Version May 2024
Nephropathic cystinosis: Note: Begin therapy as soon as the diagnosis of nephropathic cystinosis has been confirmed.
Immediate release (Cystagon):
Oral: Initial: 1/6 to 1/4 of target maintenance dose administered in 4 divided doses; gradually increase dose over 4 to 6 weeks to a target maintenance dose of 500 mg 4 times daily (maximum: 1.95 g/m2/day).
Dosage adjustment: Adjust dose if needed to maintain target WBC cystine concentrations of <1 nmol/half-cystine/mg protein; patients experiencing therapy intolerance may still receive benefit when WBC cystine levels are <2 nmol/half-cystine/mg protein. Note: Before making dose adjustments, confirm therapy adherence, proper administration (including dosing interval and timing with food), and correct timing of blood draws.
Missed doses: Administer missed dose as soon as possible. If the next scheduled dose is due in <2 hours, skip the missed dose and resume the regular dosing schedule. Do not administer 2 doses at one time to make up for the missed dose.
Switching from cysteamine hydrochloride or phosphocysteamine solutions: Oral: Initiate immediate release cysteamine bitartrate at an equimolar dose to the cysteamine hydrochloride or phosphocysteamine dose; monitor WBC cystine concentrations 2 weeks after the switch, then every 3 months thereafter.
Delayed-release capsules, oral granules (Procysbi): Note: Round dose calculations to the nearest incremental dosage that can be administered using the available strengths of delayed-release capsules or packets of oral granules. Only use whole capsules or entire contents of the packets.
Oral: Initial: 0.2 to 0.3 g/m2/day in 2 divided doses every 12 hours; increase dose gradually over 4 to 6 weeks to target maintenance dose of 1.3 g/m2/day in 2 divided doses every 12 hours. May further increase in 10% increments if needed up to a maximum daily dose of 1.95 g/m2/day.
Missed doses: Administer missed dose as soon as possible up to 8 hours after the scheduled dose. If the next scheduled dose is due in <4 hours, skip the missed dose and resume the regular dosing schedule. Do not administer 2 doses at one time to make up for the missed dose.
Switching from immediate release cysteamine bitartrate to delayed release cysteamine bitartrate: Oral: Initiate delayed release cysteamine bitartrate at a total daily dose equal to the total daily dose of the immediate release formulation; divide the total daily dose in half and administer every 12 hours. If patient is unable to tolerate initial dose, decrease dose and gradually increase to maintenance dose. Monitor WBC cystine levels 2 weeks after the switch, then quarterly for 6 months, then a minimum of 2 times annually thereafter. Titrate the dose as needed to achieve target WBC cystine concentrations (maximum dose: 1.95 g/m2/day).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Gastrointestinal symptoms, (GI bleeding, nausea, vomiting, anorexia, or abdominal pain), transient skin rashes, CNS symptoms (eg, seizures, lethargy, somnolence, depression, encephalopathy):
Immediate release: Temporarily discontinue therapy. Reinitiate at a lower dose; titrate slowly.
Delayed release: Decrease dose. May temporarily discontinue therapy and reinitiate at a lower dose; titrate slowly. Some patients may be unable to achieve their therapeutic target.
Severe skin rashes (eg, erythema multiforme bullosa, toxic epidermal necrolysis): Permanently discontinue therapy.
Refer to adult dosing.
(For additional information see "Cysteamine (systemic): Pediatric drug information")
Note: Dosing presented as cysteamine base; may be presented as g/m2 or mg/kg; verify dosage unit for calculations; extra precautions should be taken.
Nephropathic cystinosis: Note: Begin therapy as soon as the diagnosis of nephropathic cystinosis has been confirmed.
Immediate release: Cystagon:
Manufacturer's labeling:
Initial dose: Infants, Children, and Adolescents: Oral: To avoid intolerance, initiate therapy with 1/6 to 1/4 of maintenance dose (see below for maintenance doses); titrate slowly upward over 4 to 6 weeks. Dosage adjustments should be made based on target WBC cystine levels.
Maintenance dose:Infants, Children, and Adolescents:
BSA-directed dosing: Oral: 1.3 g/m2/day divided into 4 doses up to 2,000 mg/day (500 mg 4 times daily); maximum daily dose: 1.95 g/m2/day.
Weight-directed dosing: Approximates dose of 1.3 g/m2/day; may increase if needed to achieve target WBC cystine concentrations; maximum daily dose: 1.95 g/m2/day: Oral:
<5 kg: 100 mg every 6 hours.
