Hydroxyurea Protocol PDF Print E-mail
Health Care Providers - Care Paths And Protocols - Children & Adolescents

Higher levels of fetal hemoglobin (Hb F) and lower leukocyte counts are thought to be beneficial in patients with sickle cell disease and can be achieved with daily oral administration of hydroxyurea (HU). A placebo-controlled, double-blind, prospective trial in severely affected adults with Hb SS showed that HU significantly reduced the incidence of vaso-occlusive pain, acute chest syndrome, and blood transfusions. A multi-center phase I/II trial in children >5 years-of-age showed safety and hematologic effects similar to those observed in adults. Clinical benefit in children with Hb SS has been suggested by a number of open-label trials. The drug is FDA-approved for selected adult patients, with the important caution that the drug is not curative and requires close hematologic monitoring for myelotoxicity and the strict use of contraception by both men and women who are sexually active. Use of HU in patients with Hb SC or Sb +- thalassemia is under investigation.

The clinical course of each patient with sickle cell disease should be regularly reviewed by a pediatric hematologist/sickle cell program and the possibility of hydroxyurea treatment and its pros and cons considered. Many patients with severe complications may also be candidates for either a program of chronic transfusions (p. 27) or, if an HLA-matched sibling is available, stem cell transplantation (p.29). HU is generally not considered appropriate for patients with stroke, and it is not useful in the treatment of acute sickle pain. No improvement is expected until the drug has been taken daily for 3-6 months. HU may alter the natural history of the sickle cell disease; for example splenomegaly or splenic sequestration may occur in relatively older patients. HU is a potentially toxic chemotherapeutic agent whose long-term toxicity (including concerns about carcinogenicity and teratogenicity) is unresolved. Thus the drug should be initiated and monitored only by hematologists with expertise in chemotherapy and sickle cell disease and after written documentation of patient education and consent.

Indications (Inclusion criteria)

  • Dx: Hb SS or S b o-thalassemia

  • ³ 3 years-of-age

  • ³ 3 severe vaso-occlusive pain events/year, or

  • ³ 2 episodes of acute chest syndrome/year, or

  • Any combination of ³ 3 episodes of acute chest syndrome and severe pain/year

Exclusion criteria

  • Pregnancy

  • Inability to use reliable contraception if sexually active (men and women)

  • Inability to comply with daily dosing and frequent laboratory monitoring


Hydroxyurea 15-20 mg/kg p.o. q.d.(supplied as Droxia [200, 300, and 400mg] and Hydrea [500mg] capsules). All size capsules must be available for accurate dosing. Liquid suspensions, 100mg/ml in flavored syrup, are stable for at least 1 month and can be prepared for younger children. The dose may be increased by approximately 5 mg/kg/day every 8-12 weeks to a maximum dose of 30 mg/kg/day or until there is evidence of toxicity (see below).

Consider folate supplementation, 0.4-1 mg p.o. q.d.


1. CBC, reticulocyte count: baseline, then every 2 weeks until maximum dose tolerated without toxicity for 8-12 weeks; then every 4 weeks.

2. History and physical examination: baseline, then every 4 weeks until maximum dose tolerated for 8-12 weeks, then every 8 weeks. Be alert to the possibility of recurrent or new splenomegaly and risk of splenic sequestration.

3. Fractionated bilirubin, ALT, and creatinine: baseline, then every 12-24 weeks.

4. Quantitation of hemoglobin F: baseline, every 3 months x 2, then every 6 months.

5. Pregnancy test (if menstruating): baseline, then prn. (Stop HU immediately for positive result and offer teratogen risk counseling. Information is available from the Organization of Teratogen Information Services at 888-285-3410 or www.otispregnancy.org).

Toxicity: Toxicity from hydroxyurea is generally defined as any of the following:

  • ANC <2000 x 106/L

  • platelet count <80,000 x 106/L

  • absolute reticulocyte count <80,000 x 106/L if hemoglobin <9.0 gm/dl

  • hemoglobin <5 gm/dl or >20% below baseline

  • serum creatinine >1.0 mg/dl or 50% above baseline

  • 100% increase in ALT

If toxicity occurs, treatment will be stopped for at least 1 week and until toxicity resolves. HU will then be resumed at the same dose or a dose decreased by 2.5-5 mg/kg/d. If toxicity does not recur after 12 wks on the lower dose, the dose may then be increased by 2.5-5 mg/kg/d. If toxicity recurs on the higher dose, then HU will be stopped again until toxicity resolves, and hydroxyurea can then be resumed at the lower dose.

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