Section 18 · Monograph
Penicillamine
Reviewed Nov 2026FDA label
Cuprimine / DepenCopper chelator
- Forms
- Cap: 250mg | Tab: 250mg
- Dose
- Wilson's disease: 250mg QID initially; adjust to urinary copper excretion 0.5-1mg/day; max 2g/day (750mg/day in pregnancy)
- MOA
- Chelates copper, promotes urinary excretion
Black Box Warning
- Physicians planning to use penicillamine should thoroughly familiarize themselves with its toxicity, special dosage considerations and therapeutic benefits; it should be used only by physicians experienced in its use, and patients should be warned to report promptly any symptoms suggesting toxicity
Indications
- Wilson's diseaseFDA-labeled
- CystinuriaFDA-labeled
- Severe active rheumatoid arthritisFDA-labeled
Mechanism of Action
- Chelates copper (and cystine), forming soluble complexes excreted in urine
Full Dosing
Adult / usual
- Wilson's disease: 250mg four times daily initially, adjusted to urinary copper excretion of about 0.5-1.0mg/day; maximum 2g/day (750mg/day in pregnancy)
- Take on an empty stomach, 1 hour before or 2 hours after meals; separate from iron, zinc and antacids
- Give pyridoxine 25mg/day as a supplement
Contraindications
- History of penicillamine-related aplastic anemia or agranulocytosis
- Known hypersensitivity
Drug Interactions
- Iron, zinc and antacids reduce absorption
- Gold, antimalarials and cytotoxic drugs increase hematologic and renal toxicity
- May lower digoxin levels
Adverse Effects
- Rash, fever, taste disturbance
- Bone marrow suppression (aplastic anemia, agranulocytosis)
- Proteinuria and nephrotic syndrome
- Early neurologic worsening in neurologic Wilson's disease
- Drug-induced lupus, myasthenia gravis-like syndrome and Goodpasture syndrome
Monitoring Parameters
- CBC with differential and urinalysis at frequent intervals early in treatment
- 24-hour urinary copper and non-ceruloplasmin copper
- Neurologic status including new weakness (myasthenic syndrome)
Pregnancy & Lactation
- Birth defects reported; maximum 750mg/day in Wilson's pregnancy — weigh risk and benefit because untreated Wilson's disease is dangerous
- Breastfeeding not recommended