Penicillamine

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Related FACEM curriculum (2022) learning objectives:

• ME 3.8.1.6(e) Principles of management of toxicological presentations including: Indications for antidotes
• ME 3.8.2.4 Identify the appropriate antidote or antivenom.

Toxicological Indications

• Copper toxicity (e.g., Wilson’s disease).
• Second-line chelation therapy for other heavy metals, including arsenic, iron, lead, mercury, and zinc.

Contraindications

• Penicillin allergy.
• Pregnancy (teratogenic).
• Renal failure (impaired excretion of chelates).

Mechanism of Action

• Penicillamine is a penicillin derivative lacking antibiotic activity.
• Binds to heavy metals to form soluble chelates eliminated via renal excretion.

Pharmacokinetics

• Well absorbed orally, with peak concentrations within hours.
• Distributed in body water.
• Eliminated primarily in urine as sulfide conjugates.
• Elimination half-life: up to 90 hours.

Administration

• Dosage: 4–7 mg/kg orally, four times daily.
  • Maximum adult dose: 2 g/day.
• Monitor for adverse effects:
  • Full blood count and urinalysis every two weeks.
  • Weekly urine or blood testing for target heavy metal.
• Start therapy at lower doses to reduce adverse effects.
• Treatment duration depends on tolerance and metal elimination rate; may require months.

Therapeutic Endpoints

• Blood metal concentrations within the desired range.

Adverse Drug Reactions

• Frequent and dose-dependent, often leading to therapy cessation:
  • Cutaneous hypersensitivity: erythematous skin reactions.
  • Systemic hypersensitivity: fever, proteinuria, haematuria, erythema multiforme.
  • Haematological: bone marrow hypoplasia, thrombocytopenia, leucopenia, agranulocytosis (fatal in severe cases).
  • Neurological: myasthenia gravis, peripheral neuropathy.
  • Nephrotoxicity: nephrotic syndrome, glomerulonephritis.
  • Other: Goodpasture’s syndrome, hepatotoxicity, pancreatitis.
• Discontinue therapy for significant skin reactions, abnormal urinalysis, or falling white cell/platelet counts.

Specific Considerations

• Pregnancy: Avoid due to teratogenic effects.
• Paediatrics: Dose similarly to adults; use lower doses to reduce adverse effects.

Handy Tip

• Prescribe only under the supervision of experienced clinicians familiar with its use and adverse effects.

Controversy

• Lower dose regimens may offer similar clinical efficacy with fewer adverse effects.