Penicillamine

• Wilson’s Disease:
  Used to reduce copper accumulation in patients with Wilson’s disease.
• Rheumatoid Arthritis:
  As a disease-modifying antirheumatic drug (DMARD) in patients with severe, active rheumatoid arthritis unresponsive to conventional therapy.
• Cystinuria:
  To decrease cystine levels and prevent cystine kidney stone formation.
• Off-label Uses:
  Treatment of heavy metal poisoning (e.g., lead), and other rare conditions involving metal toxicity.

• Route: Oral.
• Wilson’s Disease:
  Initial dose: 250 mg orally 4 times daily (total 1 gram per day).
  Maintenance dose: 750 mg to 1.5 g daily in divided doses, adjusted per patient response.
• Rheumatoid Arthritis:
  Start with 125 mg daily or every other day, gradually increased to 1 to 2 grams daily in divided doses.
• Cystinuria:
  Typical dose: 600 mg to 1.5 grams daily in divided doses.
• Pediatrics:
  Dosage individualized based on weight and clinical condition.
• Elderly:
  Initiate with lower doses; monitor closely for adverse effects.
• Renal Impairment:
  Use cautiously; dose adjustment and frequent monitoring advised.
• Hepatic Impairment:
  Use with caution; no specific guidelines for dose adjustment.

Penicillamine acts as a chelating agent by binding to metals such as copper and lead, forming soluble complexes that are excreted renally. In rheumatoid arthritis, it exerts immunomodulatory effects by suppressing T-cell function and decreasing rheumatoid factor synthesis, thus reducing inflammation and joint damage. In cystinuria, penicillamine forms mixed disulfides with cystine, increasing its solubility and preventing stone formation.

• Absorption: Approximately 40–70% oral bioavailability; absorption reduced by food and iron supplements.
• Distribution: Widely distributed; crosses placenta and excreted in breast milk.
• Metabolism: Hepatic metabolism to inactive metabolites.
• Half-life: Approximately 1.6 hours.
• Elimination: Primarily renal excretion of unchanged drug and metabolites.

• Pregnancy: Category D. Teratogenic risk; use only if benefits outweigh risks.
• Lactation: Excreted in breast milk; breastfeeding is not recommended.

• Chelating agent
• Disease-modifying antirheumatic drug (DMARD)

• Hypersensitivity to penicillamine or excipients.
• Severe renal impairment (unless benefits outweigh risks).
• Pregnancy unless clearly necessary.
• History of penicillamine-induced aplastic anemia or thrombocytopenia.

• Monitor blood counts regularly due to risk of bone marrow suppression.
• Monitor renal function to detect nephrotoxicity.
• Watch for signs of autoimmune disorders.
• May cause severe skin reactions.
• Avoid concomitant iron or zinc supplements due to decreased absorption.
• Gradually increase dose to reduce adverse effects.

• Common: Rash, nausea, vomiting, altered taste, proteinuria.
• Serious: Aplastic anemia, thrombocytopenia, agranulocytosis, lupus-like syndrome, nephrotic syndrome, myasthenia gravis, severe hypersensitivity reactions.
• Side effects are often dose-dependent and may develop within weeks to months.

• Iron and zinc supplements reduce absorption; separate dosing by at least 2 hours.
• Increased toxicity risk with gold therapy.
• May potentiate effects of antihypertensive and anticoagulant agents.
• Avoid live vaccines during treatment.

• Emphasis on regular monitoring for hematologic and renal toxicity.
• Gradual dose escalation recommended for rheumatoid arthritis.
• No recent major changes to indications or dosing.

• Store at 20–25°C (68–77°F).
• Protect from moisture and light.
• Keep container tightly closed.
• Keep out of reach of children.