CYSTAGON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CYSTAGON (CYSTAGON).
Cysteamine reduces cystine accumulation in lysosomes by reacting with cystine to form cysteine and a mixed disulfide of cysteine and cysteamine, which can exit lysosomes via the lysosomal cystine transporter and the lysosomal lysine transporter, thereby decreasing intra-lysosomal cystine levels.
| Metabolism | Extensively metabolized in the liver and intestinal mucosa via oxidation to taurine and other metabolites; also involves mixed disulfide formation. |
| Excretion | Renal elimination of unchanged drug is the primary route. After oral administration, approximately 50% of a dose is excreted unchanged in urine within 24 hours. Minimal biliary/fecal excretion (<5%). |
| Half-life | Terminal elimination half-life is approximately 2-3 hours in patients with normal renal function. Clinically, this necessitates dosing every 6 hours to maintain therapeutic trough concentrations above the threshold required for cystine depletion. |
| Protein binding | Cysteamine (active metabolite) is minimally protein bound; approximately 10% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is approximately 0.5-1.0 L/kg, indicating distribution into total body water and some tissue binding. |
| Bioavailability | Absolute bioavailability of cysteamine (Cystagon) is approximately 40-75% after oral administration due to first-pass metabolism. Food may reduce absorption; administered as immediate-release capsules. |
| Onset of Action | Oral: Reduction in intracellular cystine levels begins within 1-2 hours after administration, with maximal cystine depletion achieved after several days of consistent dosing. |
| Duration of Action | Duration of cystine-lowering effect is approximately 6-8 hours post-dose, consistent with the dosing interval of every 6 hours. Clinical effect on stone prevention requires continuous therapy. |
1.95 g/m²/day orally in 4 divided doses, up to a maximum of 1.95 g/day.
| Dosage form | CAPSULE |
| Renal impairment | No specific dose adjustment guidelines for GFR; use with caution in renal impairment as drug is renally excreted. |
| Liver impairment | No specific dose adjustment guidelines for Child-Pugh class; monitor hepatic function. |
| Pediatric use | Weight-based dosing: 50 mg/kg/day orally in 4 divided doses, titrated to maintain leukocyte cystine level <1 nmol half-cystine/mg protein. |
| Geriatric use | No specific dose adjustment; start at lower end of dosing range due to potential age-related renal decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CYSTAGON (CYSTAGON).
| Breastfeeding | No data available on excretion into human breast milk. M/P ratio unknown. Due to potential for adverse reactions in nursing infants, caution is advised; consider alternative treatments or discontinue breastfeeding during therapy. |
| Teratogenic Risk | FDA Pregnancy Category C. Animal studies have shown teratogenic effects (embryotoxicity, skeletal anomalies) at doses near the human therapeutic dose. There are no adequate and well-controlled studies in pregnant women. Potential risks to fetus cannot be ruled out; use only if benefit outweighs risk. First trimester: highest risk for congenital anomalies; second and third trimesters: risk of fetal nephrolithiasis and possible growth retardation. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to cysteamine or any component of the formulation; concurrent use with vitamin K antagonists (e.g., warfarin) due to increased INR and bleeding risk.
| Precautions | Monitor for neutropenia, seizure activity, gastrointestinal ulceration, and rash. Caution in patients with renal impairment or hepatic disease. May cause lethargy, somnolence, and depression. Avoid abrupt discontinuation. |
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| Fetal Monitoring | Monitor maternal renal function (serum creatinine, BUN, urinalysis) regularly due to risk of nephrolithiasis. Ultrasound monitoring of fetal kidney development and amniotic fluid volume during pregnancy. Monitor fetal growth and development via serial ultrasounds. Assess for maternal symptoms of cystinuria exacerbation (e.g., urinary tract infections, colic). |
| Fertility Effects | No clinical studies on fertility effects in humans. Animal studies have not shown impairment of fertility at therapeutic doses. However, the underlying disease (cystinuria) may affect reproductive health; consider individualized assessment. |