DESCRIPTION

Pencillamine is a medication that increases urinary excretion of some metals (copper, lead, mercury, and arsenic).

FORMS AND USES

• Pencillamine is primarily used in the treatment of chronic copper toxicity (Wilson's disease).
• It is a second-line therapy for lead, mercury, copper, or arsenic toxicity.
• It is also used in treating rheumatoid arthritis, Wilson's disease, and cystinuria.
• It is available as Cuprimine (125 mg, 250 mg capsules) or Depen (250 mg tablets).

MECHANISM OF ACTION

• Penicillamine is a chelating agent that directly binds several heavy metals.
• The drug-penicillamine complex is excreted in the urine, thereby decreasing the body burden of the metal.

DRUG AND DISEASE INTERACTIONS

Penicillamine may potentiate the effects of immunosuppressive therapy.

PREGNANCY AND LACTATION

• US FDA Pregnancy Category D. Evidence of human fetal risk exists, but benefits in certain situations (e.g., life-threatening situations or serious diseases) may make use of the drug acceptable despite its risks.
• Penicillamine is appropriate therapy during pregnancy for treatment of Wilson's disease.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

LEAD POISONING WITHOUT ENCEPHALOPATHY

Adults

• It is a second-line agent behind succimer for the treatment of lead poisoning without encephalopathy.
• In some cases it may be used with a parenteral chelator for treatment of lead poisoning with encephalopathy.

Pediatric

• Penicillamine has been used for treating asymptomatic or minimally symptomatic children.
• Succimer is the preferred agent.

MERCURY TOXICITY

• Penicillamine has been used for treatment of symptomatic acute or chronic elemental mercury poisoning or elevated urinary excretion of mercury.
• Penicillamine has been used for neuropathy induced by inorganic mercury.

COPPER TOXICITY

• Penicillamine is the mainstay of therapy for chronic copper toxicity in Wilson's disease but has not been well studied in acute copper poisoning.
• Penicillamine can be used in symptomatic chronic copper intoxication when levels remain elevated despite the discontinuation of exposure.

ARSENIC TOXICITY

Penicillamine has been used for symptomatic arsenic toxicity if BAL and succimer are not available.

Section Outline:

• LEAD POISONING WITHOUT ENCEPHALOPATHY
  • Adults
  • Pediatric
• MERCURY TOXICITY
• COPPER TOXICITY
• ARSENIC TOXICITY

CONTRAINDICATIONS

• Penicillin allergy precludes use.
• Renal insufficiency is a relative contraindicator because the metal-penicillamine complex is renally excreted.
• Penicillamine should not be used in conjunction with other drugs that cause bone marrow depression or in patients with abnormal bone marrow function.

ADVERSE EFFECTS

• Allergic reactions occur in 5% of patients.
• Penicillamine increases the need for pyridoxine. Pyridoxine therapy should be considered in long-term pencillamine therapy (e.g., Wilson's disease), but should not be needed for intermittent treatment of heavy metal poisoning.
• Chronic therapy has been associated with optic neuritis, myasthenia gravis, retinopathy, pulmonary alveolitis and hemorrhage, seizures, neuropathy, gastroenteritis, cholestasis, hepatitis, pancreatitis, polyarteritis nodosa, bone marrow suppression, thrombocytopenia, aplastic anemia, proteinuria, and nephrotic syndrome.
• There is no specific therapy for these adverse effects; symptomatic and supportive care should be provided.

Section Outline:

• CONTRAINDICATIONS
• ADVERSE EFFECTS

LEAD POISONING WITHOUT ENCEPHALOPATHY

• The clinician must first ensure that lead exposure has stopped.
• Adult dose is 15 to 40 mg/kg/day orally in four divided doses, up to a maximum of 250 to 500 mg, four times per day for 5 days, administered before meals.
• Pediatric dose is 20 to 30 mg/kg/day, given orally once or twice daily before meals.
• Blood lead levels should be measured.
  • Levels should be repeated once several days after completion of each course of therapy and every 2 to 4 weeks thereafter until the level stabilizes.
  • If the blood lead level rebounds to 45 µg/dl, the clinician should investigate whether repeat exposure could have occurred in the interim; if it has not, the course of chelation should be repeated.
  • If repeat exposure has occurred, the patient should be moved to lead-free housing and the course of chelation repeated.
  • If the level rebounds to 20 to 45 µg/dl, treatment recommendations are uncertain. Many centers would perform at least one more course of chelation. Serial blood lead levels should be followed to assess efficacy.
• If repeated courses of treatment are used, the white blood cell count should be monitored biweekly.

MERCURY TOXICITY

• Adult dose is 15 to 40 mg/kg/day orally, up to a maximum of 250 to 500 mg, given four times a day, before meals.
• Pediatric dose is 20 to 30 mg/kg/day, given orally once or twice daily before meals.
• The treatment should be administered for 5 to 10 days.
• Urinary excretion of mercury should be monitored.
  • If urine mercury decreases rapidly, the body burden of mercury is probably small; after 10 days, the urine mercury level should be repeated.
  • If urine mercury is elevated, another course of chelation may be needed.

COPPER TOXICITY

• For treatment of Wilson's disease, the adult dose is 15 to 40 mg/kg/day orally, up to a maximum of 250 to 500 mg, given four times a day, before meals.
• Pediatric dose is 20 to 30 mg/kg/day, given orally once or twice daily before meals.
• The dose for treatment of copper poisoning following acute ingestion is uncertain. Empiric use of the same dose as for lead or mercury poisoning may be used initially.

ARSENIC TOXICITY

• Adult dose is 15 to 40 mg/kg/day orally, up to a maximum of 250 to 500 mg, given four times a day for 5 days, before meals.
• Pediatric dose is 20 to 30 mg/kg/day, given orally once or twice daily before meals.
• The clinician should observe 24-hour urinary arsenic levels and stop therapy when levels are less than 50 µg/24-hour specimen.

Section Outline:

• LEAD POISONING WITHOUT ENCEPHALOPATHY
• MERCURY TOXICITY
• COPPER TOXICITY
• ARSENIC TOXICITY

• Prevention of ongoing exposure is critical for all types of heavy metal poisoning.
• Side effects are generally related to rapid increase in dose.

Poisoning by primarily systemic agents: other specified systemic agents (heavy metal antagonists).

See Also: SECTION IV, Arsenic, Copper, Lead, Mercury, and Succimer chapters.

RECOMMENDED READING

Shannon M, Graef J, Lovejoy FH. Efficacy and toxicity of D-penicillamine in low-level lead poisoning. J Pediatr 1988;112:799-804.

Author: Kennon Heard

Reviewer: Katherine M. Hurlbut