Conventional DMARD — Chelating Agent Pregnancy: Safety in pregnancy not established. Should not be given for rheumatoid arthritis or chronic active hepatitis in pregnancy (stop when pregnancy diagnosed or suspected) unless absolutely essential; in Wilson's disease/cystinuria weigh benefit against fetal risk and use the lowest effective dose (reversible cutis laxa reported in exposed infants). Use while breast-feeding only if considered absolutely essential.

Penicillamine

Brand names: Distamine

Penicillamine is a chelating agent and disease-modifying drug used in rheumatoid arthritis, Wilson's disease (copper overload) and cystinuria.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Rheumatoid arthritis (adults): 125–250 mg daily for the first month, increased by the same amount every 4–12 weeks until remission occurs; usual maintenance 500–750 mg daily

Route: Oral (on an empty stomach, at least 30 minutes before meals in adults, or on retiring)

Frequency: Once daily to divided doses depending on indication; maintenance titrated to the minimum effective dose

Max: Rheumatoid arthritis: up to 1500 mg daily may be required. Elderly: daily dose should not exceed 1000 mg

eMC SPC covers several indications. Rheumatoid arthritis maintenance dose may be reduced by 125–250 mg every 12 weeks after 6 months' continuous remission; discontinue if no improvement within 12 months. Wilson's disease (adults): 1500–2000 mg daily in divided doses, reduced to 750–1000 mg/day on remission — 2000 mg/day should not be continued for more than 12 months. Cystinuria (adults): dissolution of cystine stones 1000–3000 mg daily in divided doses (keep urine cystine <200 mg/L); prevention 500–1000 mg at bedtime (keep urine cystine <300 mg/L); maintain fluid intake not less than 3 L/day. Lead poisoning (adults): 1000–1500 mg daily in divided doses until urinary lead stabilised at <0.5 mg/day. Chronic active hepatitis (adults): initial 500 mg daily in divided doses, increased gradually over 3 months to a maintenance dose of 1250 mg daily (as corticosteroids are phased out). Elderly: initial dose ≤125 mg daily for the first month. Paediatric dosing is stated per body weight and differs by indication: rheumatoid arthritis — usual maintenance 15–20 mg/kg/day (initial 2.5–5 mg/kg/day, increased every 4 weeks over 3–6 months); Wilson's disease — 20 mg/kg/day in 2–3 divided doses 1 hour before meals (older children ≥12 years usual maintenance 750–1000 mg daily); cystinuria — 20–30 mg/kg/day in 2–3 divided doses 1 hour before meals, adjusted to keep urinary cystine below 200 mg/L; lead poisoning — 15–20 mg/kg/day in 2–3 doses, only where blood lead ≥45 mcg/dL. Safety and efficacy in chronic active hepatitis not established in children under 18. Verify paediatric dosing against a children's formulary.

Dose adjustments

Renal

Contraindicated in moderate or severe renal impairment. Where used, initiate at a low dose with at least 12-week intervals between dose increases and monitor closely for toxicity; in cystinuria with renal insufficiency use a lower starting dose.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

US labelling (FDA)

Reference — US labelling, may differ from UK

DOSAGE AND ADMINISTRATION In all patients receiving penicillamine, it is important that penicillamine capsules be given on an empty stomach, at least one hour before meals or two hours after meals, and at least one hour apart from any other drug, food, or milk. Because penicillamine increases the requirement for pyridoxine, patients may require a daily supplement of pyridoxine (see PRECAUTIONS ). W i l s on 's Disease — Optimal dosage can be determined by measurement of urinary copper excretion and the determination of free copper in the serum. The urine must be collected in copper-free glassware, and should be quantitatively analyzed for copper before and soon after initiation of therapy …

Source: US FDA prescribing information (openFDA / DailyMed), label dated 2024-09-24. Accessed 2026-06-12. US dosing and indications can differ from UK practice — use UK sources for prescribing decisions.

Contraindications

Hypersensitivity to penicillamine or to any of the excipients
Agranulocytosis, aplastic anaemia or severe thrombocytopenia due to penicillamine
Lupus erythematosus
Moderate or severe renal impairment

Side effects

Thrombocytopenia
Proteinuria (up to 30% of patients)
Rashes / urticarial reactions
Loss of taste (reversible)
Nausea and anorexia

Interactions

Clozapine — penicillamine may potentiate its bone marrow suppression
NSAIDs and other nephrotoxic drugs — may increase the risk of renal damage
Gold — avoid concomitant use; use with caution in patients who have had adverse reactions to gold
Antimalarials (hydroxychloroquine, chloroquine) — do not use concurrently (synergistic haematologic/renal toxicity)
Oral iron, digoxin or antacids — do not give within 2 hours of penicillamine

Clinical monograph

How it works

It chelates metal ions such as copper, promoting their urinary excretion in Wilson's disease, and reduces cystine concentrations in cystinuria. Its immunomodulatory action in rheumatoid arthritis is not fully understood but reduces disease activity over time.

Prescribing in practice

It can cause serious toxicity, including proteinuria and nephrotic syndrome and bone-marrow suppression (such as thrombocytopenia and neutropenia), requiring regular urine testing and full blood counts as set out in the SPC.
Autoimmune syndromes (for example a lupus-like illness, myasthenia gravis or skin disorders) can develop during treatment.
It should be taken on an empty stomach, well separated from food, iron, antacids and other mineral-containing products, which reduce its absorption.

Monitoring

Perform regular full blood counts and urinalysis for proteinuria and haematuria, with renal function checks, in line with current prescribing references. Be alert for emerging autoimmune features and for skin or mucosal reactions, and adjust or stop treatment promptly if significant toxicity develops.

Counselling the patient

Take this medicine on an empty stomach, at least an hour before or two hours after food, and well apart from iron tablets, antacids and milk.
Attend for your regular blood and urine tests, as they pick up serious side effects early.
Report a sore throat, fever, unusual bruising or bleeding, or a skin rash promptly.

Evidence & guidelines

A long-established disease-modifying and chelating agent; UK practice emphasises strict haematological and urinary monitoring because of its toxicity profile.

Reference: MHRA Drug Safety Update; BSR/BHPR DMARD Guidelines; SPC Distamine; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways