CUPRIMINE
Clinical safety rating
cautionComprehensive clinical and safety monograph for CUPRIMINE (CUPRIMINE).
Chelates copper, forming a stable complex that is excreted renally, reducing systemic copper accumulation.
| Metabolism | Metabolized by oxidation and reduction; primarily renal elimination. |
| Excretion | Renal: ~80% as unchanged drug, biliary/fecal: <5% |
| Half-life | Terminal half-life: 4–6 hours. Clinical context: After discontinuation, urinary copper excretion declines within 2–3 hours but may persist for several days due to tissue redistribution. |
| Protein binding | ~70% bound, primarily to serum albumin. |
| Volume of Distribution | Vd: 0.5–1.0 L/kg (approximately 70 L in adults). Indicates distribution into total body water with moderate tissue binding. |
| Bioavailability | Oral: Approximately 40–70% (variable, reduced by food, especially high-protein meals; administration on empty stomach recommended). |
| Onset of Action | Oral: Reduction in urinary copper excretion begins within 1–2 hours; clinical chelation effect (e.g., decoppering) observed within days to weeks. |
| Duration of Action | Urinary copper excretion increases for 4–6 hours post-dose. Continuous therapy required for sustained decoppering in Wilson's disease; intermittent administration for non-Wilson indications. |
| Molecular Weight | 149.21 |
250-500 mg orally 4 times daily, titrated to maintain urinary copper excretion >2 mg/day. Maximum: 2 g/day.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated in severe renal impairment (GFR <30 mL/min). For GFR 30-60 mL/min: reduce dose by 25-50%. Monitor urinary copper and adjust accordingly. |
| Liver impairment | No specific adjustment for Child-Pugh class A or B; use with caution in severe hepatic impairment (Child-Pugh C) due to hepatotoxicity risk. Monitor liver function. |
| Pediatric use | 10-20 mg/kg/day orally divided into 2-4 doses; typical starting dose 15 mg/kg/day for Wilson disease (max 1 g/day). Titrate based on urinary copper. |
| Geriatric use | Start at lower end of dosing range (250 mg twice daily) due to age-related renal decline; monitor renal function and copper levels. |
| 1st trimester | Contraindicated due to teratogenicity; associated with cutis laxa and other congenital defects. |
| 2nd trimester | Contraindicated unless essential for maternal condition; may cause fetal harm. |
| 3rd trimester | Contraindicated unless essential; risk of fetal and neonatal connective tissue abnormalities. |
Clinical note
Comprehensive clinical and safety monograph for CUPRIMINE (CUPRIMINE).
| Placental transfer | Crosses placenta readily; achieves fetal serum concentrations similar to maternal. |
| Breastfeeding | Compatible with caution. Low levels excreted; monitor infant for rash, blood dyscrasias. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: High risk of congenital anomalies including cutis laxa, micrognathia, limb deformities, and CNS defects. Second trimester: Continued risk of fetal harm, potential for growth restriction. Third trimester: Risk of fetal copper deficiency and associated neurological impairment. Pregnancy category D. |
| Fetal Monitoring | Monitor maternal blood counts (CBC with differential), urinalysis, serum copper levels, and liver function tests monthly. Fetal ultrasound for growth and anatomy. Consider amniocentesis for karyotype if exposure in first trimester. |
| Fertility Effects | May cause reversible oligospermia and decreased sperm motility in males. In females, data limited; potential for menstrual irregularities. |
■ FDA Black Box Warning
WARNING: CUPRIMINE can cause severe bone marrow depression leading to aplastic anemia, leukopenia, thrombocytopenia, and agranulocytosis. Deaths have occurred. Monitor blood counts closely.
| Serious Effects |
PregnancyHistory of penicillamine-related aplastic anemiaHistory of agranulocytosis with penicillamine
| Precautions | Bone marrow suppression, renal toxicity (proteinuria, hematuria), lupus-like syndrome, myasthenia gravis-like syndrome, rash, and hypersensitivity reactions. Monitor renal function, blood counts, and urinalysis regularly. |
| Food/Dietary | Take on an empty stomach. Avoid food, especially milk, and any mineral supplements (iron, zinc, calcium) for at least 1 hour before and 2 hours after dosing, as they reduce absorption. Alcohol should be avoided due to potential hepatotoxicity. |
| Clinical Pearls | Monitor for proteinuria and hematuria; perform urinalysis weekly initially, then monthly. Penicillamine can cause bone marrow suppression; obtain baseline CBC and differential, then monitor every 2 weeks for first 6 months, then monthly. Drug-induced lupus and myasthenia gravis are rare but serious autoimmune adverse effects. Avoid in patients with a history of penicillin allergy due to potential cross-sensitivity. Administer on an empty stomach at least 1 hour before or 2 hours after meals to enhance absorption. Dose adjustments needed in renal impairment. Pyridoxine (vitamin B6) supplementation (25-50 mg/day) is recommended to prevent deficiency caused by penicillamine. For Wilson disease, monitor 24-hour urinary copper excretion to guide therapy. |
| Patient Advice | Take this medication on an empty stomach, at least 1 hour before or 2 hours after meals. · Do not skip doses; take exactly as prescribed and do not double up if a dose is missed. · Report any signs of allergy promptly: rash, itching, fever, joint pain, or swollen lymph nodes. · Contact your doctor immediately if you experience easy bruising, bleeding, or signs of infection such as fever or sore throat. · Inform your doctor about any planned vaccinations; avoid live vaccines while on this medication. · You may need regular blood and urine tests to monitor for side effects. · If you are taking iron supplements or other mineral supplements, take them at least 2 hours apart from this medication to prevent reduced absorption. · Use effective contraception if you are of childbearing age; this drug can harm an unborn baby. · Avoid alcohol as it may increase the risk of liver toxicity. · Notify your dentist about your medication history before any dental procedures. |
Loading safety data…