Can penicillamine cause pancytopenia?

From the Guidelines

Yes, penicillamine can cause pancytopenia, a serious condition characterized by a reduction in all three blood cell types: red blood cells, white blood cells, and platelets. This adverse effect is considered rare but potentially life-threatening. Patients taking penicillamine (typically prescribed for conditions like Wilson's disease, rheumatoid arthritis, or cystinuria) should undergo regular blood count monitoring, especially during the first 6 months of treatment when hematologic complications are most likely to occur. The recommended monitoring schedule includes complete blood counts every 2 weeks for the first 6 months and monthly thereafter. If pancytopenia develops, penicillamine should be discontinued immediately and the patient should receive appropriate medical care. The mechanism behind penicillamine-induced pancytopenia is thought to involve immune-mediated bone marrow suppression or direct toxicity to hematopoietic cells, as suggested by studies such as 1. Other hematologic adverse effects of penicillamine include isolated thrombocytopenia, leukopenia, or aplastic anemia. Patients should be educated to report symptoms such as unusual bleeding, bruising, persistent fever, or signs of infection promptly to their healthcare provider. It's also important to note that penicillamine use is associated with numerous side effects, including severe side effects requiring the drug to be discontinued, which occur in approximately 30% of patients, as reported in 1. Early sensitivity reactions, such as fever and cutaneous eruptions, lymphadenopathy, neutropenia or thrombocytopenia, and proteinuria, may occur during the first 1-3 weeks of treatment, and penicillamine should be discontinued immediately if these reactions occur. Regular monitoring and prompt reporting of any adverse effects are crucial to minimize the risk of pancytopenia and other serious side effects associated with penicillamine treatment. Key points to consider when prescribing penicillamine include:

• Regular blood count monitoring
• Discontinuation of penicillamine if pancytopenia or other severe side effects occur
• Patient education on reporting symptoms promptly
• Awareness of the potential for immune-mediated bone marrow suppression or direct toxicity to hematopoietic cells.

From the FDA Drug Label

The use of penicillamine has been associated with fatalities due to certain diseases such as aplastic anemia, agranulocytosis, thrombocytopenia Penicillamine can cause bone marrow depression (see WARNINGS). Leukopenia (2%) and thrombocytopenia (4%) have occurred. Fatalities have been reported as a result of thrombocytopenia, agranulocytosis, aplastic anemia, and sideroblastic anemia Thrombotic thrombocytopenic purpura, hemolytic anemia, red cell aplasia, monocytosis, leukocytosis, eosinophilia, and thrombocytosis have also been reported.

Pancytopenia is a condition where there is a reduction in the number of red and white blood cells, as well as platelets. While the drug labels do not explicitly mention pancytopenia, they do report aplastic anemia, agranulocytosis, thrombocytopenia, and leukopenia, which are all conditions that can be associated with pancytopenia.

• Aplastic anemia is a condition where the bone marrow fails to produce enough blood cells.
• Agranulocytosis is a condition where there is a severe reduction in the number of white blood cells.
• Thrombocytopenia is a condition where there is a low platelet count.
• Leukopenia is a condition where there is a low white blood cell count. Given that penicillamine can cause these conditions, it is possible that it could also cause pancytopenia. However, this is not explicitly stated in the drug labels. 2 2

From the Research

Pancytopenia and Penicillamine

• Pancytopenia is a condition characterized by a reduction in the number of red and white blood cells, as well as platelets [ 3, 4 ].
• Penicillamine, a drug used to treat Wilson's disease and rheumatoid arthritis, has been associated with various adverse events, including hematological effects [ 3, 4 ].
• Studies have reported cases of pancytopenia in patients treated with penicillamine, suggesting a possible link between the drug and the development of this condition [ 3, 4 ].

Evidence from Studies

• A case report published in the Journal of pharmacy practice described a patient with Wilson's disease who developed pancytopenia after starting penicillamine therapy [ 3 ].
• A retrospective audit of patients with hepatic Wilson's disease found that 25% of patients experienced adverse events related to penicillamine, including hematological effects such as pancytopenia [ 4 ].
• Other studies have reported various side effects of penicillamine, including skin rashes, proteinuria, and systemic lupus erythematosus, but did not specifically mention pancytopenia [ 5, 6 ].

Hematological Effects of Penicillamine

• The exact mechanism by which penicillamine causes pancytopenia is not fully understood, but it is thought to be related to the drug's effects on the bone marrow [ 3, 4 ].
• Pancytopenia has been reported to occur in patients taking penicillamine, even at low doses, and may be a rare but serious side effect of the drug [ 3, 4 ].