5 to <9.5 kg: 150 mg every 6 hours.
9.5 to <14 kg: 200 mg every 6 hours.
14 to <18.5 kg: 250 mg every 6 hours.
18.5 to <23 kg: 300 mg every 6 hours.
23 to <32 kg: 350 mg every 6 hours.
32 to <41 kg: 400 mg every 6 hours.
41 to ≤50 kg: 450 mg every 6 hours.
>50 kg: 500 mg every 6 hours.
Alternate dosing: Infants, Children, and Adolescents: Limited data available:
Weight-based dosing: Oral: Initial: 10 mg/kg/day divided into 4 doses daily; increase in 10 mg/kg/day increments until maintenance dose of 60 to 90 mg/kg/day divided into 4 doses daily is achieved (Gahl 2002); maximum daily dose: 1.95 g/m2/day.
Weight-directed dosing: Oral: Based on a population pharmacokinetic model (n=69, mean age: 12.5 years, range: 0.4 to 36 years) (Bouazza 2011); maximum daily dose: 1.95 g/m2/day.
10 to <17 kg: 20 mg/kg/dose every 6 hours.
17 to <25 kg: 17.5 mg/kg/dose every 6 hours.
25 to <40 kg: 15 mg/kg/dose every 6 hours.
40 to 70 kg: 12.5 mg/kg/dose every 6 hours.
Switching from cysteamine hydrochloride or phosphocysteamine solutions to cysteamine bitartrate: Initiate immediate release cysteamine bitartrate at an equimolar dose to the cysteamine hydrochloride or phosphocysteamine.
Delayed release: Procysbi: Capsules, granules for oral suspension: Note: Round dose to nearest available strength of granule packet size or capsule; packets and capsule contents should not be split.
Children and Adolescents:
Initial dose: Oral: Initiate therapy with 1/6 to 1/4 of maintenance dose and round as appropriate based on available dosage forms:
<6 kg: 25 to 50 mg every 12 hours.
6 to <11 kg: 50 to 75 mg every 12 hours.
11 to <16 kg: 75 to 100 mg every 12 hours.
16 to < 21 kg: 100 to 125 mg every 12 hours.
21 to < 26 kg: 100 to 150 mg every 12 hours.
26 to <31 kg: 125 to 175 mg every 12 hours.
31 to <41 kg: 125 to 200 mg every 12 hours.
41 to <51 kg: 150 to 225 mg every 12 hours.
≥51 kg: 175 to 250 mg every 12 hours.
Titration:
Children <6 years: Gradually increase dose in 10% increments every 2 weeks (or longer) until target WBC cystine concentration or maintenance dose is achieved. If the therapeutic target WBC cystine concentration is achieved at a dosage below the recommended maintenance dose, discontinue dose escalation and use dose as the maintenance dose.
Children ≥6 years and Adolescents: Gradually increase dose in 10% increments over 4 to 6 weeks until maintenance dose is achieved.
Maintenance dose: Note: In some cases, higher doses may be necessary to achieve target therapeutic WBC cysteine concentrations.
BSA-directed dosing: Oral: 1.3 g/m2/day divided every 12 hours; may increase as needed in 10% increments to achieve target WBC cystine concentrations; maximum daily dose: 1.95 g/m2/day.
Weight-directed dosing: Oral:
<6 kg: 200 mg every 12 hours.
6 to <11 kg: 300 mg every 12 hours.
11 to <16 kg: 400 mg every 12 hours.
16 to <21 kg: 500 mg every 12 hours.
21 to <26 kg: 600 mg every 12 hours.
26 to <31 kg: 700 mg every 12 hours.
31 to <41 kg: 800 mg every 12 hours.
41 to <51 kg: 900 mg every 12 hours.
≥51 kg: 1,000 mg every 12 hours.
Switching from immediate release cysteamine bitartrate to delayed release cysteamine bitartrate: Initiate delayed release cysteamine bitartrate at a total daily dose equal to the total daily dose of the immediate release formulation and divide into 2 doses per day every 12 hours.
Dosing adjustment for toxicity:
Gastrointestinal symptoms (gastrointestinal bleeding, nausea, vomiting, anorexia, or abdominal pain), transient skin rashes, CNS symptoms (eg, seizures, lethargy, somnolence, depression, encephalopathy):
Immediate release (Cystagon): Infants, Children, and Adolescents: Temporarily discontinue therapy. Reinitiate at a lower dose; titrate slowly.
