes resulting in GI ulceration and GI bleeding. Evaluate patients with severe, persistent, and/or worsening abdominal pain for fibrosing colonopathy. Interrupt therapy and adjust the cysteamine dose if signs of GI toxicity occur. If signs of fibrosing colonopathy occur, permanently discontinue delayed-release cysteamine and switch to immediate-release cysteamine capsules. During postmarketing use, fibrosing colonopathy, including colonic stricture formation, was reported in pediatric and young adult patients with nephropathic cystinosis receiving delayed-release cysteamine capsules or oral granules. An association between methacrylic acid-ethyl acrylate copolymer (an inactive ingredient in delayed-release cysteamine) and fibrosing colonopathy cannot be ruled out.
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.
Cysteamine ophthalmic solution contains benzalkonium chloride, which may be absorbed by soft contact lenses. Remove contact lenses prior to administration; may reinsert 15 minutes following administration.
Advise patients to avoid ethanol ingestion during treatment with delayed-release cysteamine. Consumption of ethanol may increase the rate of cysteamine release and/or adversely affect the pharmacokinetics of cysteamine, altering the safety and effectiveness.
Serious dermatologic reactions are possible with systemic cysteamine therapy; monitor patients carefully. If a skin rash develops, withhold cysteamine therapy until the rash resolves. In clinical trials, non-serious reactions responded to cysteamine dose reduction. If a serious rash develops, such as erythema multiforme bullosa or toxic epidermal necrolysis, discontinue cysteamine permanently.
Bone lesions (e.g., osteopenia, compression bone fractures, scoliosis, and genu valgum) have been reported in some patients receiving high doses of cysteamine. These reactions have responded to cysteamine dose reduction. Monitor patients closely for bone abnormalities, and if such abnormalities occur, the dose of cysteamine should be reduced.
General dosing information
-Initiate cysteamine treatment immediately after diagnosis.
-Some patients may be unable to achieve their therapeutic target due to poor tolerability of delayed-release cysteamine.
For the treatment of cystinosis:
NOTE: The FDA has granted cysteamine orphan drug status for this indication.
-for the systemic treatment of nephropathic cystinosis:
Oral dosage (immediate-release capsules):
Adults: 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.
Adolescents weighing 50.5 kg or more: 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.
Children and Adolescents weighing 41.4 to 50.4 kg: 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.
Children and Adolescents weighing 32.3 to 41.3 kg: 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.
Children and Adolescents weighing 23.2 to 32.2 kg: 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.
Children weighing 18.7 to 23.1 kg: 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.
Children weighing 14.1 to 18.6 kg: 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.
Infants and Children weighing 9.6 to 14 kg: 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.
Infants and Children weighing 5 to 9.5 kg: 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.
Infants weighing less than 5 kg: 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.
Neonates weighing 5 to 9.5 kg: 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.
Neonates weighing less than 5 kg: 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.
Oral dosage (delayed-release capsules or granules):
Adults: 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.
Children and Adolescents weighing 51 kg or more: 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.
Children and Adolescents weighing 41 to 50 kg: 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.
Children and Adolescents weighing 31 to 40 kg: 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.
Children and Adolescents weighing 26 to 30 kg: 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.
Children and Adolescents weighing 21 to 25 kg: 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.
Children weighing 16 to 20 kg: 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.
Children weighing 11 to 15 kg: 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.
Children weighing 6 to 10 kg: 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.
Children weighing 5 kg or less: 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.
-for the treatment of corneal cystine crystal accumulation in patients with cystinosis:
Ophthalmic dosage (0.44% ophthalmic solution):
Adults: Instill 1 drop in each eye, every waking hour.
Infants, Children, and Adolescents: Instill 1 drop in each eye, every waking hour.
Neonates: Instill 1 drop in each eye, every waking hour.
Ophthalmic dosage (0.37% ophthalmic solution):
Adults: Instill 1 drop in each eye 4 times daily during waking hours.
Infants, Children, and Adolescents: Instill 1 drop in each eye 4 times daily during waking hours.
Neonates: Instill 1 drop in each eye 4 times daily during waking hours.
Therapeutic Drug Monitoring:
Target WBC cystine concentration (mixed leukocyte assay): less than 1 nmol/half cystine/mg protein
NOTE: WBC cystine concentrations may be measured using the mixed leukocyte assay or assays for specific WBC subsets (e.g., granulocyte method). Normal WBC cystine ranges and therapeutic targets for cystine depletion depend upon the assay used by the individual laboratory. Values using different assay methods may not be interchangeable. The assay-specific therapeutic target for cystine should be used to evaluate measurements.
