(FDA approved in bold)

• Wilson’s disease (WD)
  
• Cystinuria
  
• Rheumatoid arthritis (severe, active)

• In WD, copper accumulates in body tissues, causing neurological/psychiatric problems and/or liver failure. Penicillamine is cysteine, doubly substituted with methyl groups. Penicillamine binds to (chelates) copper, allowing it to be excreted in the urine

• Urinary excretion of copper will increase in less than 24 hours. Clinical improvement usually takes 6 months or more; many patients may experience paradoxical worsening after starting treatment

• Continue treatment, if tolerated, and aim for 24-hour urine copper excretion of 2 mg. Most patients remain on drug for the rest of their life but if all results return to normal (serum copper < 10 µg/dL), consider changing to zinc. Monitor for recurrence of symptoms or changes in urinary copper excretion

• Increase to as much as 2 g daily. Intolerance is more common than ineffectiveness. Change to trientine, and for liver failure or truly refractory patients, liver transplantation is curative

• Change to trientine if ineffective or poorly tolerated. A diet low in copper-containing foods, such as nuts, chocolate, liver, and dried fruit, is recommended

• Patients with WD have low serum ceruloplasmin and serum copper, but increased urinary excretion of copper is diagnostic. In pediatric patients, a 24-hour urinary copper excretion more than 1600 µg after 500 mg dose of penicillamine is considered diagnostic of WD. While on treatment, check blood counts and urinalysis, and monitor for skin changes and fever twice weekly for 1 month, then every 2 weeks for the next 5 months, and monthly for the remainder of treatment