Delayed release (Procysbi): Children and Adolescents: Decrease dose. May temporarily discontinue therapy and reinitiate at a lower dose; titrate slowly.
Severe skin rashes (eg, erythema multiforme bullosa, toxic epidermal necrolysis): Infants, Children, and Adolescents: Permanently discontinue therapy.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Immediate release as reported in children. Delayed release as reported in children, adolescents, and adults.
>10%:
Gastrointestinal: Abdominal distress (delayed release: ≤14%), abdominal pain (≤14%), anorexia (immediate release: 31%; delayed release: 2%), diarrhea (16%), nausea (≤16%), vomiting (immediate release: 35%; delayed release: 19%)
Nervous system: Lethargy (immediate release: 11%)
Miscellaneous: Fever (immediate release: 22%)
1% to 10%:
Cardiovascular: Hypertension (immediate release: ≤5%)
Dermatologic: Skin rash (>5% to 7%), urticaria (immediate release: ≤5%)
Endocrine & metabolic: Dehydration (immediate release: ≤5%)
Gastrointestinal: Constipation (immediate release: ≤5%), duodenitis (immediate release: ≤5%), dyspepsia (immediate release: ≤5%), gastroenteritis (immediate release: ≤5%), gastrointestinal hemorrhage (immediate release: ≤5%), gastrointestinal ulcer (immediate release: ≤5%), halitosis (immediate release: ≤5%)
Hematologic & oncologic: Anemia (immediate release: ≤5%), leukopenia (immediate release: ≤5%)
Hepatic: Abnormal hepatic function tests (immediate release: ≤5%)
Nervous system: Abnormality in thinking (immediate release: ≤5%), ataxia (immediate release: ≤5%), confusion (immediate release: ≤5%), depression (immediate release: ≤5%), dizziness (≤5%), drowsiness (immediate release: ≤5%), emotional lability (immediate release: ≤5%), encephalopathy (immediate release: ≤5%), hallucination (immediate release: ≤5%), headache (5% to 9%), jitteriness (immediate release: ≤5%), nervousness (immediate release: ≤5%), nightmares (immediate release: ≤5%), seizure (immediate release: ≤5%)
Neuromuscular & skeletal: Hyperkinetic muscle activity (immediate release: ≤5%), tremor (immediate release: ≤5%)
Otic: Hearing loss (immediate release: ≤5%)
Renal: Interstitial nephritis (immediate release: ≤5%), renal failure syndrome (immediate release: ≤5%)
Frequency not defined:
Endocrine & metabolic: Electrolyte disorder
Gastrointestinal: Viral gastroenteritis
Hepatic: Increased serum alkaline phosphatase
Hypersensitivity: Anaphylaxis, hypersensitivity reaction
Postmarketing:
Dermatologic: Atrophic striae, cutaneous nodule (molluscoid pseudotumors), fragile skin, skin lesion, Stevens-Johnson syndrome, toxic epidermal necrolysis
Gastrointestinal: Gastrointestinal disease (fibrosing colonopathy [including colonic stricture])
Nervous System: Idiopathic intracranial hypertension
Neuromuscular & skeletal: Abnormal bone growth (genu valgum), arthropathy (joint hyperextension), connective tissue disease (Ehlers Danlos-like syndrome), lower extremity pain, osteopenia, scoliosis, vertebral compression fracture
Ophthalmic: Papilledema
Hypersensitivity to cysteamine, penicillamine, or any component of the formulation
Concerns related to adverse effects:
• CNS symptoms: Depression, lethargy, seizures, somnolence, and encephalopathy have been reported in patients receiving the immediate-release formulation; may also occur due to cystinosis not treated with cysteamine. Treatment interruption or dosage reduction may be required in patients with severe or persistent/progressive symptoms. Patients should use caution when driving or operating heavy machinery until the effects are known.
• Dermatologic: Skin rashes (including erythema multiforme bullosa and toxic epidermal necrolysis) have occurred in patients receiving the immediate-release formulation. In patients who develop severe skin rashes, permanently discontinue therapy.
• Ehlers-Danlos-like syndrome: Ehlers-Danlos-like clinical findings, including skin lesions (eg, molluscoid pseudotumors, skin striae), bone lesions (osteopenia, compression fractures, scoliosis, and genu valgum), leg pain, and joint hyperextension, have occurred with high doses of the immediate-release formulation. A fatality (with serious skin lesions on immediate-release formulation) has been reported. Monitor for development of skin or bone lesions; interruption of therapy and subsequent dosage reduction with slow titration to therapeutic dose may be required if these symptoms develop.
