From the Guidelines
Penicillamine is associated with numerous common side effects, including gastrointestinal disturbances, skin reactions, blood abnormalities, and kidney problems, which can affect up to 30% of patients on long-term therapy. This medication, used to treat conditions like Wilson's disease, rheumatoid arthritis, and certain types of kidney stones, frequently causes nausea, vomiting, diarrhea, and loss of appetite. Skin reactions such as rash, itching, and drug-induced lupus-like syndrome are also common. Many patients experience taste alterations, particularly a metallic taste. Blood abnormalities including reduced white blood cell count (leukopenia), reduced platelet count (thrombocytopenia), and aplastic anemia can occur. Kidney problems, including proteinuria (protein in urine) and nephrotic syndrome, affect approximately 30% of patients on long-term therapy. Other common side effects include fever, weakness, joint pain, and lymph node enlargement. These side effects occur because penicillamine works by chelating metals and altering immune function, which while therapeutic, can disrupt normal physiological processes. Regular blood tests and urine analysis are necessary during treatment to monitor for these potential side effects, as severe side effects requiring the drug to be discontinued occur in approximately 30% of patients 1.
Some of the key side effects to monitor for include:
- Early sensitivity reactions marked by fever and cutaneous eruptions, lymphadenopathy, neutropenia or thrombocytopenia, and proteinuria, which may occur during the first 1-3 weeks of treatment 1
- Late reactions, such as nephrotoxicity, usually heralded by proteinuria or the appearance of other cellular elements in the urine, for which discontinuation of D-penicillamine should be immediate 1
- Dermatological toxicities, including progeric changes in the skin and elastosis perforans serpingosa, pemphigous or pemphigoid lesions, lichen planus, and aphthous stomatitis 1
- Very late side effects, such as nephrotoxicity, myasthenia gravis, polymyositis, loss of taste, immunoglobulin A depression, and serous retinitis, which are rare but can occur 1
It is essential to note that the side effects of penicillamine can be significant, and regular monitoring and dose adjustments are necessary to minimize the risk of adverse effects. The most recent and highest quality study, published in 2012, provides guidance on the management of Wilson's disease, including the use of D-penicillamine and the monitoring of side effects 1.
From the FDA Drug Label
ADVERSE REACTIONS Penicillamine is a drug with a high incidence of untoward reactions, some of which are potentially fatal. Reported incidences (%) for the most commonly occurring adverse reactions in rheumatoid arthritis patients are noted, based on 17 representative clinical trials reported in the literature (1270 patients) Allergic Generalized pruritus, early and late rashes (5%), pemphigus (see WARNINGS), and drug eruptions, which may be accompanied by fever, arthralgia, or lymphadenopathy have occurred (see WARNINGS and PRECAUTIONS). Gastrointestinal Anorexia, epigastric pain, nausea, vomiting, or occasional diarrhea may occur (17%). Hematological Penicillamine can cause bone marrow depression (see WARNINGS). Leukopenia (2%) and thrombocytopenia (4%) have occurred. Renal Patients on penicillamine therapy may develop proteinuria (6%) and/or hematuria which, in some, may progress to the development of the nephrotic syndrome as a result of an immune complex membranous glomerulopathy (see WARNINGS)
Common side effects of penicillamine include:
- Allergic reactions, such as generalized pruritus and rashes
- Gastrointestinal symptoms, such as anorexia, epigastric pain, nausea, vomiting, and diarrhea
- Hematological effects, such as leukopenia and thrombocytopenia
- Renal effects, such as proteinuria and hematuria 2 2
From the Research
Common Side Effects of Penicillamine
- Skin rashes, as reported in 27 out of 84 toxic reactions in a study on rheumatoid arthritis patients treated with D-penicillamine 3
- Proteinuria, which occurred in 15 out of 84 toxic reactions in the same study 3
- Low platelets, found in 14 out of 84 toxic reactions 3
- Taste abnormalities, experienced by 10 out of 84 patients 3
- Hypersensitivity to penicillamine, observed in one patient with Wilson's disease 4
- Decreased WBC and platelet count, found in 3 patients after treatment with penicillamine and zinc salts 4
- Systemic lupus erythematosus, polymyositis, and myasthenia gravis, all recorded as complications of penicillamine therapy in patients with rheumatoid arthritis 5
- Elastosis perforans serpiginosa, a rare side effect reported in a patient with rheumatoid arthritis treated with penicillamine 5