CUPRIMINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CUPRIMINE (CUPRIMINE).

How it works

Chelates copper, forming a stable complex that is excreted renally, reducing systemic copper accumulation.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for CUPRIMINE (CUPRIMINE).

Breastfeeding	Excreted in breast milk. M/P ratio not established. Contraindicated in breastfeeding due to potential for severe adverse effects (hypersensitivity, bone marrow suppression) in the infant.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

History of penicillamine-related aplastic anemia or agranulocytosis; concurrent gold therapy, antimalarial drugs, or immunosuppressants; rheumatoid arthritis patients with renal insufficiency.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

Loading safety data…

CUPRIMINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CUPRIMINE (CUPRIMINE).

How it works

Chelates copper, forming a stable complex that is excreted renally, reducing systemic copper accumulation.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for CUPRIMINE (CUPRIMINE).

Breastfeeding	Excreted in breast milk. M/P ratio not established. Contraindicated in breastfeeding due to potential for severe adverse effects (hypersensitivity, bone marrow suppression) in the infant.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

History of penicillamine-related aplastic anemia or agranulocytosis; concurrent gold therapy, antimalarial drugs, or immunosuppressants; rheumatoid arthritis patients with renal insufficiency.