Immediate-release capsules
-The goal of therapy is to keep the leukocyte cystine concentration less than 1 nmol/half cystine/mg protein 5 to 6 hours after administration of cysteamine. Patients with poor tolerability still significantly benefit if the leukocyte cystine concentration is less than 2 nmol/half cystine/mg protein.
-Increase the dose if leukocyte cystine concentration remains above 2 nmol/half cystine/mg protein.
-For treatment naive patients, measure leukocyte cystine concentrations every 3 months.
-Obtain measurements 5 to 6 hours after dose administration once the maintenance dose is achieved.
Delayed-release capsules
-The goal of therapy is to achieve a target leukocyte cysteine concentration of less than 1 nmol/half cystine/mg protein.
-For treatment naive patients 1 to 5 years, obtain measurement 2 weeks after cysteamine initiation and continue monitoring during dosage titration period until the therapeutic target WBC cystine concentration is achieved. After reaching the therapeutic target, continue monitoring monthly for 3 months, quarterly for 1 year, then twice yearly at a minimum.
-For treatment naive patients older than 6 years, obtain measurement after reaching the maintenance dose, monthly for 3 months, quarterly for 1 year, then twice yearly at a minimum.
-For patients switching from immediate-release cysteamine, obtain measurement after 2 weeks of treatment while titrating the dose, quarterly for 6 months, then twice yearly at a minimum.
-Obtain blood samples for a trough concentration, 12 hours after dosing and prior to administration of the next dose.
-If the measured WBC cystine concentration is above the target concentration for cystine depletion, consider adherence to medication, dosing interval, timing between last dose and blood draw, and the timing of administration in relation to food or other administration instructions.
Maximum Dosage Limits:
-Adults
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.
-Geriatric
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.
-Adolescents
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.
-Children
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.
-Infants
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.
-Neonates
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.
Patients with Hepatic Impairment Dosing
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.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
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.
Magnesium Salts: (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.
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.
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. 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.
-Route-Specific Pharmacokinetics
Oral Route
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.
Other Route(s)
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.
-Special Populations
Renal Impairment
The pharmacokinetics of delayed-release cysteamine were studied in non-cystinosis patients with renal impairment and healthy patients with normal renal function matched for age, body mass index, and sex. The exposure to cysteamine was increased in patients with renal impairment; however, this increase is not considered to be clinically meaningful. The mean AUC and mean Cmax after a single dose of 600 mg were 8% and 3% lower, respectively, in patients with mild renal impairment (eGFR 60 to 89 mL/minute/1.73 m2) compared to healthy patients. In patients with moderate renal impairment (eGFR 30 to 59 mL/minute/1.73 m2) and severe renal impairment (eGFR 29 mL/minute/1.73 m2 or less), the mean AUC was 49% and 35% higher and the mean Cmax was 27% and 11% higher, respectively, compared to healthy patients. The mean half-life was 7 hours, 8.3 hours, and 8.8 hours in patients with mild, moderate, and severe renal impairment, respectively, compared to 6.6 to 7.5 hours in healthy patients. In patients with end-stage renal disease receiving 4 hours of hemodialysis, the geometric mean Cmax and AUC of cysteamine was 60% higher when cysteamine was administered 3 hours before hemodialysis and 22% higher when administered 1 hour after completion of hemodialysis compared to healthy patients. Approximately 4.3% (25.6 mg) of the 600 mg cysteamine dose was removed with hemodialysis. The apparent clearance of cysteamine in patients who received the dose before hemodialysis was approximately 65 mL/minute.
Pediatrics
Children and Adolescents
The pharmacokinetics and pharmacodynamics of cysteamine bitartrate immediate-release were studied in 11 pediatric patients with nephropathic cystinosis who received 225 to 550 mg every 6 hours for more than 1 year. Tmax occurred at approximately 1.4 hours, and the Cmax was 2.6 mcg/mL. The apparent volume of distribution and plasma clearance of cysteamine were 156 L and 1.2 L/minute, respectively. The pharmacokinetics of delayed-release cysteamine were studied in 11 cysteamine treatment-naive patients ages 1 to 5 years with nephropathic cystinosis. The Cmax was reached at an average Tmax of 199 +/- 138 minutes and the mean 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 average half-life was 270 +/- 56 minutes. The pharmacokinetics of patients between the ages of 1 and 5 years of age are comparable with those in older pediatric patients and adults.