Penicillamine

BRAND NAMES

• Cuprimine: A widely recognized brand of Penicillamine, primarily used for treating Wilson’s disease by promoting copper excretion.

• Depen: Another common brand of Penicillamine, used in long-term therapy for copper metabolism disorders and some autoimmune conditions.

• Generic Penicillamine: Available in many countries as non-branded formulations, often more affordable while providing the same therapeutic effect.

MECHANISM OF ACTION

Penicillamine acts as a chelating agent, binding to heavy metals such as copper, lead, and mercury. In Wilson’s disease, it promotes urinary excretion of copper, reducing toxic accumulation in tissues. In rheumatoid arthritis, it has immunomodulatory effects, reducing inflammation and joint damage. It also reduces cystine levels in urine, preventing kidney stone formation in cystinuria. Overall, its effects are mediated through metal binding and immune modulation.

PHARMACOKINETICS

Absorption: Penicillamine is well absorbed orally, but absorption can be reduced by food, especially proteins.

Distribution: It is widely distributed in body tissues, including the liver and kidneys.

Metabolism: Penicillamine undergoes minimal metabolism, with most of the active drug remaining unchanged.

Excretion: The drug and its metal complexes are primarily excreted in urine, with a half-life of approximately 1–3 hours.

PHARMACODYNAMICS

Penicillamine decreases the body burden of toxic metals through chelation and excretion. In autoimmune disorders like rheumatoid arthritis, it modulates immune responses and reduces inflammation. By reducing cystine levels in urine, it prevents cystine stone formation. The therapeutic effect depends on consistent long-term administration. Its efficacy is dose-dependent and closely monitored via laboratory tests.

ADMINISTRATION

Penicillamine is administered orally in tablet or capsule form. To ensure optimal absorption, it is generally taken on an empty stomach. The dose may be divided into multiple daily doses depending on the condition. Patients are advised to avoid taking it with food, iron, or zinc supplements, which can interfere with absorption. Continuous medical supervision is required due to potential toxicity and side effects.

DOSAGE AND STRENGTH

For Wilson’s disease, initial doses range from 250–500 mg daily, gradually increasing to 1–2 g/day as tolerated. In rheumatoid arthritis, typical doses are 125–500 mg daily, adjusted based on response. For cystinuria, doses of 1–2 g/day are used to reduce cystine levels. Penicillamine tablets are commonly available in 125 mg, 250 mg, and 500 mg strengths. Dosage adjustments are necessary in renal impairment or adverse reactions.

DRUG INTERACTIONS

Penicillamine may interact with metal supplements like iron, zinc, or copper, reducing its absorption. Concomitant use with gold salts or antimalarials can increase the risk of toxicity. Methotrexate or immunosuppressants may potentiate immunomodulatory effects. Penicillamine may reduce the efficacy of penicillin, as it can form complexes. Patients should inform their doctor about all medications and supplements to prevent interactions.

FOOD INTERACTIONS

Penicillamine absorption is decreased by food, particularly proteins, so it is usually taken 1 hour before or 2 hours after meals. Dairy products and metal-containing foods can interfere with drug absorption. Alcohol does not significantly affect its action, but a balanced diet is recommended for overall health.

CONTRAINDICATIONS

Penicillamine is contraindicated in patients with hypersensitivity to the drug. It should be avoided in individuals with severe renal or hepatic impairment. It is not recommended during pregnancy or breastfeeding unless clearly necessary. Patients with autoimmune disorders like lupus should use caution, as it may exacerbate symptoms. Close monitoring is essential in elderly patients or those with blood disorders.

SIDE EFFECTS

• Nausea, vomiting, diarrhea – common gastrointestinal side effects.

• Rash and fever – mild to moderate allergic or immune reactions.

• Bone marrow suppression – may lead to anemia, leukopenia, or thrombocytopenia (serious).

• Proteinuria and nephrotic syndrome – kidney-related complications.

• Hepatotoxicity – elevated liver enzymes or liver injury in some cases.

• Autoimmune reactions (rare) – can trigger lupus-like syndromes.

• Myasthenia-like symptoms (rare) – muscle weakness similar to myasthenia gravis.

• Dose-dependence – side effects often correlate with higher doses.

• Reversibility – most side effects improve after discontinuing the drug.

• Monitoring required – regular blood counts, kidney, and liver function tests are essential during therapy.

OVER DOSE

Overdose of penicillamine can lead to severe gastrointestinal symptoms, including vomiting and diarrhea. It may also cause bone marrow suppression and immune system disturbances. Hypersensitivity reactions, hypotension, and acute kidney injury are possible. Management includes discontinuation of the drug and supportive care, such as IV fluids and symptomatic treatment. Early medical attention is crucial to prevent life-threatening complications.

TOXICITY

Penicillamine toxicity primarily affects the hematologic, renal, and hepatic systems. Long-term use may lead to leukopenia, thrombocytopenia, proteinuria, or liver enzyme elevation. Severe hypersensitivity reactions or autoimmune syndromes are rare but possible. Toxicity risk increases with high doses or prolonged therapy, particularly without monitoring. Most toxic effects are reversible with drug discontinuation and appropriate supportive care.