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 15 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 – 3000/microL • ARC 80 – 100,000/microL • PLT 80,000 – 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 two 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 two to three 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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