Maximum Doses for Hydroxyurea
The maximum dose of hydroxyurea is 2 grams per day (or 2.5 g/day in patients weighing >80 kg) for myeloproliferative neoplasms, while for sickle cell disease the maximum tolerated dose averages 25-30 mg/kg/day. 1, 2
Myeloproliferative Neoplasms (Polycythemia Vera and Essential Thrombocythemia)
For polycythemia vera and essential thrombocythemia, the maximum dose is 2 g/day (2.5 g/day if body weight >80 kg). 1
The European LeukemiaNet and NCCN guidelines define resistance to hydroxyurea based on failure to achieve therapeutic goals after 3 months at at least 2 g/day (or 2.5 g/day in patients >80 kg). 1
These maximum doses represent the threshold at which treatment failure is assessed, not necessarily the highest safe dose, but they establish the practical upper limit for therapeutic efficacy. 1
If patients fail to respond at these doses (inadequate hematocrit control, uncontrolled myeloproliferation, or persistent splenomegaly after 3 months), second-line therapy with ruxolitinib or interferon-alpha should be considered rather than further dose escalation. 1
Sickle Cell Disease
For sickle cell disease, hydroxyurea should be escalated to maximum tolerated dose (MTD), which averages 25-30 mg/kg/day. 2, 3
The MTD approach involves dose escalation until mild myelosuppression occurs (typically absolute neutrophil count 2.0-4.0 × 10⁹/L), with average achieved doses of 25.4 ± 5.4 mg/kg/day in pediatric studies. 2
This MTD strategy has demonstrated sustained hematologic efficacy for up to 8 years without adverse effects on growth or increased DNA mutations. 2
Some studies suggest fixed low-dose hydroxyurea (10 mg/kg/day) may provide clinical benefit with reduced monitoring requirements, though current guidelines favor MTD escalation for optimal outcomes. 4, 5, 6
The MTD approach requires careful monitoring every 2 weeks during dose escalation, then monthly once stable dosing is achieved. 2
Psoriasis
For psoriasis, typical doses range from 0.5 to 1.5 g/day, though specific maximum doses are not well-established in guidelines. 1
Most patients with psoriasis are treated with 1.0-1.5 g/day, with 60-75% achieving significant improvement. 1
The lack of randomized controlled trials for psoriasis limits definitive dosing recommendations compared to hematologic indications. 1
Critical Monitoring Considerations
Dose reduction or discontinuation is mandatory if absolute neutrophil count falls below 1.0 × 10⁹/L, platelet count below 100 × 10⁹/L, or hemoglobin below 10 g/dL at any dose. 1
Hydroxyurea causes bone marrow suppression affecting all cell lines, requiring vigilant monitoring during infections when cytopenia risk is heightened. 7
The drug should be used with particular caution in young patients (<40 years) with polycythemia vera due to potential long-term leukemogenic risk. 1