What drugs are known to cause bone marrow suppression?

Drugs Known to Cause Bone Marrow Suppression

Multiple chemotherapeutic agents, immunosuppressants, and certain antibiotics are the most common drugs known to cause bone marrow suppression, with taxanes, anthracyclines, alkylating agents, and methotrexate carrying particularly high risk. 1

Major Drug Categories Causing Bone Marrow Suppression

Chemotherapeutic Agents

• Taxanes (paclitaxel, docetaxel): 65-86% incidence of grade 3-4 neutropenia 1
• Anthracyclines (doxorubicin): Significant risk of neutropenia, particularly when used in combination regimens 2
• Alkylating agents (cyclophosphamide, busulfan): Cause myelosuppression affecting multiple cell lines 3, 4
• Platinum compounds (cisplatin): Associated with dose-dependent bone marrow suppression 2
• Antimetabolites (methotrexate, fluorouracil): High risk of myelosuppression, especially with methotrexate 1
• PARP inhibitors: Cause anemia, neutropenia, and thrombocytopenia 1

Immunosuppressants

• Azathioprine: Causes severe, potentially life-threatening myelotoxicity 1
• Methotrexate: Can cause bone marrow suppression, particularly in first 4-6 weeks of treatment 1
• Mycophenolate mofetil (MMF): Significant risk of leukopenia and lymphopenia 5

Antibiotics

• Trimethoprim-sulfamethoxazole: Can cause bone marrow suppression, especially when combined with other myelosuppressive agents 1, 6, 5
• Ganciclovir/Valganciclovir: Significant risk of neutropenia 1

Other Medications

• Carbamazepine: Can cause bone marrow depression requiring monitoring 7
• Trastuzumab, bevacizumab, venetoclax: Emerging evidence of association with myelosuppression 8

Mechanism and Manifestations

Bone marrow suppression typically manifests as:

1. Neutropenia: Most common and earliest manifestation, increasing infection risk
2. Thrombocytopenia: Increases bleeding risk
3. Anemia: Causes fatigue, decreased exercise tolerance

The nadir of blood counts typically occurs:

• 1-2 weeks after chemotherapy administration 1
• Early in treatment (first 4-6 weeks) for drugs like methotrexate 1

Risk Factors for Severe Bone Marrow Suppression

• Combination therapy: Multiple myelosuppressive agents significantly increase risk 1
• Age: Older adults have decreased bone marrow reserve 6
• Renal dysfunction: Impairs drug clearance 1
• Low body weight: Associated with higher risk (e.g., with PARP inhibitors) 1
• Prior myelosuppressive treatments: Reduces bone marrow reserve 1
• Drug interactions: Particularly important with azathioprine (e.g., allopurinol) 1

Monitoring and Prevention

• Baseline assessment: Complete blood count before starting high-risk medications 1
• Regular monitoring: CBC with differential during treatment 1
• Timing of labs: For methotrexate, check labs 4-6 days after dosing to avoid transient abnormalities 1
• Dose adjustments: Based on body weight, renal function, and blood counts 1
• Growth factor support: Consider in selected cases, particularly with chemotherapy 1

Common Pitfalls

1. Failure to recognize drug combinations that potentiate myelosuppression (e.g., trimethoprim-sulfamethoxazole with methotrexate)
2. Inadequate monitoring frequency, especially during early treatment
3. Missing the timing of nadirs specific to each medication
4. Overlooking less common causative agents (e.g., carbamazepine, antibiotics)
5. Continuing medication despite early signs of bone marrow suppression

When bone marrow suppression is detected, prompt evaluation of the severity and consideration of dose reduction or drug discontinuation is essential to prevent potentially life-threatening complications such as severe infections or bleeding 1, 3.