What medications cause pancytopenia (a condition characterized by a reduction in the number of red blood cells, white blood cells, and platelets)?

From the Guidelines

Pancytopenia can be caused by several medications, including chemotherapy drugs, antibiotics, antiepileptic medications, immunosuppressants, and other classes of drugs, with the most recent and highest quality evidence suggesting that tyrosine kinase inhibitors (TKIs) such as dasatinib, nilotinib, and bosutinib are associated with a higher risk of myelosuppression, including neutropenia, thrombocytopenia, and anemia, as reported in the 2016 European LeukemiaNet recommendations 1. Medications that can cause pancytopenia include:

• Chemotherapy drugs like methotrexate, cyclophosphamide, and 5-fluorouracil, which directly inhibit cell division in the bone marrow
• Antibiotics such as chloramphenicol, trimethoprim-sulfamethoxazole, and linezolid, particularly with prolonged use
• Antiepileptic medications including carbamazepine, phenytoin, and valproic acid, which may trigger this condition through immune-mediated mechanisms
• Immunosuppressants like azathioprine, mycophenolate mofetil, and sirolimus, which can cause dose-dependent bone marrow suppression
• Other medications associated with pancytopenia include certain NSAIDs (particularly indomethacin), gold compounds used for rheumatoid arthritis, antithyroid drugs (methimazole, propylthiouracil), and some antipsychotics like clozapine The risk of developing pancytopenia varies based on individual factors, medication dosage, and duration of treatment, with the incidence of grade 3 or 4 cytopenias being highest at the initiation of treatment and decreasing substantially with longer exposures to any TKI, as reported in the 2016 European LeukemiaNet recommendations 1. Regular blood count monitoring is essential when taking these medications, especially during the initial treatment period, and any signs of infection, unusual bleeding, or fatigue should prompt immediate medical attention, with the management of cytopenias depending on the severity and duration of the toxicity, as well as the specific medication and patient population, as outlined in the 2016 European LeukemiaNet recommendations 1.

From the FDA Drug Label

Methotrexate can suppress hematopoiesis and cause anemia, aplastic anemia, pancytopenia, leukopenia, neutropenia, and/or thrombocytopenia. In controlled clinical trials in rheumatoid arthritis (n=128), leukopenia (WBC <3000/mm3) was seen in 2 patients, thrombocytopenia (platelets <100,000/mm3) in 6 patients, and pancytopenia in 2 patients.

Medications that cause pancytopenia include:

• Methotrexate: as it can suppress hematopoiesis and cause pancytopenia, especially in patients with malignancy and preexisting hematopoietic impairment 2.

From the Research

Medications Causing Pancytopenia

• Trimethoprim-sulfamethoxazole (TMP-SMX) has been reported to cause pancytopenia in several studies 3, 4, 5, 6
• Methotrexate (MTX) is another medication that can cause pancytopenia, especially when used in combination with TMP-SMX 7, 4, 5

Risk Factors for Pancytopenia

• Concomitant use of TMP-SMX and MTX increases the risk of pancytopenia 4, 5
• Elevated BUN or creatinine levels, increasing mean corpuscular volume values, and increased age are also risk factors for pancytopenia associated with MTX therapy 5
• Hypoalbuminemia, renal insufficiency, dosing errors, and non-supplementation of folates are potential risk factors for MTX-induced pancytopenia 7

Clinical Presentation and Management

• Pancytopenia can present with symptoms such as oral mucositis, fever, diarrhea, bleeding gums, and purpura 7, 6
• Discontinuation of the offending medication and supportive care are essential in the management of drug-induced pancytopenia 3, 7, 6