Consensus Treatment Protocol and Technical remarks for the implementation of Hydroxyurea Therapy

The following laboratory tests are recommended before starting hydroxyurea:
Complete blood count (CBC) with white blood cell (WBC) differential, reticulocyte count, platelet count,and RBC MCV

Quantitative measurement of HbF if available (e.g., hemoglobin electrophoresis, high-performance liquid chromatography (HPLC))

Comprehensive metabolic profile, including renal and liver function tests, Pregnancy test for women
Initiating and Monitoring Therapy

Baseline elevation of HbF should not affect the decision to initiate hydroxyurea therapy.
Both males and females of reproductive age should be counseled regarding the need for contraception while taking hydroxyurea.

Starting dosage for adults (500 mg capsules): 15 mg/kg/day (round up to the nearest 500 mg); 5-10 mg/kg/day if patient has chronic kidney disease

Starting dosage for infants and children: 20 mg/kg/day

Monitor CBC with WBC differential and reticulocyte count at least every 4 weeks when adjusting dosage.
Aim for a target absolute neutrophil count :2,000/ul; however, younger patients with lower baseline counts may safely tolerate absolute neutrophil counts down to1,250/ul.

Maintain platelet count :80,000/ul
If neutropenia or thrombocytopenia occurs:
Hold hydroxyurea dosing, Monitor CBC with WBC differential weekly

When blood counts have recovered, reinstitute hydroxyurea at a dose 5 mg/kg/day lower than the dose given before onset of cytopenias

If dose escalation is warranted based on clinical and laboratory findings, proceed as follows:
Increase by 5 mg/kg/day increments every 8 weeks

Give until mild myelosuppression (absolute neutrophil count 2,000/ul to 4,000/ul) is achieved, up to a maximum of 35 mg/kg/day.

Once a stable dose is established,laboratory safety monitoring should include:
CBC with WBC differential, reticulocyte count, and platelet count every 2-3 months
People should be reminded that the effectiveness of hydroxyurea depends on their adherence to daily dosing. They should be counseled not to double up doses if a dose is missed.

A clinical response to treatment with hydroxyurea may take 3–6 months. Therefore, a 6- month trial on the maximum tolerated dose is required prior to considering discontinuation due to treatment failure, whether due to lack of adherence or failure to respond to therapy.

Monitor RBC MCV and HbF levels for evidence of consistent or progressive laboratory response.
A lack of increase in MCV and/or HbF is not an indication to discontinue therapy.
For the patient who has a clinical response, long-term hydroxyurea therapy is indicated.
Hydroxyurea therapy should be continued during hospitalizations or illness.