Possible Dose Adjustment of Hydroxyurea In Young Patients with Sickle Cell Disease and Followed In the Belgian Registry

In August 2009, 138/230 patients included in the Belgian Registry of SCD were on HU. The criteria for HU treatment were mainly recurrent ACS or > 2 hospitalisations/year for vaso-occlusive crisis. Based upon patient's age and mean weight, we calculated theoretically the possibilities of giving the adequate HU daily dose by prescribing either 500 mg capsules or the new formulation with the possibility of adjustment by increment of 250 mg or 100 mg. Dose regimens were defined as starting dose (15-20 mg/kg/day), normal dose (20-25 mg/kg/day), increased dose (25-30 mg/kg/day), high dose (30-35 mg/kg/day) and very high dose (>35 mg/kg/day). “Daily intake” is defined as HU administration during 7 days per week with a constant daily posology, “daily alternating intake” is defined as a different posology for at least one day per week. When a daily dose is judged outside the chosen posology with the available formulations, a weekly dose is calculated and given few days per week (weekly regimen) at the fixed available formulation. Neuman-Keuls Multiple Comparison Test was used; p < 0.05 is statistically significant.

Median age at start of HU therapy was 4.9 years (range, 0.7 – 35.8) and the median age in August 2009 was 11.3 years (range, 3.3–36.2). Comparison of the posology with the three HU formulations (500 mg capsules,1,000 mg breakable tablets alone or in combination with 100 mg tablets) according to the dose options at initiation of HU therapy is shown on Table1. At initiation of HU using the 500 mg capsules, the treatment is administered as weekly, daily alternating regimen and at constant daily posology for 70%, 19% and 11% of the patients, respectively. At initiation of HU treatment, using the 100 mg combination option, 96% of the patients had a constant daily posology, versus 41% and 11% with the with 250 mg alone and 500 mg formulations, respectively. Data on other dose regimens are detailed in Table1. It shows that for starting and increasing dosage a significantly higher percentage of patients can benefit of a daily constant intake when using the breakable 1,000 mg tablets (and 100 mg tablets) rather than if using the 500 mg capsules.

According to the patient's age and weight in August 2009, with the 500mg capsules, 41% and 78% can receive HU at constant daily dose if treated at starting and normal dose respectively, while the proportion increases up to 72% and 92% with the 1,000 mg breakable tablets.

Among SCD patients of the Belgian Registry, 60% are under HU therapy. Starting HU doses are generally within the range of 15–20 mg/kg/day, and escalated up to the maximum tolerated dose if judged appropriate. Both the 100 mg and 250 mg formulations allow a daily treatment at constant dose for a majority of young patients and to avoid high or very high doses of HU. With these formulations, an increased tolerance and safety is expected. In addition, a daily standard medication is probably also a factor of improved adherence to therapy. These data emphasize the need of appropriate HU formulation to treat children with SCD.

No relevant conflicts of interest to declare.