• Fibrosing colonopathy: Procysbi: Fibrosing colonopathy, advancing to colonic strictures, has been reported in pediatric and young adult patients with nephrotic cystinosis. Symptoms included abdominal pain, bloody or persistent diarrhea, fecal incontinence, and vomiting. Risk may be associated with methacrylic acid-ethyl acrylate copolymer, an inactive ingredient in delayed-release products. Permanently discontinue therapy and switch to immediate-release cysteamine in patients who develop fibrosing colonopathy.
• Gastrointestinal symptoms: Gastrointestinal ulcers and bleeding, nausea, vomiting, anorexia, and abdominal pain have been reported in patients receiving the immediate-release formulation. GI symptoms are most commonly seen during the initiation of therapy. If severe symptoms occur, consider a dosage reduction.
• Hematologic: May cause reversible leukopenia. Monitor WBCs; if leukopenia occurs, consider a dosage reduction or discontinuing the drug until values return to normal.
• Hepatic: May cause elevated alkaline phosphatase levels. Monitor alkaline phosphatase; if elevation occurs, consider a dosage reduction or discontinuing the drug until values return to normal.
• Intracranial hypertension/papilledema: Benign intracranial hypertension (pseudotumor cerebri [PTC]) and/or papilledema have been reported in patients receiving the immediate-release formulation; monitor for signs and symptoms of PTC (eg, headache, tinnitus, dizziness, nausea, diplopia, blurred vision, loss of vision, pain behind the eye or with eye movement). If symptoms persist, interrupt dosing or decrease the dose and refer to an ophthalmologist. If diagnosis is confirmed, permanently discontinue therapy.
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.
Other warnings/precautions:
• Appropriate use: Nephropathic cystinosis: Initiate therapy as soon as the diagnosis has been confirmed.
Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Cystagon: 50 mg, 150 mg
Capsule Delayed Release, Oral:
Procysbi: 25 mg, 75 mg
Packet, Oral:
Procysbi: 75 mg (1 ea); 300 mg (1 ea)
No
Capsule, delayed release (Procysbi Oral)
25 mg (per each): $137.54
75 mg (per each): $137.54
Capsules (Cystagon Oral)
50 mg (per each): $0.38
150 mg (per each): $1.11
Pack (Procysbi Oral)
75 mg (per each): $137.54
300 mg (per each): $550.19
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule Delayed Release, Oral:
Procysbi: 25 mg, 75 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Oral:
Immediate release (Cystagon): If unable to swallow capsules whole, sprinkle capsule contents over food or mix in juice (Gahl 2002).
Delayed release (Procysbi):
Capsules: Swallow capsules whole with fruit juice (except grapefruit juice) or water; do not crush or chew. Administer ≥30 minutes before and ≥2 hours after meals; if necessary, patients may eat only a small amount (~4 ounces or 1/2 cup) of food between 1 hour before and 1 hour after administration. Avoid high-fat food close to time of dose. Administer ≥1 hour before or 1 hour after medications containing bicarbonate or carbonate. Maintain consistency of administration with regard to food. Alternatively, may sprinkle intact granules from capsule on a small amount of applesauce or berry jelly (≤4 ounces, as small as necessary to be consumed in 1 feeding) or add to ~4 ounces of fruit juice (except grapefruit juice) and mix gently after adding to food or juice. Administer within 30 minutes of adding to food or drink; do not save mixture for later use or chew granules.
Oral granules: Sprinkle and mix intact granules on a small amount of applesauce or berry jelly (≤4 ounces, as small as necessary to be consumed in 1 feeding) or add to ~4 ounces of fruit juice (except grapefruit juice) and mix gently after adding to food or juice; do not crush or chew granules. Administer within 30 minutes of adding to food or drink; do not save mixture for later use. Administer ≥30 minutes before and ≥2 hours after meals; if necessary, patients may eat only a small amount (~4 ounces or 1/2 cup) of food between 1 hour before and 1 hour after administration. Avoid high-fat food close to time of dose. Administer ≥1 hour before or 1 hour after medications containing bicarbonate or carbonate. Maintain consistency of administration with regard to food.
