penicillamine (Cuprimine, Depen)

Introduction

Tradenames: Cuprimine, Depen. (D-penicillamine)

Indications

• adjunct agent in treatment of rheumatoid arthritis, vasculitis
• hepatolenticular degeneration (Wilson's disease)
• cystinuria, cystine renal calculi
• lead poisoning
• primary biliary cirrhosis

Dosage

• take on an empty stomach 1 hour before or 2 hours after meals & at least 1 hour apart from other drugs
• give 25 mg of pyridoxine daily because of increased requirements
• rheumatoid arthritis:
  • start: 125-250 mg PO QD
  • increase at 1-3 month intervals by 125-250 mg/day
  • continue to increase the dose at 2-3 month intervals until a satisfactory response is obtained
  • if no response with 1-1.5 g doses, assume that therapy with penicillamine does NOT work
• hepatolenticular degeneration (Wilson's disease)
  • 1-2 g QD
  • dose adjustment via urinary copper analysis
• cystinuria: 1-4 g/day

Capsule: (Cupramine) 125 mg.

Tablet: (Depen) 250 mg.

Pharmacokinetics

• onset of therapeutic response:
  • up to 2-3 months in rheumatoid arthritis
  • up to 1-3 months Wilson's disease
• excreted in urine & feces
• elimination 1/2life ranges from 1.7-3.2 hours

elimination via kidney

elimination via feces

1/2life = 1.7-3.2 hours

Adverse effects

• common (> 10%)
  • fever, joint pain, rash, urticaria, itching, loss of taste
• less common (1-10%)
  • sore throat, fever/chills, white spots on lips or mouth, aplastic anemia, bloody or cloudy urine, swelling of face or lower extremities, weight gain, hemolytic anemia, leukopenia, agranulocytosis, thrombocytopenia,
• uncommon (< 1%)
  • cough, wheezing, spitting of blood, weakness, tiredness, cholestatic jaundice, myasthenia gravis-like syndrome, toxic epidermal necrolysis, optic neuritis, tinnitus, pemphigus, increased friability of the skin, iron deficiency, nausea/vomiting, hepatic dysfunction, arthralgia, proteinuria, nephrotic syndrome, allergic reactions, lymphadenopathy
• other
  • drug-induced lupus erythematosus (< 1%)
    • pulmonary fibrosis
  • bronchiolitis obliterans with organizing pneumonia (BOOP)
  • Goodpasteur syndrome-like illness
  • diffuse alveolitis
  • aplastic anemia (fatalities have occurred)
  • sideroblastic anemia
  • mild elevation in serum transaminases
  • oral ulcerations
  • hematuria
  • GI intolerance

Drug interactions

• gold therapy, antimalarials, cytotoxic drugs, phenylbutazone in combination may result in serious hematologic & renal reactions
• penicillamine increases serum digoxin levels
• decreased effect with iron & zinc salts, antacids (Mg+2, Al+3, Ca+2) & food

Mechanism of action

• rheumatoid arthritis
  • unknown, but may suppress disease activity
  • diminshes IgM rheumatoid factor
  • no significant decrease in total immunoglobulins
  • may inhibit T-cell function
  • may act as an antioxidant by inhibiting release of
    • lysosomal enzymes
    • active oxygen species
• hepatolenticular degeneration (Wilson's disease)
  • chelating agent that removes excess copper
• cystinuria: reduces excess cystine excretion
• effective chelator of copper, mercury, lead, zinc

More general terms

• carboxylic acid
• thiol; sulhydryl compound; mercaptan
• amine
• pharmaceutical angiogenesis inhibitor (angiostatic agent)
• chelating agent
• disease-modifying antirheumatic agent (DMARD)

Additional terms

• bronchiolitis obliterans; constrictive bronchiolitis; cryptogenic organizing pneumonia; bronchiolitis obliterans with organizing pneumonia (BOOP)
• cystinuria
• drug-induced lupus erythematosus
• hepatolenticular degeneration; Wilson's disease
• primary biliary cirrhosis; primary biliary cholangitis
• rheumatoid arthritis (RA)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4727
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5852
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=92863
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=92173