| Laboratory testing | Dosing |
| Initiating hydroxyurea therapy |
- CBC with differential and PLT
- Reticulocyte count
- Quantitative measure of HbF (eg, HPLC)
- Kidney and liver function tests
- Pregnancy test for females of childbearing potential
| - Infants younger than 1 year: Start at 20 mg/kg daily
- Older children, adolescents and adults with CrCl >60 mL/min: Start at 20 mg/kg daily
- Patients with chronic kidney disease: Start at half the normal dose (eg, 5 to 10 mg/kg daily)
|
| Transitioning from chronic prophylactic transfusion to hydroxyurea therapy |
- All baseline testing listed above for starting hydroxyurea
- Every month: CBC with differential and PLT, ANC, ARC, HbF, kidney and liver function tests
| - Wean transfusion by lowering the post-transfusion target hemoglobin to 11.5 g/dL.
- Increase hydroxyurea dose every 8 weeks by 5 mg/kg daily to a maximum of 35 mg/kg or 2500 mg daily using MTD parameters below.
- Continue weaning transfusions. Reduce the target post-transfusion hemoglobin to 11 g/dL at 2 months and to 10.5 g/dL at 4 months.
- Discontinue transfusions when stable MTD is reached; initiate phlebotomy or continue chelation therapy if there is transfusional iron overload.
|
| Titrating hydroxyurea to MTD* |
- CBC with differential and reticulocyte count at least every month
| - Criteria for dose escalation (must meet all of the following):
- ANC >1000/microL
- ARC >100,000/microL
- PLT >150,000/microL
- Criteria for MTD (any of the following with no evidence of toxicity):
- ANC 1500 to 3000/microL
- ARC 80 to 100,000/microL
- PLT 80,000 to 100,000/microL
- Criteria for toxicity (any of the following):
- ANC <1500/microL (<1000/microL if <2 years of age)
- ARC <80,000/microL
- PLT <80,000/microL
- Monitor CBCs over at least 2 months after each dose increase to determine if MTD has been reached or further dose escalation is indicated.
|
| Chronic maintenance therapy |
- CBC with differential, PLT, and reticulocyte count every 2 to 3 months
- Creatinine and liver function tests every 6 to 12 months
- Ferritin and HbF once per year
- Urine pregnancy tests as appropriate
- For hematologic toxicity, weekly CBC until resolution
| - Reinforce importance of dose adherence
- Reinforce need for contraception if appropriate¶
- For hematologic toxicity, hold dose until recovery into target range and reinitiate at the same or lower dose (eg, previous dose reduced by 2.5 mg/kg/day), depending on the severity and duration of toxicity
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