Gastrostomy tube: In patients with a 14 French or larger gastrostomy tube, intact granules (from an opened delayed-released capsule or using oral granules) may be mixed with ~4 ounces of strained applesauce. Draw mixture into a syringe, keep the feeding tube horizontal, apply rapid and steady syringe pressure (10 mL per 10 seconds), and administer within 30 minutes of mixing; do not save mixture for later use. Fill another syringe with ≥10 mL fruit juice (except grapefruit juice) or water, swirl gently, and flush the tube.
Oral:
Immediate release: Cystagon: In infants, children <6 years of age, or those unable to swallow capsules, sprinkle capsule contents over food or mix in juice (Gahl 2002).
Missed doses: Administer missed dose as soon as possible. If the next scheduled dose is due in <2 hours, skip the missed dose and resume the regular dosing schedule.
Delayed release: Procysbi: Best if administered on an empty stomach. Avoid food consumption at least 2 hours prior to and for at least 30 minutes after cysteamine dose to maximize absorption. If patient unable to tolerate without food, patients may eat only a small amount (~4 ounces or 1/2 cup) of food between 1 hour before and 1 hour after administration; avoid high-fat food close to time of dose. Administer at least 1 hour before or 1 hour after medications containing bicarbonate or carbonate. Maintain consistency of administration with regard to food.
Capsules: Swallow capsules whole with fruit juice (except grapefruit juice) or water; do not crush or chew capsule or capsule contents. Alternatively, may open capsule and sprinkle intact granules on a small amount of applesauce or berry jelly (≤4 ounces, as small as necessary to be consumed in one feeding) or add to ~4 ounces of fruit juice (except grapefruit juice); mix gently after adding to food or juice; do not crush granules. Administer within 30 minutes of adding to food or drink; do not save mixture for later use or chew granules.
Granules: Open packet, sprinkle and mix intact granules on a small amount of applesauce or berry jelly (≤4 ounces, as small as necessary to be consumed in 1 feeding) or add to ~4 ounces of fruit juice (except grapefruit juice), and mix gently after adding to food or juice; do not crush or chew granules. Administer within 30 minutes of adding to food or drink; do not save mixture for later use.
Gastrostomy tube (≥14 French): Flush gastrostomy tube button with 5 mL of water prior to administration. Open capsule or packet and mix intact granules with ~4 ounces of strained applesauce. In children ≤25 kg (starting at a dose of 1 or 2 capsules or packets), a minimum of 1 ounce of strained applesauce may be used. Draw mixture into a syringe, keep the feeding tube horizontal, apply rapid and steady syringe pressure (10 mL/10 seconds), and administer within 30 minutes of mixing; do not save mixture for later use. Fill another syringe with ≥10 mL fruit juice (except grapefruit juice) or water, swirl gently, and flush the tube.
Missed doses: Administer missed dose as soon as possible up to 8 hours after the scheduled dose. If the next scheduled dose is due in <4 hours, skip the missed dose and resume the regular dosing schedule. Do not take 2 doses at one time to make up for the missed dose.
Nephropathic cystinosis: Management of nephropathic cystinosis in adults and pediatric patients ≥1 year of age.
Mercaptamine [multiple international markets] and also a synonym for cysteamine (systemic) may be confused with mercaptopurine
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): May enhance the adverse/toxic effect of Cysteamine (Systemic). Alcohol (Ethyl) may diminish the therapeutic effect of Cysteamine (Systemic). Risk X: Avoid combination
Antacids: May diminish the therapeutic effect of Cysteamine (Systemic). Risk C: Monitor therapy
Histamine H2 Receptor Antagonists: May diminish the therapeutic effect of Cysteamine (Systemic). Risk C: Monitor therapy
Inhibitors of the Proton Pump (PPIs and PCABs): May diminish the therapeutic effect of Cysteamine (Systemic). Risk C: Monitor therapy
Concurrent ingestion of food and the delayed-release formulation (capsules and oral granules) of cysteamine can reduce the systemic exposure of cysteamine. Management: Administer ≥30 minutes before and ≥2 hours after meals; if necessary, patients may eat only a small amount (~4 ounces or 1/2 cup) of food between 1 hour before and 1 hour after administration.
Adverse events were observed in animal reproduction studies
It is not known if cysteamine is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.
Delayed release (capsules, oral granules): Do not administer with grapefruit juice. Take ≥30 minutes before and ≥2 hours after meals; if necessary, may eat only a small amount (~4 ounces or 1/2 cup) of food between 1 hour before and 1 hour after administration. Avoid high fat food close to time of dose. Avoid alcohol intake during therapy.
