Hydroxyurea Management During Active Infection
Do not stop hydroxyurea during active infection in patients with sickle cell disease. The evidence clearly demonstrates that hydroxyurea therapy is not associated with an increased incidence of infection, and severe neutropenia when it occurs has not been complicated by infection in clinical trials 1.
Key Evidence Supporting Continuation
Safety Profile During Infection
- Hydroxyurea therapy was not associated with an increased incidence of infection in long-term follow-up studies of patients with sickle cell disease 1.
- Severe neutropenia (absolute neutrophil count <500/mm³) was rare in clinical trials and was not complicated by infection 1.
- The American Thoracic Society guidelines explicitly state that infection risk is not increased with hydroxyurea use 1.
Neutropenia Management Without Infection Risk
- Mild to moderate neutropenia (absolute neutrophil count 500-1,249/mm³) occurred in approximately 47% of patients but required only dose reductions, not discontinuation 1.
- When bone marrow suppression occurs, it typically resolves within 2 weeks of temporary discontinuation if needed, and therapy can be resumed at a lower dose 1.
- The myelosuppression is dose-limiting but manageable and does not translate to increased infection risk 1.
Specific Guidance on Antibiotic Interactions
Do not suspend hydroxyurea when initiating doxycycline or other antibiotics 2. This explicit guidance from the American Society of Hematology reinforces that concurrent infection treatment and hydroxyurea therapy are compatible.
When to Consider Temporary Discontinuation
The only scenarios requiring hydroxyurea suspension are:
- Severe myelosuppression with significant decreases in multiple cell lines (not infection itself) 1.
- At least 72 hours before CAR-T cell infusion if the patient is on a transplant protocol 2.
- Hyperleukocytosis management where higher doses (50-60 mg/kg/day) may be used temporarily 2.
Clinical Rationale
Continuing hydroxyurea during infection is critical because:
- Patients with sickle cell disease have increased mortality risk, and prolonged hydroxyurea therapy (≥5 years) reduces mortality from 51.1% to 30.4% 1.
- Stopping hydroxyurea increases the risk of vaso-occlusive crises, acute chest syndrome, and hospitalizations—complications that can be triggered or worsened by infection 1.
- The mortality benefit requires continuous therapy, and interruptions may compromise long-term outcomes 1, 3.
Common Pitfall to Avoid
Do not confuse neutropenia with infection risk. While hydroxyurea causes predictable neutropenia, this has not translated to increased infection rates in any clinical trial 1. The decision to temporarily hold hydroxyurea should be based on absolute neutrophil count thresholds and severity of myelosuppression, not on the presence of infection itself 1.