Cuprimine, Depen
Classifications: chelating agent;
Therapeutic: chelating agent

Pregnancy Category: D


250 mg capsules


Combines chemically with cystine to form a soluble disulfide complex that prevents stone formation and may even dissolve existing cystic stones. Mechanism of action in rheumatoid arthritis appears to be related to inhibition of collagen formation. Forms stable soluble chelate with copper, zinc, iron, lead, mercury, and possibly other heavy metals and promotes their excretion in urine.

Therapeutic Effect

With Wilson's disease, therapeutic effectiveness is indicated by improvement in psychiatric and neurologic symptoms, visual symptoms, and liver function. With rheumatoid arthritis, therapeutic effectiveness is indicated by improvement in grip strength, decrease in stiffness following immobility, reduction of pain, decrease in sedimentation rate and rheumatoid factor.


To promote renal excretion of excess copper in Wilson's disease (hepatolenticular degeneration). Active rheumatoid arthritis in patients who have failed to respond to conventional therapy. Cystinuria.

Unlabeled Uses

Scleroderma, primary biliary cirrhosis, porphyria cutanea tarda, lead poisoning.


Hypersensitivity to penicillamine or to any penicillin; history of penicillamine-related aplastic anemia or agranulocytosis; patients with rheumatoid arthritis who have renal insufficiency or who are pregnant; pregnancy (category D), lactation; renal failure; concomitant administration with drugs that can cause severe hematologic or renal reactions (e.g., antimalarials, gold salts).

Cautious Use

Allergy-prone individuals; diabetes mellitus.

Route & Dosage

Wilson's Disease
Adult: PO 250 mg q.i.d., with 3 doses 1 h a.c. and the last dose at least 2 h after the last meal
Child: PO 20 mg/kg/d in 2–4 divided doses (max: 1 g/d)

Adult: PO 250–500 mg q.i.d., with doses adjusted to limit urinary excretion of cystine to 100–200 mg/d
Child: PO 30 mg/kg/d in 4 divided doses with doses adjusted to limit urinary excretion of cystine to 100–200 mg/d

Rheumatoid Arthritis (RA)
Adult: PO 125–250 mg/d; may increase at 1–3 mo intervals up to 1–1.5 g/d
Child: PO 3 mg/kg/d (≤250 mg/d) x 3 mo, then 6 mg/kg/d (≤500 mg/d) in 2 divided doses x 3 mo [max: of 10 mg/kg/d (≤1.5 g/d) in 3–4 divided doses]

Lead Poisoning
Child: PO 30–40 mg/kg/d in 3–4 divided doses (max: 1.5 g/d); initiate at 25% target dose,  gradually increase to full dose over 2–3 wk

Renal Impairment
If Clcr <50 mL/min, avoid use.
Hemodialysis: In RA patients dose may be decreased from 250 mg daily to 250 mg 3 times/wk


  • Give on empty stomach (60 min before or 2 h after meals) to avoid absorption of metals in foods by penicillamine.
  • Give contents in 15–30 mL of chilled fruit juice or pureed fruit (e.g., applesauce) if patient cannot swallow capsules or tablets.

Adverse Effects (≥1%)

Body as a Whole: Fever, arthralgia, lymphadenopathy, thyroiditis, SLE-like syndrome, thrombophlebitis, hyperpyrexia, myasthenia gravis syndrome, tingling of feet, weakness. GI: Anorexia, nausea, vomiting, epigastric pain, diarrhea, oral lesions, reduction or loss of taste perception (particularly salt and sweet), metallic taste, activation of peptic ulcer, pancreatitis. Urogenital: Membranous glomerulopathy, proteinuria, hematuria. Hematologic: Thrombocytopenia, leukopenia, agranulocytosis, thrombotic thrombocytopenic purpura, hemolytic anemia, aplastic anemia. Metabolic: Pyridoxine deficiency. Skin: Generalized pruritus, urticaria, mammary hyperplasia, alveolitis, skin friability, excessive skin wrinkling, early and late occurring rashes, pemphigus-like rash, alopecia. Special Senses: Tinnitus, optic neuritis, ptosis.


Drug: antimalarials, cytotoxics, gold therapy may potentiate hematologic and renal adverse effects; iron may decrease penicillamine absorption.


Absorption: Readily from GI tract. Peak: 1 h. Distribution: Crosses placenta. Metabolism: In liver. Elimination: In urine. Half-Life: 1–7 h.

Nursing Implications

Assessment & Drug Effects

  • Lab tests: Check WBC with differential, direct platelet counts, Hgb, and urinalyses prior to initiation of therapy and every 3 d during the first month of therapy, then every 2 wk thereafter. Perform liver function tests and eye examinations before start of therapy and at least twice yearly thereafter.
  • Withhold drug and contact physician if the patient with rheumatoid arthritis develops proteinuria >1 g (some clinicians accept >2 g) or if platelet count drops to <100,000/mm3, or platelet count falls below 3500–4000/mm3, or neutropenia occurs.

Patient & Family Education

  • Note: Clinical evidence of therapeutic effectiveness may not be apparent until 1–3 mo of drug therapy.
  • Take exactly as prescribed. Allergic reactions occur in about one third of patients receiving penicillamine. Temporary interruptions of therapy increase possibility of sensitivity reactions.
  • Take temperature nightly during first few months of therapy. Fever is a possible early sign of allergy.
  • Observe skin over pressure sites: knees, elbows, shoulder blades, toes, buttocks. Penicillamine increases skin friability.
  • Report unusual bruising or bleeding, sore mouth or throat, fever, skin rash, or any other unusual symptoms to physician.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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