General: Monitor blood counts and LFTs (including alkaline phosphatase) during therapy; monitor for signs and symptoms of GI ulceration and bleeding, skin and bone lesions, skin rashes, pseudotumor cerebri, and fibrosing colonopathy (delayed-release products). Perform periodic ophthalmic examinations.
Cysteamine-naive patients starting on the immediate-release capsule formulation: Monitor WBC cystine after reaching maintenance dose, then a minimum of every 3 months thereafter.
Cysteamine-naive patients starting directly on the delayed-release formulation:
Children <6 years of age: Monitor WBC cystine 2 weeks after treatment initiation and continue monitoring during dosage titration period until the therapeutic target WBC cystine concentration is achieved. Once the therapeutic target is achieved, monitor monthly for 3 months, then every 3 months for 1 year, and then a minimum of twice annually thereafter.
Children ≥6 years of age, Adolescents, and Adults: Monitor WBC cystine after reaching maintenance dose, then monthly for 3 months, then every 3 months for 1 year, then a minimum of twice annually thereafter.
Switching from cysteamine hydrochloride or phosphocysteamine solutions to cysteamine bitartrate: Monitor WBC cystine concentrations 2 weeks after the switch, then every 3 months thereafter.
Patients switching to the delayed-release formulation from the immediate-release formulation: Monitor WBC cystine concentrations 2 weeks after the switch; continue monitoring if further dosage adjustment is needed. Once therapeutic target WBC cystine concentration is achieved, monitor every 3 months for 6 months, and then a minimum of twice annually thereafter.
Note: Normal WBC cystine ranges and therapeutic target concentrations for cystine depletion may vary based on the assay method used. WBC cystine values obtained using different assay methods may not be interchangeable. Check with institution laboratory to determine assay method used and associated concentrations.
WBC (leukocyte) cystine (using the mixed leukocyte assay):
Normal individual: WBC cystine: <0.2 nmol/half-cystine/mg protein
Cystinosis target: WBC cystine: <1 nmol/half-cystine/mg protein (if poor tolerability to cysteamine, may still benefit from leukocyte cystine levels <2 nmol/half-cystine/mg protein)
Timing of samples (WBC cystine):
Immediate release: 5 to 6 hours postdose
Delayed release: 12 hours postdose (immediately prior to next dose)
Reacts with cystine within the lysosome to convert it to cysteine and to a cysteine-cysteamine mixed disulfide, both of which can then exit the lysosome in patients with cystinosis, an inherited defect of lysosomal transport
Onset of action: Immediate release: 1.8 ± 0.8 hours; Delayed release: 3 to 3.5 hours
Duration: Immediate release: 6 hours; Delayed release: ~12 hours
Distribution: Vd: Immediate release: Pediatric patients: 156 L; however variability has been reported 180 ± 112 L (Langman 2012); reported data adjusted for weight: Children and Adolescents 3 to 15 years: Median 9.9 L/kg (range: 2.7 to 32.3 L/kg) (Belldina 2003); Adults: ~198 L; Delayed release: Children and Adolescents: 356 ± 376 L (Langman 2012); Adults: ~382 L
Protein binding: ~52%, predominantly to albumin
Half-life elimination: Immediate release: Children and Adolescents: 1.5 ± 0.4 hours (Langman 2012); Adults: 1.5 hours; Delayed release: Children and Adolescents: 4.2 ± 6.8 hours (Langman 2012); Adults: 4.2 hours
Time to peak, plasma: Immediate release: Children and Adolescents: Mean range: 1.2 to 1.4 hours (range 1 to 2 hours) (Belldina 2003; Langman 2012); Adults: ~1.4 hours; Delayed release: 3 to 4.6 hours
Altered kidney function: Following a single 600 mg dose of delayed-release cysteamine in noncystinosis subjects with moderate renal impairment (eGFR 30 to 59 mL/minute/1.73 m2) and severe renal impairment (≤29 mL/minute/1.73 m2), the mean cysteamine AUCinf was 49% and 35% higher and Cmax was 27% and 11% higher, respectively, compared to healthy subjects. Mean t½ was 8.3 hours and 8.8 hours in subjects with moderate and severe renal impairment, respectively, compared to a range of 6.6 to 7.5 hours in healthy subjects. In subjects with end-stage renal disease, mean cysteamine Cmax and AUCinf was 60% higher when dose administered 3 hours before hemodialysis and 22% higher when administered 1 hour following hemodialysis, compared to healthy subjects. Approximately 4.3% of the 600 mg dose was removed by hemodialysis.
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