PROCYSBI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROCYSBI (PROCYSBI).
PROCYSBI (cysteamine bitartrate) delayed-release capsules are a cystine-depleting agent. Cysteamine reacts with cystine to form cysteine and a cysteine-cysteamine mixed disulfide, thereby reducing intralysosomal cystine accumulation in cells.
| Metabolism | Extensively metabolized primarily by flavin-containing monooxygenase (FMO) and to a lesser extent by CYP450 isozymes (CYP3A4, CYP2C19, CYP2C9, CYP2D6, CYP1A2, and CYP2E1) to various metabolites. |
| Excretion | Primarily renal (approximately 50% of the absorbed dose excreted unchanged in urine); fecal elimination accounts for about 3-4%. |
| Half-life | 2.5-3 hours for cysteamine; clinical efficacy is related to maintaining low intracellular cystine levels, requiring administration every 12 hours. |
| Protein binding | Negligible (<5%) to plasma proteins. |
| Volume of Distribution | Approximately 0.4 L/kg, indicating distribution primarily in total body water. |
| Bioavailability | Oral bioavailability is approximately 30% (range 20-40%) due to first-pass metabolism. |
| Onset of Action | Absorption begins within 1-2 hours; clinical reduction in leukocyte cystine levels observed within 2-4 weeks of consistent dosing. |
| Duration of Action | Dosing interval of 12 hours maintains therapeutic cystine levels; leukocyte cystine levels return to baseline if dose is missed. |
250 mg to 500 mg twice daily (every 12 hours) orally for patients weighing >50 kg; adjust based on cystine concentrations.
| Dosage form | GRANULE, DELAYED RELEASE |
| Renal impairment | No specific dose adjustment recommended; monitor renal function and adjust per cystine levels. |
| Liver impairment | No specific Child-Pugh-based adjustments; use with caution in severe impairment. |
| Pediatric use | Children ≥6 years: 250 mg to 500 mg twice daily based on body weight (target dose 1.0-1.3 g/m²/day) or 20-30 mg/kg/day divided every 12 hours. |
| Geriatric use | No specific adjustments; start at lower end of dosing range and titrate based on response and tolerance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROCYSBI (PROCYSBI).
| Breastfeeding | It is unknown whether cysteamine is excreted in human breast milk. The M/P ratio has not been determined. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy. Consider discontinuation of nursing or drug, taking into account importance of drug to mother. |
| Teratogenic Risk | Procysbi (cysteamine bitartrate) is classified as FDA Pregnancy Category C. In animal studies, cysteamine caused fetal malformations and embryotoxicity at doses similar to human therapeutic levels. There are no adequate and well-controlled studies in pregnant women. During the first trimester, there is potential risk for structural abnormalities. In the second and third trimesters, there is ongoing risk of adverse effects on fetal growth and development. Use only if potential benefit justifies potential risk to the fetus. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to cysteamine or penicillamine.","Breastfeeding: not recommended due to potential adverse effects.","Concurrent use with alcohol or alcohol-containing products."]
| Precautions | ["Eosinophilia and severe skin reactions (e.g., erythema multiforme, Stevens-Johnson syndrome) have been reported; discontinue if severe or with associated symptoms.","CNS symptoms: benign intracranial hypertension (pseudotumor cerebri), seizures, lethargy, somnolence, depression, and encephalopathy; monitor and discontinue if symptoms develop.","Gastrointestinal ulceration and bleeding: use with caution in patients with a history of peptic ulcer disease.","Neutropenia and/or pancytopenia: monitor white blood cell counts regularly.","Vitamin and mineral deficiencies (e.g., vitamin B12, iron, zinc) due to gastrointestinal effects may occur.","Hemorrhagic cystitis: discontinue if occurs.","Renal function: monitor renal parameters.","Drug interactions: coadministration with alcohol may cause disulfiram-like reaction."] |
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| Fetal Monitoring | Monitor maternal serum cysteamine levels to ensure therapeutic range (typically 50-150 µmol/L). Perform periodic liver function tests (AST, ALT, alkaline phosphatase), complete blood counts, and renal function tests (serum creatinine, BUN). Monitor for vitamin B12 deficiency and hyperammonemia. In pregnant women, perform fetal ultrasound to assess growth and anatomy as per standard obstetrical care. |
| Fertility Effects | In animal studies, cysteamine caused decreased fertility and implantations at high doses. Human data on fertility effects are lacking. Male patients should be aware of potential oligospermia or azoospermia. Fertility recovery after discontinuation is not well characterized. |