Penicillamine

Penicillamine, commonly referred to as D-penicillamine, is an oral chelating agent used in select medical conditions. It is derived from penicillin and acts as a sulfhydryl-containing compound that binds various metals and other molecules to promote their excretion or dissolution.

The principal current indication is Wilson's disease, where penicillamine chelates copper and increases its urinary elimination. It has also been used to prevent recurrent cystine stone formation in cystinuria by forming a soluble penicillamine-cysteine disulfide complex. Historically, penicillamine was prescribed for rheumatoid arthritis, but its use for this purpose has declined because of a profile of serious adverse effects.

Mechanistically, penicillamine chelates copper and other metals, reducing their tissue accumulation. In cystinuria, it forms mixed disulfides with cysteine, lowering cystine concentration and stone risk. Its copper-binding action underpins its therapeutic role in Wilson’s disease, but it can generate immune-related and hematologic toxicities.

Administration typically involves oral dosing with gradual up-titration to a therapeutic level, allowing monitoring for adverse effects. Initiation requires regular laboratory surveillance, including complete blood counts and renal and liver function tests, given risks of nephrotoxicity, cytopenias, and hepatic injury. Patients are advised to report symptoms such as rash, fever, swelling, or unusual bleeding.

Adverse effects range from hypersensitivity reactions and rash to nephrotoxicity, proteinuria, and hematologic abnormalities (agranulocytosis, thrombocytopenia). Autoimmune phenomena such as drug-induced lupus and, rarely, neurotoxic symptoms may occur. Penicillamine is contraindicated in hypersensitivity to the drug and used with caution in kidney disease, autoimmune disorders, and during pregnancy, with careful risk–benefit assessment.