Medications That Can Cause Leukopenia
Numerous medications across different drug classes can cause leukopenia, with chemotherapy agents, immunosuppressants, and certain antibiotics posing the highest risk. 1
Chemotherapy Agents
- Chemotherapy drugs frequently cause leukopenia due to their direct myelosuppressive effects on bone marrow 1
- Specific chemotherapy regimens associated with leukopenia include:
- Dose intensity and scheduling significantly impact leukopenia risk 1
Immunosuppressants
- Azathioprine can cause leukopenia, especially when used with allopurinol 3
- Mycophenolate mofetil has myelosuppressive effects often associated with leukopenia 2
- Cyclophosphamide causes myelosuppression and immunosuppression, leading to increased infection risk 4
- Sirolimus has been associated with dose-dependent anemia and potential leukopenia 2
Antibiotics and Antimicrobials
- Trimethoprim-sulfamethoxazole can lead to leukopenia 2, 1
- Ganciclovir and other antiviral medications can cause leukopenia 2, 1
- Beta-lactam antibiotics have been associated with neutropenia 5
- Rifampin and isoniazid combination therapy has been linked to leukopenia 6
Antipsychotics and Psychotropic Medications
- Clozapine has the highest incidence of leukopenia among psychotropics and requires blood monitoring 7
- Carbamazepine can cause bone marrow suppression through direct toxic effects 7
- Olanzapine has been associated with dose-dependent leukopenia 8
Other Medications
- ACE inhibitors can cause leukopenia, especially in transplant recipients 2, 4
- Vancomycin has been associated with neutropenia or agranulocytosis 5
- Ticlopidine, diclofenac, and spironolactone have been linked to neutropenia 5
- Antithyroid drugs (e.g., propylthiouracil) can cause leukopenia 5
Risk Factors for Medication-Induced Leukopenia
- Advanced age 1
- Renal or hepatic dysfunction 1, 6
- Concomitant use of multiple myelosuppressive medications 4
- Genetic factors affecting drug metabolism (e.g., TPMT or NUDT15 deficiency with azathioprine) 3
Monitoring and Management
- Baseline complete blood count before starting high-risk medications 1, 3
- Regular monitoring during treatment, especially with high-risk drugs 3
- For chemotherapy-induced leukopenia, consider granulocyte colony-stimulating factors (G-CSF) for high-risk patients 1
- Dose reduction may be effective for some medications (e.g., olanzapine) 8
- Drug discontinuation may be necessary in severe cases, particularly with allergic or hypersensitivity reactions 7
Clinical Pearls
- Leukopenia may occur without other cytopenias or may be part of pancytopenia 2
- The risk of infection increases significantly when neutrophil counts fall below 500 cells/μL 5
- Drug-induced immune neutropenia occurs when drug-dependent antibodies form against neutrophil membrane glycoproteins 5
- Some medications (like azathioprine) require genetic testing before initiation to identify patients at high risk for severe myelosuppression 3