SYPRINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SYPRINE (SYPRINE).
Syprine (trientine hydrochloride) is a chelating agent that forms stable complexes with copper, thereby increasing urinary excretion of copper and reducing pathological copper accumulation in tissues.
| Metabolism | Trientine is metabolized by acetylation, primarily to N1-acetyltrientine, with minor pathways involving N1,N10-diacetyltrientine. The exact enzymes involved in acetylation are unknown but likely include N-acetyltransferases. |
| Excretion | Primarily renal (approximately 50% unchanged within 24 hours after oral administration); biliary/fecal elimination accounts for a minor fraction (less than 10%). |
| Half-life | Approximately 48 hours in healthy subjects, reflecting prolonged accumulation with regular dosing, requiring careful monitoring for toxicity. |
| Protein binding | Approximately 50% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 3.5 L/kg, indicating extensive distribution into total body water and tissues, including copper accumulation sites (liver, brain). |
| Bioavailability | Oral: Approximately 30% due to variable intestinal absorption and first-pass metabolism; food reduces absorption, so administer on an empty stomach. |
| Onset of Action | Oral: Clinical effect (copper chelation) may become evident within 2 to 4 weeks; maximal reduction of serum free copper typically occurs after 4 to 6 weeks of continuous therapy. |
| Duration of Action | Chelation effect persists for up to 6 to 8 hours after a single oral dose; however, clinical benefit requires sustained therapy with doses spaced every 6 to 12 hours. |
250 mg to 500 mg orally 4 times daily, maximum 2000 mg daily.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 25%; GFR 15-29 mL/min: reduce dose by 50%; GFR <15 mL/min: avoid use. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use. |
| Pediatric use | Children 2-12 years: 12.5 mg/kg orally twice daily, titrating to 25 mg/kg twice daily; maximum 1500 mg daily. |
| Geriatric use | Start at 125 mg orally 4 times daily; titrate based on renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SYPRINE (SYPRINE).
| Breastfeeding | Trientine is excreted into breast milk in low concentrations. The M/P ratio is not established. Limited data suggest infant doses are less than 1% of maternal weight-adjusted dose, but due to potential for copper deficiency in the infant, breastfeeding is not recommended during therapy unless benefits outweigh risks. |
| Teratogenic Risk | Trientine hydrochloride (SYPRINE) is classified as FDA Pregnancy Category C. In animal studies, trientine caused fetal skeletal abnormalities and increased resorptions at doses similar to human therapeutic doses. Human data are limited; however, case reports suggest possible teratogenic effects including skeletal defects and developmental delay. First trimester exposure carries highest risk; risk in second and third trimesters is lower but may affect fetal copper metabolism and growth. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to trientine or any component of the formulation","Rheumatoid arthritis (due to risk of iron deficiency anemia and potential for systemic lupus erythematosus-like reactions)"]
| Precautions | ["Monitor for signs of copper deficiency (e.g., anemia, leukopenia, thrombocytopenia)","Monitor neurologic symptoms; worsening may occur upon initiation due to mobilization of copper","Monitor for hypersensitivity reactions; discontinue if systemic lupus erythematosus-like reactions or other allergic manifestations occur","Avoid concomitant iron supplementation, as iron complexes with trientine reducing efficacy; separate administration by at least 2 hours if iron required","Monitor liver function and copper levels regularly"] |
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| Fetal Monitoring | Monitor maternal: serum copper (total and free), ceruloplasmin, liver function tests, complete blood count, urinalysis, and neurological exams. Fetal: serial ultrasound for growth and anatomy, consider fetal echocardiogram. Neonatal: copper levels, ceruloplasmin, and neurological assessment after birth. |
| Fertility Effects | No specific human studies on fertility. In animal studies, trientine did not impair fertility. However, copper deficiency induced by therapy may theoretically affect ovulation or spermatogenesis. In Wilson disease, untreated disease may impair fertility; treatment may restore reproductive function. |