What medications can cause leukopenia (low white blood cell count)?

Medication Causes of Leukopenia

Numerous medications can cause leukopenia, with chemotherapy agents being the most common culprits, followed by certain antibiotics, anticonvulsants, and immunosuppressants. 1

Chemotherapy Agents

• Chemotherapy drugs frequently cause leukopenia due to their direct myelosuppressive effects on bone marrow, with different regimens showing varying rates of leukopenia 1:

  • Gemcitabine + cisplatin: 21.5-30.5% incidence of leukopenia 1
  • Gemcitabine + cisplatin + cetuximab: 30.5% incidence of leukopenia 1
  • Paclitaxel + gemcitabine + cisplatin: 49% incidence of leukopenia 1
  • MVAC (methotrexate, vinblastine, doxorubicin, cisplatin): 44.8% incidence of leukopenia 1
  • Cyclophosphamide: significant risk of leukopenia, especially when combined with other myelosuppressive agents 2

• Dose-intensity and scheduling of chemotherapy significantly impact the risk of leukopenia 1:

  • Higher doses and more frequent administration increase risk
  • Combination regimens generally have higher rates than single agents

Antibiotics

• Beta-lactam antibiotics (penicillins and cephalosporins) can cause leukopenia, particularly with high doses and prolonged use 3, 4:

  • Risk increases with doses ≥150 mg/kg/day
  • Duration of therapy >2 weeks significantly increases risk
  • Leukopenia is uncommon within the first week of treatment

• Specific antibiotics associated with leukopenia include:

  • Cefazolin and cefoxitin (rechallenge with different cephalosporins may trigger recurrent leukopenia) 4
  • Trimethoprim-sulfamethoxazole 1
  • Ganciclovir (antiviral) 1

Anticonvulsants

• Carbamazepine can cause transient leukopenia and neutropenia 5:
  • Most common during the first month of therapy
  • Patients with low baseline white blood cell counts are at higher risk
  • Discontinuation usually not necessary unless counts fall below 500/mm³ or symptoms develop
  • Careful monitoring of blood counts is essential, especially during the first month 6, 5

Immunosuppressants

• Immunosuppressive medications used in transplant recipients frequently cause leukopenia 1:
  • Azathioprine and mycophenolate mofetil are myelosuppressive and often cause leukopenia alongside thrombocytopenia
  • Sirolimus can inhibit erythropoiesis and may contribute to cytopenias

Antipsychotics

• Olanzapine has been associated with dose-dependent leukopenia 7:
  • Reducing the dose may normalize white blood cell counts without discontinuation
  • Careful monitoring is recommended

Other Medications

• ACE inhibitors can cause leukopenia 2
• Natalizumab 2
• Zidovudine 2

Risk Factors and Monitoring

• Risk factors for medication-induced leukopenia include 5, 8:

  • Pre-existing low white blood cell counts
  • Concurrent use of multiple myelosuppressive medications
  • Advanced age
  • Renal or hepatic dysfunction

• Monitoring recommendations 1, 5:

  • Baseline complete blood count before starting high-risk medications
  • Regular monitoring during treatment, especially during the first month
  • Increased frequency of monitoring if abnormalities develop
  • Consider G-CSF (granulocyte colony-stimulating factor) for high-risk patients with febrile neutropenia 1

Management Considerations

• For chemotherapy-induced leukopenia 1:

  • Colony-stimulating factors (CSFs) should be considered for patients with fever and neutropenia who are at high risk for infection-related complications
  • High-risk features include prolonged (≥10 days) and profound (≤0.1 x 10⁹/L) neutropenia, age >65 years, uncontrolled primary disease, pneumonia, hypotension, or sepsis syndrome

• For non-chemotherapy medication-induced leukopenia 5, 8, 7:

  • Consider dose reduction before discontinuation when possible
  • Discontinue medication if severe neutropenia (ANC <500/mm³) or signs of infection develop
  • Monitor for recovery of white blood cell counts after medication discontinuation

• Combined or sequential use of medications with similar myelosuppressive toxicities can potentiate leukopenia and should be avoided when possible 2