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. |
| Molecular Weight | 293.44 |
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 | Risk cannot be ruled out. Animal studies have shown teratogenic effects. Use only if potential benefit justifies potential risk to fetus. |
| 2nd trimester | Risk cannot be ruled out. Limited human data. Use only if clearly needed. |
| 3rd trimester | Risk cannot be ruled out. May cause copper deficiency in newborn if used near term. |
Clinical note
Comprehensive clinical and safety monograph for SYPRINE (SYPRINE).
| Placental transfer | Trientine crosses the placenta based on animal studies and detection in cord blood. Extent of transfer is unknown but likely moderate. |
| Breastfeeding | Trientine is excreted into breast milk in low amounts. Consider risk of copper deficiency in infant; monitor infant's serum copper levels. Use with caution, only if clearly needed. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to trientine or any componentRheumatoid arthritis (due to risk of developing autoimmune disordersCystinuria (trientine can increase urinary cystine excretion)
| 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 |
| Food/Dietary | Take on an empty stomach; food reduces absorption. Avoid high-copper foods: chocolate, nuts, seeds, shellfish, liver, mushrooms, and whole grains. Separate from dairy products and mineral supplements by at least 1 hour. |
Loading safety data…
| Lactation Rating |
| L3 - Limited data, probably compatible |
| 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. |
| 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. |
| Clinical Pearls | SYPRINE (trientine hydrochloride) is a copper-chelating agent used for Wilson disease. Monitor for iron deficiency anemia due to chelation; avoid concurrent iron supplementation. Administer on an empty stomach (at least 1 hour before or 2 hours after meals) to maximize absorption. Monitor urine copper levels to assess compliance and efficacy. Neurologic worsening may occur initially; slow dose titration is recommended. |
| Patient Advice | Take SYPRINE on an empty stomach, at least 1 hour before or 2 hours after meals, and at least 1 hour apart from any other medications, supplements, or food. · Do not take iron supplements or mineral supplements containing zinc, iron, or other metals within 2 hours of SYPRINE, as they can reduce its effectiveness. · Report any signs of iron deficiency anemia such as fatigue, paleness, or shortness of breath to your healthcare provider. · Adhere to a low-copper diet as recommended by your healthcare provider; avoid foods high in copper like chocolate, nuts, shellfish, liver, and mushrooms. · Do not stop taking SYPRINE abruptly; consult your healthcare provider before discontinuing. · Keep all appointments for blood and urine tests to monitor treatment response and side effects. |