Penicillamine
Chelating agents
Chelating agentsPregnancy: contraindicated
Contraindicated in pregnancy, except in Wilson disease and some patients with cystinuria, where stopping treatment carries greater risk.
An oral chelator for copper in Wilson disease, which also prevents cystine stones and is an old second-line drug for rheumatoid arthritis.
Also called: D-penicillamine
Quick facts
- Group
- Chelating agents
- Target
- Copper and cystine
- Used for
- Wilson disease · Cystinuria
- Key effects
- Loss or change of taste · Rash and itching · Nausea
- Monitor
- Urinalysis · Liver function tests
- ATC
- M01CC01
No doses: the clinician sets them by the current guideline.
Mechanism of action
Penicillamine is a thiol amino acid derived from penicillin. In Wilson disease it binds excess copper so that it is excreted in urine. In cystinuria it forms a mixed disulfide with cysteine that dissolves far better than cystine, so fewer stones form. In rheumatoid arthritis its action is not understood: it lowers IgM rheumatoid factor, dampens T-cell activity and interferes with collagen cross-linking.
- Penicillamine's thiol grips copper
- The copper complex is excreted in urine
- With cystine it forms a soluble mixed disulfide
- Fewer cystine stones form
Indications
- Wilson disease (copper overload) Wilson disease →
- Cystinuria, to reduce cystine stone formation Cystinuria →
- Severe active rheumatoid arthritis that has not responded to conventional therapy Rheumatoid arthritis →
Adverse effects
Common
- Loss or change of taste
- Rash and itching
- Nausea, vomiting, diarrhoea and loss of appetite
- Increased need for vitamin B6 (pyridoxine)
Contraindications
- Pregnancy, except in Wilson disease and some cases of cystinuria
- Breastfeeding
- Previous penicillamine-related aplastic anaemia or agranulocytosis
- Rheumatoid arthritis with kidney insufficiency
Key interactions
- Food, antacids and iron
- Reduce its absorption; iron is given well apart from it
- Zinc, mineral supplements and milk
- Can interfere with its absorption or effect
- Gold, antimalarials and cytotoxic drugs
- Not combined: they add serious blood and kidney toxicity
What is monitored
- Urinalysis, white cell count with differential, haemoglobin and platelets: frequently at first, then at longer intervals
- Liver function tests, more often in Wilson disease
- Urine copper in Wilson disease; stone imaging in cystinuria
Administration and safety
- Given by mouth on an empty stomach, apart from meals, antacids and iron
- Pyridoxine supplementation is usually added, especially in Wilson disease and cystinuria
- Not stopped for early neurological worsening in Wilson disease: interruptions raise the risk of a sensitivity reaction on restart
Pregnancy and breastfeeding
Contraindicated in pregnancy, except in Wilson disease and some patients with cystinuria, where stopping treatment carries greater risk.
Nursing care
- Teach the patient to report fever, sore throat, bruising or bleeding at once
- Check urine for protein and blood as scheduled
- Report new muscle weakness, drooping eyelids, blisters or coughing up blood
- Explain that a change in taste is common and usually passes
Pharmacokinetics
- Absorption
- Oral; absorption is incomplete and reduced by food, antacids and iron
- Distribution
- Highly bound to plasma proteins
- Elimination
- Mainly by the kidneys, largely as disulfides
Test yourself
Think of the answer, then tap the question to see it.
What are the three labelled uses of penicillamine?
Wilson disease, cystinuria and severe rheumatoid arthritis that has not responded to conventional therapy.
How does penicillamine reduce cystine stones?
It forms a mixed disulfide with cysteine that is much more soluble than cystine.
Which vitamin is supplemented during penicillamine treatment, and why?
Pyridoxine (vitamin B6), because penicillamine increases the body's need for it.
Which blood test results lead to stopping penicillamine?
Falling white cell or platelet counts, which can signal agranulocytosis, thrombocytopenia or aplastic anaemia.
Connections
← Back to the class: Chelating agents
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - PENICILLAMINE capsule (DailyMed (U.S. National Library of Medicine), 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.